Schizophrenia & Other Psychotic Disorders

The other day, I saw a patient who really brought home the importance of considering culture in psychiatry. The patient’s chief complaint was that he had been hearing the voice of an “invisible man.” I noticed he had an accent I was familiar with, and it sounded like he was from Haiti. Indeed, he was born there.

Accordingly, I asked him about voodoo. He said he is not a voodoo worshiper but he believes in voodoo – and he thought that that was what was happening to him. He reported this was the second time he heard the voices – the last time was less than a year ago. He said he came to the hospital because he was trying to wash dishes when he felt some invisible force holding him down. The patient got upset, and he broke the dishes he was washing. Of course, a big melee ensued, and the police were called. They brought the patient to my hospital.

When I spoke with him, he said he was doing pretty well with his Parkinson’s disease but he was a little stiff. The patient was on carbidopa-levodopa 25-100 mg 1.5 t.i.d. for his Parkinson’s, quetiapine 50 mg b.i.d. for his psychotic symptoms, amantadine 100 mg b.i.d. to stimulate his dopamine, ropinirole 1 mg t.i.d. for restless legs, and baclofen 10 mg t.i.d. for muscle spasms.

This is a 66-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic, and he had a wide range of affect as he was able to smile, get serious, and be sad (about his problems). His speech was relevant, linear, and goal directed. His thought processes did not show any signs of loose associations, tangentiality or circumstantiality, but he did have delusions, and current auditory and visual hallucinations. His thought content was surrounding his problems, which because of the culture he is from, were attributed by him to voodoo. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was average. Despite my explaining to him that his psychotic symptoms were caused by the medication he was taking, his judgment and insight were fair as he explained to me the things that were happening to him were so tangible they had to be real. He had no suicidal or homicidal ideation.

I decided to leave his meds as is, and I gave him 25 mg loxapine at h.s.

When I saw him a few days later, I asked him how he was doing, and he reported that the invisible man and all of his shenanigans were gone. I again explained that the medication he was taking for his Parkinson’s was causing his psychotic symptoms, and now I had proof. Had the voices been tied to voodoo, the medication would not have stopped the symptoms. He looked skeptical.

This struck me as a perfect example of the importance of culture in psychiatry, and I thought it instructive to share.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of the Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), all in Chicago. He is recipient of the American Psychiatric Association’s 2019 Adolph Meyer Award for Lifetime Achievement in Psychiatric Research. Check out Dr. Bell’s new book, Fetal Alcohol Exposure in the African-American Community, at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community.

The other day, I saw a patient who really brought home the importance of considering culture in psychiatry. The patient’s chief complaint was that he had been hearing the voice of an “invisible man.” I noticed he had an accent I was familiar with, and it sounded like he was from Haiti. Indeed, he was born there.

Accordingly, I asked him about voodoo. He said he is not a voodoo worshiper but he believes in voodoo – and he thought that that was what was happening to him. He reported this was the second time he heard the voices – the last time was less than a year ago. He said he came to the hospital because he was trying to wash dishes when he felt some invisible force holding him down. The patient got upset, and he broke the dishes he was washing. Of course, a big melee ensued, and the police were called. They brought the patient to my hospital.

When I spoke with him, he said he was doing pretty well with his Parkinson’s disease but he was a little stiff. The patient was on carbidopa-levodopa 25-100 mg 1.5 t.i.d. for his Parkinson’s, quetiapine 50 mg b.i.d. for his psychotic symptoms, amantadine 100 mg b.i.d. to stimulate his dopamine, ropinirole 1 mg t.i.d. for restless legs, and baclofen 10 mg t.i.d. for muscle spasms.

This is a 66-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic, and he had a wide range of affect as he was able to smile, get serious, and be sad (about his problems). His speech was relevant, linear, and goal directed. His thought processes did not show any signs of loose associations, tangentiality or circumstantiality, but he did have delusions, and current auditory and visual hallucinations. His thought content was surrounding his problems, which because of the culture he is from, were attributed by him to voodoo. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was average. Despite my explaining to him that his psychotic symptoms were caused by the medication he was taking, his judgment and insight were fair as he explained to me the things that were happening to him were so tangible they had to be real. He had no suicidal or homicidal ideation.

I decided to leave his meds as is, and I gave him 25 mg loxapine at h.s.

When I saw him a few days later, I asked him how he was doing, and he reported that the invisible man and all of his shenanigans were gone. I again explained that the medication he was taking for his Parkinson’s was causing his psychotic symptoms, and now I had proof. Had the voices been tied to voodoo, the medication would not have stopped the symptoms. He looked skeptical.

This struck me as a perfect example of the importance of culture in psychiatry, and I thought it instructive to share.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of the Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), all in Chicago. He is recipient of the American Psychiatric Association’s 2019 Adolph Meyer Award for Lifetime Achievement in Psychiatric Research. Check out Dr. Bell’s new book, Fetal Alcohol Exposure in the African-American Community, at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community.

The other day, I saw a patient who really brought home the importance of considering culture in psychiatry. The patient’s chief complaint was that he had been hearing the voice of an “invisible man.” I noticed he had an accent I was familiar with, and it sounded like he was from Haiti. Indeed, he was born there.

Accordingly, I asked him about voodoo. He said he is not a voodoo worshiper but he believes in voodoo – and he thought that that was what was happening to him. He reported this was the second time he heard the voices – the last time was less than a year ago. He said he came to the hospital because he was trying to wash dishes when he felt some invisible force holding him down. The patient got upset, and he broke the dishes he was washing. Of course, a big melee ensued, and the police were called. They brought the patient to my hospital.

When I spoke with him, he said he was doing pretty well with his Parkinson’s disease but he was a little stiff. The patient was on carbidopa-levodopa 25-100 mg 1.5 t.i.d. for his Parkinson’s, quetiapine 50 mg b.i.d. for his psychotic symptoms, amantadine 100 mg b.i.d. to stimulate his dopamine, ropinirole 1 mg t.i.d. for restless legs, and baclofen 10 mg t.i.d. for muscle spasms.

This is a 66-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic, and he had a wide range of affect as he was able to smile, get serious, and be sad (about his problems). His speech was relevant, linear, and goal directed. His thought processes did not show any signs of loose associations, tangentiality or circumstantiality, but he did have delusions, and current auditory and visual hallucinations. His thought content was surrounding his problems, which because of the culture he is from, were attributed by him to voodoo. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was average. Despite my explaining to him that his psychotic symptoms were caused by the medication he was taking, his judgment and insight were fair as he explained to me the things that were happening to him were so tangible they had to be real. He had no suicidal or homicidal ideation.

I decided to leave his meds as is, and I gave him 25 mg loxapine at h.s.

When I saw him a few days later, I asked him how he was doing, and he reported that the invisible man and all of his shenanigans were gone. I again explained that the medication he was taking for his Parkinson’s was causing his psychotic symptoms, and now I had proof. Had the voices been tied to voodoo, the medication would not have stopped the symptoms. He looked skeptical.

This struck me as a perfect example of the importance of culture in psychiatry, and I thought it instructive to share.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of the Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), all in Chicago. He is recipient of the American Psychiatric Association’s 2019 Adolph Meyer Award for Lifetime Achievement in Psychiatric Research. Check out Dr. Bell’s new book, Fetal Alcohol Exposure in the African-American Community, at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community.

SAN FRANCISCO – Assessing the impact of tardive dyskinesia on the lives of patients requires more than just visual observation, Stanley N. Caroff, MD, said at the annual meeting of the American Psychiatric Association.

“You really need to ask the patient a lot of questions – and the family and the caregivers – about how much tardive dyskinesia affects their lives,” he said.

Those were some of the early results of RE-KINECT, an ongoing study of patients with schizophrenia and schizoaffective disorder who were being treated with antipsychotic agents.

TD occurs in more than 25% of patients in outpatient practices who are exposed to dopamine receptor blockers. Symptoms can include involuntary movements of the tongue, hands, and feet; facial distortions; rapid eye blinking; and difficulty speaking. In some cases, the side effects resolve after patients stop taking the medications.

In this video, Dr. Caroff discussed the studies’ findings and their implications for everyday clinical practice. He also presented some of the early RE-KINECT findings in a poster at the meeting.

Dr. Caroff is professor of psychiatry at the University of Pennsylvania, Philadelphia. He also is affiliated with the Michael J. Crescenz VA Medical Center in Philadelphia. He disclosed working as a consultant for and receiving research funding from Neurocrine Biosciences. He also is a consultant for DisperSol Technologies, Osmotica Pharmaceuticals, Teva Pharmaceutical.

ghenderson@mdedge.com

SAN FRANCISCO – Assessing the impact of tardive dyskinesia on the lives of patients requires more than just visual observation, Stanley N. Caroff, MD, said at the annual meeting of the American Psychiatric Association.

“You really need to ask the patient a lot of questions – and the family and the caregivers – about how much tardive dyskinesia affects their lives,” he said.

Those were some of the early results of RE-KINECT, an ongoing study of patients with schizophrenia and schizoaffective disorder who were being treated with antipsychotic agents.

TD occurs in more than 25% of patients in outpatient practices who are exposed to dopamine receptor blockers. Symptoms can include involuntary movements of the tongue, hands, and feet; facial distortions; rapid eye blinking; and difficulty speaking. In some cases, the side effects resolve after patients stop taking the medications.

In this video, Dr. Caroff discussed the studies’ findings and their implications for everyday clinical practice. He also presented some of the early RE-KINECT findings in a poster at the meeting.

Dr. Caroff is professor of psychiatry at the University of Pennsylvania, Philadelphia. He also is affiliated with the Michael J. Crescenz VA Medical Center in Philadelphia. He disclosed working as a consultant for and receiving research funding from Neurocrine Biosciences. He also is a consultant for DisperSol Technologies, Osmotica Pharmaceuticals, Teva Pharmaceutical.

ghenderson@mdedge.com

SAN FRANCISCO – Assessing the impact of tardive dyskinesia on the lives of patients requires more than just visual observation, Stanley N. Caroff, MD, said at the annual meeting of the American Psychiatric Association.

“You really need to ask the patient a lot of questions – and the family and the caregivers – about how much tardive dyskinesia affects their lives,” he said.

Those were some of the early results of RE-KINECT, an ongoing study of patients with schizophrenia and schizoaffective disorder who were being treated with antipsychotic agents.

TD occurs in more than 25% of patients in outpatient practices who are exposed to dopamine receptor blockers. Symptoms can include involuntary movements of the tongue, hands, and feet; facial distortions; rapid eye blinking; and difficulty speaking. In some cases, the side effects resolve after patients stop taking the medications.

In this video, Dr. Caroff discussed the studies’ findings and their implications for everyday clinical practice. He also presented some of the early RE-KINECT findings in a poster at the meeting.

Dr. Caroff is professor of psychiatry at the University of Pennsylvania, Philadelphia. He also is affiliated with the Michael J. Crescenz VA Medical Center in Philadelphia. He disclosed working as a consultant for and receiving research funding from Neurocrine Biosciences. He also is a consultant for DisperSol Technologies, Osmotica Pharmaceuticals, Teva Pharmaceutical.

ghenderson@mdedge.com

CASE Irritable and short of breath

Mr. B, age 75, who lives alone, is brought to the emergency department (ED) for evaluation of shortness of breath. Mr. B is normally highly independent, and is able to drive, manage his own finances, attend to activities of daily living, and participate in social functions at church. On the day before he was taken to the ED, his home nurse had come to his home to dispense medications and found Mr. B was irritable, verbally rude, and repeatedly scratching the right side of his head. The nurse was unsure if Mr. B had taken his medications over the weekend. She called for emergency services, but Mr. B refused to go to the ED, and he was able to decline care because he was not in an acute medical emergency (95% oxygen on pulse oximetry).

The next day, when Mr. B’s nurse returned to his home, she found him to be tachypneic and verbigerating the phrase “I don’t know.” She contacted emergency services again, and Mr. B was taken to the ED.

In the ED, Mr. B has tachycardia, tachypnea, increased work of breathing, and diffuse rhonchi. He continues to repeat the phrase “I don’t know” and scratches the right side of his head repeatedly. The ED clinicians consult Psychiatry due to Mr. B’s confusion and because his nurse reports that his presentation is similar to a previous psychiatric hospitalization 9 years earlier.

[polldaddy:10332862]

EVALUATION Complex comorbidities

Mr. B has a lengthy history of schizophrenia, chronic right-sided heart failure secondary to pulmonary hypertension, moderate chronic obstructive pulmonary disease, hypertension, type 2 diabetes mellitus, and prostatic adenocarcinoma after external beam radiation therapy.

His symptoms of schizophrenia had been stable on his long-standing outpatient psychotropic regimen of haloperidol, 5 mg nightly; mirtazapine, 15 mg nightly, for appetite stimulation and insomnia; and trazodone, 100 mg nightly for insomnia. Mr. B has been receiving assertive community treatment (ACT) psychiatric services for schizophrenia; a nurse refills his pill box with his medications weekly. He does not have a history of medication nonadherence, and his nurse did not think he had missed any doses before the weekend.

He has acute changes in depressed mood, perseveration, and a Mini-Mental State Examination (MMSE) score of 26 (missing points for delayed recall and inability to construct a sentence), which indicates a cognitive assessment score on the low end of the normal range for people with at least an eighth grade education.

At the hospital, the psychiatrist diagnoses hypoactive delirium due to Mr. B’s fluctuating attention and disorientation. She also recommends that Mr. B continue his outpatient psychotropic regimen, and adds oral haloperidol, 5 mg, as needed for agitation (his QTc interval is 451 ms; reference range for men <430 ms, borderline prolonged 431 to 450 ms, prolonged >450 ms).

Continue to: An initial laboratory workup...

An initial laboratory workup and electrocardiogram reveal that Mr. B has an elevated troponin level (0.21 ng/mL; reference range <0.04; 0.04 to 0.39 ng/mL is elevated above the 99th percentile of a healthy population), non-ST-elevation myocardial infarction type II, Q waves in lead III, arteriovenous fistula with right axis deviation, acute on chronic kidney failure (creatinine level of 2.1 mg/dL, up from baseline of 1.4 mg/dL; reference range 0.84 to 1.21 mg/dL), elevated brain natriuretic peptide (111 pg/mL; reference range <125 pg/mL), and an elevated lactate level of 5.51 mmol/L (reference range 0.5 to 1 mmol/L). He also has a mixed respiratory alkalosis and metabolic acidosis with increased anion gap, transaminitis (aspartate aminotransferase 149 U/L; reference range 10 to 40 U/L), and elevated alkaline phosphatase (151 IU/L; reference range 44 to 147 IU/L). Urinalysis shows moderate ketones and is negative for nitrite or leukocyte esterase.

A brain CT rules out stroke. A chest X-ray shows subtle left basilar reticular opacity with a follow-up lateral view showing no consolidation and prominent pulmonary vasculature without overt edema.

In the ED, Mr. B is determined to have decision-making capacity and is able to authorize all treatment. Cardiology is also consulted, and Mr. B is admitted to the cardiac intensive care unit (CCU) for cardiogenic shock with close cardiac monitoring.

The Psychiatry and Cardiology teams discuss the risks and benefits of continuing antipsychotics. Due to the imminent risk of harm to Mr. B because of his significant agitation in the ED, which required treatment with one dose of IM haloperidol, 5 mg, and lorazepam, 2 mg, and close monitoring, the teams agree that the benefits of continuing haloperidol outweigh the risks.

On hospital Day 2, Mr. B’s repetitive scratching resolves. He is moved from the CCU to a general medical unit, where he begins to have episodes of mutism and negativism. By hospital Day 6, catatonia is suspected due to a MMSE of 6/30 and a Bush- Francis Catatonia Rating Scale (BFCRS) score of 14 for predominant stereotypy, perseveration, and withdrawal (Table 1). The teams determine that Mr. B lacks decisionmaking capacity due to his inability to rationally manipulate information. His brother is contacted and authorizes all treatment, deferring decision-making to the medical teams caring for Mr. B.

Continue to: Mr. B undergoes an EEG...

Mr. B undergoes an EEG, which rules out nonconvulsive status epilepticus and is consistent with encephalopathy/delirium. Neuroleptic malignant syndrome (NMS) is considered but is less likely because Mr. B had been receiving a stable dose of haloperidol for several years, is afebrile, has stable vital signs, has no muscle rigidity, and no evidence of leukocytosis, creatine kinase elevation, myoglobinuria, hyperkalemia, hyperphosphatemia, thrombocytosis, or hypocalcemia.

Based on these clinical findings, Mr. B is diagnosed with catatonia and delirium.

The authors’ observations

Delirium, characterized by inattention and changes in mental status, is a syndrome due to acute brain dysfunction. It can be subclassified as hyperactive or hypoactive based on the change of activity. Simple catatonia is characterized by changes in behavior, affect, and motor function (with hyper- or hypoactivity). It may arise from gammaaminobutyric acid hypoactivity, dopamine (D2) hypoactivity, and possibly glutamate N-methyl-d-aspartate (NMDA) hyperactivity.¹ Malignant catatonia is simple catatonia combined with autonomic instability and hyperthermia, which is a life-threatening condition. The BFCRS is commonly used to assess symptoms.²

Both catatonia and delirium result in significant morbidity and mortality. The 2 conditions share signs and symptoms yet rarely are diagnosed at the same time. DSM-IV, DSM-IV-TR, and DSM-5 state that a diagnosis of catatonia due to another medical condition cannot be made exclusively in the presence of delirium.^3,4 DSM-IV and DSM-IV-TR required at least 2 criteria from 5 areas, including motoric immobility, excessive motor activity, extreme negativism or mutism, peculiarities of voluntary movement, and echolalia or echopraxia. Instead of grouping symptoms into clusters, DSM-5 requires 3 criteria of 12 individual symptoms.^3,4 A co-occurrence with a medical illness precludes using the DSM-5 “catatonia associated with another mental disorder (catatonia specifier)” with the “unspecified catatonia” diagnosis category.⁴

However, a growing body of literature suggests that delirium and catatonia can cooccur.^5,6 In 2017, Wilson et al⁶ found that of 136 critically ill patients in the ICU, 43% (58 patients) had only delirium, 3% (4 patients) had only catatonia, 31% (42 patients) had both, and 24% (32 patients) had neither. In patients with both catatonia and delirium, the most common signs of catatonia were autonomic abnormalities (96%), immobility/ stupor (87%), staring (77%), mutism (60%), and posturing (60%).

Continue to: The differential diagnosis...

The differential diagnosis of catatonia is extensive and varied.^3,4 The most common psychiatric causes are mood disorders (13% to 31%) and psychotic disorders (7% to 17%).⁷ Neuromedical etiologies account for 4% to 46% of cases.⁷ The most common medical and neurologic causes are seizure disorder, acute intermittent porphyria, systemic lupus erythematosus, and drugrelated adverse effects (particularly due to clozapine withdrawal, risperidone, and phencyclidine).⁷

A workup that includes physical examination, laboratory testing, and neuroimaging can be helpful to identify delirium and catatonia, but there is limited literature to guide identifying coexisting delirium and catatonia other than a blend of physical exam findings of delirium and catatonia. Electroencephalogram may be normal in primary catatonia or may show nonspecific changes in secondary catatonia.⁸ Additionally, discharges in the frontal lobes and anterior limbic systems with diffuse background slowing and dysrhythmic patterns may be seen.⁷ Neuroimaging with MRI can help to evaluate catatonia.⁹ Laboratory testing such as creatine phosphokinase levels can be high in simple catatonia and are often elevated in malignant catatonia.⁷ Considering the possible co-occurrence of delirium and catatonia is critical to providing good patient care because the 2 conditions are treated differently.

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TREATMENT A balancing act

Over the next month, Mr. B alternates between appearing catatonic or delirious. When he appears more catatonic, the dose of lorazepam is increased, which results in increased impulsivity and agitation and leads to multiple interventions from the behavioral emergency response team. At times, the team must use restraints and haloperidol because Mr. B pulls out IV lines and is considered at high risk for falls. When Mr. B appears more delirious and the dose of lorazepam is decreased, he becomes more catatonic.

Following the diagnosis of catatonia on Day 6, oral haloperidol is discontinued to further mitigate Mr. B’s risk of developing NMS. On hospital Day 6, Mr. B improves significantly after a 2-mg IV lorazepam challenge, with a BFCRS score of 6. At this point, he is started on lorazepam, 1 mg IV 3 times a day.

On Day 7, based on the complicated nature of Mr. B’s medical and psychiatric comorbidities, the treatment team considers ECT to minimize medication adverse effects, but Mr. B’s medical condition is too tenuous.

Continue to: On Day 7...

On Day 7, lorazepam is decreased to 0.5 mg/0.5 mg/1 mg IV. On Day 9, it is further decreased to 0.5 mg IV 3 times a day because Mr. B appears to be more delirious. On Day 10, lorazepam is increased to 1 mg IV 3 times a day, and oral haloperidol, 2 mg as needed for agitation, is restarted after multiple nights when Mr. B had behavioral emergencies and was treated with IM haloperidol and lorazepam. On Day 11, lorazepam is decreased and switched from IV formulation to oral, 0.5 mg 3 times a day. On Day 13, oral haloperidol is increased to 2 mg twice a day because of overnight behavioral emergencies requiring treatment with IV haloperidol, 4 mg. On Day 17, oral haloperidol is increased to 2 mg in the morning and 3 mg every night at bedtime because Mr. B has increased morning agitation. On Day 19, oral lorazepam is increased to 1 mg 3 times a day because Mr. B appears more catatonic. On Day 21, oral haloperidol is consolidated to 5 mg every night at bedtime. On Day 31, oral lorazepam is increased to 2 mg/1 mg/1 mg because he appears more catatonic with increased stuttering and mannerisms. On Day 33, oral haloperidol is increased to 6 mg every night at bedtime because Mr. B has morning agitation.

Multiple lorazepam and haloperidol dose adjustments are needed to balance the situation: combating catatonia, addressing delirium, managing schizophrenia symptoms, and improving Mr. B’s cardiac status. Finally, Mr. B is stabilized on oral lorazepam, 2 mg every morning, 1 mg every day at noon, and 1 mg every day at bedtime, and oral haloperidol, 6 mg every day at bedtime. This regimen, Mr. B has a BFCRS score of 1 (Table 2) and returns to his baseline mental status.

The authors’ observations

Delirium and catatonia typically have different treatments. Delirium is routinely treated by addressing the underlying medical and environmental factors, and managing comorbid symptoms such as agitation and disturbing hallucinations by prescribing antipsychotics, restoring the sleep-wake cycle with melatonin, initiating nonpharmacologic behavioral management, and avoiding deliriogenic medications such as benzodiazepines, opioids, and steroids.¹⁰ Catatonia is managed by prescribing benzodiazepines (with or without ECT) and by avoiding dopamine antagonists such as antipsychotics and metoclopramide (which may worsen catatonia or precipitate malignant catatonia).

The first-line treatment for catatonia is benzodiazepines, with IV preferred over IM, sublingual, or oral formulations. Electroconvulsive therapy is commonly used with benzodiazepines and is effective in 85% to 90% of patients. For ECT, bitemporal placement and daily treatment with brief pulses are frequently used. It is also effective in 60% of patients who fail to respond to benzodiazepines. Thus, ECT should be considered within the first 48 to 72 hours of benzodiazepine failure.⁷

Amantadine, a NMDA antagonist, may be a possible treatment for catatonia. A case report published in 1986 described a patient who developed catatonia after the abrupt withdrawal of amantadine during neuroleptic therapy.¹¹ Memantine also may serve as a treatment for catatonia through glutamate antagonism. A review identified 25 cases of patients with catatonia who were treated with amantadine or memantine.¹² Oral amantadine was administered at 100 to 400 mg/d in divided doses, with lower doses for patients with diminished renal function.¹² Memantine was administered at 5 to 20 mg/d.¹² All patients showed improvement after 1 to 7 days of treatment.¹² Thus, memantine may be considered for patients with catatonic schizophrenia or comorbid catatonia and delirium. Although memantine was not considered in Mr. B’s case, he would have been a good candidate for treatment with this agent.

Continue to: There are also case reports of...

There are also case reports of aripiprazole being used for catatonia in the context of psychosis or delirium in both adults and adolescents.^13-15 Other medications used in case reports for treating catatonia include carbamazepine, valproate, and secondgeneration antipsychotics.⁷

Because most of the literature on pharmacotherapy for catatonia consists of case reports or small case series, further research on medication management of catatonia and delirium is needed to guide treatment.

OUTCOME Multiple rehospitalizations

On Day 57, Mr. B is discharged to a skilled nursing facility due to significant deconditioning. He is discharged with continued follow-up with his ACT psychiatrist and nurse. Mr. B’s catatonia remains resolved; however, he is unable to be safely managed at the skilled nursing facility.

During the next 7 months, he is readmitted to the ICU for acute on chronic hypoxic respiratory failure 5 times; his rehospitalizations are complicated by delirium due to cardiogenic shock and urosepsis. Mild hyperactive delirium re-emerges after worsening respiratory failure and contributes to falls in the skilled nursing facility.

Six months later, Mr. B continues to receive the initial hospital discharge lorazepam regimen of 2 mg every morning, 1 mg every day at noon, and 1 mg every night at bedtime. The Psychiatry team slowly tapers this to 0.5 mg twice daily.

Continue to: On Day 5...

On Day 5 of Mr. B’s fifth hospital readmission, based on his advance directive, Mr. B’s family implements the do-not-resuscitate and do-not-intubate orders. He is transitioned to comfort measures, and dies on Day 6 with his brother and the hospital chaplain present.

Bottom Line

Delirium and catatonia share signs and symptoms, yet rarely are diagnosed at the same time. Both conditions result in significant morbidity and mortality. An emerging literature supports the concurrence of these 2 syndromes and aids in their diagnosis and treatment. Comorbidity with other medical conditions, common with both delirium and catatonia, substantially complicates treatment; thus, additional research into new treatment approaches is critical.

Related Resources

• Wilson JE, Carlson R, Duggan MC, et al. Delirium and catatonia in critically ill patients: the delirium and catatonia prospective cohort investigation. Crit Care Med. 2017;45(11):1837-1844.
• Catatonia Information Center. Penn State University. http://catatonia.org/.

Drug Brand Names

Amantadine • Symmetrel
Aripiprazole • Abilify
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Haloperidol • Haldol
Lorazepam • Ativan
Memantine • Namenda
Metoclopramide • Reglan
Mirtazapine • Remeron
Risperidone • Risperdal
Topiramate • Topamax
Trazodone • Desyrel
Valproate • Depacon, Depakene, Depakote

CASE Irritable and short of breath

Mr. B, age 75, who lives alone, is brought to the emergency department (ED) for evaluation of shortness of breath. Mr. B is normally highly independent, and is able to drive, manage his own finances, attend to activities of daily living, and participate in social functions at church. On the day before he was taken to the ED, his home nurse had come to his home to dispense medications and found Mr. B was irritable, verbally rude, and repeatedly scratching the right side of his head. The nurse was unsure if Mr. B had taken his medications over the weekend. She called for emergency services, but Mr. B refused to go to the ED, and he was able to decline care because he was not in an acute medical emergency (95% oxygen on pulse oximetry).

The next day, when Mr. B’s nurse returned to his home, she found him to be tachypneic and verbigerating the phrase “I don’t know.” She contacted emergency services again, and Mr. B was taken to the ED.

In the ED, Mr. B has tachycardia, tachypnea, increased work of breathing, and diffuse rhonchi. He continues to repeat the phrase “I don’t know” and scratches the right side of his head repeatedly. The ED clinicians consult Psychiatry due to Mr. B’s confusion and because his nurse reports that his presentation is similar to a previous psychiatric hospitalization 9 years earlier.

[polldaddy:10332862]

EVALUATION Complex comorbidities

Mr. B has a lengthy history of schizophrenia, chronic right-sided heart failure secondary to pulmonary hypertension, moderate chronic obstructive pulmonary disease, hypertension, type 2 diabetes mellitus, and prostatic adenocarcinoma after external beam radiation therapy.

His symptoms of schizophrenia had been stable on his long-standing outpatient psychotropic regimen of haloperidol, 5 mg nightly; mirtazapine, 15 mg nightly, for appetite stimulation and insomnia; and trazodone, 100 mg nightly for insomnia. Mr. B has been receiving assertive community treatment (ACT) psychiatric services for schizophrenia; a nurse refills his pill box with his medications weekly. He does not have a history of medication nonadherence, and his nurse did not think he had missed any doses before the weekend.

He has acute changes in depressed mood, perseveration, and a Mini-Mental State Examination (MMSE) score of 26 (missing points for delayed recall and inability to construct a sentence), which indicates a cognitive assessment score on the low end of the normal range for people with at least an eighth grade education.

At the hospital, the psychiatrist diagnoses hypoactive delirium due to Mr. B’s fluctuating attention and disorientation. She also recommends that Mr. B continue his outpatient psychotropic regimen, and adds oral haloperidol, 5 mg, as needed for agitation (his QTc interval is 451 ms; reference range for men <430 ms, borderline prolonged 431 to 450 ms, prolonged >450 ms).

Continue to: An initial laboratory workup...

An initial laboratory workup and electrocardiogram reveal that Mr. B has an elevated troponin level (0.21 ng/mL; reference range <0.04; 0.04 to 0.39 ng/mL is elevated above the 99th percentile of a healthy population), non-ST-elevation myocardial infarction type II, Q waves in lead III, arteriovenous fistula with right axis deviation, acute on chronic kidney failure (creatinine level of 2.1 mg/dL, up from baseline of 1.4 mg/dL; reference range 0.84 to 1.21 mg/dL), elevated brain natriuretic peptide (111 pg/mL; reference range <125 pg/mL), and an elevated lactate level of 5.51 mmol/L (reference range 0.5 to 1 mmol/L). He also has a mixed respiratory alkalosis and metabolic acidosis with increased anion gap, transaminitis (aspartate aminotransferase 149 U/L; reference range 10 to 40 U/L), and elevated alkaline phosphatase (151 IU/L; reference range 44 to 147 IU/L). Urinalysis shows moderate ketones and is negative for nitrite or leukocyte esterase.

A brain CT rules out stroke. A chest X-ray shows subtle left basilar reticular opacity with a follow-up lateral view showing no consolidation and prominent pulmonary vasculature without overt edema.

In the ED, Mr. B is determined to have decision-making capacity and is able to authorize all treatment. Cardiology is also consulted, and Mr. B is admitted to the cardiac intensive care unit (CCU) for cardiogenic shock with close cardiac monitoring.

The Psychiatry and Cardiology teams discuss the risks and benefits of continuing antipsychotics. Due to the imminent risk of harm to Mr. B because of his significant agitation in the ED, which required treatment with one dose of IM haloperidol, 5 mg, and lorazepam, 2 mg, and close monitoring, the teams agree that the benefits of continuing haloperidol outweigh the risks.

On hospital Day 2, Mr. B’s repetitive scratching resolves. He is moved from the CCU to a general medical unit, where he begins to have episodes of mutism and negativism. By hospital Day 6, catatonia is suspected due to a MMSE of 6/30 and a Bush- Francis Catatonia Rating Scale (BFCRS) score of 14 for predominant stereotypy, perseveration, and withdrawal (Table 1). The teams determine that Mr. B lacks decisionmaking capacity due to his inability to rationally manipulate information. His brother is contacted and authorizes all treatment, deferring decision-making to the medical teams caring for Mr. B.

Continue to: Mr. B undergoes an EEG...

Mr. B undergoes an EEG, which rules out nonconvulsive status epilepticus and is consistent with encephalopathy/delirium. Neuroleptic malignant syndrome (NMS) is considered but is less likely because Mr. B had been receiving a stable dose of haloperidol for several years, is afebrile, has stable vital signs, has no muscle rigidity, and no evidence of leukocytosis, creatine kinase elevation, myoglobinuria, hyperkalemia, hyperphosphatemia, thrombocytosis, or hypocalcemia.

Based on these clinical findings, Mr. B is diagnosed with catatonia and delirium.

The authors’ observations

Delirium, characterized by inattention and changes in mental status, is a syndrome due to acute brain dysfunction. It can be subclassified as hyperactive or hypoactive based on the change of activity. Simple catatonia is characterized by changes in behavior, affect, and motor function (with hyper- or hypoactivity). It may arise from gammaaminobutyric acid hypoactivity, dopamine (D2) hypoactivity, and possibly glutamate N-methyl-d-aspartate (NMDA) hyperactivity.¹ Malignant catatonia is simple catatonia combined with autonomic instability and hyperthermia, which is a life-threatening condition. The BFCRS is commonly used to assess symptoms.²

Both catatonia and delirium result in significant morbidity and mortality. The 2 conditions share signs and symptoms yet rarely are diagnosed at the same time. DSM-IV, DSM-IV-TR, and DSM-5 state that a diagnosis of catatonia due to another medical condition cannot be made exclusively in the presence of delirium.^3,4 DSM-IV and DSM-IV-TR required at least 2 criteria from 5 areas, including motoric immobility, excessive motor activity, extreme negativism or mutism, peculiarities of voluntary movement, and echolalia or echopraxia. Instead of grouping symptoms into clusters, DSM-5 requires 3 criteria of 12 individual symptoms.^3,4 A co-occurrence with a medical illness precludes using the DSM-5 “catatonia associated with another mental disorder (catatonia specifier)” with the “unspecified catatonia” diagnosis category.⁴

However, a growing body of literature suggests that delirium and catatonia can cooccur.^5,6 In 2017, Wilson et al⁶ found that of 136 critically ill patients in the ICU, 43% (58 patients) had only delirium, 3% (4 patients) had only catatonia, 31% (42 patients) had both, and 24% (32 patients) had neither. In patients with both catatonia and delirium, the most common signs of catatonia were autonomic abnormalities (96%), immobility/ stupor (87%), staring (77%), mutism (60%), and posturing (60%).

Continue to: The differential diagnosis...

The differential diagnosis of catatonia is extensive and varied.^3,4 The most common psychiatric causes are mood disorders (13% to 31%) and psychotic disorders (7% to 17%).⁷ Neuromedical etiologies account for 4% to 46% of cases.⁷ The most common medical and neurologic causes are seizure disorder, acute intermittent porphyria, systemic lupus erythematosus, and drugrelated adverse effects (particularly due to clozapine withdrawal, risperidone, and phencyclidine).⁷

A workup that includes physical examination, laboratory testing, and neuroimaging can be helpful to identify delirium and catatonia, but there is limited literature to guide identifying coexisting delirium and catatonia other than a blend of physical exam findings of delirium and catatonia. Electroencephalogram may be normal in primary catatonia or may show nonspecific changes in secondary catatonia.⁸ Additionally, discharges in the frontal lobes and anterior limbic systems with diffuse background slowing and dysrhythmic patterns may be seen.⁷ Neuroimaging with MRI can help to evaluate catatonia.⁹ Laboratory testing such as creatine phosphokinase levels can be high in simple catatonia and are often elevated in malignant catatonia.⁷ Considering the possible co-occurrence of delirium and catatonia is critical to providing good patient care because the 2 conditions are treated differently.

[polldaddy:10332867]

TREATMENT A balancing act

Over the next month, Mr. B alternates between appearing catatonic or delirious. When he appears more catatonic, the dose of lorazepam is increased, which results in increased impulsivity and agitation and leads to multiple interventions from the behavioral emergency response team. At times, the team must use restraints and haloperidol because Mr. B pulls out IV lines and is considered at high risk for falls. When Mr. B appears more delirious and the dose of lorazepam is decreased, he becomes more catatonic.

Following the diagnosis of catatonia on Day 6, oral haloperidol is discontinued to further mitigate Mr. B’s risk of developing NMS. On hospital Day 6, Mr. B improves significantly after a 2-mg IV lorazepam challenge, with a BFCRS score of 6. At this point, he is started on lorazepam, 1 mg IV 3 times a day.

On Day 7, based on the complicated nature of Mr. B’s medical and psychiatric comorbidities, the treatment team considers ECT to minimize medication adverse effects, but Mr. B’s medical condition is too tenuous.

Continue to: On Day 7...

On Day 7, lorazepam is decreased to 0.5 mg/0.5 mg/1 mg IV. On Day 9, it is further decreased to 0.5 mg IV 3 times a day because Mr. B appears to be more delirious. On Day 10, lorazepam is increased to 1 mg IV 3 times a day, and oral haloperidol, 2 mg as needed for agitation, is restarted after multiple nights when Mr. B had behavioral emergencies and was treated with IM haloperidol and lorazepam. On Day 11, lorazepam is decreased and switched from IV formulation to oral, 0.5 mg 3 times a day. On Day 13, oral haloperidol is increased to 2 mg twice a day because of overnight behavioral emergencies requiring treatment with IV haloperidol, 4 mg. On Day 17, oral haloperidol is increased to 2 mg in the morning and 3 mg every night at bedtime because Mr. B has increased morning agitation. On Day 19, oral lorazepam is increased to 1 mg 3 times a day because Mr. B appears more catatonic. On Day 21, oral haloperidol is consolidated to 5 mg every night at bedtime. On Day 31, oral lorazepam is increased to 2 mg/1 mg/1 mg because he appears more catatonic with increased stuttering and mannerisms. On Day 33, oral haloperidol is increased to 6 mg every night at bedtime because Mr. B has morning agitation.

Multiple lorazepam and haloperidol dose adjustments are needed to balance the situation: combating catatonia, addressing delirium, managing schizophrenia symptoms, and improving Mr. B’s cardiac status. Finally, Mr. B is stabilized on oral lorazepam, 2 mg every morning, 1 mg every day at noon, and 1 mg every day at bedtime, and oral haloperidol, 6 mg every day at bedtime. This regimen, Mr. B has a BFCRS score of 1 (Table 2) and returns to his baseline mental status.

The authors’ observations

Delirium and catatonia typically have different treatments. Delirium is routinely treated by addressing the underlying medical and environmental factors, and managing comorbid symptoms such as agitation and disturbing hallucinations by prescribing antipsychotics, restoring the sleep-wake cycle with melatonin, initiating nonpharmacologic behavioral management, and avoiding deliriogenic medications such as benzodiazepines, opioids, and steroids.¹⁰ Catatonia is managed by prescribing benzodiazepines (with or without ECT) and by avoiding dopamine antagonists such as antipsychotics and metoclopramide (which may worsen catatonia or precipitate malignant catatonia).

The first-line treatment for catatonia is benzodiazepines, with IV preferred over IM, sublingual, or oral formulations. Electroconvulsive therapy is commonly used with benzodiazepines and is effective in 85% to 90% of patients. For ECT, bitemporal placement and daily treatment with brief pulses are frequently used. It is also effective in 60% of patients who fail to respond to benzodiazepines. Thus, ECT should be considered within the first 48 to 72 hours of benzodiazepine failure.⁷

Amantadine, a NMDA antagonist, may be a possible treatment for catatonia. A case report published in 1986 described a patient who developed catatonia after the abrupt withdrawal of amantadine during neuroleptic therapy.¹¹ Memantine also may serve as a treatment for catatonia through glutamate antagonism. A review identified 25 cases of patients with catatonia who were treated with amantadine or memantine.¹² Oral amantadine was administered at 100 to 400 mg/d in divided doses, with lower doses for patients with diminished renal function.¹² Memantine was administered at 5 to 20 mg/d.¹² All patients showed improvement after 1 to 7 days of treatment.¹² Thus, memantine may be considered for patients with catatonic schizophrenia or comorbid catatonia and delirium. Although memantine was not considered in Mr. B’s case, he would have been a good candidate for treatment with this agent.

Continue to: There are also case reports of...

There are also case reports of aripiprazole being used for catatonia in the context of psychosis or delirium in both adults and adolescents.^13-15 Other medications used in case reports for treating catatonia include carbamazepine, valproate, and secondgeneration antipsychotics.⁷

Because most of the literature on pharmacotherapy for catatonia consists of case reports or small case series, further research on medication management of catatonia and delirium is needed to guide treatment.

OUTCOME Multiple rehospitalizations

On Day 57, Mr. B is discharged to a skilled nursing facility due to significant deconditioning. He is discharged with continued follow-up with his ACT psychiatrist and nurse. Mr. B’s catatonia remains resolved; however, he is unable to be safely managed at the skilled nursing facility.

During the next 7 months, he is readmitted to the ICU for acute on chronic hypoxic respiratory failure 5 times; his rehospitalizations are complicated by delirium due to cardiogenic shock and urosepsis. Mild hyperactive delirium re-emerges after worsening respiratory failure and contributes to falls in the skilled nursing facility.

Six months later, Mr. B continues to receive the initial hospital discharge lorazepam regimen of 2 mg every morning, 1 mg every day at noon, and 1 mg every night at bedtime. The Psychiatry team slowly tapers this to 0.5 mg twice daily.

Continue to: On Day 5...

On Day 5 of Mr. B’s fifth hospital readmission, based on his advance directive, Mr. B’s family implements the do-not-resuscitate and do-not-intubate orders. He is transitioned to comfort measures, and dies on Day 6 with his brother and the hospital chaplain present.

Bottom Line

Delirium and catatonia share signs and symptoms, yet rarely are diagnosed at the same time. Both conditions result in significant morbidity and mortality. An emerging literature supports the concurrence of these 2 syndromes and aids in their diagnosis and treatment. Comorbidity with other medical conditions, common with both delirium and catatonia, substantially complicates treatment; thus, additional research into new treatment approaches is critical.

Related Resources

• Wilson JE, Carlson R, Duggan MC, et al. Delirium and catatonia in critically ill patients: the delirium and catatonia prospective cohort investigation. Crit Care Med. 2017;45(11):1837-1844.
• Catatonia Information Center. Penn State University. http://catatonia.org/.

Drug Brand Names

Amantadine • Symmetrel
Aripiprazole • Abilify
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Haloperidol • Haldol
Lorazepam • Ativan
Memantine • Namenda
Metoclopramide • Reglan
Mirtazapine • Remeron
Risperidone • Risperdal
Topiramate • Topamax
Trazodone • Desyrel
Valproate • Depacon, Depakene, Depakote

CASE Irritable and short of breath

Mr. B, age 75, who lives alone, is brought to the emergency department (ED) for evaluation of shortness of breath. Mr. B is normally highly independent, and is able to drive, manage his own finances, attend to activities of daily living, and participate in social functions at church. On the day before he was taken to the ED, his home nurse had come to his home to dispense medications and found Mr. B was irritable, verbally rude, and repeatedly scratching the right side of his head. The nurse was unsure if Mr. B had taken his medications over the weekend. She called for emergency services, but Mr. B refused to go to the ED, and he was able to decline care because he was not in an acute medical emergency (95% oxygen on pulse oximetry).

The next day, when Mr. B’s nurse returned to his home, she found him to be tachypneic and verbigerating the phrase “I don’t know.” She contacted emergency services again, and Mr. B was taken to the ED.

In the ED, Mr. B has tachycardia, tachypnea, increased work of breathing, and diffuse rhonchi. He continues to repeat the phrase “I don’t know” and scratches the right side of his head repeatedly. The ED clinicians consult Psychiatry due to Mr. B’s confusion and because his nurse reports that his presentation is similar to a previous psychiatric hospitalization 9 years earlier.

[polldaddy:10332862]

EVALUATION Complex comorbidities

Mr. B has a lengthy history of schizophrenia, chronic right-sided heart failure secondary to pulmonary hypertension, moderate chronic obstructive pulmonary disease, hypertension, type 2 diabetes mellitus, and prostatic adenocarcinoma after external beam radiation therapy.

His symptoms of schizophrenia had been stable on his long-standing outpatient psychotropic regimen of haloperidol, 5 mg nightly; mirtazapine, 15 mg nightly, for appetite stimulation and insomnia; and trazodone, 100 mg nightly for insomnia. Mr. B has been receiving assertive community treatment (ACT) psychiatric services for schizophrenia; a nurse refills his pill box with his medications weekly. He does not have a history of medication nonadherence, and his nurse did not think he had missed any doses before the weekend.

He has acute changes in depressed mood, perseveration, and a Mini-Mental State Examination (MMSE) score of 26 (missing points for delayed recall and inability to construct a sentence), which indicates a cognitive assessment score on the low end of the normal range for people with at least an eighth grade education.

At the hospital, the psychiatrist diagnoses hypoactive delirium due to Mr. B’s fluctuating attention and disorientation. She also recommends that Mr. B continue his outpatient psychotropic regimen, and adds oral haloperidol, 5 mg, as needed for agitation (his QTc interval is 451 ms; reference range for men <430 ms, borderline prolonged 431 to 450 ms, prolonged >450 ms).

Continue to: An initial laboratory workup...

An initial laboratory workup and electrocardiogram reveal that Mr. B has an elevated troponin level (0.21 ng/mL; reference range <0.04; 0.04 to 0.39 ng/mL is elevated above the 99th percentile of a healthy population), non-ST-elevation myocardial infarction type II, Q waves in lead III, arteriovenous fistula with right axis deviation, acute on chronic kidney failure (creatinine level of 2.1 mg/dL, up from baseline of 1.4 mg/dL; reference range 0.84 to 1.21 mg/dL), elevated brain natriuretic peptide (111 pg/mL; reference range <125 pg/mL), and an elevated lactate level of 5.51 mmol/L (reference range 0.5 to 1 mmol/L). He also has a mixed respiratory alkalosis and metabolic acidosis with increased anion gap, transaminitis (aspartate aminotransferase 149 U/L; reference range 10 to 40 U/L), and elevated alkaline phosphatase (151 IU/L; reference range 44 to 147 IU/L). Urinalysis shows moderate ketones and is negative for nitrite or leukocyte esterase.

A brain CT rules out stroke. A chest X-ray shows subtle left basilar reticular opacity with a follow-up lateral view showing no consolidation and prominent pulmonary vasculature without overt edema.

In the ED, Mr. B is determined to have decision-making capacity and is able to authorize all treatment. Cardiology is also consulted, and Mr. B is admitted to the cardiac intensive care unit (CCU) for cardiogenic shock with close cardiac monitoring.

The Psychiatry and Cardiology teams discuss the risks and benefits of continuing antipsychotics. Due to the imminent risk of harm to Mr. B because of his significant agitation in the ED, which required treatment with one dose of IM haloperidol, 5 mg, and lorazepam, 2 mg, and close monitoring, the teams agree that the benefits of continuing haloperidol outweigh the risks.

On hospital Day 2, Mr. B’s repetitive scratching resolves. He is moved from the CCU to a general medical unit, where he begins to have episodes of mutism and negativism. By hospital Day 6, catatonia is suspected due to a MMSE of 6/30 and a Bush- Francis Catatonia Rating Scale (BFCRS) score of 14 for predominant stereotypy, perseveration, and withdrawal (Table 1). The teams determine that Mr. B lacks decisionmaking capacity due to his inability to rationally manipulate information. His brother is contacted and authorizes all treatment, deferring decision-making to the medical teams caring for Mr. B.

Continue to: Mr. B undergoes an EEG...

Mr. B undergoes an EEG, which rules out nonconvulsive status epilepticus and is consistent with encephalopathy/delirium. Neuroleptic malignant syndrome (NMS) is considered but is less likely because Mr. B had been receiving a stable dose of haloperidol for several years, is afebrile, has stable vital signs, has no muscle rigidity, and no evidence of leukocytosis, creatine kinase elevation, myoglobinuria, hyperkalemia, hyperphosphatemia, thrombocytosis, or hypocalcemia.

Based on these clinical findings, Mr. B is diagnosed with catatonia and delirium.

The authors’ observations

Delirium, characterized by inattention and changes in mental status, is a syndrome due to acute brain dysfunction. It can be subclassified as hyperactive or hypoactive based on the change of activity. Simple catatonia is characterized by changes in behavior, affect, and motor function (with hyper- or hypoactivity). It may arise from gammaaminobutyric acid hypoactivity, dopamine (D2) hypoactivity, and possibly glutamate N-methyl-d-aspartate (NMDA) hyperactivity.¹ Malignant catatonia is simple catatonia combined with autonomic instability and hyperthermia, which is a life-threatening condition. The BFCRS is commonly used to assess symptoms.²

Both catatonia and delirium result in significant morbidity and mortality. The 2 conditions share signs and symptoms yet rarely are diagnosed at the same time. DSM-IV, DSM-IV-TR, and DSM-5 state that a diagnosis of catatonia due to another medical condition cannot be made exclusively in the presence of delirium.^3,4 DSM-IV and DSM-IV-TR required at least 2 criteria from 5 areas, including motoric immobility, excessive motor activity, extreme negativism or mutism, peculiarities of voluntary movement, and echolalia or echopraxia. Instead of grouping symptoms into clusters, DSM-5 requires 3 criteria of 12 individual symptoms.^3,4 A co-occurrence with a medical illness precludes using the DSM-5 “catatonia associated with another mental disorder (catatonia specifier)” with the “unspecified catatonia” diagnosis category.⁴

However, a growing body of literature suggests that delirium and catatonia can cooccur.^5,6 In 2017, Wilson et al⁶ found that of 136 critically ill patients in the ICU, 43% (58 patients) had only delirium, 3% (4 patients) had only catatonia, 31% (42 patients) had both, and 24% (32 patients) had neither. In patients with both catatonia and delirium, the most common signs of catatonia were autonomic abnormalities (96%), immobility/ stupor (87%), staring (77%), mutism (60%), and posturing (60%).

Continue to: The differential diagnosis...

The differential diagnosis of catatonia is extensive and varied.^3,4 The most common psychiatric causes are mood disorders (13% to 31%) and psychotic disorders (7% to 17%).⁷ Neuromedical etiologies account for 4% to 46% of cases.⁷ The most common medical and neurologic causes are seizure disorder, acute intermittent porphyria, systemic lupus erythematosus, and drugrelated adverse effects (particularly due to clozapine withdrawal, risperidone, and phencyclidine).⁷

A workup that includes physical examination, laboratory testing, and neuroimaging can be helpful to identify delirium and catatonia, but there is limited literature to guide identifying coexisting delirium and catatonia other than a blend of physical exam findings of delirium and catatonia. Electroencephalogram may be normal in primary catatonia or may show nonspecific changes in secondary catatonia.⁸ Additionally, discharges in the frontal lobes and anterior limbic systems with diffuse background slowing and dysrhythmic patterns may be seen.⁷ Neuroimaging with MRI can help to evaluate catatonia.⁹ Laboratory testing such as creatine phosphokinase levels can be high in simple catatonia and are often elevated in malignant catatonia.⁷ Considering the possible co-occurrence of delirium and catatonia is critical to providing good patient care because the 2 conditions are treated differently.

[polldaddy:10332867]

TREATMENT A balancing act

Over the next month, Mr. B alternates between appearing catatonic or delirious. When he appears more catatonic, the dose of lorazepam is increased, which results in increased impulsivity and agitation and leads to multiple interventions from the behavioral emergency response team. At times, the team must use restraints and haloperidol because Mr. B pulls out IV lines and is considered at high risk for falls. When Mr. B appears more delirious and the dose of lorazepam is decreased, he becomes more catatonic.

Following the diagnosis of catatonia on Day 6, oral haloperidol is discontinued to further mitigate Mr. B’s risk of developing NMS. On hospital Day 6, Mr. B improves significantly after a 2-mg IV lorazepam challenge, with a BFCRS score of 6. At this point, he is started on lorazepam, 1 mg IV 3 times a day.

On Day 7, based on the complicated nature of Mr. B’s medical and psychiatric comorbidities, the treatment team considers ECT to minimize medication adverse effects, but Mr. B’s medical condition is too tenuous.

Continue to: On Day 7...

On Day 7, lorazepam is decreased to 0.5 mg/0.5 mg/1 mg IV. On Day 9, it is further decreased to 0.5 mg IV 3 times a day because Mr. B appears to be more delirious. On Day 10, lorazepam is increased to 1 mg IV 3 times a day, and oral haloperidol, 2 mg as needed for agitation, is restarted after multiple nights when Mr. B had behavioral emergencies and was treated with IM haloperidol and lorazepam. On Day 11, lorazepam is decreased and switched from IV formulation to oral, 0.5 mg 3 times a day. On Day 13, oral haloperidol is increased to 2 mg twice a day because of overnight behavioral emergencies requiring treatment with IV haloperidol, 4 mg. On Day 17, oral haloperidol is increased to 2 mg in the morning and 3 mg every night at bedtime because Mr. B has increased morning agitation. On Day 19, oral lorazepam is increased to 1 mg 3 times a day because Mr. B appears more catatonic. On Day 21, oral haloperidol is consolidated to 5 mg every night at bedtime. On Day 31, oral lorazepam is increased to 2 mg/1 mg/1 mg because he appears more catatonic with increased stuttering and mannerisms. On Day 33, oral haloperidol is increased to 6 mg every night at bedtime because Mr. B has morning agitation.

Multiple lorazepam and haloperidol dose adjustments are needed to balance the situation: combating catatonia, addressing delirium, managing schizophrenia symptoms, and improving Mr. B’s cardiac status. Finally, Mr. B is stabilized on oral lorazepam, 2 mg every morning, 1 mg every day at noon, and 1 mg every day at bedtime, and oral haloperidol, 6 mg every day at bedtime. This regimen, Mr. B has a BFCRS score of 1 (Table 2) and returns to his baseline mental status.

The authors’ observations

Delirium and catatonia typically have different treatments. Delirium is routinely treated by addressing the underlying medical and environmental factors, and managing comorbid symptoms such as agitation and disturbing hallucinations by prescribing antipsychotics, restoring the sleep-wake cycle with melatonin, initiating nonpharmacologic behavioral management, and avoiding deliriogenic medications such as benzodiazepines, opioids, and steroids.¹⁰ Catatonia is managed by prescribing benzodiazepines (with or without ECT) and by avoiding dopamine antagonists such as antipsychotics and metoclopramide (which may worsen catatonia or precipitate malignant catatonia).

The first-line treatment for catatonia is benzodiazepines, with IV preferred over IM, sublingual, or oral formulations. Electroconvulsive therapy is commonly used with benzodiazepines and is effective in 85% to 90% of patients. For ECT, bitemporal placement and daily treatment with brief pulses are frequently used. It is also effective in 60% of patients who fail to respond to benzodiazepines. Thus, ECT should be considered within the first 48 to 72 hours of benzodiazepine failure.⁷

Amantadine, a NMDA antagonist, may be a possible treatment for catatonia. A case report published in 1986 described a patient who developed catatonia after the abrupt withdrawal of amantadine during neuroleptic therapy.¹¹ Memantine also may serve as a treatment for catatonia through glutamate antagonism. A review identified 25 cases of patients with catatonia who were treated with amantadine or memantine.¹² Oral amantadine was administered at 100 to 400 mg/d in divided doses, with lower doses for patients with diminished renal function.¹² Memantine was administered at 5 to 20 mg/d.¹² All patients showed improvement after 1 to 7 days of treatment.¹² Thus, memantine may be considered for patients with catatonic schizophrenia or comorbid catatonia and delirium. Although memantine was not considered in Mr. B’s case, he would have been a good candidate for treatment with this agent.

Continue to: There are also case reports of...

There are also case reports of aripiprazole being used for catatonia in the context of psychosis or delirium in both adults and adolescents.^13-15 Other medications used in case reports for treating catatonia include carbamazepine, valproate, and secondgeneration antipsychotics.⁷

Because most of the literature on pharmacotherapy for catatonia consists of case reports or small case series, further research on medication management of catatonia and delirium is needed to guide treatment.

OUTCOME Multiple rehospitalizations

On Day 57, Mr. B is discharged to a skilled nursing facility due to significant deconditioning. He is discharged with continued follow-up with his ACT psychiatrist and nurse. Mr. B’s catatonia remains resolved; however, he is unable to be safely managed at the skilled nursing facility.

During the next 7 months, he is readmitted to the ICU for acute on chronic hypoxic respiratory failure 5 times; his rehospitalizations are complicated by delirium due to cardiogenic shock and urosepsis. Mild hyperactive delirium re-emerges after worsening respiratory failure and contributes to falls in the skilled nursing facility.

Six months later, Mr. B continues to receive the initial hospital discharge lorazepam regimen of 2 mg every morning, 1 mg every day at noon, and 1 mg every night at bedtime. The Psychiatry team slowly tapers this to 0.5 mg twice daily.

Continue to: On Day 5...

On Day 5 of Mr. B’s fifth hospital readmission, based on his advance directive, Mr. B’s family implements the do-not-resuscitate and do-not-intubate orders. He is transitioned to comfort measures, and dies on Day 6 with his brother and the hospital chaplain present.

Bottom Line

Delirium and catatonia share signs and symptoms, yet rarely are diagnosed at the same time. Both conditions result in significant morbidity and mortality. An emerging literature supports the concurrence of these 2 syndromes and aids in their diagnosis and treatment. Comorbidity with other medical conditions, common with both delirium and catatonia, substantially complicates treatment; thus, additional research into new treatment approaches is critical.

Related Resources

• Wilson JE, Carlson R, Duggan MC, et al. Delirium and catatonia in critically ill patients: the delirium and catatonia prospective cohort investigation. Crit Care Med. 2017;45(11):1837-1844.
• Catatonia Information Center. Penn State University. http://catatonia.org/.

Drug Brand Names

Amantadine • Symmetrel
Aripiprazole • Abilify
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Haloperidol • Haldol
Lorazepam • Ativan
Memantine • Namenda
Metoclopramide • Reglan
Mirtazapine • Remeron
Risperidone • Risperdal
Topiramate • Topamax
Trazodone • Desyrel
Valproate • Depacon, Depakene, Depakote

SAN FRANCISCO – In a proof-of-concept study, music provided an alternative to oral psychotropic medication in calming agitated patients at an inpatient psychiatric facility. Music has been studied as a treatment for agitation in dementia patients but not so much in psychiatric patients, according to Trevor Scudamore, MD, who is a resident fellow at State University of New York, Syracuse.

Jim Kling/MDedge News

“The other thing is that music has been more looked at in group therapy settings than as adjunct therapy, or as an option as an as-needed medication for agitation,” Dr. Scudamore said in an interview. He presented the study at a poster session at the annual meeting of the American Psychiatric Association.

When agitation arose, the program allowed patients to choose between an oral medication or music, which entailed a 30-minute session listening to a preset playlist using a wireless headphone. Playlist options included a variety of musical genres, and participants could sit in one place or roam around while listening.

Traditionally, agitated patients had the choice of an oral medication. If the patient refused and then escalated, they had to accept an intravenous medication. “Now there’s a choice between an oral medication and music, almost like a third layer in defusing agitation in the patient. If they refuse music, then they could go for oral medication, and then [IV medication]. They’re given a little bit more options. Maybe they don’t feel so confined, which is an interesting way of helping possibly defuse anxiety from a situation. That needs to be explored further,” Dr. Scudamore said.

The study had a two-phase, cross-sectional design. The first 3 months, the study included 71 patients, who were used to establish a baseline of agitation and psychotropic medication use. They introduced the music intervention during the second 3-month period, with 101 participants. After they listened to music, the patients completed a self-report form using the Likert scale, and nursing staff observed the patients status during the initial anxiety/agitation, while they listened to music, and 15 minutes after the listening session.

That need for commitment from nurses presented a challenge to implementation. They had to hand out headphones, keep track of them, and make sure they got the headphones back. “It is a lot more work than just giving 50 mg of hydroxyzine,” said coauthor Christopher Botash, MD, who also is a resident at the university.

Study participants had a range of psychiatric ills, including substance abuse (61%), depression (51%), psychosis (28%), trauma (26%), personality disorder (20%), and anxiety (17%).

As part of a preliminary report, the researchers presented data from surveys completed by nine nurses and 31 patients. After the music implementation, the average length of stay declined (10.49 to 8.20 days; difference, 2.29 days), as did the median length of stay (6.5 to 5.0 days). The two most commonly prescribed antipsychotics saw a decrease in administrations, from 3.37 to 2.93/month for haloperidol, and from 3.83 to 2.73 administrations/month for olanzapine.

A total of 56% of the nursing staff stated that the music therapy program helped calm down the patients. Nurses who disagreed cited the tendency for patients to intrude at the nursing station asking for the music, though this improved as patients learned the routine. Ninety-six percent of the patients reported satisfaction with the experience.

It was challenging for the researchers to implement the study, since offering music was a break in the routine. “The staff really does rely a lot on the meds, so oftentimes we would have to say, ‘Hey, have you offered the music yet?’ It’s a bit of a culture change,” Dr. Botash said.

The study, which Dr. Scudamore and Dr. Botash coauthored with Nekpen S. Ekure, MD, did not receive external funding. Dr. Scudamore and Dr. Botash had no relevant financial disclosures.

SAN FRANCISCO – In a proof-of-concept study, music provided an alternative to oral psychotropic medication in calming agitated patients at an inpatient psychiatric facility. Music has been studied as a treatment for agitation in dementia patients but not so much in psychiatric patients, according to Trevor Scudamore, MD, who is a resident fellow at State University of New York, Syracuse.

Jim Kling/MDedge News

“The other thing is that music has been more looked at in group therapy settings than as adjunct therapy, or as an option as an as-needed medication for agitation,” Dr. Scudamore said in an interview. He presented the study at a poster session at the annual meeting of the American Psychiatric Association.

When agitation arose, the program allowed patients to choose between an oral medication or music, which entailed a 30-minute session listening to a preset playlist using a wireless headphone. Playlist options included a variety of musical genres, and participants could sit in one place or roam around while listening.

Traditionally, agitated patients had the choice of an oral medication. If the patient refused and then escalated, they had to accept an intravenous medication. “Now there’s a choice between an oral medication and music, almost like a third layer in defusing agitation in the patient. If they refuse music, then they could go for oral medication, and then [IV medication]. They’re given a little bit more options. Maybe they don’t feel so confined, which is an interesting way of helping possibly defuse anxiety from a situation. That needs to be explored further,” Dr. Scudamore said.

The study had a two-phase, cross-sectional design. The first 3 months, the study included 71 patients, who were used to establish a baseline of agitation and psychotropic medication use. They introduced the music intervention during the second 3-month period, with 101 participants. After they listened to music, the patients completed a self-report form using the Likert scale, and nursing staff observed the patients status during the initial anxiety/agitation, while they listened to music, and 15 minutes after the listening session.

That need for commitment from nurses presented a challenge to implementation. They had to hand out headphones, keep track of them, and make sure they got the headphones back. “It is a lot more work than just giving 50 mg of hydroxyzine,” said coauthor Christopher Botash, MD, who also is a resident at the university.

Study participants had a range of psychiatric ills, including substance abuse (61%), depression (51%), psychosis (28%), trauma (26%), personality disorder (20%), and anxiety (17%).

As part of a preliminary report, the researchers presented data from surveys completed by nine nurses and 31 patients. After the music implementation, the average length of stay declined (10.49 to 8.20 days; difference, 2.29 days), as did the median length of stay (6.5 to 5.0 days). The two most commonly prescribed antipsychotics saw a decrease in administrations, from 3.37 to 2.93/month for haloperidol, and from 3.83 to 2.73 administrations/month for olanzapine.

A total of 56% of the nursing staff stated that the music therapy program helped calm down the patients. Nurses who disagreed cited the tendency for patients to intrude at the nursing station asking for the music, though this improved as patients learned the routine. Ninety-six percent of the patients reported satisfaction with the experience.

It was challenging for the researchers to implement the study, since offering music was a break in the routine. “The staff really does rely a lot on the meds, so oftentimes we would have to say, ‘Hey, have you offered the music yet?’ It’s a bit of a culture change,” Dr. Botash said.

The study, which Dr. Scudamore and Dr. Botash coauthored with Nekpen S. Ekure, MD, did not receive external funding. Dr. Scudamore and Dr. Botash had no relevant financial disclosures.

SAN FRANCISCO – In a proof-of-concept study, music provided an alternative to oral psychotropic medication in calming agitated patients at an inpatient psychiatric facility. Music has been studied as a treatment for agitation in dementia patients but not so much in psychiatric patients, according to Trevor Scudamore, MD, who is a resident fellow at State University of New York, Syracuse.

Jim Kling/MDedge News

“The other thing is that music has been more looked at in group therapy settings than as adjunct therapy, or as an option as an as-needed medication for agitation,” Dr. Scudamore said in an interview. He presented the study at a poster session at the annual meeting of the American Psychiatric Association.

When agitation arose, the program allowed patients to choose between an oral medication or music, which entailed a 30-minute session listening to a preset playlist using a wireless headphone. Playlist options included a variety of musical genres, and participants could sit in one place or roam around while listening.

Traditionally, agitated patients had the choice of an oral medication. If the patient refused and then escalated, they had to accept an intravenous medication. “Now there’s a choice between an oral medication and music, almost like a third layer in defusing agitation in the patient. If they refuse music, then they could go for oral medication, and then [IV medication]. They’re given a little bit more options. Maybe they don’t feel so confined, which is an interesting way of helping possibly defuse anxiety from a situation. That needs to be explored further,” Dr. Scudamore said.

The study had a two-phase, cross-sectional design. The first 3 months, the study included 71 patients, who were used to establish a baseline of agitation and psychotropic medication use. They introduced the music intervention during the second 3-month period, with 101 participants. After they listened to music, the patients completed a self-report form using the Likert scale, and nursing staff observed the patients status during the initial anxiety/agitation, while they listened to music, and 15 minutes after the listening session.

That need for commitment from nurses presented a challenge to implementation. They had to hand out headphones, keep track of them, and make sure they got the headphones back. “It is a lot more work than just giving 50 mg of hydroxyzine,” said coauthor Christopher Botash, MD, who also is a resident at the university.

Study participants had a range of psychiatric ills, including substance abuse (61%), depression (51%), psychosis (28%), trauma (26%), personality disorder (20%), and anxiety (17%).

As part of a preliminary report, the researchers presented data from surveys completed by nine nurses and 31 patients. After the music implementation, the average length of stay declined (10.49 to 8.20 days; difference, 2.29 days), as did the median length of stay (6.5 to 5.0 days). The two most commonly prescribed antipsychotics saw a decrease in administrations, from 3.37 to 2.93/month for haloperidol, and from 3.83 to 2.73 administrations/month for olanzapine.

A total of 56% of the nursing staff stated that the music therapy program helped calm down the patients. Nurses who disagreed cited the tendency for patients to intrude at the nursing station asking for the music, though this improved as patients learned the routine. Ninety-six percent of the patients reported satisfaction with the experience.

It was challenging for the researchers to implement the study, since offering music was a break in the routine. “The staff really does rely a lot on the meds, so oftentimes we would have to say, ‘Hey, have you offered the music yet?’ It’s a bit of a culture change,” Dr. Botash said.

The study, which Dr. Scudamore and Dr. Botash coauthored with Nekpen S. Ekure, MD, did not receive external funding. Dr. Scudamore and Dr. Botash had no relevant financial disclosures.

ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.

Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.

“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.

The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.

Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.

One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.

Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.

“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”

Researchers also saw differences in volume in key areas of the brain, before symptoms arose, among those who eventually developed psychosis symptoms, Dr. Gur said. They are continuing to explore and assess these findings.

The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.

“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”

Dr. Gur reported no relevant financial disclosures.

ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.

Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.

“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.

The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.

Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.

One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.

Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.

“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”

Researchers also saw differences in volume in key areas of the brain, before symptoms arose, among those who eventually developed psychosis symptoms, Dr. Gur said. They are continuing to explore and assess these findings.

The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.

“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”

Dr. Gur reported no relevant financial disclosures.

ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.

Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.

“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.

The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.

Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.

One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.

Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.

“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”

Researchers also saw differences in volume in key areas of the brain, before symptoms arose, among those who eventually developed psychosis symptoms, Dr. Gur said. They are continuing to explore and assess these findings.

The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.

“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”

Dr. Gur reported no relevant financial disclosures.

Over the past few decades, it has become increasingly clear that cannabis use can increase the risk of developing a psychotic disorder and worsen the course of existing schizophrenia in a dose-dependent fashion.^1-3 Beyond psychosis, although many patients with mental illness use cannabis for recreational purposes or as purported “self-medication,” currently available evidence suggests that marijuana is more likely to represent a harm than a benefit for psychi­atric disorders⁴ (Box^4-8). Our current state of knowledge therefore suggests that psychiatrists should caution their patients against using cannabis and prioritize interventions to reduce or discontinue use, especially among those with psychotic disorders.

Box

Despite that conclusion, because cannabis is classified as a Schedule I drug by the US Drug Enforcement Agency, clinical research investigating the risks and benefits of cannabis has been limited. It therefore remains possible that cannabis, or individual cannabinoids such as cannabidiol (CBD), may yet find a therapeutic niche in psychiatry. This article reviews evidence on CBD for the treatment of schizophrenia.

Cannabinergic drugs as potential antipsychotics

Although the bulk of evidence indicates a harmful effect of cannabis in individuals with or at risk for psychosis, there have been a few published cases of schizophrenia improving with dronabinol, an FDA-approved, synthetic form of delta-9-tetrahydrocannabinol (THC).^9,10 THC is the constituent of cannabis that produces euphoric effects. These provocative findings have not been replicated in controlled clinical trials, but suggest at least the theoretical possibility of idiosyncratic benefits from THC for some individuals within the psychotic spectrum.

Still, given that most available evidence supports that THC has a harmful effect on psychosis and psychosis risk, researchers have instead performed randomized controlled trials (RCTs) to investigate a possible therapeutic role for medications that oppose the agonist effects of THC at cannabinoid type 1 (CB1) receptors. To date, 2 RCTs comparing rimonabant, a CB1 inverse agonist, with placebo (PLB) in patients with schizophrenia have failed to demonstrate any benefit for psychotic symptoms or cognitive deficits.^11,12 A third trial examining rimonabant for people diagnosed with schizophrenia who were overweight found significant benefits for anxiety and depressive symptoms, but none for positive symptoms or the primary outcome of weight loss.¹³ While these results are discouraging, the role of THC in precipitating psychosis suggests that novel agents opposing the actions of THC on the cannabinoid system could have antipsychotic properties.¹⁴

Cannabidiol: An antipsychotic medication?

In contrast to THC, CBD has minimal euphorigenic properties and has recently been heralded in the popular press as a “miracle drug” with benefits for medical and psychiatric disorders alike.¹⁵ It has even been speculated that it could become a popular food supplement.¹⁶ In 2018, the FDA gave full approval to a pharmaceutically manufactured form of CBD (brand name: Epidiolex) as a novel treatment for 2 rare and severe forms of pediatric epilepsy, Lennox-Gastaut syndrome and Dravet syndrome,¹⁷ based on RCTs supporting its efficacy for these often refractory and life-threatening conditions.^18-20

In psychiatry, there have not yet been enough robust clinical studies to support broad therapeutic claims for CBD as a treatment for any mental disorder.²¹ However, there is growing evidence that CBD has potential as an antipsychotic medication. In 1995, the first case report was published describing the efficacy of CBD, 1,500 mg/d, as standalone therapy in a single individual with schizophrenia.²² In 2006, the same research group followed up with a case series in which only 1 out of 3 patients with treatment-refractory schizophrenia improved with flexible dosing of CBD to a maximum dose of 1,280 mg/d.²³

There have been 3 published RCTs exploring the efficacy of CBD in schizophrenia (Table^24-26). The first study, published in 2012, included 39 adults with schizophrenia who were randomized to 800 mg/d of CBD or amisulpride (AMS), a second-generation antipsychotic that is popular in Europe but is not available in the United States.²⁴ Over 4 weeks of randomized treatment, CBD resulted in as much improvement in overall symptoms and positive symptoms as AMS, and improvement of negative symptoms was significantly greater with CBD. Compared with patients treated with antipsychotic medication, patients who were treated with CBD had fewer extrapyramidal symptoms, less weight gain, and less prolactin elevation. This initial trial suggests that CBD might be as efficacious in schizophrenia as antipsychotic medication, without its burdensome adverse effects. However, this is the only RCT of CBD monotherapy published to date.

Continue to: Two other recently published RCTs...

Two other recently published RCTs compared CBD with PLB as add-on therapy to antipsychotics. McGuire et al²⁵ compared CBD, 1,000 mg/d, to PLB over 6 weeks in 88 patients with schizophrenia. Positive symptom improvement was statistically greater with CBD than with PLB, although the magnitude of clinical change was modest (using the Positive and Negative Syndrome Scale [PANSS] positive symptom subscale: −3.2 points for CBD vs −1.7 points for PLB). Changes in PANSS total score and subscales for general and negative symptoms were not significantly different between treatment groups. There was also no significant difference in overall change in neurocognitive symptoms, although post-hoc analysis revealed significantly greater improvement in motor speed for patients treated with CBD. More than twice the number of patients treated with CBD were rated as “much improved” by the Clinical Global Impressions scale compared with patients treated with PLB, but this was not a statistically significant finding, and most patients experienced only “minimal” or “no improvement.” In terms of adverse events, there were no significant differences between patients in the CBD and PLB groups. Although this study is technically “positive” for CBD and suggests minimal adverse effects, it is not clear whether the statistically significant positive symptom improvements (+1.5 PANSS points for CBD over PLB) were clinically significant.

The most recently published placebo-controlled RCT of CBD as add-on therapy to antipsychotic medication included 36 patients with schizophrenia treated over 6 weeks.²⁶ In this study, there was no benefit of CBD, 600 mg/d, on any PANSS score outcome (total, general, positive, or negative symptoms). For the primary outcome of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, there were no significant drug × time effects, and post-hoc analyses showed that only patients treated with PLB improved with time. Sedation was more common among patients treated with CBD compared with PLB.

Making sense of the data

There have been mixed results from the few case reports and 3 RCTs of patients with schizophrenia who were treated with CBD. How can we resolve these disparate findings? A few possible interpretations of the data that warrant clarification through additional research include:

Dosing. In the first case report with positive results, CBD was dosed at 1,500 mg/d,²² whereas in the subsequent case series with mixed results, the maximum allowable dose of CBD was 1,280 mg/d.²³ Likewise, in the RCTs, positive results were found when CBD was dosed at 800 to 1,000 mg/d,^24,25 but not at 600 mg/d.²⁶ The efficacy of CBD for schizophrenia might depend on higher doses.

Treatment resistance. In the second case series in which only 1 out of 3 patients responded to treatment with CBD,²³ the patients had demonstrated previous nonresponse to at least 2 first-generation antipsychotics (FGAs) and risperidone, 6 mg/d. In the RCTs, all patients were antipsychotic-responsive.^24-26 Cannabidiol may not be as effective for patients with treatment-refractory schizophrenia as it is for patients with schizophrenia who respond to antipsychotics.

Continue to: Clinical stability

Answering questions about CBD

Cannabidiol is becoming increasingly popular for its purported health benefits. The mixed results of the few studies published on CBD for schizophrenia place clinicians in a difficult position when attempting to answer questions about how cannabinoids might fit into treatment of patients with psychosis. Consider the following:

Is cannabis helpful for patients with schizophrenia? No. Aside from the few case reports suggesting that FDA-approved THC (dronabinol) can improve symptoms in some patients,^9,10 most of the evidence from anecdotal reports and both experimental and observational studies indicate that cannabis, THC, and synthetic cannabinoids have a harmful effect in patients with or at risk for psychosis.^1-3

If you are considering recommending some form of cannabis to patients with schizophrenia, what kind should you recommend? Recommending or encouraging cannabis use for patients with psychosis is ill-advised. Although certain types of cannabis might contain more THC (eg, Cannabis indica vs Cannabis sativa) or variable amounts of CBD, in general the amount of CBD in whole leaf cannabis is minimal, with the ratio of THC to CBD increasingly significantly over the past decade.^3,27 Most forms of cannabis should therefore be avoided by individuals with or at risk for psychotic disorders.

Continue to: What about CBD oil and other CBD products sold in dispensaries?

What about CBD oil and other CBD products sold in dispensaries? Cannabidiol is increasingly available in various forms based on its ability to be designated as a legal hemp product (containing <0.3% THC) at the federal level or as a cannabinoid in states where cannabis is legal. However, several studies have now shown that cannabis products sold online or in dispensaries are often labeled inaccurately, with both under- and over-reporting of THC and CBD content.^28-30 Some CBD products have been found to have almost no CBD at all.^29,30 The unreliability of product labeling makes it difficult to predict the effects of CBD products that are not subject to FDA purity standards for medications or dietary supplements. It also raises questions about the sources of CBD and the reliability of dosing in the studies discussed above.

Why might CBD work as an antipsychotic? Although CBD has minimal affinity for cannabinoid receptors, it appears to act as a partial agonist of dopamine D2 receptors and an agonist at 5-HT1A receptors, with overall effects that decrease mesolimbic dopamine activity.^31,32 In addition, CBD increases the availability of the endogenous cannabinoid anandamide, which may have antipsychotic properties.^14,33

Now that the FDA has approved CBD manufactured by a pharmaceutical company, should it be prescribed “off-label” for patients with schizophrenia? This is the “million dollar question,” with insufficient evidence to provide a clear answer. It should now be possible to prescribe FDA-approved CBD for off-label purposes, including the treatment of schizophrenia and other psychiatric disorders. No doubt, some clinicians are already doing so. This will predictably yield more anecdotal evidence about efficacy and adverse effects in the future, but there is not yet adequate evidence to support an FDA indication for CBD in schizophrenia. Additional studies of CBD for schizophrenia are ongoing.

Bottom Line

Cannabidiol (CBD) is becoming increasingly popular based on its purported health benefits, but the evidence supporting a therapeutic role in psychiatry is preliminary at best. Although CBD is now available by prescription as an FDA-approved drug for the treatment of 2 rare forms of epilepsy, its benefits in patients with schizophrenia are uncertain based on mixed results in clinical trials.

Related Resources

• Clinicaltrials.gov. Studies of “cannabidiol” and “schizophrenia.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/results?cond=Schizophrenia&term=cannabidiol.
• Grinspoon P. Cannabidiol (CBD) – what we know and what we don’t. Harvard Health Blog. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-wedont-2018082414476. Published August 24, 2018.

Drug Brand Names

Cannabidiol • Epidiolex
Dronabinol • Marinol
Risperidone • Risperdal

Over the past few decades, it has become increasingly clear that cannabis use can increase the risk of developing a psychotic disorder and worsen the course of existing schizophrenia in a dose-dependent fashion.^1-3 Beyond psychosis, although many patients with mental illness use cannabis for recreational purposes or as purported “self-medication,” currently available evidence suggests that marijuana is more likely to represent a harm than a benefit for psychi­atric disorders⁴ (Box^4-8). Our current state of knowledge therefore suggests that psychiatrists should caution their patients against using cannabis and prioritize interventions to reduce or discontinue use, especially among those with psychotic disorders.

Box

Despite that conclusion, because cannabis is classified as a Schedule I drug by the US Drug Enforcement Agency, clinical research investigating the risks and benefits of cannabis has been limited. It therefore remains possible that cannabis, or individual cannabinoids such as cannabidiol (CBD), may yet find a therapeutic niche in psychiatry. This article reviews evidence on CBD for the treatment of schizophrenia.

Cannabinergic drugs as potential antipsychotics

Although the bulk of evidence indicates a harmful effect of cannabis in individuals with or at risk for psychosis, there have been a few published cases of schizophrenia improving with dronabinol, an FDA-approved, synthetic form of delta-9-tetrahydrocannabinol (THC).^9,10 THC is the constituent of cannabis that produces euphoric effects. These provocative findings have not been replicated in controlled clinical trials, but suggest at least the theoretical possibility of idiosyncratic benefits from THC for some individuals within the psychotic spectrum.

Still, given that most available evidence supports that THC has a harmful effect on psychosis and psychosis risk, researchers have instead performed randomized controlled trials (RCTs) to investigate a possible therapeutic role for medications that oppose the agonist effects of THC at cannabinoid type 1 (CB1) receptors. To date, 2 RCTs comparing rimonabant, a CB1 inverse agonist, with placebo (PLB) in patients with schizophrenia have failed to demonstrate any benefit for psychotic symptoms or cognitive deficits.^11,12 A third trial examining rimonabant for people diagnosed with schizophrenia who were overweight found significant benefits for anxiety and depressive symptoms, but none for positive symptoms or the primary outcome of weight loss.¹³ While these results are discouraging, the role of THC in precipitating psychosis suggests that novel agents opposing the actions of THC on the cannabinoid system could have antipsychotic properties.¹⁴

Cannabidiol: An antipsychotic medication?

In contrast to THC, CBD has minimal euphorigenic properties and has recently been heralded in the popular press as a “miracle drug” with benefits for medical and psychiatric disorders alike.¹⁵ It has even been speculated that it could become a popular food supplement.¹⁶ In 2018, the FDA gave full approval to a pharmaceutically manufactured form of CBD (brand name: Epidiolex) as a novel treatment for 2 rare and severe forms of pediatric epilepsy, Lennox-Gastaut syndrome and Dravet syndrome,¹⁷ based on RCTs supporting its efficacy for these often refractory and life-threatening conditions.^18-20

In psychiatry, there have not yet been enough robust clinical studies to support broad therapeutic claims for CBD as a treatment for any mental disorder.²¹ However, there is growing evidence that CBD has potential as an antipsychotic medication. In 1995, the first case report was published describing the efficacy of CBD, 1,500 mg/d, as standalone therapy in a single individual with schizophrenia.²² In 2006, the same research group followed up with a case series in which only 1 out of 3 patients with treatment-refractory schizophrenia improved with flexible dosing of CBD to a maximum dose of 1,280 mg/d.²³

There have been 3 published RCTs exploring the efficacy of CBD in schizophrenia (Table^24-26). The first study, published in 2012, included 39 adults with schizophrenia who were randomized to 800 mg/d of CBD or amisulpride (AMS), a second-generation antipsychotic that is popular in Europe but is not available in the United States.²⁴ Over 4 weeks of randomized treatment, CBD resulted in as much improvement in overall symptoms and positive symptoms as AMS, and improvement of negative symptoms was significantly greater with CBD. Compared with patients treated with antipsychotic medication, patients who were treated with CBD had fewer extrapyramidal symptoms, less weight gain, and less prolactin elevation. This initial trial suggests that CBD might be as efficacious in schizophrenia as antipsychotic medication, without its burdensome adverse effects. However, this is the only RCT of CBD monotherapy published to date.

Continue to: Two other recently published RCTs...

Two other recently published RCTs compared CBD with PLB as add-on therapy to antipsychotics. McGuire et al²⁵ compared CBD, 1,000 mg/d, to PLB over 6 weeks in 88 patients with schizophrenia. Positive symptom improvement was statistically greater with CBD than with PLB, although the magnitude of clinical change was modest (using the Positive and Negative Syndrome Scale [PANSS] positive symptom subscale: −3.2 points for CBD vs −1.7 points for PLB). Changes in PANSS total score and subscales for general and negative symptoms were not significantly different between treatment groups. There was also no significant difference in overall change in neurocognitive symptoms, although post-hoc analysis revealed significantly greater improvement in motor speed for patients treated with CBD. More than twice the number of patients treated with CBD were rated as “much improved” by the Clinical Global Impressions scale compared with patients treated with PLB, but this was not a statistically significant finding, and most patients experienced only “minimal” or “no improvement.” In terms of adverse events, there were no significant differences between patients in the CBD and PLB groups. Although this study is technically “positive” for CBD and suggests minimal adverse effects, it is not clear whether the statistically significant positive symptom improvements (+1.5 PANSS points for CBD over PLB) were clinically significant.

The most recently published placebo-controlled RCT of CBD as add-on therapy to antipsychotic medication included 36 patients with schizophrenia treated over 6 weeks.²⁶ In this study, there was no benefit of CBD, 600 mg/d, on any PANSS score outcome (total, general, positive, or negative symptoms). For the primary outcome of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, there were no significant drug × time effects, and post-hoc analyses showed that only patients treated with PLB improved with time. Sedation was more common among patients treated with CBD compared with PLB.

Making sense of the data

There have been mixed results from the few case reports and 3 RCTs of patients with schizophrenia who were treated with CBD. How can we resolve these disparate findings? A few possible interpretations of the data that warrant clarification through additional research include:

Dosing. In the first case report with positive results, CBD was dosed at 1,500 mg/d,²² whereas in the subsequent case series with mixed results, the maximum allowable dose of CBD was 1,280 mg/d.²³ Likewise, in the RCTs, positive results were found when CBD was dosed at 800 to 1,000 mg/d,^24,25 but not at 600 mg/d.²⁶ The efficacy of CBD for schizophrenia might depend on higher doses.

Treatment resistance. In the second case series in which only 1 out of 3 patients responded to treatment with CBD,²³ the patients had demonstrated previous nonresponse to at least 2 first-generation antipsychotics (FGAs) and risperidone, 6 mg/d. In the RCTs, all patients were antipsychotic-responsive.^24-26 Cannabidiol may not be as effective for patients with treatment-refractory schizophrenia as it is for patients with schizophrenia who respond to antipsychotics.

Continue to: Clinical stability

Answering questions about CBD

Cannabidiol is becoming increasingly popular for its purported health benefits. The mixed results of the few studies published on CBD for schizophrenia place clinicians in a difficult position when attempting to answer questions about how cannabinoids might fit into treatment of patients with psychosis. Consider the following:

Is cannabis helpful for patients with schizophrenia? No. Aside from the few case reports suggesting that FDA-approved THC (dronabinol) can improve symptoms in some patients,^9,10 most of the evidence from anecdotal reports and both experimental and observational studies indicate that cannabis, THC, and synthetic cannabinoids have a harmful effect in patients with or at risk for psychosis.^1-3

If you are considering recommending some form of cannabis to patients with schizophrenia, what kind should you recommend? Recommending or encouraging cannabis use for patients with psychosis is ill-advised. Although certain types of cannabis might contain more THC (eg, Cannabis indica vs Cannabis sativa) or variable amounts of CBD, in general the amount of CBD in whole leaf cannabis is minimal, with the ratio of THC to CBD increasingly significantly over the past decade.^3,27 Most forms of cannabis should therefore be avoided by individuals with or at risk for psychotic disorders.

Continue to: What about CBD oil and other CBD products sold in dispensaries?

What about CBD oil and other CBD products sold in dispensaries? Cannabidiol is increasingly available in various forms based on its ability to be designated as a legal hemp product (containing <0.3% THC) at the federal level or as a cannabinoid in states where cannabis is legal. However, several studies have now shown that cannabis products sold online or in dispensaries are often labeled inaccurately, with both under- and over-reporting of THC and CBD content.^28-30 Some CBD products have been found to have almost no CBD at all.^29,30 The unreliability of product labeling makes it difficult to predict the effects of CBD products that are not subject to FDA purity standards for medications or dietary supplements. It also raises questions about the sources of CBD and the reliability of dosing in the studies discussed above.

Why might CBD work as an antipsychotic? Although CBD has minimal affinity for cannabinoid receptors, it appears to act as a partial agonist of dopamine D2 receptors and an agonist at 5-HT1A receptors, with overall effects that decrease mesolimbic dopamine activity.^31,32 In addition, CBD increases the availability of the endogenous cannabinoid anandamide, which may have antipsychotic properties.^14,33

Now that the FDA has approved CBD manufactured by a pharmaceutical company, should it be prescribed “off-label” for patients with schizophrenia? This is the “million dollar question,” with insufficient evidence to provide a clear answer. It should now be possible to prescribe FDA-approved CBD for off-label purposes, including the treatment of schizophrenia and other psychiatric disorders. No doubt, some clinicians are already doing so. This will predictably yield more anecdotal evidence about efficacy and adverse effects in the future, but there is not yet adequate evidence to support an FDA indication for CBD in schizophrenia. Additional studies of CBD for schizophrenia are ongoing.

Bottom Line

Cannabidiol (CBD) is becoming increasingly popular based on its purported health benefits, but the evidence supporting a therapeutic role in psychiatry is preliminary at best. Although CBD is now available by prescription as an FDA-approved drug for the treatment of 2 rare forms of epilepsy, its benefits in patients with schizophrenia are uncertain based on mixed results in clinical trials.

Related Resources

• Clinicaltrials.gov. Studies of “cannabidiol” and “schizophrenia.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/results?cond=Schizophrenia&term=cannabidiol.
• Grinspoon P. Cannabidiol (CBD) – what we know and what we don’t. Harvard Health Blog. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-wedont-2018082414476. Published August 24, 2018.

Drug Brand Names

Cannabidiol • Epidiolex
Dronabinol • Marinol
Risperidone • Risperdal

Over the past few decades, it has become increasingly clear that cannabis use can increase the risk of developing a psychotic disorder and worsen the course of existing schizophrenia in a dose-dependent fashion.^1-3 Beyond psychosis, although many patients with mental illness use cannabis for recreational purposes or as purported “self-medication,” currently available evidence suggests that marijuana is more likely to represent a harm than a benefit for psychi­atric disorders⁴ (Box^4-8). Our current state of knowledge therefore suggests that psychiatrists should caution their patients against using cannabis and prioritize interventions to reduce or discontinue use, especially among those with psychotic disorders.

Box

Despite that conclusion, because cannabis is classified as a Schedule I drug by the US Drug Enforcement Agency, clinical research investigating the risks and benefits of cannabis has been limited. It therefore remains possible that cannabis, or individual cannabinoids such as cannabidiol (CBD), may yet find a therapeutic niche in psychiatry. This article reviews evidence on CBD for the treatment of schizophrenia.

Cannabinergic drugs as potential antipsychotics

Although the bulk of evidence indicates a harmful effect of cannabis in individuals with or at risk for psychosis, there have been a few published cases of schizophrenia improving with dronabinol, an FDA-approved, synthetic form of delta-9-tetrahydrocannabinol (THC).^9,10 THC is the constituent of cannabis that produces euphoric effects. These provocative findings have not been replicated in controlled clinical trials, but suggest at least the theoretical possibility of idiosyncratic benefits from THC for some individuals within the psychotic spectrum.

Still, given that most available evidence supports that THC has a harmful effect on psychosis and psychosis risk, researchers have instead performed randomized controlled trials (RCTs) to investigate a possible therapeutic role for medications that oppose the agonist effects of THC at cannabinoid type 1 (CB1) receptors. To date, 2 RCTs comparing rimonabant, a CB1 inverse agonist, with placebo (PLB) in patients with schizophrenia have failed to demonstrate any benefit for psychotic symptoms or cognitive deficits.^11,12 A third trial examining rimonabant for people diagnosed with schizophrenia who were overweight found significant benefits for anxiety and depressive symptoms, but none for positive symptoms or the primary outcome of weight loss.¹³ While these results are discouraging, the role of THC in precipitating psychosis suggests that novel agents opposing the actions of THC on the cannabinoid system could have antipsychotic properties.¹⁴

Cannabidiol: An antipsychotic medication?

In contrast to THC, CBD has minimal euphorigenic properties and has recently been heralded in the popular press as a “miracle drug” with benefits for medical and psychiatric disorders alike.¹⁵ It has even been speculated that it could become a popular food supplement.¹⁶ In 2018, the FDA gave full approval to a pharmaceutically manufactured form of CBD (brand name: Epidiolex) as a novel treatment for 2 rare and severe forms of pediatric epilepsy, Lennox-Gastaut syndrome and Dravet syndrome,¹⁷ based on RCTs supporting its efficacy for these often refractory and life-threatening conditions.^18-20

In psychiatry, there have not yet been enough robust clinical studies to support broad therapeutic claims for CBD as a treatment for any mental disorder.²¹ However, there is growing evidence that CBD has potential as an antipsychotic medication. In 1995, the first case report was published describing the efficacy of CBD, 1,500 mg/d, as standalone therapy in a single individual with schizophrenia.²² In 2006, the same research group followed up with a case series in which only 1 out of 3 patients with treatment-refractory schizophrenia improved with flexible dosing of CBD to a maximum dose of 1,280 mg/d.²³

There have been 3 published RCTs exploring the efficacy of CBD in schizophrenia (Table^24-26). The first study, published in 2012, included 39 adults with schizophrenia who were randomized to 800 mg/d of CBD or amisulpride (AMS), a second-generation antipsychotic that is popular in Europe but is not available in the United States.²⁴ Over 4 weeks of randomized treatment, CBD resulted in as much improvement in overall symptoms and positive symptoms as AMS, and improvement of negative symptoms was significantly greater with CBD. Compared with patients treated with antipsychotic medication, patients who were treated with CBD had fewer extrapyramidal symptoms, less weight gain, and less prolactin elevation. This initial trial suggests that CBD might be as efficacious in schizophrenia as antipsychotic medication, without its burdensome adverse effects. However, this is the only RCT of CBD monotherapy published to date.

Continue to: Two other recently published RCTs...

Two other recently published RCTs compared CBD with PLB as add-on therapy to antipsychotics. McGuire et al²⁵ compared CBD, 1,000 mg/d, to PLB over 6 weeks in 88 patients with schizophrenia. Positive symptom improvement was statistically greater with CBD than with PLB, although the magnitude of clinical change was modest (using the Positive and Negative Syndrome Scale [PANSS] positive symptom subscale: −3.2 points for CBD vs −1.7 points for PLB). Changes in PANSS total score and subscales for general and negative symptoms were not significantly different between treatment groups. There was also no significant difference in overall change in neurocognitive symptoms, although post-hoc analysis revealed significantly greater improvement in motor speed for patients treated with CBD. More than twice the number of patients treated with CBD were rated as “much improved” by the Clinical Global Impressions scale compared with patients treated with PLB, but this was not a statistically significant finding, and most patients experienced only “minimal” or “no improvement.” In terms of adverse events, there were no significant differences between patients in the CBD and PLB groups. Although this study is technically “positive” for CBD and suggests minimal adverse effects, it is not clear whether the statistically significant positive symptom improvements (+1.5 PANSS points for CBD over PLB) were clinically significant.

The most recently published placebo-controlled RCT of CBD as add-on therapy to antipsychotic medication included 36 patients with schizophrenia treated over 6 weeks.²⁶ In this study, there was no benefit of CBD, 600 mg/d, on any PANSS score outcome (total, general, positive, or negative symptoms). For the primary outcome of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, there were no significant drug × time effects, and post-hoc analyses showed that only patients treated with PLB improved with time. Sedation was more common among patients treated with CBD compared with PLB.

Making sense of the data

There have been mixed results from the few case reports and 3 RCTs of patients with schizophrenia who were treated with CBD. How can we resolve these disparate findings? A few possible interpretations of the data that warrant clarification through additional research include:

Dosing. In the first case report with positive results, CBD was dosed at 1,500 mg/d,²² whereas in the subsequent case series with mixed results, the maximum allowable dose of CBD was 1,280 mg/d.²³ Likewise, in the RCTs, positive results were found when CBD was dosed at 800 to 1,000 mg/d,^24,25 but not at 600 mg/d.²⁶ The efficacy of CBD for schizophrenia might depend on higher doses.

Treatment resistance. In the second case series in which only 1 out of 3 patients responded to treatment with CBD,²³ the patients had demonstrated previous nonresponse to at least 2 first-generation antipsychotics (FGAs) and risperidone, 6 mg/d. In the RCTs, all patients were antipsychotic-responsive.^24-26 Cannabidiol may not be as effective for patients with treatment-refractory schizophrenia as it is for patients with schizophrenia who respond to antipsychotics.

Continue to: Clinical stability

Answering questions about CBD

Cannabidiol is becoming increasingly popular for its purported health benefits. The mixed results of the few studies published on CBD for schizophrenia place clinicians in a difficult position when attempting to answer questions about how cannabinoids might fit into treatment of patients with psychosis. Consider the following:

Is cannabis helpful for patients with schizophrenia? No. Aside from the few case reports suggesting that FDA-approved THC (dronabinol) can improve symptoms in some patients,^9,10 most of the evidence from anecdotal reports and both experimental and observational studies indicate that cannabis, THC, and synthetic cannabinoids have a harmful effect in patients with or at risk for psychosis.^1-3

If you are considering recommending some form of cannabis to patients with schizophrenia, what kind should you recommend? Recommending or encouraging cannabis use for patients with psychosis is ill-advised. Although certain types of cannabis might contain more THC (eg, Cannabis indica vs Cannabis sativa) or variable amounts of CBD, in general the amount of CBD in whole leaf cannabis is minimal, with the ratio of THC to CBD increasingly significantly over the past decade.^3,27 Most forms of cannabis should therefore be avoided by individuals with or at risk for psychotic disorders.

Continue to: What about CBD oil and other CBD products sold in dispensaries?

What about CBD oil and other CBD products sold in dispensaries? Cannabidiol is increasingly available in various forms based on its ability to be designated as a legal hemp product (containing <0.3% THC) at the federal level or as a cannabinoid in states where cannabis is legal. However, several studies have now shown that cannabis products sold online or in dispensaries are often labeled inaccurately, with both under- and over-reporting of THC and CBD content.^28-30 Some CBD products have been found to have almost no CBD at all.^29,30 The unreliability of product labeling makes it difficult to predict the effects of CBD products that are not subject to FDA purity standards for medications or dietary supplements. It also raises questions about the sources of CBD and the reliability of dosing in the studies discussed above.

Why might CBD work as an antipsychotic? Although CBD has minimal affinity for cannabinoid receptors, it appears to act as a partial agonist of dopamine D2 receptors and an agonist at 5-HT1A receptors, with overall effects that decrease mesolimbic dopamine activity.^31,32 In addition, CBD increases the availability of the endogenous cannabinoid anandamide, which may have antipsychotic properties.^14,33

Now that the FDA has approved CBD manufactured by a pharmaceutical company, should it be prescribed “off-label” for patients with schizophrenia? This is the “million dollar question,” with insufficient evidence to provide a clear answer. It should now be possible to prescribe FDA-approved CBD for off-label purposes, including the treatment of schizophrenia and other psychiatric disorders. No doubt, some clinicians are already doing so. This will predictably yield more anecdotal evidence about efficacy and adverse effects in the future, but there is not yet adequate evidence to support an FDA indication for CBD in schizophrenia. Additional studies of CBD for schizophrenia are ongoing.

Bottom Line

Cannabidiol (CBD) is becoming increasingly popular based on its purported health benefits, but the evidence supporting a therapeutic role in psychiatry is preliminary at best. Although CBD is now available by prescription as an FDA-approved drug for the treatment of 2 rare forms of epilepsy, its benefits in patients with schizophrenia are uncertain based on mixed results in clinical trials.

Related Resources

• Clinicaltrials.gov. Studies of “cannabidiol” and “schizophrenia.” U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/results?cond=Schizophrenia&term=cannabidiol.
• Grinspoon P. Cannabidiol (CBD) – what we know and what we don’t. Harvard Health Blog. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-wedont-2018082414476. Published August 24, 2018.

Drug Brand Names

Cannabidiol • Epidiolex
Dronabinol • Marinol
Risperidone • Risperdal

ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.

It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.

“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”

Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.

There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.

“It seems that early childhood is a sensitive period with regards to the effects of infection on IQ and risk of psychosis in adult life,” Dr. Khandaker said.

Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.

Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.

“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”

When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).

“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”

Dr. Khandaker disclosed no relevant financial relationships.

ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.

It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.

“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”

Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.

There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.

“It seems that early childhood is a sensitive period with regards to the effects of infection on IQ and risk of psychosis in adult life,” Dr. Khandaker said.

Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.

Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.

“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”

When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).

“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”

Dr. Khandaker disclosed no relevant financial relationships.

ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.

It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.

“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”

Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.

There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.

“It seems that early childhood is a sensitive period with regards to the effects of infection on IQ and risk of psychosis in adult life,” Dr. Khandaker said.

Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.

Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.

“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”

When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).

“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”

Dr. Khandaker disclosed no relevant financial relationships.

ORLANDO – Using games to promote exercise – or “exergaming” – is proving to boost the motivation of schizophrenia patients to engage in physical activity and help with symptoms, researchers said at the annual congress of the Schizophrenia International Research Society.

Physical fitness has been shown to boost cognitive function in people with schizophrenia – a particularly attractive option because it does not create stigma in the way that engaging in in-person therapy or taking medications might – and it is essentially free of side effects, said Jimmy Choi, PsyD, a senior scientist at the Olin Neuropsychiatry Research Center and staff neuropsychologist at the Institute of Living’s Schizophrenia Rehabilitation Program in Hartford, Conn.

The problem, Dr. Choi said, is that many studies have shown that compliance – or completion of half of an exercise program by participants – is fairly low, at 65%-68%. Among those who are not compliant, the benefits of exercise programs on cognition, psychosis symptoms, and mental status are conspicuously lower.

Effect sizes in laboratory trials on the efficacy of physical fitness are much higher than effectiveness seen in studies of community programs, Dr. Choi said, likely because laboratory trials offer participants a monetary reward for participation, while community studies might offer less attractive incentives, such as tickets for weekly or monthly raffles.

At Olin, a more true-to-life community program of exergaming – which included the use of virtual reality – was created by recreational therapists, exercise physiologists, psychologists, and technology experts to optimize the experience and outcomes, each with a distinct role – either developing the overall experience to promote enjoyment, achieving exhaustion but without an injury risk, incorporating patients’ baseline cognitive profile to make the programs suitable, or tailoring virtual experiences for each participant.

With 35 participants, researchers saw encouraging effects on working memory, processing speed, as well as positive and negative schizophrenia symptoms – with effect sizes ranging from 0.54 for working memory scores to 0.19 for positive schizophrenia symptoms, such as hallucinations.

The attrition rate of 14% was the same for those assessed as having low motivation as it was for those assessed as having high motivation, suggesting that exergaming helped boost and sustain motivation among patients for whom it is usually difficult, said Dr. Choi, who added that he and his colleagues have a paper in press outlining these results in Schizophrenia Research: Cognition.

“Exergaming shows promise in improving adherence to physical exercise and reducing attrition,” he said. “Highly motivated participants benefited more in terms of cognition and symptoms, but even those with low motivation saw improvements in working memory and negative symptoms.”

Dr. Choi added that his center is continuing to evaluate exergaming.

“A nice bike exercise or treadmill, that’s still more portable and cheaper for community clinics to do,” he said. “That’s one of the reasons ... we’re currently doing a randomized, controlled trial looking to see if exergaming could stand up to doing a singular exercise aerobic program.”

The study and Exergame equipment were funded by a Hartford Hospital auxiliary special projects grant. Dr. Choi reported having no financial conflicts.

ORLANDO – Using games to promote exercise – or “exergaming” – is proving to boost the motivation of schizophrenia patients to engage in physical activity and help with symptoms, researchers said at the annual congress of the Schizophrenia International Research Society.

Physical fitness has been shown to boost cognitive function in people with schizophrenia – a particularly attractive option because it does not create stigma in the way that engaging in in-person therapy or taking medications might – and it is essentially free of side effects, said Jimmy Choi, PsyD, a senior scientist at the Olin Neuropsychiatry Research Center and staff neuropsychologist at the Institute of Living’s Schizophrenia Rehabilitation Program in Hartford, Conn.

The problem, Dr. Choi said, is that many studies have shown that compliance – or completion of half of an exercise program by participants – is fairly low, at 65%-68%. Among those who are not compliant, the benefits of exercise programs on cognition, psychosis symptoms, and mental status are conspicuously lower.

Effect sizes in laboratory trials on the efficacy of physical fitness are much higher than effectiveness seen in studies of community programs, Dr. Choi said, likely because laboratory trials offer participants a monetary reward for participation, while community studies might offer less attractive incentives, such as tickets for weekly or monthly raffles.

At Olin, a more true-to-life community program of exergaming – which included the use of virtual reality – was created by recreational therapists, exercise physiologists, psychologists, and technology experts to optimize the experience and outcomes, each with a distinct role – either developing the overall experience to promote enjoyment, achieving exhaustion but without an injury risk, incorporating patients’ baseline cognitive profile to make the programs suitable, or tailoring virtual experiences for each participant.

With 35 participants, researchers saw encouraging effects on working memory, processing speed, as well as positive and negative schizophrenia symptoms – with effect sizes ranging from 0.54 for working memory scores to 0.19 for positive schizophrenia symptoms, such as hallucinations.

The attrition rate of 14% was the same for those assessed as having low motivation as it was for those assessed as having high motivation, suggesting that exergaming helped boost and sustain motivation among patients for whom it is usually difficult, said Dr. Choi, who added that he and his colleagues have a paper in press outlining these results in Schizophrenia Research: Cognition.

“Exergaming shows promise in improving adherence to physical exercise and reducing attrition,” he said. “Highly motivated participants benefited more in terms of cognition and symptoms, but even those with low motivation saw improvements in working memory and negative symptoms.”

Dr. Choi added that his center is continuing to evaluate exergaming.

“A nice bike exercise or treadmill, that’s still more portable and cheaper for community clinics to do,” he said. “That’s one of the reasons ... we’re currently doing a randomized, controlled trial looking to see if exergaming could stand up to doing a singular exercise aerobic program.”

The study and Exergame equipment were funded by a Hartford Hospital auxiliary special projects grant. Dr. Choi reported having no financial conflicts.

ORLANDO – Using games to promote exercise – or “exergaming” – is proving to boost the motivation of schizophrenia patients to engage in physical activity and help with symptoms, researchers said at the annual congress of the Schizophrenia International Research Society.

Physical fitness has been shown to boost cognitive function in people with schizophrenia – a particularly attractive option because it does not create stigma in the way that engaging in in-person therapy or taking medications might – and it is essentially free of side effects, said Jimmy Choi, PsyD, a senior scientist at the Olin Neuropsychiatry Research Center and staff neuropsychologist at the Institute of Living’s Schizophrenia Rehabilitation Program in Hartford, Conn.

The problem, Dr. Choi said, is that many studies have shown that compliance – or completion of half of an exercise program by participants – is fairly low, at 65%-68%. Among those who are not compliant, the benefits of exercise programs on cognition, psychosis symptoms, and mental status are conspicuously lower.

Effect sizes in laboratory trials on the efficacy of physical fitness are much higher than effectiveness seen in studies of community programs, Dr. Choi said, likely because laboratory trials offer participants a monetary reward for participation, while community studies might offer less attractive incentives, such as tickets for weekly or monthly raffles.

At Olin, a more true-to-life community program of exergaming – which included the use of virtual reality – was created by recreational therapists, exercise physiologists, psychologists, and technology experts to optimize the experience and outcomes, each with a distinct role – either developing the overall experience to promote enjoyment, achieving exhaustion but without an injury risk, incorporating patients’ baseline cognitive profile to make the programs suitable, or tailoring virtual experiences for each participant.

With 35 participants, researchers saw encouraging effects on working memory, processing speed, as well as positive and negative schizophrenia symptoms – with effect sizes ranging from 0.54 for working memory scores to 0.19 for positive schizophrenia symptoms, such as hallucinations.

The attrition rate of 14% was the same for those assessed as having low motivation as it was for those assessed as having high motivation, suggesting that exergaming helped boost and sustain motivation among patients for whom it is usually difficult, said Dr. Choi, who added that he and his colleagues have a paper in press outlining these results in Schizophrenia Research: Cognition.

“Exergaming shows promise in improving adherence to physical exercise and reducing attrition,” he said. “Highly motivated participants benefited more in terms of cognition and symptoms, but even those with low motivation saw improvements in working memory and negative symptoms.”

Dr. Choi added that his center is continuing to evaluate exergaming.

“A nice bike exercise or treadmill, that’s still more portable and cheaper for community clinics to do,” he said. “That’s one of the reasons ... we’re currently doing a randomized, controlled trial looking to see if exergaming could stand up to doing a singular exercise aerobic program.”

The study and Exergame equipment were funded by a Hartford Hospital auxiliary special projects grant. Dr. Choi reported having no financial conflicts.

I was talking to a physical therapy (PT) colleague and she was lamenting how much she hated doing documentation on patients she was treating. I suggested to her that she make her evaluations and progress notes sing. This is a concept I would sometimes use with patients who might be depressed, for example, I would ask them if anything made their heart sing to get an idea how “depressed” they might be. If they were unhappy or sad, I would advise that they engage in “heart singing” activities and behaviors, as I believe it is the “simple pleasures” in life that keep us resilient and persistent.

It is funny, when I was a resident and working in Jackson Park Hospital’s first psychiatric ward in 1972, one day in a note I wrote “I am going to give this acutely psychotic patient the big T – Thorazine to help them get some sleep at night,” I did not really think much about it until one of the nurses brought it to my attention because she thought it was unique – and a funny way of reporting plans in my progress notes.

My PT colleague told me that she remembered the first time she read one of my notes on a patient we were treating together (she needed to know the patient’s psychiatric status before she engaged them in physical therapy), and it struck her that I reported the patient was “befuddled,” and she wondered who would use befuddled in a note (lately, I have started using “flummoxed”). Another time, I was charting on a patient, and I used the word “flapdoodle” to describe the nonsense the patient was spewing (I recall this particular patient told me they graduated from grammar school at 5 years old). Another favorite word of mine that I use to describe nonsense is “claptrap.”

So, I have been making my evaluations and progress notes sing for a very long time, as doing so improves my writing skills, stimulates my thinking, turns the drudgery of charting into some fun, and creates an adventure in writing. This approach and skill has made my charting work easier for me to do – and colleagues actually read my notes.

I have also been a big user of mental status templates to cut down my time. The essential elements of a mental status are in the narrative template, and all I need to do is to edit the verbiage in the template to fit the patient’s presentation so that the mental status sings. Early on, I understood that, to be a good psychiatrist, you needed a good vocabulary so you can speak with as much precision as possible when describing a patient’s mental status.

I was seeing many Alzheimer’s patients at one point. So I developed a special mental status template for them (female and male), so all I had to do to it was cut and paste, and then edit the template to fit the patient like a glove. Template example: This is a xx-year-old female who was appropriately groomed and who was cooperative with the interview, but she could not give much information. She was not hyperactive or lethargic. Her mood was bland, and her affect was flat and bland. Her speech did not contain any relevant information. Thought processes were not evident, although she was awake. I could not get a history of delusions or current auditory or visual hallucinations. Her thought content was nondescript. She was attentive, and her recent and remote memory were poor. Clinical estimate of her intelligence could not be determined. Her judgment and insight were poor. I could not determine whether there was any suicidal or homicidal ideation.

Formulation: This is a xx-year-old female who has a major neurocognitive disorder (formerly known as dementia). She is not overtly psychotic, suicidal, homicidal, or gravely disabled, but her level of functioning leaves a lot to be desired, which is why she needs a sheltered living circumstance.

Dx: Major neurocognitive disorder (formerly known as dementia).

Here’s another example: This is a xx-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic and he had a wide range of affect as he was able to smile, get serious, and be sad (about xxx). His speech was relevant, linear, and goal directed. Thought processes did not show any signs of loose associations, tangentiality, or circumstantiality. He denies any delusions or current auditory or visual hallucinations. His thought content was surrounding xxx. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was xxx average. His judgment and insight were poor as xxx. No report of suicidal or homicidal ideation.

Formulation: xxx. He is not overtly psychotic, suicidal, homicidal, or gravely disabled so I will clear him for psychiatric discharge.

Dx: xxx.

Just me trying to make work a little easier for myself and everyone else.
 

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

I was talking to a physical therapy (PT) colleague and she was lamenting how much she hated doing documentation on patients she was treating. I suggested to her that she make her evaluations and progress notes sing. This is a concept I would sometimes use with patients who might be depressed, for example, I would ask them if anything made their heart sing to get an idea how “depressed” they might be. If they were unhappy or sad, I would advise that they engage in “heart singing” activities and behaviors, as I believe it is the “simple pleasures” in life that keep us resilient and persistent.

It is funny, when I was a resident and working in Jackson Park Hospital’s first psychiatric ward in 1972, one day in a note I wrote “I am going to give this acutely psychotic patient the big T – Thorazine to help them get some sleep at night,” I did not really think much about it until one of the nurses brought it to my attention because she thought it was unique – and a funny way of reporting plans in my progress notes.

My PT colleague told me that she remembered the first time she read one of my notes on a patient we were treating together (she needed to know the patient’s psychiatric status before she engaged them in physical therapy), and it struck her that I reported the patient was “befuddled,” and she wondered who would use befuddled in a note (lately, I have started using “flummoxed”). Another time, I was charting on a patient, and I used the word “flapdoodle” to describe the nonsense the patient was spewing (I recall this particular patient told me they graduated from grammar school at 5 years old). Another favorite word of mine that I use to describe nonsense is “claptrap.”

So, I have been making my evaluations and progress notes sing for a very long time, as doing so improves my writing skills, stimulates my thinking, turns the drudgery of charting into some fun, and creates an adventure in writing. This approach and skill has made my charting work easier for me to do – and colleagues actually read my notes.

I have also been a big user of mental status templates to cut down my time. The essential elements of a mental status are in the narrative template, and all I need to do is to edit the verbiage in the template to fit the patient’s presentation so that the mental status sings. Early on, I understood that, to be a good psychiatrist, you needed a good vocabulary so you can speak with as much precision as possible when describing a patient’s mental status.

I was seeing many Alzheimer’s patients at one point. So I developed a special mental status template for them (female and male), so all I had to do to it was cut and paste, and then edit the template to fit the patient like a glove. Template example: This is a xx-year-old female who was appropriately groomed and who was cooperative with the interview, but she could not give much information. She was not hyperactive or lethargic. Her mood was bland, and her affect was flat and bland. Her speech did not contain any relevant information. Thought processes were not evident, although she was awake. I could not get a history of delusions or current auditory or visual hallucinations. Her thought content was nondescript. She was attentive, and her recent and remote memory were poor. Clinical estimate of her intelligence could not be determined. Her judgment and insight were poor. I could not determine whether there was any suicidal or homicidal ideation.

Formulation: This is a xx-year-old female who has a major neurocognitive disorder (formerly known as dementia). She is not overtly psychotic, suicidal, homicidal, or gravely disabled, but her level of functioning leaves a lot to be desired, which is why she needs a sheltered living circumstance.

Dx: Major neurocognitive disorder (formerly known as dementia).

Here’s another example: This is a xx-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic and he had a wide range of affect as he was able to smile, get serious, and be sad (about xxx). His speech was relevant, linear, and goal directed. Thought processes did not show any signs of loose associations, tangentiality, or circumstantiality. He denies any delusions or current auditory or visual hallucinations. His thought content was surrounding xxx. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was xxx average. His judgment and insight were poor as xxx. No report of suicidal or homicidal ideation.

Formulation: xxx. He is not overtly psychotic, suicidal, homicidal, or gravely disabled so I will clear him for psychiatric discharge.

Dx: xxx.

Just me trying to make work a little easier for myself and everyone else.
 

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

I was talking to a physical therapy (PT) colleague and she was lamenting how much she hated doing documentation on patients she was treating. I suggested to her that she make her evaluations and progress notes sing. This is a concept I would sometimes use with patients who might be depressed, for example, I would ask them if anything made their heart sing to get an idea how “depressed” they might be. If they were unhappy or sad, I would advise that they engage in “heart singing” activities and behaviors, as I believe it is the “simple pleasures” in life that keep us resilient and persistent.

It is funny, when I was a resident and working in Jackson Park Hospital’s first psychiatric ward in 1972, one day in a note I wrote “I am going to give this acutely psychotic patient the big T – Thorazine to help them get some sleep at night,” I did not really think much about it until one of the nurses brought it to my attention because she thought it was unique – and a funny way of reporting plans in my progress notes.

My PT colleague told me that she remembered the first time she read one of my notes on a patient we were treating together (she needed to know the patient’s psychiatric status before she engaged them in physical therapy), and it struck her that I reported the patient was “befuddled,” and she wondered who would use befuddled in a note (lately, I have started using “flummoxed”). Another time, I was charting on a patient, and I used the word “flapdoodle” to describe the nonsense the patient was spewing (I recall this particular patient told me they graduated from grammar school at 5 years old). Another favorite word of mine that I use to describe nonsense is “claptrap.”

So, I have been making my evaluations and progress notes sing for a very long time, as doing so improves my writing skills, stimulates my thinking, turns the drudgery of charting into some fun, and creates an adventure in writing. This approach and skill has made my charting work easier for me to do – and colleagues actually read my notes.

I have also been a big user of mental status templates to cut down my time. The essential elements of a mental status are in the narrative template, and all I need to do is to edit the verbiage in the template to fit the patient’s presentation so that the mental status sings. Early on, I understood that, to be a good psychiatrist, you needed a good vocabulary so you can speak with as much precision as possible when describing a patient’s mental status.

I was seeing many Alzheimer’s patients at one point. So I developed a special mental status template for them (female and male), so all I had to do to it was cut and paste, and then edit the template to fit the patient like a glove. Template example: This is a xx-year-old female who was appropriately groomed and who was cooperative with the interview, but she could not give much information. She was not hyperactive or lethargic. Her mood was bland, and her affect was flat and bland. Her speech did not contain any relevant information. Thought processes were not evident, although she was awake. I could not get a history of delusions or current auditory or visual hallucinations. Her thought content was nondescript. She was attentive, and her recent and remote memory were poor. Clinical estimate of her intelligence could not be determined. Her judgment and insight were poor. I could not determine whether there was any suicidal or homicidal ideation.

Formulation: This is a xx-year-old female who has a major neurocognitive disorder (formerly known as dementia). She is not overtly psychotic, suicidal, homicidal, or gravely disabled, but her level of functioning leaves a lot to be desired, which is why she needs a sheltered living circumstance.

Dx: Major neurocognitive disorder (formerly known as dementia).

Here’s another example: This is a xx-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic and he had a wide range of affect as he was able to smile, get serious, and be sad (about xxx). His speech was relevant, linear, and goal directed. Thought processes did not show any signs of loose associations, tangentiality, or circumstantiality. He denies any delusions or current auditory or visual hallucinations. His thought content was surrounding xxx. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was xxx average. His judgment and insight were poor as xxx. No report of suicidal or homicidal ideation.

Formulation: xxx. He is not overtly psychotic, suicidal, homicidal, or gravely disabled so I will clear him for psychiatric discharge.

Dx: xxx.

Just me trying to make work a little easier for myself and everyone else.
 

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit in Chicago, clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago, former president/CEO of Community Mental Health Council, and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

ORLANDO – Smartphones offer a way to give people with schizophrenia access to immediate medical guidance in times of need and clinicians a convenient way to check in with patients, an expert said at the annual congress of the Schizophrenia International Research Society.

Dror Ben-Zeev, PhD, professor of psychiatry and behavioral sciences at the University of Washington, Seattle, said that, despite the many differences in the habits and experiences of people with schizophrenia, there do not appear to be many differences in the way they use mobile technology, compared with the general population.

Even as far back as 2012, when smartphone technology was much less widely adopted, and he and his colleagues conducted a survey of patients in the Chicago area, 63% of schizophrenia patients said they had a mobile device. Ninety percent of them said they used the device to talk, one-third used it for text messaging, and 13% used it to browse the Internet.

More recently, a meta-analysis of 15 studies, published in 2016, found that, among those with psychotic disorders who were surveyed since 2014, 81% owned a mobile device. A majority said they favored using mobile technology for contact with medical services and for supporting self-management (Schizophr Bull. 2016 Mar;42[2]:448-55).

“Do they own phones? Do they use phones? Absolutely, they do,” Dr. Ben-Zeev said. “And in a surprising way, it might be one of the areas where the gap between psychotic illness and the general population is close to nonexistent.”

FOCUS, a smartphone app designed for easy use by patients to allow them to quickly cope with symptoms and to allow clinicians to ask how they’re doing, has helped to improve patient symptoms, Dr. Ben-Zeev said. Patients receive three daily prompts to check in with the app, which offers a chance to report symptoms. It also offers “on-demand” resources 24 hours a day for help with handling voices, social challenges, medications, sleep issues, and mood difficulties.

When patients report hearing voices, for instance, they are asked to describe them in multiple choice fashion, including an option to supply their own description. If a patient reports that, for example, the voices “know everything,” the app asks them to think of a time when the voices were sure something would happen, but it didn’t. The app also offers videos in which therapists give advice to help patients with symptoms.

In a 30-day trial, participants used the FOCUS app an average of five times a day in the previous week, and 63% of the uses were participant initiated rather than app initiated. Positive and Negative Syndrome Scale scores (77.6 vs. 71.5; P less than .001) and depression scores (19.7 vs. 13.9; P less than .01) were both significantly improved after the trial, compared with before (Schizophr Bull. 2014 Nov;40[6]:1244-53).

Meanwhile, a 3-month randomized, controlled trial comparing the FOCUS intervention with Wellness Recovery Action Plan (WRAP), a clinic-based group intervention, had what Dr. Ben-Zeev referred in an interview as “very compelling findings” (Psychiatr Serv. 2018 Sep 1;69[9]:978-85). That study, lead by Dr. Ben-Zeev and his colleagues, found that participants with serious mental illness who were assigned to FOCUS were more likely than those assigned to WRAP to begin treatment (90% vs. 58%) and to remain fully engaged in care over an 8-week period.

Researchers are also exploring the benefits of a program called CrossCheck, in which patients’ use of smartphones relays information that could predict a psychosis relapse (Psychiatr Rehab J. 2017 Sep;40[3]:266-75). For instance, use in the middle of the night indicates sleeping difficulties, and location data could indicate a change in residence. Both are warning signs of a possible impending relapse.

“There is a unique opportunity,” Dr. Ben-Zeev said, “to leverage this status to try to improve what we do.”

Dr. Ben-Zeev also is codirector of the university’s Behavioral Research in Technology and Engineering Center and director of the mHealth for Mental Health Program, a research collaborative that focuses on developing, evaluating, and implementing mobile technologies. Dr. Ben-Zeev has a licensing and consulting agreement with Pear Therapeutics and a consulting agreement with eQuility.

ORLANDO – Smartphones offer a way to give people with schizophrenia access to immediate medical guidance in times of need and clinicians a convenient way to check in with patients, an expert said at the annual congress of the Schizophrenia International Research Society.

Dror Ben-Zeev, PhD, professor of psychiatry and behavioral sciences at the University of Washington, Seattle, said that, despite the many differences in the habits and experiences of people with schizophrenia, there do not appear to be many differences in the way they use mobile technology, compared with the general population.

Even as far back as 2012, when smartphone technology was much less widely adopted, and he and his colleagues conducted a survey of patients in the Chicago area, 63% of schizophrenia patients said they had a mobile device. Ninety percent of them said they used the device to talk, one-third used it for text messaging, and 13% used it to browse the Internet.

More recently, a meta-analysis of 15 studies, published in 2016, found that, among those with psychotic disorders who were surveyed since 2014, 81% owned a mobile device. A majority said they favored using mobile technology for contact with medical services and for supporting self-management (Schizophr Bull. 2016 Mar;42[2]:448-55).

“Do they own phones? Do they use phones? Absolutely, they do,” Dr. Ben-Zeev said. “And in a surprising way, it might be one of the areas where the gap between psychotic illness and the general population is close to nonexistent.”

FOCUS, a smartphone app designed for easy use by patients to allow them to quickly cope with symptoms and to allow clinicians to ask how they’re doing, has helped to improve patient symptoms, Dr. Ben-Zeev said. Patients receive three daily prompts to check in with the app, which offers a chance to report symptoms. It also offers “on-demand” resources 24 hours a day for help with handling voices, social challenges, medications, sleep issues, and mood difficulties.

When patients report hearing voices, for instance, they are asked to describe them in multiple choice fashion, including an option to supply their own description. If a patient reports that, for example, the voices “know everything,” the app asks them to think of a time when the voices were sure something would happen, but it didn’t. The app also offers videos in which therapists give advice to help patients with symptoms.

In a 30-day trial, participants used the FOCUS app an average of five times a day in the previous week, and 63% of the uses were participant initiated rather than app initiated. Positive and Negative Syndrome Scale scores (77.6 vs. 71.5; P less than .001) and depression scores (19.7 vs. 13.9; P less than .01) were both significantly improved after the trial, compared with before (Schizophr Bull. 2014 Nov;40[6]:1244-53).

Meanwhile, a 3-month randomized, controlled trial comparing the FOCUS intervention with Wellness Recovery Action Plan (WRAP), a clinic-based group intervention, had what Dr. Ben-Zeev referred in an interview as “very compelling findings” (Psychiatr Serv. 2018 Sep 1;69[9]:978-85). That study, lead by Dr. Ben-Zeev and his colleagues, found that participants with serious mental illness who were assigned to FOCUS were more likely than those assigned to WRAP to begin treatment (90% vs. 58%) and to remain fully engaged in care over an 8-week period.

Researchers are also exploring the benefits of a program called CrossCheck, in which patients’ use of smartphones relays information that could predict a psychosis relapse (Psychiatr Rehab J. 2017 Sep;40[3]:266-75). For instance, use in the middle of the night indicates sleeping difficulties, and location data could indicate a change in residence. Both are warning signs of a possible impending relapse.

“There is a unique opportunity,” Dr. Ben-Zeev said, “to leverage this status to try to improve what we do.”

Dr. Ben-Zeev also is codirector of the university’s Behavioral Research in Technology and Engineering Center and director of the mHealth for Mental Health Program, a research collaborative that focuses on developing, evaluating, and implementing mobile technologies. Dr. Ben-Zeev has a licensing and consulting agreement with Pear Therapeutics and a consulting agreement with eQuility.

ORLANDO – Smartphones offer a way to give people with schizophrenia access to immediate medical guidance in times of need and clinicians a convenient way to check in with patients, an expert said at the annual congress of the Schizophrenia International Research Society.

Dror Ben-Zeev, PhD, professor of psychiatry and behavioral sciences at the University of Washington, Seattle, said that, despite the many differences in the habits and experiences of people with schizophrenia, there do not appear to be many differences in the way they use mobile technology, compared with the general population.

Even as far back as 2012, when smartphone technology was much less widely adopted, and he and his colleagues conducted a survey of patients in the Chicago area, 63% of schizophrenia patients said they had a mobile device. Ninety percent of them said they used the device to talk, one-third used it for text messaging, and 13% used it to browse the Internet.

More recently, a meta-analysis of 15 studies, published in 2016, found that, among those with psychotic disorders who were surveyed since 2014, 81% owned a mobile device. A majority said they favored using mobile technology for contact with medical services and for supporting self-management (Schizophr Bull. 2016 Mar;42[2]:448-55).

“Do they own phones? Do they use phones? Absolutely, they do,” Dr. Ben-Zeev said. “And in a surprising way, it might be one of the areas where the gap between psychotic illness and the general population is close to nonexistent.”

FOCUS, a smartphone app designed for easy use by patients to allow them to quickly cope with symptoms and to allow clinicians to ask how they’re doing, has helped to improve patient symptoms, Dr. Ben-Zeev said. Patients receive three daily prompts to check in with the app, which offers a chance to report symptoms. It also offers “on-demand” resources 24 hours a day for help with handling voices, social challenges, medications, sleep issues, and mood difficulties.

When patients report hearing voices, for instance, they are asked to describe them in multiple choice fashion, including an option to supply their own description. If a patient reports that, for example, the voices “know everything,” the app asks them to think of a time when the voices were sure something would happen, but it didn’t. The app also offers videos in which therapists give advice to help patients with symptoms.

In a 30-day trial, participants used the FOCUS app an average of five times a day in the previous week, and 63% of the uses were participant initiated rather than app initiated. Positive and Negative Syndrome Scale scores (77.6 vs. 71.5; P less than .001) and depression scores (19.7 vs. 13.9; P less than .01) were both significantly improved after the trial, compared with before (Schizophr Bull. 2014 Nov;40[6]:1244-53).

Meanwhile, a 3-month randomized, controlled trial comparing the FOCUS intervention with Wellness Recovery Action Plan (WRAP), a clinic-based group intervention, had what Dr. Ben-Zeev referred in an interview as “very compelling findings” (Psychiatr Serv. 2018 Sep 1;69[9]:978-85). That study, lead by Dr. Ben-Zeev and his colleagues, found that participants with serious mental illness who were assigned to FOCUS were more likely than those assigned to WRAP to begin treatment (90% vs. 58%) and to remain fully engaged in care over an 8-week period.

Researchers are also exploring the benefits of a program called CrossCheck, in which patients’ use of smartphones relays information that could predict a psychosis relapse (Psychiatr Rehab J. 2017 Sep;40[3]:266-75). For instance, use in the middle of the night indicates sleeping difficulties, and location data could indicate a change in residence. Both are warning signs of a possible impending relapse.

“There is a unique opportunity,” Dr. Ben-Zeev said, “to leverage this status to try to improve what we do.”

Dr. Ben-Zeev also is codirector of the university’s Behavioral Research in Technology and Engineering Center and director of the mHealth for Mental Health Program, a research collaborative that focuses on developing, evaluating, and implementing mobile technologies. Dr. Ben-Zeev has a licensing and consulting agreement with Pear Therapeutics and a consulting agreement with eQuility.