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CASE: Scared and confused
Mr. C, age 28, presents to the emergency department (ED) in police custody with agitation and altered mental status. Earlier that evening, Mr. C’s girlfriend noticed he was talking to himself while watching television. A few hours later, Mr. C thought someone was breaking into his house. Mr. C ran out of the house screaming for help, broke his neighbor’s window, and eventually called the police. When the police arrived Mr. C was wearing only his underwear, shaking, and bleeding from his hands. He said he was afraid and refused to respond to police instructions. Police officers used an electronic stun gun to facilitate transport to the hospital.
Mr. C admits to smoking 3 to 4 marijuana joints daily for the past 16 years. His last drug use was 2 hours before his symptoms began. Mr. C suggests that someone may have adulterated his marijuana joint but he has no factual basis for this accusation. He denies using alcohol and other illicit drugs and has no personal or family psychiatric history. He denies recent fever, loss of consciousness, chest pain, weakness, myalgia, or headache. Medically stable, his only complaint is mild hand pain.
Mr. C is alert, awake, and oriented to his name, and he responds properly to questions. He is tachycardic (101 bpm), his blood pressure is 149/57 mm Hg with normal S1 and S2 sounds, and he has no meningismus or nystagmus. Glasgow Coma Scale score is 15. He has increased deep tendon reflexes on the right upper and lower limb with good hand-grip and multiple abrasions and lacerations on his hands.
The authors’ observations
New-onset psychosis can have a wide differential diagnosis, particularly when reliable history is not available. Mr. C’s allegation that someone tampered with his marijuana raises 2 possibilities: embalming fluid (form-aldehyde) toxicity or PCP intoxication.
Embalming fluid toxicity can cause:
- agitation and sudden unpredictable behavior
- confusion or toxic delirium
- coma or seizure
- cerebral and pulmonary edema or death in severe cases.
The terms “wet,” “sherm,” “fly,” “amp,” or “illy” are used to describe a marijuana cigarette that has been dipped into embalming fluid, dried, and then smoked.1 The effect is similar to that of PCP and causes extreme hallucinations. Reported highs last 30 minutes to 1 hour.2
Symptomatology of PCP intoxication may be indistinguishable from functional psychosis (Table 1).3 Visual, auditory, and tactile misperceptions are common and highly changeable disorientation often is accompanied by alternating periods of lethargy and fearful agitation. These patients typically show catatonic posturing and/or stereotyped movement. Somatic sensations appear to be disassociated; patients may misperceive pain, distance, and time. Patients taking PCP rarely admit to true hallucinations; however their thinking usually is grossly disoriented.4 Symptoms of delirium may last from 30 minutes to 6 hours in 80% of cases; 12% of patients may remain symptomatic for 12 hours. Violent behavior and agitation usually lasts only a few hours.5
Long-term marijuana abuse can lead to psychosis6 but acute onset is not typical, and recent prospective trials raised doubts that cannabis would be a sole factor.7 Instead, cannabis may be 1 of several factors that contribute to psychosis, particularly in patients who are predisposed.
Table 1
Phencyclidine (PCP) intoxication: What to look for
| Findings | Percentage of cases |
|---|---|
| Nystagmus | 57.4% |
| Hypertension | 57.0% |
| Delirium | 36.9% |
| Violent behavior | 35.4% |
| Agitation | 34.0% |
| Tachycardia | 30.0% |
| Bizarre behavior | 28.5% |
| Hallucinations/delusions | 18.5% |
| Unconsciousness | 10.6% |
| Lethargy/stupor | 6.6% |
| Hypothermia | 6.4% |
| Generalized rigidity | 5.2% |
| Profuse sweating | 3.9% |
| No behavior effect | 3.5% |
| Grand mal seizure | 3.1% |
| Source: Reference 3 | |
Possible neurologic causes
Complex partial seizures—also known as psychomotor epilepsy—are caused by a surge of electrical activity in the brain. Seizures often involve 1 of the brain’s temporal lobes but can affect any brain region. Symptoms include:
- impaired social interaction
- inability to control one’s movements
- alogia
- amnesia.
Episodes typically start with a blank stare followed by automatisms. The actions and movements often are unorganized or confused. Motor symptoms typically last for 1 to 2 minutes and confusion persists for another 1 to 2 minutes.8 In rare cases, a patient may become agitated or engage in behaviors such as undressing. Complex partial seizures may cause a person to run in apparent fear, cry out, or repeat a phrase.9 Electroencephalogram, CT, MRI, or positron-emission tomography scan could reveal any intracranial focus of complex partial seizures.
We suspect PCP or embalming fluid intoxication and initiate supportive therapy.
EVALUATION: Still confused
Initial baseline labs include a urine drug screen (UDS), chest radiography, ECG, and head CT. Mr. C’s UDS is positive for cannabis. A specific PCP assay is negative. White blood cell count (WBC) is 22,000/μL with high neutrophil count (88%), creatine kinase (CK) is 458 U/L, and urinalyis reveals protein 75 mg/dL and ketone 50 mg/dL. Head CT is negative for any acute process (click here for detailed description of Mr. C�s hospital course while in the ED).
During psychiatric evaluation 7 hours after presentation, Mr. C’s speech is loose and somewhat pressured, but intelligible. He cannot follow commands. Mr. C is delusional and appears to be hallucinating. He can repeat 3 words immediately but not after 3 minutes. We start Mr. C on divalproex, 1,500 mg/d, haloperidol, 6 mg/d, and IV lorazepam, 2 mg as needed for agitation. Although mildly disoriented, he gradually becomes less agitated.
The authors’ observations
At this point further evaluation is needed. Mr. C’s elevated WBC count could explain his fluctuating symptoms. He cannot provide further history and his family denies any past psychiatric episodes. Thyroid-stimulating hormone, B12, and folate levels are within normal limits. A negative LP rules out meningitic infection. We give Mr. C a diagnosis of psychosis NOS (Table 2).10
Table 2
DSM-IV-TR criteria for psychotic disorder, not otherwise specified
| This category includes psychotic symptomatology (ie, delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior) about which there is inadequate information to make a specific diagnosis or about which there is contradictory information, or disorders with psychotic symptoms that do not meet the criteria for any specific psychotic disorder. Examples include: |
|
| Source: Reference 10 |
TREATMENT: Medication choices
After 8 hours in the ED, Mr. C is transferred to the medical unit, where he becomes agitated and complains of auditory and visual hallucinations. He receives divalproex, 750 mg, haloperidol, 3 mg, and IM diphenhydramine, 50 mg, to calm him. He remains agitated but not violent until bedtime. At midnight he is agitated and violent and receives another dose of haloperidol and IM diphenhydramine with IV lorazepam, 2 mg. These medications calm him and he is able to sleep until morning.
Morning labs reveal CK is 674 U/L and WBC decreased to 13,200/μL. Mr. C denies any distress but after the fourth dose of haloperidol, he develops dystonia of his arms so we discontinue this medication. We start aripiprazole, 10 mg/d gradually increased to 30 mg/d, and Mr. C receives 1 injection of diphenhydramine. He responds well to the treatment.
The next few hours are uneventful but then Mr. C becomes verbally abusive to his relatives and sitter; physical restraints are ordered and he receives IM ziprasidone, 20 mg, and IV lorazepam, 2 mg. He remains awake and babbling. His perception continues to wax and wane and his words are jumbled. He remains calm until the next morning (click here for detailed description of Mr. C�s hospital course while on the medical unit).
After 4 days on the medical unit Mr. C is transferred to the psychiatry unit, where he is angry, belligerent, and hostile, but not placed in restraints. His symptoms resolve in 2 days without any further episodes of violent behavior.
OUTCOME: Solving the puzzle
When Mr. C becomes cooperative, he gives a detailed history. He repeats his suspicion of smoking adulterated marijuana, but during detailed questioning, he admits to using alprazolam, which he purchased illegally, to sleep for the past 6 to 7 months. He started with 1 or 2 “footballs” (1 to 2 mg) and gradually increased to 3 or 4 “bars” (6 to 8 mg) each day. Mr. C could no longer afford the drug and last took alprazolam 6 days before his symptoms began. He says that after stopping alprazolam he felt anxious and could not sleep. His girlfriend adds that he was irritable and “he had not been acting himself” several days before admission. She says he complained of hearing the voice of God, particularly when he was not taking alprazolam.
Mr. C’s hand wounds heal and his vitals are normal during his 1-week stay on the psychiatric unit. His interactions with staff and peers improve. Aripiprazole is tapered and discontinued; divalproex is reduced to 1,000 mg/d. Mr. C is discharged 11 days after presentation and prescribed divalproex, 1,000 mg/d, with instructions to taper the drug over several days to prevent withdrawal seizures before stopping it in 1 week.
Mr. C does not return for his follow-up appointment; however, in a telephone follow-up 6 months later, he denies experiencing withdrawal symptoms after discharge. Mr. C is now undergoing drug rehabilitation.
The authors’ observations
Benzodiazepine withdrawal symptoms occur 7 to 10 days after abrupt cessation (Table 3).10 Symptoms are similar to those of alcohol withdrawal and include tachycardia, hypertension, clouding of consciousness, and auditory and visual hallucinations.11 Serious reactions to benzodiazepine withdrawal include seizures and death.12
Because of the high prevalence of poly-substance misuse, obtain a detailed substance use history in patients undergoing benzodiazepine withdrawal to determine the likelihood of polysubstance withdrawal.13 A cross-tolerant sedative such as clonazepam could prevent withdrawal symptoms as the dose is gradually decreased. Long-acting benzodiazepines such as clonazepam or diazepam are recommended.14
In Mr. C’s case, minor withdrawal symptoms, such as disturbed sleep and irritability, began 3 to 4 days after discontinuing benzodiazepines15 and preceded development of psychosis. Withdrawal symptoms usually resolve after 2 weeks.16 Mr. C responded only partially to IV lorazepam because he did not receive the total replacement dose. Had we known he was experiencing benzodiazepine withdrawal, Mr. C could have been managed with detoxi"cation of the primary drug, alprazolam, with diazepam substitution and tapering over 3 weeks.17
Table 3
Criteria for sedative, hypnotic, or anxiolytic withdrawal
| A. Cessation of (or reduction in) sedative, hypnotic, or anxiolytic use that has been heavy and prolonged |
B. Two (or more) of the following, developing within several hours to a few days after Criterion A:
|
| C. The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning |
| D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder |
| Source: Reference 10 |
Related Resource
- Vikander B, Koechling UM, Borg S, et al. Benzodiazepine tapering: a prospective study. Nord J Psychiatry. 2010; 64(4):273-282.
Drug Brand Names
- Alprazolam • Xanax
- Aripiprazole • Abilify
- Chlordiazepoxide • Librium
- Diazepam • Valium
- Diphenhydramine • Diphenhydramine injection
- Divalproex • Depakote
- Haloperidol • Haldol
- Lorazepam • Ativan
- Ziprasidone • Geodon
Acknowledgements
The authors wish to thank Reena Kumar, MD, and Sonja Gennuso, fourth-year medical student at Louisiana State University Health Sciences Center, Shreveport, for their help in preparing this manuscript.
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Table 1
Mr. C’s hospital course in the emergency department
| Time after presentation | Description |
|---|---|
| 2 hours | Mr. C is alert and oriented to his name and place. He rests comfortably but asks questions about his girlfriend and uncle, falsely believing they are in the emergency department |
| 4 hours | Hand lacerations are repaired, but Mr. C continues to dig in his wounds with the opposite hand and place it over his mouth despite constant redirection. He reports hearing his uncle’s voice behind the curtain. He then uses the pulse oximeter as a telephone and holds a conversation with his uncle on the other side of the curtain. On redirection, Mr. C replies that the pulse oximeter looks like a telephone and begins mumbling to himself |
| 5 hours | Mr. C continues to mumble but responds when directly questioned. He keeps insisting that the pulse oximeter is a telephone and that he can tell his uncle to come over from the other side of the curtain. He continues to act inappropriately despite the presence of family members but he is aware of their identities |
| 6 hours | Mr. C becomes disoriented and agitated and pulls out his IV line. Because of the high WBC count, we order blood cultures and a urine culture and give him IV antibiotics |
| WBC: white blood cell count | |
Table 2
Mr. C’s hospital course on the medical unit
| Time after presentation | Description |
|---|---|
| 54 hours | He is oriented to person and place. Staff notices he is talking to someone in the room but no one is present. Mr. C appears to be responding to visual hallucinations, but upon questioning he denies any symptoms. Restraints are discontinued. Divalproex is increased to 2,000 mg/d |
| 62 hours | Mr. C remains calm for several hours but later begins hallucinating and calls to his mother and others when no one is in the room. He receives IV lorazepam, 2 mg, without much response. Again he is placed in restraints and receives another dose of IV lorazepam, 3 mg, and IM ziprasidone, 20 mg. He becomes calmer. Restraints are continued as a precautionary measure. Mr. C calms down after several hours but cannot sleep |
| 78 hours | The next morning, Mr. C remains agitated and aggressive with loud speech. He denies any further hallucinations but talks to an invisible person. He remains in restraints and receives his routine medications. His blood pressure is 141/99 mm Hg and pulse is 110. Pulse rate normalizes during the day and he becomes calmer but seclusive |
1. Office of National Drug Control Policy. Street terms: drugs and the drug trade. Available at:http://www.whitehousedrugpolicy.gov/streetterms/ByType.asp?intTypeID=1. Accessed July 26, 2010.
2. Elwood WN. TCADA research brief: “Fry:” a study of adolescents’ use of embalming fluid with marijuana and tobacco. Texas Commission on Alcohol and Drug Abuse. 1998. Available at:http://www.dshs.state.tx.us/sa/research/populations/fry.pdf. Accessed August 9, 2010.
3. McCarron MM, Schulze BW, Thomson GA, et al. Acute phencyclidine intoxication: incidence of clinical findings in 1,000 cases. Ann Emerg Med. 1981;10(5):237-242.
4. Aniline O, Pitts FN, Jr. Phencyclidine (PCP): a review and perspectives. Crit Rev Toxicol. 1982;10(2):145-177.
5. McCarron MM, Schulze BW, Thomson GA, et al. Acute phencyclidine intoxication: clinical patterns, complications, and treatment. Ann Emerg Med. 1981;10(6):290-297.
6. Semple DM, McIntosh AM, Lawrie SM. Cannabis as a risk factor for psychosis: systematic review. J Psychopharmacol. 2005;19(2):187-194.
7. Degenhardt L, Hall W. Cannabis and psychosis. Curr Psychiatry Rep. 2002;4(3):191-196.
8. Carroll E, Benbadis SR. Complex partial seizures. eMedicine. April 21, 2010. Available at:http://emedicine.medscape.com/article/1183962-overview. Accessed July 20, 2010.
9. Epilepsy.com. Complex partial seizures. Available at: http://www.epilepsy.com/epilepsy/seizure_complexpartial. Accessed July 20, 2010.
10. Diagnostic and statistical manual of mental disorders 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
11. Mellor CS, Jain VK. Diazepam withdrawal syndrome: its prolonged and changing nature. Can Med Assoc J. 1982;127(11):1093-1096.
12. Lann MA, Molina DK. A fatal case of benzodiazepine withdrawal. Am J Forensic Med Pathol. 2009;30(2):177-179.
13. Busto UE, Romach MK, Sellers EM. Multiple drug use and psychiatric comorbidity in patients admitted to the hospital with severe benzodiazepine dependence. J Clin Psychopharmacol. 1996;16(1):51-57.
14. Franklin JE, Jr., Levenson JL, McCance-Katz EF. Substance-related disorders. In: Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. Arlington, VA: American Psychiatric Publishing, Inc.; 2005:400–401.
15. Preskorn SH, Denner LJ. Benzodiazepines and withdrawal psychosis. Report of three cases. JAMA. 1977;237(1):36-38.
16. Miller F, Nulsen J. Single case study. Diazepam (valium) detoxification. J Nerv Ment Dis. 1979;167:637-638.
17. Seivewright N, Dougal W. Withdrawal symptoms from high dose benzodiazepines in poly drug users. Drug Alcohol Depend. 1993;32(1):15-23.
CASE: Scared and confused
Mr. C, age 28, presents to the emergency department (ED) in police custody with agitation and altered mental status. Earlier that evening, Mr. C’s girlfriend noticed he was talking to himself while watching television. A few hours later, Mr. C thought someone was breaking into his house. Mr. C ran out of the house screaming for help, broke his neighbor’s window, and eventually called the police. When the police arrived Mr. C was wearing only his underwear, shaking, and bleeding from his hands. He said he was afraid and refused to respond to police instructions. Police officers used an electronic stun gun to facilitate transport to the hospital.
Mr. C admits to smoking 3 to 4 marijuana joints daily for the past 16 years. His last drug use was 2 hours before his symptoms began. Mr. C suggests that someone may have adulterated his marijuana joint but he has no factual basis for this accusation. He denies using alcohol and other illicit drugs and has no personal or family psychiatric history. He denies recent fever, loss of consciousness, chest pain, weakness, myalgia, or headache. Medically stable, his only complaint is mild hand pain.
Mr. C is alert, awake, and oriented to his name, and he responds properly to questions. He is tachycardic (101 bpm), his blood pressure is 149/57 mm Hg with normal S1 and S2 sounds, and he has no meningismus or nystagmus. Glasgow Coma Scale score is 15. He has increased deep tendon reflexes on the right upper and lower limb with good hand-grip and multiple abrasions and lacerations on his hands.
The authors’ observations
New-onset psychosis can have a wide differential diagnosis, particularly when reliable history is not available. Mr. C’s allegation that someone tampered with his marijuana raises 2 possibilities: embalming fluid (form-aldehyde) toxicity or PCP intoxication.
Embalming fluid toxicity can cause:
- agitation and sudden unpredictable behavior
- confusion or toxic delirium
- coma or seizure
- cerebral and pulmonary edema or death in severe cases.
The terms “wet,” “sherm,” “fly,” “amp,” or “illy” are used to describe a marijuana cigarette that has been dipped into embalming fluid, dried, and then smoked.1 The effect is similar to that of PCP and causes extreme hallucinations. Reported highs last 30 minutes to 1 hour.2
Symptomatology of PCP intoxication may be indistinguishable from functional psychosis (Table 1).3 Visual, auditory, and tactile misperceptions are common and highly changeable disorientation often is accompanied by alternating periods of lethargy and fearful agitation. These patients typically show catatonic posturing and/or stereotyped movement. Somatic sensations appear to be disassociated; patients may misperceive pain, distance, and time. Patients taking PCP rarely admit to true hallucinations; however their thinking usually is grossly disoriented.4 Symptoms of delirium may last from 30 minutes to 6 hours in 80% of cases; 12% of patients may remain symptomatic for 12 hours. Violent behavior and agitation usually lasts only a few hours.5
Long-term marijuana abuse can lead to psychosis6 but acute onset is not typical, and recent prospective trials raised doubts that cannabis would be a sole factor.7 Instead, cannabis may be 1 of several factors that contribute to psychosis, particularly in patients who are predisposed.
Table 1
Phencyclidine (PCP) intoxication: What to look for
| Findings | Percentage of cases |
|---|---|
| Nystagmus | 57.4% |
| Hypertension | 57.0% |
| Delirium | 36.9% |
| Violent behavior | 35.4% |
| Agitation | 34.0% |
| Tachycardia | 30.0% |
| Bizarre behavior | 28.5% |
| Hallucinations/delusions | 18.5% |
| Unconsciousness | 10.6% |
| Lethargy/stupor | 6.6% |
| Hypothermia | 6.4% |
| Generalized rigidity | 5.2% |
| Profuse sweating | 3.9% |
| No behavior effect | 3.5% |
| Grand mal seizure | 3.1% |
| Source: Reference 3 | |
Possible neurologic causes
Complex partial seizures—also known as psychomotor epilepsy—are caused by a surge of electrical activity in the brain. Seizures often involve 1 of the brain’s temporal lobes but can affect any brain region. Symptoms include:
- impaired social interaction
- inability to control one’s movements
- alogia
- amnesia.
Episodes typically start with a blank stare followed by automatisms. The actions and movements often are unorganized or confused. Motor symptoms typically last for 1 to 2 minutes and confusion persists for another 1 to 2 minutes.8 In rare cases, a patient may become agitated or engage in behaviors such as undressing. Complex partial seizures may cause a person to run in apparent fear, cry out, or repeat a phrase.9 Electroencephalogram, CT, MRI, or positron-emission tomography scan could reveal any intracranial focus of complex partial seizures.
We suspect PCP or embalming fluid intoxication and initiate supportive therapy.
EVALUATION: Still confused
Initial baseline labs include a urine drug screen (UDS), chest radiography, ECG, and head CT. Mr. C’s UDS is positive for cannabis. A specific PCP assay is negative. White blood cell count (WBC) is 22,000/μL with high neutrophil count (88%), creatine kinase (CK) is 458 U/L, and urinalyis reveals protein 75 mg/dL and ketone 50 mg/dL. Head CT is negative for any acute process (click here for detailed description of Mr. C�s hospital course while in the ED).
During psychiatric evaluation 7 hours after presentation, Mr. C’s speech is loose and somewhat pressured, but intelligible. He cannot follow commands. Mr. C is delusional and appears to be hallucinating. He can repeat 3 words immediately but not after 3 minutes. We start Mr. C on divalproex, 1,500 mg/d, haloperidol, 6 mg/d, and IV lorazepam, 2 mg as needed for agitation. Although mildly disoriented, he gradually becomes less agitated.
The authors’ observations
At this point further evaluation is needed. Mr. C’s elevated WBC count could explain his fluctuating symptoms. He cannot provide further history and his family denies any past psychiatric episodes. Thyroid-stimulating hormone, B12, and folate levels are within normal limits. A negative LP rules out meningitic infection. We give Mr. C a diagnosis of psychosis NOS (Table 2).10
Table 2
DSM-IV-TR criteria for psychotic disorder, not otherwise specified
| This category includes psychotic symptomatology (ie, delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior) about which there is inadequate information to make a specific diagnosis or about which there is contradictory information, or disorders with psychotic symptoms that do not meet the criteria for any specific psychotic disorder. Examples include: |
|
| Source: Reference 10 |
TREATMENT: Medication choices
After 8 hours in the ED, Mr. C is transferred to the medical unit, where he becomes agitated and complains of auditory and visual hallucinations. He receives divalproex, 750 mg, haloperidol, 3 mg, and IM diphenhydramine, 50 mg, to calm him. He remains agitated but not violent until bedtime. At midnight he is agitated and violent and receives another dose of haloperidol and IM diphenhydramine with IV lorazepam, 2 mg. These medications calm him and he is able to sleep until morning.
Morning labs reveal CK is 674 U/L and WBC decreased to 13,200/μL. Mr. C denies any distress but after the fourth dose of haloperidol, he develops dystonia of his arms so we discontinue this medication. We start aripiprazole, 10 mg/d gradually increased to 30 mg/d, and Mr. C receives 1 injection of diphenhydramine. He responds well to the treatment.
The next few hours are uneventful but then Mr. C becomes verbally abusive to his relatives and sitter; physical restraints are ordered and he receives IM ziprasidone, 20 mg, and IV lorazepam, 2 mg. He remains awake and babbling. His perception continues to wax and wane and his words are jumbled. He remains calm until the next morning (click here for detailed description of Mr. C�s hospital course while on the medical unit).
After 4 days on the medical unit Mr. C is transferred to the psychiatry unit, where he is angry, belligerent, and hostile, but not placed in restraints. His symptoms resolve in 2 days without any further episodes of violent behavior.
OUTCOME: Solving the puzzle
When Mr. C becomes cooperative, he gives a detailed history. He repeats his suspicion of smoking adulterated marijuana, but during detailed questioning, he admits to using alprazolam, which he purchased illegally, to sleep for the past 6 to 7 months. He started with 1 or 2 “footballs” (1 to 2 mg) and gradually increased to 3 or 4 “bars” (6 to 8 mg) each day. Mr. C could no longer afford the drug and last took alprazolam 6 days before his symptoms began. He says that after stopping alprazolam he felt anxious and could not sleep. His girlfriend adds that he was irritable and “he had not been acting himself” several days before admission. She says he complained of hearing the voice of God, particularly when he was not taking alprazolam.
Mr. C’s hand wounds heal and his vitals are normal during his 1-week stay on the psychiatric unit. His interactions with staff and peers improve. Aripiprazole is tapered and discontinued; divalproex is reduced to 1,000 mg/d. Mr. C is discharged 11 days after presentation and prescribed divalproex, 1,000 mg/d, with instructions to taper the drug over several days to prevent withdrawal seizures before stopping it in 1 week.
Mr. C does not return for his follow-up appointment; however, in a telephone follow-up 6 months later, he denies experiencing withdrawal symptoms after discharge. Mr. C is now undergoing drug rehabilitation.
The authors’ observations
Benzodiazepine withdrawal symptoms occur 7 to 10 days after abrupt cessation (Table 3).10 Symptoms are similar to those of alcohol withdrawal and include tachycardia, hypertension, clouding of consciousness, and auditory and visual hallucinations.11 Serious reactions to benzodiazepine withdrawal include seizures and death.12
Because of the high prevalence of poly-substance misuse, obtain a detailed substance use history in patients undergoing benzodiazepine withdrawal to determine the likelihood of polysubstance withdrawal.13 A cross-tolerant sedative such as clonazepam could prevent withdrawal symptoms as the dose is gradually decreased. Long-acting benzodiazepines such as clonazepam or diazepam are recommended.14
In Mr. C’s case, minor withdrawal symptoms, such as disturbed sleep and irritability, began 3 to 4 days after discontinuing benzodiazepines15 and preceded development of psychosis. Withdrawal symptoms usually resolve after 2 weeks.16 Mr. C responded only partially to IV lorazepam because he did not receive the total replacement dose. Had we known he was experiencing benzodiazepine withdrawal, Mr. C could have been managed with detoxi"cation of the primary drug, alprazolam, with diazepam substitution and tapering over 3 weeks.17
Table 3
Criteria for sedative, hypnotic, or anxiolytic withdrawal
| A. Cessation of (or reduction in) sedative, hypnotic, or anxiolytic use that has been heavy and prolonged |
B. Two (or more) of the following, developing within several hours to a few days after Criterion A:
|
| C. The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning |
| D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder |
| Source: Reference 10 |
Related Resource
- Vikander B, Koechling UM, Borg S, et al. Benzodiazepine tapering: a prospective study. Nord J Psychiatry. 2010; 64(4):273-282.
Drug Brand Names
- Alprazolam • Xanax
- Aripiprazole • Abilify
- Chlordiazepoxide • Librium
- Diazepam • Valium
- Diphenhydramine • Diphenhydramine injection
- Divalproex • Depakote
- Haloperidol • Haldol
- Lorazepam • Ativan
- Ziprasidone • Geodon
Acknowledgements
The authors wish to thank Reena Kumar, MD, and Sonja Gennuso, fourth-year medical student at Louisiana State University Health Sciences Center, Shreveport, for their help in preparing this manuscript.
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Table 1
Mr. C’s hospital course in the emergency department
| Time after presentation | Description |
|---|---|
| 2 hours | Mr. C is alert and oriented to his name and place. He rests comfortably but asks questions about his girlfriend and uncle, falsely believing they are in the emergency department |
| 4 hours | Hand lacerations are repaired, but Mr. C continues to dig in his wounds with the opposite hand and place it over his mouth despite constant redirection. He reports hearing his uncle’s voice behind the curtain. He then uses the pulse oximeter as a telephone and holds a conversation with his uncle on the other side of the curtain. On redirection, Mr. C replies that the pulse oximeter looks like a telephone and begins mumbling to himself |
| 5 hours | Mr. C continues to mumble but responds when directly questioned. He keeps insisting that the pulse oximeter is a telephone and that he can tell his uncle to come over from the other side of the curtain. He continues to act inappropriately despite the presence of family members but he is aware of their identities |
| 6 hours | Mr. C becomes disoriented and agitated and pulls out his IV line. Because of the high WBC count, we order blood cultures and a urine culture and give him IV antibiotics |
| WBC: white blood cell count | |
Table 2
Mr. C’s hospital course on the medical unit
| Time after presentation | Description |
|---|---|
| 54 hours | He is oriented to person and place. Staff notices he is talking to someone in the room but no one is present. Mr. C appears to be responding to visual hallucinations, but upon questioning he denies any symptoms. Restraints are discontinued. Divalproex is increased to 2,000 mg/d |
| 62 hours | Mr. C remains calm for several hours but later begins hallucinating and calls to his mother and others when no one is in the room. He receives IV lorazepam, 2 mg, without much response. Again he is placed in restraints and receives another dose of IV lorazepam, 3 mg, and IM ziprasidone, 20 mg. He becomes calmer. Restraints are continued as a precautionary measure. Mr. C calms down after several hours but cannot sleep |
| 78 hours | The next morning, Mr. C remains agitated and aggressive with loud speech. He denies any further hallucinations but talks to an invisible person. He remains in restraints and receives his routine medications. His blood pressure is 141/99 mm Hg and pulse is 110. Pulse rate normalizes during the day and he becomes calmer but seclusive |
CASE: Scared and confused
Mr. C, age 28, presents to the emergency department (ED) in police custody with agitation and altered mental status. Earlier that evening, Mr. C’s girlfriend noticed he was talking to himself while watching television. A few hours later, Mr. C thought someone was breaking into his house. Mr. C ran out of the house screaming for help, broke his neighbor’s window, and eventually called the police. When the police arrived Mr. C was wearing only his underwear, shaking, and bleeding from his hands. He said he was afraid and refused to respond to police instructions. Police officers used an electronic stun gun to facilitate transport to the hospital.
Mr. C admits to smoking 3 to 4 marijuana joints daily for the past 16 years. His last drug use was 2 hours before his symptoms began. Mr. C suggests that someone may have adulterated his marijuana joint but he has no factual basis for this accusation. He denies using alcohol and other illicit drugs and has no personal or family psychiatric history. He denies recent fever, loss of consciousness, chest pain, weakness, myalgia, or headache. Medically stable, his only complaint is mild hand pain.
Mr. C is alert, awake, and oriented to his name, and he responds properly to questions. He is tachycardic (101 bpm), his blood pressure is 149/57 mm Hg with normal S1 and S2 sounds, and he has no meningismus or nystagmus. Glasgow Coma Scale score is 15. He has increased deep tendon reflexes on the right upper and lower limb with good hand-grip and multiple abrasions and lacerations on his hands.
The authors’ observations
New-onset psychosis can have a wide differential diagnosis, particularly when reliable history is not available. Mr. C’s allegation that someone tampered with his marijuana raises 2 possibilities: embalming fluid (form-aldehyde) toxicity or PCP intoxication.
Embalming fluid toxicity can cause:
- agitation and sudden unpredictable behavior
- confusion or toxic delirium
- coma or seizure
- cerebral and pulmonary edema or death in severe cases.
The terms “wet,” “sherm,” “fly,” “amp,” or “illy” are used to describe a marijuana cigarette that has been dipped into embalming fluid, dried, and then smoked.1 The effect is similar to that of PCP and causes extreme hallucinations. Reported highs last 30 minutes to 1 hour.2
Symptomatology of PCP intoxication may be indistinguishable from functional psychosis (Table 1).3 Visual, auditory, and tactile misperceptions are common and highly changeable disorientation often is accompanied by alternating periods of lethargy and fearful agitation. These patients typically show catatonic posturing and/or stereotyped movement. Somatic sensations appear to be disassociated; patients may misperceive pain, distance, and time. Patients taking PCP rarely admit to true hallucinations; however their thinking usually is grossly disoriented.4 Symptoms of delirium may last from 30 minutes to 6 hours in 80% of cases; 12% of patients may remain symptomatic for 12 hours. Violent behavior and agitation usually lasts only a few hours.5
Long-term marijuana abuse can lead to psychosis6 but acute onset is not typical, and recent prospective trials raised doubts that cannabis would be a sole factor.7 Instead, cannabis may be 1 of several factors that contribute to psychosis, particularly in patients who are predisposed.
Table 1
Phencyclidine (PCP) intoxication: What to look for
| Findings | Percentage of cases |
|---|---|
| Nystagmus | 57.4% |
| Hypertension | 57.0% |
| Delirium | 36.9% |
| Violent behavior | 35.4% |
| Agitation | 34.0% |
| Tachycardia | 30.0% |
| Bizarre behavior | 28.5% |
| Hallucinations/delusions | 18.5% |
| Unconsciousness | 10.6% |
| Lethargy/stupor | 6.6% |
| Hypothermia | 6.4% |
| Generalized rigidity | 5.2% |
| Profuse sweating | 3.9% |
| No behavior effect | 3.5% |
| Grand mal seizure | 3.1% |
| Source: Reference 3 | |
Possible neurologic causes
Complex partial seizures—also known as psychomotor epilepsy—are caused by a surge of electrical activity in the brain. Seizures often involve 1 of the brain’s temporal lobes but can affect any brain region. Symptoms include:
- impaired social interaction
- inability to control one’s movements
- alogia
- amnesia.
Episodes typically start with a blank stare followed by automatisms. The actions and movements often are unorganized or confused. Motor symptoms typically last for 1 to 2 minutes and confusion persists for another 1 to 2 minutes.8 In rare cases, a patient may become agitated or engage in behaviors such as undressing. Complex partial seizures may cause a person to run in apparent fear, cry out, or repeat a phrase.9 Electroencephalogram, CT, MRI, or positron-emission tomography scan could reveal any intracranial focus of complex partial seizures.
We suspect PCP or embalming fluid intoxication and initiate supportive therapy.
EVALUATION: Still confused
Initial baseline labs include a urine drug screen (UDS), chest radiography, ECG, and head CT. Mr. C’s UDS is positive for cannabis. A specific PCP assay is negative. White blood cell count (WBC) is 22,000/μL with high neutrophil count (88%), creatine kinase (CK) is 458 U/L, and urinalyis reveals protein 75 mg/dL and ketone 50 mg/dL. Head CT is negative for any acute process (click here for detailed description of Mr. C�s hospital course while in the ED).
During psychiatric evaluation 7 hours after presentation, Mr. C’s speech is loose and somewhat pressured, but intelligible. He cannot follow commands. Mr. C is delusional and appears to be hallucinating. He can repeat 3 words immediately but not after 3 minutes. We start Mr. C on divalproex, 1,500 mg/d, haloperidol, 6 mg/d, and IV lorazepam, 2 mg as needed for agitation. Although mildly disoriented, he gradually becomes less agitated.
The authors’ observations
At this point further evaluation is needed. Mr. C’s elevated WBC count could explain his fluctuating symptoms. He cannot provide further history and his family denies any past psychiatric episodes. Thyroid-stimulating hormone, B12, and folate levels are within normal limits. A negative LP rules out meningitic infection. We give Mr. C a diagnosis of psychosis NOS (Table 2).10
Table 2
DSM-IV-TR criteria for psychotic disorder, not otherwise specified
| This category includes psychotic symptomatology (ie, delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior) about which there is inadequate information to make a specific diagnosis or about which there is contradictory information, or disorders with psychotic symptoms that do not meet the criteria for any specific psychotic disorder. Examples include: |
|
| Source: Reference 10 |
TREATMENT: Medication choices
After 8 hours in the ED, Mr. C is transferred to the medical unit, where he becomes agitated and complains of auditory and visual hallucinations. He receives divalproex, 750 mg, haloperidol, 3 mg, and IM diphenhydramine, 50 mg, to calm him. He remains agitated but not violent until bedtime. At midnight he is agitated and violent and receives another dose of haloperidol and IM diphenhydramine with IV lorazepam, 2 mg. These medications calm him and he is able to sleep until morning.
Morning labs reveal CK is 674 U/L and WBC decreased to 13,200/μL. Mr. C denies any distress but after the fourth dose of haloperidol, he develops dystonia of his arms so we discontinue this medication. We start aripiprazole, 10 mg/d gradually increased to 30 mg/d, and Mr. C receives 1 injection of diphenhydramine. He responds well to the treatment.
The next few hours are uneventful but then Mr. C becomes verbally abusive to his relatives and sitter; physical restraints are ordered and he receives IM ziprasidone, 20 mg, and IV lorazepam, 2 mg. He remains awake and babbling. His perception continues to wax and wane and his words are jumbled. He remains calm until the next morning (click here for detailed description of Mr. C�s hospital course while on the medical unit).
After 4 days on the medical unit Mr. C is transferred to the psychiatry unit, where he is angry, belligerent, and hostile, but not placed in restraints. His symptoms resolve in 2 days without any further episodes of violent behavior.
OUTCOME: Solving the puzzle
When Mr. C becomes cooperative, he gives a detailed history. He repeats his suspicion of smoking adulterated marijuana, but during detailed questioning, he admits to using alprazolam, which he purchased illegally, to sleep for the past 6 to 7 months. He started with 1 or 2 “footballs” (1 to 2 mg) and gradually increased to 3 or 4 “bars” (6 to 8 mg) each day. Mr. C could no longer afford the drug and last took alprazolam 6 days before his symptoms began. He says that after stopping alprazolam he felt anxious and could not sleep. His girlfriend adds that he was irritable and “he had not been acting himself” several days before admission. She says he complained of hearing the voice of God, particularly when he was not taking alprazolam.
Mr. C’s hand wounds heal and his vitals are normal during his 1-week stay on the psychiatric unit. His interactions with staff and peers improve. Aripiprazole is tapered and discontinued; divalproex is reduced to 1,000 mg/d. Mr. C is discharged 11 days after presentation and prescribed divalproex, 1,000 mg/d, with instructions to taper the drug over several days to prevent withdrawal seizures before stopping it in 1 week.
Mr. C does not return for his follow-up appointment; however, in a telephone follow-up 6 months later, he denies experiencing withdrawal symptoms after discharge. Mr. C is now undergoing drug rehabilitation.
The authors’ observations
Benzodiazepine withdrawal symptoms occur 7 to 10 days after abrupt cessation (Table 3).10 Symptoms are similar to those of alcohol withdrawal and include tachycardia, hypertension, clouding of consciousness, and auditory and visual hallucinations.11 Serious reactions to benzodiazepine withdrawal include seizures and death.12
Because of the high prevalence of poly-substance misuse, obtain a detailed substance use history in patients undergoing benzodiazepine withdrawal to determine the likelihood of polysubstance withdrawal.13 A cross-tolerant sedative such as clonazepam could prevent withdrawal symptoms as the dose is gradually decreased. Long-acting benzodiazepines such as clonazepam or diazepam are recommended.14
In Mr. C’s case, minor withdrawal symptoms, such as disturbed sleep and irritability, began 3 to 4 days after discontinuing benzodiazepines15 and preceded development of psychosis. Withdrawal symptoms usually resolve after 2 weeks.16 Mr. C responded only partially to IV lorazepam because he did not receive the total replacement dose. Had we known he was experiencing benzodiazepine withdrawal, Mr. C could have been managed with detoxi"cation of the primary drug, alprazolam, with diazepam substitution and tapering over 3 weeks.17
Table 3
Criteria for sedative, hypnotic, or anxiolytic withdrawal
| A. Cessation of (or reduction in) sedative, hypnotic, or anxiolytic use that has been heavy and prolonged |
B. Two (or more) of the following, developing within several hours to a few days after Criterion A:
|
| C. The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning |
| D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder |
| Source: Reference 10 |
Related Resource
- Vikander B, Koechling UM, Borg S, et al. Benzodiazepine tapering: a prospective study. Nord J Psychiatry. 2010; 64(4):273-282.
Drug Brand Names
- Alprazolam • Xanax
- Aripiprazole • Abilify
- Chlordiazepoxide • Librium
- Diazepam • Valium
- Diphenhydramine • Diphenhydramine injection
- Divalproex • Depakote
- Haloperidol • Haldol
- Lorazepam • Ativan
- Ziprasidone • Geodon
Acknowledgements
The authors wish to thank Reena Kumar, MD, and Sonja Gennuso, fourth-year medical student at Louisiana State University Health Sciences Center, Shreveport, for their help in preparing this manuscript.
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Table 1
Mr. C’s hospital course in the emergency department
| Time after presentation | Description |
|---|---|
| 2 hours | Mr. C is alert and oriented to his name and place. He rests comfortably but asks questions about his girlfriend and uncle, falsely believing they are in the emergency department |
| 4 hours | Hand lacerations are repaired, but Mr. C continues to dig in his wounds with the opposite hand and place it over his mouth despite constant redirection. He reports hearing his uncle’s voice behind the curtain. He then uses the pulse oximeter as a telephone and holds a conversation with his uncle on the other side of the curtain. On redirection, Mr. C replies that the pulse oximeter looks like a telephone and begins mumbling to himself |
| 5 hours | Mr. C continues to mumble but responds when directly questioned. He keeps insisting that the pulse oximeter is a telephone and that he can tell his uncle to come over from the other side of the curtain. He continues to act inappropriately despite the presence of family members but he is aware of their identities |
| 6 hours | Mr. C becomes disoriented and agitated and pulls out his IV line. Because of the high WBC count, we order blood cultures and a urine culture and give him IV antibiotics |
| WBC: white blood cell count | |
Table 2
Mr. C’s hospital course on the medical unit
| Time after presentation | Description |
|---|---|
| 54 hours | He is oriented to person and place. Staff notices he is talking to someone in the room but no one is present. Mr. C appears to be responding to visual hallucinations, but upon questioning he denies any symptoms. Restraints are discontinued. Divalproex is increased to 2,000 mg/d |
| 62 hours | Mr. C remains calm for several hours but later begins hallucinating and calls to his mother and others when no one is in the room. He receives IV lorazepam, 2 mg, without much response. Again he is placed in restraints and receives another dose of IV lorazepam, 3 mg, and IM ziprasidone, 20 mg. He becomes calmer. Restraints are continued as a precautionary measure. Mr. C calms down after several hours but cannot sleep |
| 78 hours | The next morning, Mr. C remains agitated and aggressive with loud speech. He denies any further hallucinations but talks to an invisible person. He remains in restraints and receives his routine medications. His blood pressure is 141/99 mm Hg and pulse is 110. Pulse rate normalizes during the day and he becomes calmer but seclusive |
1. Office of National Drug Control Policy. Street terms: drugs and the drug trade. Available at:http://www.whitehousedrugpolicy.gov/streetterms/ByType.asp?intTypeID=1. Accessed July 26, 2010.
2. Elwood WN. TCADA research brief: “Fry:” a study of adolescents’ use of embalming fluid with marijuana and tobacco. Texas Commission on Alcohol and Drug Abuse. 1998. Available at:http://www.dshs.state.tx.us/sa/research/populations/fry.pdf. Accessed August 9, 2010.
3. McCarron MM, Schulze BW, Thomson GA, et al. Acute phencyclidine intoxication: incidence of clinical findings in 1,000 cases. Ann Emerg Med. 1981;10(5):237-242.
4. Aniline O, Pitts FN, Jr. Phencyclidine (PCP): a review and perspectives. Crit Rev Toxicol. 1982;10(2):145-177.
5. McCarron MM, Schulze BW, Thomson GA, et al. Acute phencyclidine intoxication: clinical patterns, complications, and treatment. Ann Emerg Med. 1981;10(6):290-297.
6. Semple DM, McIntosh AM, Lawrie SM. Cannabis as a risk factor for psychosis: systematic review. J Psychopharmacol. 2005;19(2):187-194.
7. Degenhardt L, Hall W. Cannabis and psychosis. Curr Psychiatry Rep. 2002;4(3):191-196.
8. Carroll E, Benbadis SR. Complex partial seizures. eMedicine. April 21, 2010. Available at:http://emedicine.medscape.com/article/1183962-overview. Accessed July 20, 2010.
9. Epilepsy.com. Complex partial seizures. Available at: http://www.epilepsy.com/epilepsy/seizure_complexpartial. Accessed July 20, 2010.
10. Diagnostic and statistical manual of mental disorders 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
11. Mellor CS, Jain VK. Diazepam withdrawal syndrome: its prolonged and changing nature. Can Med Assoc J. 1982;127(11):1093-1096.
12. Lann MA, Molina DK. A fatal case of benzodiazepine withdrawal. Am J Forensic Med Pathol. 2009;30(2):177-179.
13. Busto UE, Romach MK, Sellers EM. Multiple drug use and psychiatric comorbidity in patients admitted to the hospital with severe benzodiazepine dependence. J Clin Psychopharmacol. 1996;16(1):51-57.
14. Franklin JE, Jr., Levenson JL, McCance-Katz EF. Substance-related disorders. In: Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. Arlington, VA: American Psychiatric Publishing, Inc.; 2005:400–401.
15. Preskorn SH, Denner LJ. Benzodiazepines and withdrawal psychosis. Report of three cases. JAMA. 1977;237(1):36-38.
16. Miller F, Nulsen J. Single case study. Diazepam (valium) detoxification. J Nerv Ment Dis. 1979;167:637-638.
17. Seivewright N, Dougal W. Withdrawal symptoms from high dose benzodiazepines in poly drug users. Drug Alcohol Depend. 1993;32(1):15-23.
1. Office of National Drug Control Policy. Street terms: drugs and the drug trade. Available at:http://www.whitehousedrugpolicy.gov/streetterms/ByType.asp?intTypeID=1. Accessed July 26, 2010.
2. Elwood WN. TCADA research brief: “Fry:” a study of adolescents’ use of embalming fluid with marijuana and tobacco. Texas Commission on Alcohol and Drug Abuse. 1998. Available at:http://www.dshs.state.tx.us/sa/research/populations/fry.pdf. Accessed August 9, 2010.
3. McCarron MM, Schulze BW, Thomson GA, et al. Acute phencyclidine intoxication: incidence of clinical findings in 1,000 cases. Ann Emerg Med. 1981;10(5):237-242.
4. Aniline O, Pitts FN, Jr. Phencyclidine (PCP): a review and perspectives. Crit Rev Toxicol. 1982;10(2):145-177.
5. McCarron MM, Schulze BW, Thomson GA, et al. Acute phencyclidine intoxication: clinical patterns, complications, and treatment. Ann Emerg Med. 1981;10(6):290-297.
6. Semple DM, McIntosh AM, Lawrie SM. Cannabis as a risk factor for psychosis: systematic review. J Psychopharmacol. 2005;19(2):187-194.
7. Degenhardt L, Hall W. Cannabis and psychosis. Curr Psychiatry Rep. 2002;4(3):191-196.
8. Carroll E, Benbadis SR. Complex partial seizures. eMedicine. April 21, 2010. Available at:http://emedicine.medscape.com/article/1183962-overview. Accessed July 20, 2010.
9. Epilepsy.com. Complex partial seizures. Available at: http://www.epilepsy.com/epilepsy/seizure_complexpartial. Accessed July 20, 2010.
10. Diagnostic and statistical manual of mental disorders 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
11. Mellor CS, Jain VK. Diazepam withdrawal syndrome: its prolonged and changing nature. Can Med Assoc J. 1982;127(11):1093-1096.
12. Lann MA, Molina DK. A fatal case of benzodiazepine withdrawal. Am J Forensic Med Pathol. 2009;30(2):177-179.
13. Busto UE, Romach MK, Sellers EM. Multiple drug use and psychiatric comorbidity in patients admitted to the hospital with severe benzodiazepine dependence. J Clin Psychopharmacol. 1996;16(1):51-57.
14. Franklin JE, Jr., Levenson JL, McCance-Katz EF. Substance-related disorders. In: Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. Arlington, VA: American Psychiatric Publishing, Inc.; 2005:400–401.
15. Preskorn SH, Denner LJ. Benzodiazepines and withdrawal psychosis. Report of three cases. JAMA. 1977;237(1):36-38.
16. Miller F, Nulsen J. Single case study. Diazepam (valium) detoxification. J Nerv Ment Dis. 1979;167:637-638.
17. Seivewright N, Dougal W. Withdrawal symptoms from high dose benzodiazepines in poly drug users. Drug Alcohol Depend. 1993;32(1):15-23.