Somatic Disorders

HISTORY: A sudden vision

Ms. K, 73, was in reasonably good health when one day she suddenly noticed red, green, and yellow birds and butterflies covering her wall.

Ms. K, who lives alone, was frightened at first, but she did not immediately alert anyone because she thought she “was just seeing things, and they’ll go away.”

Instead, she saw more visions over the next 3 months. She once “watched” as two doctors and a nun carried a middle-aged burn victim into her apartment. She remembers seeing the doctors put a “patch” over the woman’s body. To Ms. K, this experience seemed so shockingly real that she called 911, reporting, “That woman should have been in the hospital!”

She reports that a pack of butterflies once “followed” her to the market. She vividly recalls how they crawled about her shoes and legs as she entered the store. When asked if anyone noticed her insect-covered extremities, she replied matter-of-factly, “Maybe it’s not for them to see, maybe it’s just for me,” as if her hallucinations were a divine gift.

Ms. K’s hallucinations usually occur at home, where she spends most of her time. She says that the images are fleeting, lasting from a few seconds to several minutes, and that the creatures fly silently around her room.

Ms. K’s daughter grew concerned that the hallucinations were increasingly diminishing her mother’s ability to care for herself. She brought Ms. K into our emergency department, from which the patient was admitted.

On admission, Ms. K said she had lost 20 lbs within 6 months, and that “concentrating on those things in the house” was impairing her sleep. She denied recent illness, trauma, loss of conscious ness, changes in medications, seizures, drug or alcohol use, suicidal or homicidal ideation, or specific stress in her life. She added that she often cooks for herself—only to lose her appetite after seeing bugs and other creatures crawl into her food.

Her medical history includes hypertension, type 2 diabetes mellitus, peripheral vascular disease, urinary incontinence, gastroesophageal reflux, glaucoma in her left eye, and bilateral cataracts. She denies any psychiatric history and adds that she had never experienced hallucinations until about 3 months before hospitalization. She also denies any history of auditory, tactile, or olfactory hallucinations.

Would you suspect a primary psychotic illness? What clinical tests might help us understand Ms. K’s progressively debilitating visual hallucinations?

The authors’ observations

Ms. K’s case places us at the crossroads of psychiatric disturbances and medical conditions that can present as or precipitate apparent psychiatric symptoms. Delirium, dementia, psychosis, endocrinopathies, encephalitis, electrolyte disturbances, drug abuse/withdrawal, and occipital or temporal lobe seizures are all possible differential diagnoses (Table 1).

A cognitive function screening and a battery of laboratory tests, imaging scans, and neurologic and vision exams are needed to uncover the cause of her hallucinations.

EVALUATION: Looking for clues

Ms. K’s left pupil was fixed at 6 mm and did not respond to light, while the right pupil was regular and reactive to light at 3 mm. Using a Snellen eye chart, her visual acuity was poor: 20/100 to 20/200 in her right eye and less than 20/200 in the left eye. She scored a 29 out of 30 on the Folstein Mini-Mental State Examination (MMSE), indicating her cognition was intact. The remainder of the neurologic exam was unremarkable.

At admission, Ms. K’s medications included metoprolol, 100 mg qd, for hypertension; lansoprazole, 30 mg qd, for gastroesophageal reflux; tolterodine, 2 mg bid, and oxybutynin, 10 mg qd, for urinary incontinence; repaglinide, 2 mg bid, for type 2 diabetes; and three ophthalmic agents: brimonidine, prednisolone, and dorzolamide/timolol. The patient had been maintained on these medications for more than 2 years with no recent changes in dosing.

Results of Ms. K’s lab studies were normal, including a basic metabolic panel, CBC, liver function tests, urinalysis, B12, thyroid panel, rapid plasma reagin test, and urine drug screen.

A head CT without contrast revealed chronic small-vessel ischemic white matter disease and a chronic infarct of the left cerebellar hemisphere. No acute intracranial hemorrhages, masses, or other abnormalities were noted. No seizures were seen on EEG.

Table 1

Common causes of visual hallucinations

What do the laboratory and imaging tests reveal about Ms. K’s hallucinations? Is her diagnosis delirium? Alzheimer’s or other type of dementia? Schizophrenia?

The authors’ observations

Visual hallucinations—often of deceased parents or siblings, unknown intruders, and animals—can occur in up to 25% of patients with Alzheimer’s-type dementia.¹ Also, patients with Lewy body dementia often present with well-formed visual hallucinations, which are thought to result from temporal lobe involvement by the characteristic Lewy bodies.

To diagnose dementia, DSM-IV requires the presence of multiple cognitive deficits manifested by memory impairment and one or more of the following:

• aphasia
• apraxia
• agnosia
• disturbance of executive functioning.²

Ms. K exhibited none of these characteristics, and she retained full executive function—she could balance her checkbook, buy groceries, and cook for herself. Also, her MMSE score was high.

Ms. K showed no consciousness fluctuations or attention deficits, two features commonly seen in delirium. She was alert and oriented throughout the interview, and her flow of thought, speech, language, and attention were appropriate. Therefore, delirium can be reasonably excluded.

The hallucinations probably do not signal onset of schizophrenia because of Ms. K’s age at presentation, lack of family history of psychotic disorder, and paucity of negative symptoms. Auditory hallucinations are much more common in psychosis, and isolated visual hallucinations rarely occur in schizophrenia.

Finally, Ms. K’s electrophysiologic, laboratory, and imaging studies revealed isolated systolic hypertension, low visual acuity, and a mild gait disturbance. Severe left lens opacification accounted for the patient’s discordant pupillary light reflex. None of these findings explained her visual hallucinations, however.

Is a non-psychiatric disorder causing Ms. K’s hallucinations? What type of medication might alleviate her symptoms?

The authors’ observations

Given Ms. K’s strong cognitive function and poor visual acuity, we concluded that her hallucinations may fit the criteria for Charles Bonnet syndrome (CBS), a poorly understood medical phenomenon.

CBS is characterized by complex visual hallucinations in visually impaired elderly patients without cognitive deficits (Table 2).^3,4 Swiss philosopher Charles Bonnet first described the disorder in 1760 to explain the vivid visual hallucinations of his 89-year-old grandfather, who had severe cataracts but no cognitive deficits.³ Bonnet’s grandfather claimed to have visions of men, women, birds, buildings, and tapestries.³

CBS is increasingly recognized and reported, but the medical community has never formed a universally accepted definition for this phenomenon. Persons with CBS react positively or negatively to their hallucinations, and the images may stimulate anxiety, anger, or mild paranoia. Research has focused on prevalence, risk indicators, and treatment.

Table 2

Charles Bonnet syndrome: fast facts

Teunisse et al determined that visual hallucinations plague up to 14% of sight-impaired persons.^4,5 The hallucinations vary widely: people, animals, flowers, vehicles, buildings, and sometimes complete scenes.^4,5 Significant risk factors for CBS include advanced age and low visual acuity.^4,5 Loneliness, introversion, and shyness are additional risk indicators in older, visually handicapped persons.⁶ Therefore, social isolation may be a predisposing factor.

Drug treatment of visual hallucinations in CBS currently includes antipsychotics, such as quetiapine (25 to 100 mg/d) and risperidone (0.25 to 1.0 mg/d).⁷ However, mixed results have been reported after use of antipsychotics in CBS; one patient’s visual hallucinations were exacerbated after risperidone was initiated.⁸ Case reports have also described the use of valproate, carbamazepine, and ondansetron in CBS.^9-11

Empathy and patient education are the cornerstones of CBS treatment.³ Patients need to be reassured that their visions are benign. For many, simply increasing the amount of ambient light in the home can reduce hallucinations.

TREATMENT A frog in the toilet

Ms. K was started on quetiapine, 25 mg bid, to try to promote restorative sleep and resolve her hallucinations. Up to 18% of persons treated with quetiapine report somnolence as an adverse effect, vs. 3 to 8% of those treated with risperidone.¹²

During her hospital stay, Ms. K experienced no visual hallucinations during the day but reported seeing a grayish-brown bullfrog in the toilet at night. This hallucination did not frighten her; she would simply close the bathroom door and wait until the bullfrog “disappeared.”

Her sleep improved, as did her appetite. She participated in daily group sessions and socialized with other patients.

After 12 days, Ms. K was discharged. To decrease her social isolation, we encouraged her to participate in a day program for seniors. We also continued her on quetiapine, 25 mg bid.

Five months later, her primary care physician reports that Ms. K remains symptom free while maintaining her quetiapine dosage.

Related resources

• Royal National Institute of the Blind: Fact sheet for Charles Bonnet syndrome. Available at: http://www.rnib.org.uk/info/cbsfin.htm
• Verstraten PFJ. The Charles Bonnet syndrome: Development of a protocol for clinical practice in a multidisciplinary approach from assessment to intervention. Available at: http://www.rehab-syn.enter.iris.se/kc-syn/cb.htm
• Adamczyk DT. Optometric educators. Am I seeing things? Optometry Today June 18, 1999:37-9. Available at: http://www.optometry.co.uk/articles/19990618/Adamczyk.pdf

Drug brand names

• Brimonidine Ophthalmic • Alphagan
• Carbamazepine • Tegretol
• Dorzolamide/Timolol • Cosopt
• Lansoprazole • Prevacid
• Metoprolol • Toprol XL
• Ondansetron • Zofran
• Oxybutynin • Ditropan XL
• Quetiapine • Seroquel
• Repaglinide • Prandin
• Risperidone • Risperdal
• Tolterodine • Detrol
• Valproate • Depakote

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with competing manufacturers.

HISTORY: A sudden vision

Ms. K, 73, was in reasonably good health when one day she suddenly noticed red, green, and yellow birds and butterflies covering her wall.

Ms. K, who lives alone, was frightened at first, but she did not immediately alert anyone because she thought she “was just seeing things, and they’ll go away.”

Instead, she saw more visions over the next 3 months. She once “watched” as two doctors and a nun carried a middle-aged burn victim into her apartment. She remembers seeing the doctors put a “patch” over the woman’s body. To Ms. K, this experience seemed so shockingly real that she called 911, reporting, “That woman should have been in the hospital!”

She reports that a pack of butterflies once “followed” her to the market. She vividly recalls how they crawled about her shoes and legs as she entered the store. When asked if anyone noticed her insect-covered extremities, she replied matter-of-factly, “Maybe it’s not for them to see, maybe it’s just for me,” as if her hallucinations were a divine gift.

Ms. K’s hallucinations usually occur at home, where she spends most of her time. She says that the images are fleeting, lasting from a few seconds to several minutes, and that the creatures fly silently around her room.

Ms. K’s daughter grew concerned that the hallucinations were increasingly diminishing her mother’s ability to care for herself. She brought Ms. K into our emergency department, from which the patient was admitted.

On admission, Ms. K said she had lost 20 lbs within 6 months, and that “concentrating on those things in the house” was impairing her sleep. She denied recent illness, trauma, loss of conscious ness, changes in medications, seizures, drug or alcohol use, suicidal or homicidal ideation, or specific stress in her life. She added that she often cooks for herself—only to lose her appetite after seeing bugs and other creatures crawl into her food.

Her medical history includes hypertension, type 2 diabetes mellitus, peripheral vascular disease, urinary incontinence, gastroesophageal reflux, glaucoma in her left eye, and bilateral cataracts. She denies any psychiatric history and adds that she had never experienced hallucinations until about 3 months before hospitalization. She also denies any history of auditory, tactile, or olfactory hallucinations.

Would you suspect a primary psychotic illness? What clinical tests might help us understand Ms. K’s progressively debilitating visual hallucinations?

The authors’ observations

Ms. K’s case places us at the crossroads of psychiatric disturbances and medical conditions that can present as or precipitate apparent psychiatric symptoms. Delirium, dementia, psychosis, endocrinopathies, encephalitis, electrolyte disturbances, drug abuse/withdrawal, and occipital or temporal lobe seizures are all possible differential diagnoses (Table 1).

A cognitive function screening and a battery of laboratory tests, imaging scans, and neurologic and vision exams are needed to uncover the cause of her hallucinations.

EVALUATION: Looking for clues

Ms. K’s left pupil was fixed at 6 mm and did not respond to light, while the right pupil was regular and reactive to light at 3 mm. Using a Snellen eye chart, her visual acuity was poor: 20/100 to 20/200 in her right eye and less than 20/200 in the left eye. She scored a 29 out of 30 on the Folstein Mini-Mental State Examination (MMSE), indicating her cognition was intact. The remainder of the neurologic exam was unremarkable.

At admission, Ms. K’s medications included metoprolol, 100 mg qd, for hypertension; lansoprazole, 30 mg qd, for gastroesophageal reflux; tolterodine, 2 mg bid, and oxybutynin, 10 mg qd, for urinary incontinence; repaglinide, 2 mg bid, for type 2 diabetes; and three ophthalmic agents: brimonidine, prednisolone, and dorzolamide/timolol. The patient had been maintained on these medications for more than 2 years with no recent changes in dosing.

Results of Ms. K’s lab studies were normal, including a basic metabolic panel, CBC, liver function tests, urinalysis, B12, thyroid panel, rapid plasma reagin test, and urine drug screen.

A head CT without contrast revealed chronic small-vessel ischemic white matter disease and a chronic infarct of the left cerebellar hemisphere. No acute intracranial hemorrhages, masses, or other abnormalities were noted. No seizures were seen on EEG.

Table 1

Common causes of visual hallucinations

What do the laboratory and imaging tests reveal about Ms. K’s hallucinations? Is her diagnosis delirium? Alzheimer’s or other type of dementia? Schizophrenia?

The authors’ observations

Visual hallucinations—often of deceased parents or siblings, unknown intruders, and animals—can occur in up to 25% of patients with Alzheimer’s-type dementia.¹ Also, patients with Lewy body dementia often present with well-formed visual hallucinations, which are thought to result from temporal lobe involvement by the characteristic Lewy bodies.

To diagnose dementia, DSM-IV requires the presence of multiple cognitive deficits manifested by memory impairment and one or more of the following:

• aphasia
• apraxia
• agnosia
• disturbance of executive functioning.²

Ms. K exhibited none of these characteristics, and she retained full executive function—she could balance her checkbook, buy groceries, and cook for herself. Also, her MMSE score was high.

Ms. K showed no consciousness fluctuations or attention deficits, two features commonly seen in delirium. She was alert and oriented throughout the interview, and her flow of thought, speech, language, and attention were appropriate. Therefore, delirium can be reasonably excluded.

The hallucinations probably do not signal onset of schizophrenia because of Ms. K’s age at presentation, lack of family history of psychotic disorder, and paucity of negative symptoms. Auditory hallucinations are much more common in psychosis, and isolated visual hallucinations rarely occur in schizophrenia.

Finally, Ms. K’s electrophysiologic, laboratory, and imaging studies revealed isolated systolic hypertension, low visual acuity, and a mild gait disturbance. Severe left lens opacification accounted for the patient’s discordant pupillary light reflex. None of these findings explained her visual hallucinations, however.

Is a non-psychiatric disorder causing Ms. K’s hallucinations? What type of medication might alleviate her symptoms?

The authors’ observations

Given Ms. K’s strong cognitive function and poor visual acuity, we concluded that her hallucinations may fit the criteria for Charles Bonnet syndrome (CBS), a poorly understood medical phenomenon.

CBS is characterized by complex visual hallucinations in visually impaired elderly patients without cognitive deficits (Table 2).^3,4 Swiss philosopher Charles Bonnet first described the disorder in 1760 to explain the vivid visual hallucinations of his 89-year-old grandfather, who had severe cataracts but no cognitive deficits.³ Bonnet’s grandfather claimed to have visions of men, women, birds, buildings, and tapestries.³

CBS is increasingly recognized and reported, but the medical community has never formed a universally accepted definition for this phenomenon. Persons with CBS react positively or negatively to their hallucinations, and the images may stimulate anxiety, anger, or mild paranoia. Research has focused on prevalence, risk indicators, and treatment.

Table 2

Charles Bonnet syndrome: fast facts

Teunisse et al determined that visual hallucinations plague up to 14% of sight-impaired persons.^4,5 The hallucinations vary widely: people, animals, flowers, vehicles, buildings, and sometimes complete scenes.^4,5 Significant risk factors for CBS include advanced age and low visual acuity.^4,5 Loneliness, introversion, and shyness are additional risk indicators in older, visually handicapped persons.⁶ Therefore, social isolation may be a predisposing factor.

Drug treatment of visual hallucinations in CBS currently includes antipsychotics, such as quetiapine (25 to 100 mg/d) and risperidone (0.25 to 1.0 mg/d).⁷ However, mixed results have been reported after use of antipsychotics in CBS; one patient’s visual hallucinations were exacerbated after risperidone was initiated.⁸ Case reports have also described the use of valproate, carbamazepine, and ondansetron in CBS.^9-11

Empathy and patient education are the cornerstones of CBS treatment.³ Patients need to be reassured that their visions are benign. For many, simply increasing the amount of ambient light in the home can reduce hallucinations.

TREATMENT A frog in the toilet

Ms. K was started on quetiapine, 25 mg bid, to try to promote restorative sleep and resolve her hallucinations. Up to 18% of persons treated with quetiapine report somnolence as an adverse effect, vs. 3 to 8% of those treated with risperidone.¹²

During her hospital stay, Ms. K experienced no visual hallucinations during the day but reported seeing a grayish-brown bullfrog in the toilet at night. This hallucination did not frighten her; she would simply close the bathroom door and wait until the bullfrog “disappeared.”

Her sleep improved, as did her appetite. She participated in daily group sessions and socialized with other patients.

After 12 days, Ms. K was discharged. To decrease her social isolation, we encouraged her to participate in a day program for seniors. We also continued her on quetiapine, 25 mg bid.

Five months later, her primary care physician reports that Ms. K remains symptom free while maintaining her quetiapine dosage.

Related resources

• Royal National Institute of the Blind: Fact sheet for Charles Bonnet syndrome. Available at: http://www.rnib.org.uk/info/cbsfin.htm
• Verstraten PFJ. The Charles Bonnet syndrome: Development of a protocol for clinical practice in a multidisciplinary approach from assessment to intervention. Available at: http://www.rehab-syn.enter.iris.se/kc-syn/cb.htm
• Adamczyk DT. Optometric educators. Am I seeing things? Optometry Today June 18, 1999:37-9. Available at: http://www.optometry.co.uk/articles/19990618/Adamczyk.pdf

Drug brand names

• Brimonidine Ophthalmic • Alphagan
• Carbamazepine • Tegretol
• Dorzolamide/Timolol • Cosopt
• Lansoprazole • Prevacid
• Metoprolol • Toprol XL
• Ondansetron • Zofran
• Oxybutynin • Ditropan XL
• Quetiapine • Seroquel
• Repaglinide • Prandin
• Risperidone • Risperdal
• Tolterodine • Detrol
• Valproate • Depakote

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with competing manufacturers.

HISTORY: A sudden vision

Ms. K, 73, was in reasonably good health when one day she suddenly noticed red, green, and yellow birds and butterflies covering her wall.

Ms. K, who lives alone, was frightened at first, but she did not immediately alert anyone because she thought she “was just seeing things, and they’ll go away.”

Instead, she saw more visions over the next 3 months. She once “watched” as two doctors and a nun carried a middle-aged burn victim into her apartment. She remembers seeing the doctors put a “patch” over the woman’s body. To Ms. K, this experience seemed so shockingly real that she called 911, reporting, “That woman should have been in the hospital!”

She reports that a pack of butterflies once “followed” her to the market. She vividly recalls how they crawled about her shoes and legs as she entered the store. When asked if anyone noticed her insect-covered extremities, she replied matter-of-factly, “Maybe it’s not for them to see, maybe it’s just for me,” as if her hallucinations were a divine gift.

Ms. K’s hallucinations usually occur at home, where she spends most of her time. She says that the images are fleeting, lasting from a few seconds to several minutes, and that the creatures fly silently around her room.

Ms. K’s daughter grew concerned that the hallucinations were increasingly diminishing her mother’s ability to care for herself. She brought Ms. K into our emergency department, from which the patient was admitted.

On admission, Ms. K said she had lost 20 lbs within 6 months, and that “concentrating on those things in the house” was impairing her sleep. She denied recent illness, trauma, loss of conscious ness, changes in medications, seizures, drug or alcohol use, suicidal or homicidal ideation, or specific stress in her life. She added that she often cooks for herself—only to lose her appetite after seeing bugs and other creatures crawl into her food.

Her medical history includes hypertension, type 2 diabetes mellitus, peripheral vascular disease, urinary incontinence, gastroesophageal reflux, glaucoma in her left eye, and bilateral cataracts. She denies any psychiatric history and adds that she had never experienced hallucinations until about 3 months before hospitalization. She also denies any history of auditory, tactile, or olfactory hallucinations.

Would you suspect a primary psychotic illness? What clinical tests might help us understand Ms. K’s progressively debilitating visual hallucinations?

The authors’ observations

Ms. K’s case places us at the crossroads of psychiatric disturbances and medical conditions that can present as or precipitate apparent psychiatric symptoms. Delirium, dementia, psychosis, endocrinopathies, encephalitis, electrolyte disturbances, drug abuse/withdrawal, and occipital or temporal lobe seizures are all possible differential diagnoses (Table 1).

A cognitive function screening and a battery of laboratory tests, imaging scans, and neurologic and vision exams are needed to uncover the cause of her hallucinations.

EVALUATION: Looking for clues

Ms. K’s left pupil was fixed at 6 mm and did not respond to light, while the right pupil was regular and reactive to light at 3 mm. Using a Snellen eye chart, her visual acuity was poor: 20/100 to 20/200 in her right eye and less than 20/200 in the left eye. She scored a 29 out of 30 on the Folstein Mini-Mental State Examination (MMSE), indicating her cognition was intact. The remainder of the neurologic exam was unremarkable.

At admission, Ms. K’s medications included metoprolol, 100 mg qd, for hypertension; lansoprazole, 30 mg qd, for gastroesophageal reflux; tolterodine, 2 mg bid, and oxybutynin, 10 mg qd, for urinary incontinence; repaglinide, 2 mg bid, for type 2 diabetes; and three ophthalmic agents: brimonidine, prednisolone, and dorzolamide/timolol. The patient had been maintained on these medications for more than 2 years with no recent changes in dosing.

Results of Ms. K’s lab studies were normal, including a basic metabolic panel, CBC, liver function tests, urinalysis, B12, thyroid panel, rapid plasma reagin test, and urine drug screen.

A head CT without contrast revealed chronic small-vessel ischemic white matter disease and a chronic infarct of the left cerebellar hemisphere. No acute intracranial hemorrhages, masses, or other abnormalities were noted. No seizures were seen on EEG.

Table 1

Common causes of visual hallucinations

What do the laboratory and imaging tests reveal about Ms. K’s hallucinations? Is her diagnosis delirium? Alzheimer’s or other type of dementia? Schizophrenia?

The authors’ observations

Visual hallucinations—often of deceased parents or siblings, unknown intruders, and animals—can occur in up to 25% of patients with Alzheimer’s-type dementia.¹ Also, patients with Lewy body dementia often present with well-formed visual hallucinations, which are thought to result from temporal lobe involvement by the characteristic Lewy bodies.

To diagnose dementia, DSM-IV requires the presence of multiple cognitive deficits manifested by memory impairment and one or more of the following:

• aphasia
• apraxia
• agnosia
• disturbance of executive functioning.²

Ms. K exhibited none of these characteristics, and she retained full executive function—she could balance her checkbook, buy groceries, and cook for herself. Also, her MMSE score was high.

Ms. K showed no consciousness fluctuations or attention deficits, two features commonly seen in delirium. She was alert and oriented throughout the interview, and her flow of thought, speech, language, and attention were appropriate. Therefore, delirium can be reasonably excluded.

The hallucinations probably do not signal onset of schizophrenia because of Ms. K’s age at presentation, lack of family history of psychotic disorder, and paucity of negative symptoms. Auditory hallucinations are much more common in psychosis, and isolated visual hallucinations rarely occur in schizophrenia.

Finally, Ms. K’s electrophysiologic, laboratory, and imaging studies revealed isolated systolic hypertension, low visual acuity, and a mild gait disturbance. Severe left lens opacification accounted for the patient’s discordant pupillary light reflex. None of these findings explained her visual hallucinations, however.

Is a non-psychiatric disorder causing Ms. K’s hallucinations? What type of medication might alleviate her symptoms?

The authors’ observations

Given Ms. K’s strong cognitive function and poor visual acuity, we concluded that her hallucinations may fit the criteria for Charles Bonnet syndrome (CBS), a poorly understood medical phenomenon.

CBS is characterized by complex visual hallucinations in visually impaired elderly patients without cognitive deficits (Table 2).^3,4 Swiss philosopher Charles Bonnet first described the disorder in 1760 to explain the vivid visual hallucinations of his 89-year-old grandfather, who had severe cataracts but no cognitive deficits.³ Bonnet’s grandfather claimed to have visions of men, women, birds, buildings, and tapestries.³

CBS is increasingly recognized and reported, but the medical community has never formed a universally accepted definition for this phenomenon. Persons with CBS react positively or negatively to their hallucinations, and the images may stimulate anxiety, anger, or mild paranoia. Research has focused on prevalence, risk indicators, and treatment.

Table 2

Charles Bonnet syndrome: fast facts

Teunisse et al determined that visual hallucinations plague up to 14% of sight-impaired persons.^4,5 The hallucinations vary widely: people, animals, flowers, vehicles, buildings, and sometimes complete scenes.^4,5 Significant risk factors for CBS include advanced age and low visual acuity.^4,5 Loneliness, introversion, and shyness are additional risk indicators in older, visually handicapped persons.⁶ Therefore, social isolation may be a predisposing factor.

Drug treatment of visual hallucinations in CBS currently includes antipsychotics, such as quetiapine (25 to 100 mg/d) and risperidone (0.25 to 1.0 mg/d).⁷ However, mixed results have been reported after use of antipsychotics in CBS; one patient’s visual hallucinations were exacerbated after risperidone was initiated.⁸ Case reports have also described the use of valproate, carbamazepine, and ondansetron in CBS.^9-11

Empathy and patient education are the cornerstones of CBS treatment.³ Patients need to be reassured that their visions are benign. For many, simply increasing the amount of ambient light in the home can reduce hallucinations.

TREATMENT A frog in the toilet

Ms. K was started on quetiapine, 25 mg bid, to try to promote restorative sleep and resolve her hallucinations. Up to 18% of persons treated with quetiapine report somnolence as an adverse effect, vs. 3 to 8% of those treated with risperidone.¹²

During her hospital stay, Ms. K experienced no visual hallucinations during the day but reported seeing a grayish-brown bullfrog in the toilet at night. This hallucination did not frighten her; she would simply close the bathroom door and wait until the bullfrog “disappeared.”

Her sleep improved, as did her appetite. She participated in daily group sessions and socialized with other patients.

After 12 days, Ms. K was discharged. To decrease her social isolation, we encouraged her to participate in a day program for seniors. We also continued her on quetiapine, 25 mg bid.

Five months later, her primary care physician reports that Ms. K remains symptom free while maintaining her quetiapine dosage.

Related resources

• Royal National Institute of the Blind: Fact sheet for Charles Bonnet syndrome. Available at: http://www.rnib.org.uk/info/cbsfin.htm
• Verstraten PFJ. The Charles Bonnet syndrome: Development of a protocol for clinical practice in a multidisciplinary approach from assessment to intervention. Available at: http://www.rehab-syn.enter.iris.se/kc-syn/cb.htm
• Adamczyk DT. Optometric educators. Am I seeing things? Optometry Today June 18, 1999:37-9. Available at: http://www.optometry.co.uk/articles/19990618/Adamczyk.pdf

Drug brand names

• Brimonidine Ophthalmic • Alphagan
• Carbamazepine • Tegretol
• Dorzolamide/Timolol • Cosopt
• Lansoprazole • Prevacid
• Metoprolol • Toprol XL
• Ondansetron • Zofran
• Oxybutynin • Ditropan XL
• Quetiapine • Seroquel
• Repaglinide • Prandin
• Risperidone • Risperdal
• Tolterodine • Detrol
• Valproate • Depakote

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with competing manufacturers.

Depression, anxiety, and psychosis are common complications of Parkinson’s disease (PD) and of the medications used in antiparkinsonian treatment. These psychiatric problems impair patients’ functioning throughout the course of the chronic degenerative disease.

Because medication side effects often call for adjustments and trade-offs in PD treatment, a team effort by the psychiatrist, neurologist, patient, and caregiver is the most effective approach to decision-making. From our experience in such collaborations, here’s what you need to know about PD to be a most-valuable player on that treatment team.

Presentation of PD

The classic triad of PD features consists of a pill-rolling tremor, rigidity, and bradykinesia or slowness of movement. Other common features include postural instability, flexed posture, and other motor-freezing phenomena.

Freezing phenomena occur in the later stages of PD, as the response to dopaminergic therapy becomes erratic and unpredictable. Freezing can range from hesitation—such as when the patient tries to turn or is in a doorway—to transient episodes of total inability to move. These episodes are extremely distressing for both patients and caregivers.

Patients rarely present with the full complement of symptoms, but the presence of tremor at rest and/or bradykinesia is essential for the diagnosis. While motor signs dominate the presentation, cognitive symptoms such as shortened attention span, visuospatial impairment, personality changes, and dementia are also frequently present.

Average age of diagnosis is 60, and more men are affected than women (male-to-female ratio is 3:2). Many causative factors—including genetics and environmental toxins—have been implicated, but the disorder’s etiology remains unknown.

Drug treatment side effects

PD results from the loss of neurons in the substantia nigra that produce the neurotransmitter dopamine. Pharmacologic treatment emphasizes dopamine replacement, dopamine receptor stimulation, or prevention of enzymatic breakdown of dopamine in the synaptic cleft. As treatment of PD is symptomatic and not curative, medications are instituted only when the disease begins to cause functional impairment.

Treatment begins with dopamine agonists (Table). As dopamine agonist monotherapy becomes less effective, levodopa therapy is initiated. Blocking the enzymatic breakdown of dopamine with catechol-O-methyltransferase inhibitors is the next therapeutic strategy.

Within 5 years of starting levodopa therapy 75% of patients experience unsatisfactory motor response, from unpredictable fluctuations to wearing-off phenomena (in which a dose of levodopa does not last as long as it once did). Treatment of advanced PD is complicated by the emergence of psychiatric symptoms, such as hallucinations and psychosis, as dopamine levels are increased in an attempt to smooth the motor response.

The significantly distressing level of disability associated with the prominent side effects of pharmacologic treatment has led to interest in surgical interventions. These range from pallidotomy to implantation of basal ganglia stimulators to transplantation of fetal striatal neurons. The possibility of neuroprotection has also been extensively investigated, with mixed results.

Psychiatric complications of PD

Depression. Clearly, the stress of anticipating and coping with a relentless degenerative disease helps to trigger depression and anxiety in patients with PD. Depression is the most common psychiatric syndrome, with prevalence in PD as high as 42%.¹ Patients with a history of depression are at particular risk.² Those with recent deterioration or advancing severity of PD, akinesia, history of falls, or cognitive impairment are also at increased risk for depression.

Table

MEDICATIONS COMMONLY USED IN MANAGING PARKINSON’S DISEASE

Depression correlates well with the patient’s perception of his or her degree of PD-related disability. Depression symptoms seem to peak early in the illness following diagnosis and in advanced disease.³

Patients may present with symptoms meeting diagnostic criteria ranging from dysthymic disorder to minor depression to major depressive disorder.^1,4 Although they will frequently endorse suicidal ideation, patients with PD have a low rate of suicide. Diagnosing depression, however, may be difficult because its symptoms overlap with those of the underlying neurologic disease:

• Diminished affect and psychomotor slowing may be secondary to the motor features of parkinsonism.
• Diminished concentration may be secondary to cognitive decline rather than depression.

Patients also frequently have a chief complaint of diminished energy or fatigue that should trigger further investigation into other depressive symptoms.^4,5

In addition to the obvious additional suffering it causes, depression in PD predicts impaired social, physical, and role functioning.⁶ Depression in the PD patient also results in higher distress for caregivers.⁷ In one study, depression was identified as a risk factor for development of psychosis in PD patients.⁸

Anxiety is a frequent problem for PD patients, with a prevalence of 33 to 40%.^9,10 Anxiety in PD typically presents with symptoms of panic disorder, generalized anxiety disorder, or social phobia.¹¹ It is comorbid with depression in up to 92% of cases and—like depression—frequently predates the onset of motor symptoms.¹²

Anxiety symptoms have been correlated, although not consistently, with the on-off motor phenomenon often found in advanced PD.¹³ They can also be an adverse effect of many of the antiparkinsonian medications, including anticholinergics, dopamine agonists, catechol-O-methyltransferase inhibitors, and selegiline. Both anxiety and depression have been associated with an increased risk for falls.¹⁴

Psychotic symptoms. Up to 25% of PD patients experience delusions or hallucinations.¹⁵ Risk factors include dementia, sleep disturbance, and—most commonly—the use of dopaminergic agents. Up to one-fifth of patients using dopaminergic drugs experience psychotic symptoms.¹⁶

Psychotic symptoms can occur with or without the clouded sensorium characteristic of delirium. Psychotic symptoms with an associated confusional state can be associated with use of anticholinergic agents and drugs such as selegiline and amantadine.¹⁷ Catechol-O-methyltransferase inhibitors cause more sustained dopaminergic activity of levodopa, which can result in psychotic symptoms. Therefore, the use of all known classes of antiparkinsonian medications has been associated with drug-induced psychosis.

In advanced PD, paranoid delusions, delusions of spousal infidelity, and visual hallucinations are common, whereas negative symptoms and thought disturbances are not.¹⁸ Psychosis may be a more important contributor to caregiver distress than the motor symptoms of PD and may be more likely than any other factor to lead to nursing home placement of the PD patient (Box 1).¹⁵

Psychiatric interventions

Goals for psychiatric treatment of depression, anxiety, and psychosis associated with PD seem relatively straightforward:

• improvement or remission of psychiatric symptoms
• restoration of optimal patient functioning.

Ideally, these goals would be achieved without causing sedation, orthostatic hypotension, or exacerbating motor symptoms. The older age of patients and the progressive nature of this neurodegenerative disorder predispose patients to cognitive side effects. Unfortunately, despite the high prevalence of psychiatric disturbances in PD, evidence with which to evaluate treatment efficacy and safety and to guide treatment selection is extremely limited.

For depression associated with PD, extensive clinical experience supports the efficacy of tricyclic antidepressants. Even so, selective serotonin reuptake inhibitors (SSRIs) are the preferred treatment, although only open-label trials and case reports support their efficacy.^5,12 Compared with tricyclics, SSRIs exhibit a relative lack of problems with sedation, orthostatic hypotension, and memory-impairing anticholinergic side effects. While case reports have cited worsening of motor symptoms with SSRIs, a recent prospective study found no significant worsening of PD symptoms during treatment with citalopram, fluoxetine, fluvoxamine, or sertraline.¹⁹ Co-administration of an SSRI with selegiline is not absolutely contraindicated, but the combination does carry a very small risk of development of serotonin syndrome.^1,5

Box 1

Data are even more scant on the safe use of other antidepressants in PD. Electroconvulsive therapy has been proven helpful in refractory cases and sometimes results in transient motor symptom improvement.^1,5,12 While clinical experience suggests that psychotherapy frequently helps, no extensive controlled studies exist. One small study suggests the efficacy of structured cognitive psychotherapy.²⁰

Anxiety. No studies have examined the treatment of anxiety in PD patients. Given the extremely high comorbidity of anxiety with depression, antidepressants should probably be considered as a first-line pharmacotherapy. Benzodiazepines should be used cautiously, as they increase the risk of falls, sedation, and confusion in older patients. One small controlled study found that buspirone was well tolerated in PD patients at low dosages (10 to 40 mg/d), but anxiety did not improve. At high dosages (100 mg/d), anxiety worsened.²¹

Psychosis. Data on use of antipsychotic agents in PD are also limited, but some evidence supports their use in treating PD-related psychotic symptoms. While conventional antipsychotics can help control psychosis, the potential is high for worsening of parkinsonian symptoms due to D2 receptor blockade.

Among the atypical antipsychotics, clozapine has been most extensively studied in PD and has been shown in open and double-blind trials to be effective and well tolerated at low dosages (6.25 to 50 mg/d). A limited number of open studies of some of the newer atypicals have been performed. While extreme caution must be used in comparing data from these studies due to highly variable dosing and other study design issues, clozapine and quetiapine appear to be the agents best tolerated by PD patients.^12,18,22 Initial antipsychotic dosing should be low and escalation cautious—regardless of the agent chosen—because of the dose-related potential for worsening of parkinsonian symptoms, sedation, and orthostatic hypotension.

A team approach to treatment

Because psychiatric and PD symptoms and treatments are closely interrelated, the psychiatrist, neurologist, patient, and caregiver must collaborate for the best therapeutic result. A simplistic approach to treatment can result in a catastrophic downward spiral in patient functioning.

Often, compromises must be made between optimal control of parkinsonian and psychiatric symptoms to achieve the best overall patient function. Patients and caregivers must be counseled about possible psychiatric symptoms associated with PD and antiparkinsonian therapy, as well as the potential for adverse effects from psychiatric medications. With this knowledge, patients and caregivers can help assess the severity of symptoms and set treatment priorities, depending on how symptoms may be affecting the patient’s level of functioning. For example, if an effective antiparkinsonian regimen has triggered infrequent, nondistressing hallucinations with preserved insight, intervention may not be required beyond patient and caregiver education (Box 2).

Patient workup. When intervention is required for psychiatric symptoms, it should begin with careful neurologic evaluation. Triggering factors such as infections (commonly urinary tract infections and pneumonia), metabolic disorders (hyperglycemia, hypothyroidism), subdural hematomas (if the patient is falling), and drug interactions should be ruled out or appropriately addressed.

Next, try to sequentially eliminate antiparkinsonian medications until the psychosis resolves or motor function worsens.²³ Because of considerable overlap between PD symptoms and depression (psychomotor retardation, fatigue, and anergia), optimizing PD therapy sometimes can result in substantial psychiatric improvement. Some evidence also suggests that the dopamine agonist pramipexole may be effective in treating both PD and depression.⁵

When psychiatric medications are necessary for depression, anxiety, or psychosis, carefully review target symptoms, treatment expectations, and possible adverse effects with the patient and caregiver. Keep in mind the progressive nature of PD and, in addition to frequent monitoring, educate and encourage caregivers to immediately report any suspected adverse effects.

Any motor function deterioration should trigger a re-evaluation of psychotropic medications before you presume that the patient’s PD is progressing. Because antiparkinsonian drug regimens change over time, review the patient’s medications at each appointment, and alert patients and caregivers to potential psychiatric complications of any new medication.

Caregiver treatment In addition to treating the patient, it is important to monitor the impact of psychiatric symptoms and PD on the patient’s caregiver. Frequently assess whether the caregiver and patient have adequate social supports, and address any emerging needs. Useful interventions include caregiver counseling, referrals to support groups, and respite care.²⁴

Box 2

Related resources

• Parkinson’s Disease Foundation: http://www.pdf.org
• American Parkinson Disease Association: http://apdaparkinson.com
• National Parkinson Foundation: http://www.parkinson.org
• Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease 2001: treatment guidelines. Neurology 2001;56:5(suppl):S1-S88.

Drug brand names

• Alprazolam • Xanax
• Amantadine • Symmetrel
• Benztropine • Cogentin
• Biperiden • Akineton
• Buspirone • Buspar
• Carbidopa-levodopa • Sinemet
• Citalopram • Celexa
• Clozapine • Clozaril
• Entacapone • Comtan
• Fluvoxamine • Luvox
• Hyoscyamine • Levsin
• Paroxetine • Paxil
• Pergolide • Permax
• Pramipexole • Mirapex
• Ropinirole • Requip
• Selegeline • Eldepryl
• Sertraline • Zoloft
• Tolcapone • Tasmar
• Trihexyphenidyl • Artane
• Trifluoperazine • Stelazine

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Depression, anxiety, and psychosis are common complications of Parkinson’s disease (PD) and of the medications used in antiparkinsonian treatment. These psychiatric problems impair patients’ functioning throughout the course of the chronic degenerative disease.

Because medication side effects often call for adjustments and trade-offs in PD treatment, a team effort by the psychiatrist, neurologist, patient, and caregiver is the most effective approach to decision-making. From our experience in such collaborations, here’s what you need to know about PD to be a most-valuable player on that treatment team.

Presentation of PD

The classic triad of PD features consists of a pill-rolling tremor, rigidity, and bradykinesia or slowness of movement. Other common features include postural instability, flexed posture, and other motor-freezing phenomena.

Freezing phenomena occur in the later stages of PD, as the response to dopaminergic therapy becomes erratic and unpredictable. Freezing can range from hesitation—such as when the patient tries to turn or is in a doorway—to transient episodes of total inability to move. These episodes are extremely distressing for both patients and caregivers.

Patients rarely present with the full complement of symptoms, but the presence of tremor at rest and/or bradykinesia is essential for the diagnosis. While motor signs dominate the presentation, cognitive symptoms such as shortened attention span, visuospatial impairment, personality changes, and dementia are also frequently present.

Average age of diagnosis is 60, and more men are affected than women (male-to-female ratio is 3:2). Many causative factors—including genetics and environmental toxins—have been implicated, but the disorder’s etiology remains unknown.

Drug treatment side effects

PD results from the loss of neurons in the substantia nigra that produce the neurotransmitter dopamine. Pharmacologic treatment emphasizes dopamine replacement, dopamine receptor stimulation, or prevention of enzymatic breakdown of dopamine in the synaptic cleft. As treatment of PD is symptomatic and not curative, medications are instituted only when the disease begins to cause functional impairment.

Treatment begins with dopamine agonists (Table). As dopamine agonist monotherapy becomes less effective, levodopa therapy is initiated. Blocking the enzymatic breakdown of dopamine with catechol-O-methyltransferase inhibitors is the next therapeutic strategy.

Within 5 years of starting levodopa therapy 75% of patients experience unsatisfactory motor response, from unpredictable fluctuations to wearing-off phenomena (in which a dose of levodopa does not last as long as it once did). Treatment of advanced PD is complicated by the emergence of psychiatric symptoms, such as hallucinations and psychosis, as dopamine levels are increased in an attempt to smooth the motor response.

The significantly distressing level of disability associated with the prominent side effects of pharmacologic treatment has led to interest in surgical interventions. These range from pallidotomy to implantation of basal ganglia stimulators to transplantation of fetal striatal neurons. The possibility of neuroprotection has also been extensively investigated, with mixed results.

Psychiatric complications of PD

Depression. Clearly, the stress of anticipating and coping with a relentless degenerative disease helps to trigger depression and anxiety in patients with PD. Depression is the most common psychiatric syndrome, with prevalence in PD as high as 42%.¹ Patients with a history of depression are at particular risk.² Those with recent deterioration or advancing severity of PD, akinesia, history of falls, or cognitive impairment are also at increased risk for depression.

Table

MEDICATIONS COMMONLY USED IN MANAGING PARKINSON’S DISEASE

Depression correlates well with the patient’s perception of his or her degree of PD-related disability. Depression symptoms seem to peak early in the illness following diagnosis and in advanced disease.³

Patients may present with symptoms meeting diagnostic criteria ranging from dysthymic disorder to minor depression to major depressive disorder.^1,4 Although they will frequently endorse suicidal ideation, patients with PD have a low rate of suicide. Diagnosing depression, however, may be difficult because its symptoms overlap with those of the underlying neurologic disease:

• Diminished affect and psychomotor slowing may be secondary to the motor features of parkinsonism.
• Diminished concentration may be secondary to cognitive decline rather than depression.

Patients also frequently have a chief complaint of diminished energy or fatigue that should trigger further investigation into other depressive symptoms.^4,5

In addition to the obvious additional suffering it causes, depression in PD predicts impaired social, physical, and role functioning.⁶ Depression in the PD patient also results in higher distress for caregivers.⁷ In one study, depression was identified as a risk factor for development of psychosis in PD patients.⁸

Anxiety is a frequent problem for PD patients, with a prevalence of 33 to 40%.^9,10 Anxiety in PD typically presents with symptoms of panic disorder, generalized anxiety disorder, or social phobia.¹¹ It is comorbid with depression in up to 92% of cases and—like depression—frequently predates the onset of motor symptoms.¹²

Anxiety symptoms have been correlated, although not consistently, with the on-off motor phenomenon often found in advanced PD.¹³ They can also be an adverse effect of many of the antiparkinsonian medications, including anticholinergics, dopamine agonists, catechol-O-methyltransferase inhibitors, and selegiline. Both anxiety and depression have been associated with an increased risk for falls.¹⁴

Psychotic symptoms. Up to 25% of PD patients experience delusions or hallucinations.¹⁵ Risk factors include dementia, sleep disturbance, and—most commonly—the use of dopaminergic agents. Up to one-fifth of patients using dopaminergic drugs experience psychotic symptoms.¹⁶

Psychotic symptoms can occur with or without the clouded sensorium characteristic of delirium. Psychotic symptoms with an associated confusional state can be associated with use of anticholinergic agents and drugs such as selegiline and amantadine.¹⁷ Catechol-O-methyltransferase inhibitors cause more sustained dopaminergic activity of levodopa, which can result in psychotic symptoms. Therefore, the use of all known classes of antiparkinsonian medications has been associated with drug-induced psychosis.

In advanced PD, paranoid delusions, delusions of spousal infidelity, and visual hallucinations are common, whereas negative symptoms and thought disturbances are not.¹⁸ Psychosis may be a more important contributor to caregiver distress than the motor symptoms of PD and may be more likely than any other factor to lead to nursing home placement of the PD patient (Box 1).¹⁵

Psychiatric interventions

Goals for psychiatric treatment of depression, anxiety, and psychosis associated with PD seem relatively straightforward:

• improvement or remission of psychiatric symptoms
• restoration of optimal patient functioning.

Ideally, these goals would be achieved without causing sedation, orthostatic hypotension, or exacerbating motor symptoms. The older age of patients and the progressive nature of this neurodegenerative disorder predispose patients to cognitive side effects. Unfortunately, despite the high prevalence of psychiatric disturbances in PD, evidence with which to evaluate treatment efficacy and safety and to guide treatment selection is extremely limited.

For depression associated with PD, extensive clinical experience supports the efficacy of tricyclic antidepressants. Even so, selective serotonin reuptake inhibitors (SSRIs) are the preferred treatment, although only open-label trials and case reports support their efficacy.^5,12 Compared with tricyclics, SSRIs exhibit a relative lack of problems with sedation, orthostatic hypotension, and memory-impairing anticholinergic side effects. While case reports have cited worsening of motor symptoms with SSRIs, a recent prospective study found no significant worsening of PD symptoms during treatment with citalopram, fluoxetine, fluvoxamine, or sertraline.¹⁹ Co-administration of an SSRI with selegiline is not absolutely contraindicated, but the combination does carry a very small risk of development of serotonin syndrome.^1,5

Box 1

Data are even more scant on the safe use of other antidepressants in PD. Electroconvulsive therapy has been proven helpful in refractory cases and sometimes results in transient motor symptom improvement.^1,5,12 While clinical experience suggests that psychotherapy frequently helps, no extensive controlled studies exist. One small study suggests the efficacy of structured cognitive psychotherapy.²⁰

Anxiety. No studies have examined the treatment of anxiety in PD patients. Given the extremely high comorbidity of anxiety with depression, antidepressants should probably be considered as a first-line pharmacotherapy. Benzodiazepines should be used cautiously, as they increase the risk of falls, sedation, and confusion in older patients. One small controlled study found that buspirone was well tolerated in PD patients at low dosages (10 to 40 mg/d), but anxiety did not improve. At high dosages (100 mg/d), anxiety worsened.²¹

Psychosis. Data on use of antipsychotic agents in PD are also limited, but some evidence supports their use in treating PD-related psychotic symptoms. While conventional antipsychotics can help control psychosis, the potential is high for worsening of parkinsonian symptoms due to D2 receptor blockade.

Among the atypical antipsychotics, clozapine has been most extensively studied in PD and has been shown in open and double-blind trials to be effective and well tolerated at low dosages (6.25 to 50 mg/d). A limited number of open studies of some of the newer atypicals have been performed. While extreme caution must be used in comparing data from these studies due to highly variable dosing and other study design issues, clozapine and quetiapine appear to be the agents best tolerated by PD patients.^12,18,22 Initial antipsychotic dosing should be low and escalation cautious—regardless of the agent chosen—because of the dose-related potential for worsening of parkinsonian symptoms, sedation, and orthostatic hypotension.

A team approach to treatment

Because psychiatric and PD symptoms and treatments are closely interrelated, the psychiatrist, neurologist, patient, and caregiver must collaborate for the best therapeutic result. A simplistic approach to treatment can result in a catastrophic downward spiral in patient functioning.

Often, compromises must be made between optimal control of parkinsonian and psychiatric symptoms to achieve the best overall patient function. Patients and caregivers must be counseled about possible psychiatric symptoms associated with PD and antiparkinsonian therapy, as well as the potential for adverse effects from psychiatric medications. With this knowledge, patients and caregivers can help assess the severity of symptoms and set treatment priorities, depending on how symptoms may be affecting the patient’s level of functioning. For example, if an effective antiparkinsonian regimen has triggered infrequent, nondistressing hallucinations with preserved insight, intervention may not be required beyond patient and caregiver education (Box 2).

Patient workup. When intervention is required for psychiatric symptoms, it should begin with careful neurologic evaluation. Triggering factors such as infections (commonly urinary tract infections and pneumonia), metabolic disorders (hyperglycemia, hypothyroidism), subdural hematomas (if the patient is falling), and drug interactions should be ruled out or appropriately addressed.

Next, try to sequentially eliminate antiparkinsonian medications until the psychosis resolves or motor function worsens.²³ Because of considerable overlap between PD symptoms and depression (psychomotor retardation, fatigue, and anergia), optimizing PD therapy sometimes can result in substantial psychiatric improvement. Some evidence also suggests that the dopamine agonist pramipexole may be effective in treating both PD and depression.⁵

When psychiatric medications are necessary for depression, anxiety, or psychosis, carefully review target symptoms, treatment expectations, and possible adverse effects with the patient and caregiver. Keep in mind the progressive nature of PD and, in addition to frequent monitoring, educate and encourage caregivers to immediately report any suspected adverse effects.

Any motor function deterioration should trigger a re-evaluation of psychotropic medications before you presume that the patient’s PD is progressing. Because antiparkinsonian drug regimens change over time, review the patient’s medications at each appointment, and alert patients and caregivers to potential psychiatric complications of any new medication.

Caregiver treatment In addition to treating the patient, it is important to monitor the impact of psychiatric symptoms and PD on the patient’s caregiver. Frequently assess whether the caregiver and patient have adequate social supports, and address any emerging needs. Useful interventions include caregiver counseling, referrals to support groups, and respite care.²⁴

Box 2

Related resources

• Parkinson’s Disease Foundation: http://www.pdf.org
• American Parkinson Disease Association: http://apdaparkinson.com
• National Parkinson Foundation: http://www.parkinson.org
• Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease 2001: treatment guidelines. Neurology 2001;56:5(suppl):S1-S88.

Drug brand names

• Alprazolam • Xanax
• Amantadine • Symmetrel
• Benztropine • Cogentin
• Biperiden • Akineton
• Buspirone • Buspar
• Carbidopa-levodopa • Sinemet
• Citalopram • Celexa
• Clozapine • Clozaril
• Entacapone • Comtan
• Fluvoxamine • Luvox
• Hyoscyamine • Levsin
• Paroxetine • Paxil
• Pergolide • Permax
• Pramipexole • Mirapex
• Ropinirole • Requip
• Selegeline • Eldepryl
• Sertraline • Zoloft
• Tolcapone • Tasmar
• Trihexyphenidyl • Artane
• Trifluoperazine • Stelazine

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Depression, anxiety, and psychosis are common complications of Parkinson’s disease (PD) and of the medications used in antiparkinsonian treatment. These psychiatric problems impair patients’ functioning throughout the course of the chronic degenerative disease.

Because medication side effects often call for adjustments and trade-offs in PD treatment, a team effort by the psychiatrist, neurologist, patient, and caregiver is the most effective approach to decision-making. From our experience in such collaborations, here’s what you need to know about PD to be a most-valuable player on that treatment team.

Presentation of PD

The classic triad of PD features consists of a pill-rolling tremor, rigidity, and bradykinesia or slowness of movement. Other common features include postural instability, flexed posture, and other motor-freezing phenomena.

Freezing phenomena occur in the later stages of PD, as the response to dopaminergic therapy becomes erratic and unpredictable. Freezing can range from hesitation—such as when the patient tries to turn or is in a doorway—to transient episodes of total inability to move. These episodes are extremely distressing for both patients and caregivers.

Patients rarely present with the full complement of symptoms, but the presence of tremor at rest and/or bradykinesia is essential for the diagnosis. While motor signs dominate the presentation, cognitive symptoms such as shortened attention span, visuospatial impairment, personality changes, and dementia are also frequently present.

Average age of diagnosis is 60, and more men are affected than women (male-to-female ratio is 3:2). Many causative factors—including genetics and environmental toxins—have been implicated, but the disorder’s etiology remains unknown.

Drug treatment side effects

PD results from the loss of neurons in the substantia nigra that produce the neurotransmitter dopamine. Pharmacologic treatment emphasizes dopamine replacement, dopamine receptor stimulation, or prevention of enzymatic breakdown of dopamine in the synaptic cleft. As treatment of PD is symptomatic and not curative, medications are instituted only when the disease begins to cause functional impairment.

Treatment begins with dopamine agonists (Table). As dopamine agonist monotherapy becomes less effective, levodopa therapy is initiated. Blocking the enzymatic breakdown of dopamine with catechol-O-methyltransferase inhibitors is the next therapeutic strategy.

Within 5 years of starting levodopa therapy 75% of patients experience unsatisfactory motor response, from unpredictable fluctuations to wearing-off phenomena (in which a dose of levodopa does not last as long as it once did). Treatment of advanced PD is complicated by the emergence of psychiatric symptoms, such as hallucinations and psychosis, as dopamine levels are increased in an attempt to smooth the motor response.

The significantly distressing level of disability associated with the prominent side effects of pharmacologic treatment has led to interest in surgical interventions. These range from pallidotomy to implantation of basal ganglia stimulators to transplantation of fetal striatal neurons. The possibility of neuroprotection has also been extensively investigated, with mixed results.

Psychiatric complications of PD

Depression. Clearly, the stress of anticipating and coping with a relentless degenerative disease helps to trigger depression and anxiety in patients with PD. Depression is the most common psychiatric syndrome, with prevalence in PD as high as 42%.¹ Patients with a history of depression are at particular risk.² Those with recent deterioration or advancing severity of PD, akinesia, history of falls, or cognitive impairment are also at increased risk for depression.

Table

MEDICATIONS COMMONLY USED IN MANAGING PARKINSON’S DISEASE

Depression correlates well with the patient’s perception of his or her degree of PD-related disability. Depression symptoms seem to peak early in the illness following diagnosis and in advanced disease.³

Patients may present with symptoms meeting diagnostic criteria ranging from dysthymic disorder to minor depression to major depressive disorder.^1,4 Although they will frequently endorse suicidal ideation, patients with PD have a low rate of suicide. Diagnosing depression, however, may be difficult because its symptoms overlap with those of the underlying neurologic disease:

• Diminished affect and psychomotor slowing may be secondary to the motor features of parkinsonism.
• Diminished concentration may be secondary to cognitive decline rather than depression.

Patients also frequently have a chief complaint of diminished energy or fatigue that should trigger further investigation into other depressive symptoms.^4,5

In addition to the obvious additional suffering it causes, depression in PD predicts impaired social, physical, and role functioning.⁶ Depression in the PD patient also results in higher distress for caregivers.⁷ In one study, depression was identified as a risk factor for development of psychosis in PD patients.⁸

Anxiety is a frequent problem for PD patients, with a prevalence of 33 to 40%.^9,10 Anxiety in PD typically presents with symptoms of panic disorder, generalized anxiety disorder, or social phobia.¹¹ It is comorbid with depression in up to 92% of cases and—like depression—frequently predates the onset of motor symptoms.¹²

Anxiety symptoms have been correlated, although not consistently, with the on-off motor phenomenon often found in advanced PD.¹³ They can also be an adverse effect of many of the antiparkinsonian medications, including anticholinergics, dopamine agonists, catechol-O-methyltransferase inhibitors, and selegiline. Both anxiety and depression have been associated with an increased risk for falls.¹⁴

Psychotic symptoms. Up to 25% of PD patients experience delusions or hallucinations.¹⁵ Risk factors include dementia, sleep disturbance, and—most commonly—the use of dopaminergic agents. Up to one-fifth of patients using dopaminergic drugs experience psychotic symptoms.¹⁶

Psychotic symptoms can occur with or without the clouded sensorium characteristic of delirium. Psychotic symptoms with an associated confusional state can be associated with use of anticholinergic agents and drugs such as selegiline and amantadine.¹⁷ Catechol-O-methyltransferase inhibitors cause more sustained dopaminergic activity of levodopa, which can result in psychotic symptoms. Therefore, the use of all known classes of antiparkinsonian medications has been associated with drug-induced psychosis.

In advanced PD, paranoid delusions, delusions of spousal infidelity, and visual hallucinations are common, whereas negative symptoms and thought disturbances are not.¹⁸ Psychosis may be a more important contributor to caregiver distress than the motor symptoms of PD and may be more likely than any other factor to lead to nursing home placement of the PD patient (Box 1).¹⁵

Psychiatric interventions

Goals for psychiatric treatment of depression, anxiety, and psychosis associated with PD seem relatively straightforward:

• improvement or remission of psychiatric symptoms
• restoration of optimal patient functioning.

Ideally, these goals would be achieved without causing sedation, orthostatic hypotension, or exacerbating motor symptoms. The older age of patients and the progressive nature of this neurodegenerative disorder predispose patients to cognitive side effects. Unfortunately, despite the high prevalence of psychiatric disturbances in PD, evidence with which to evaluate treatment efficacy and safety and to guide treatment selection is extremely limited.

For depression associated with PD, extensive clinical experience supports the efficacy of tricyclic antidepressants. Even so, selective serotonin reuptake inhibitors (SSRIs) are the preferred treatment, although only open-label trials and case reports support their efficacy.^5,12 Compared with tricyclics, SSRIs exhibit a relative lack of problems with sedation, orthostatic hypotension, and memory-impairing anticholinergic side effects. While case reports have cited worsening of motor symptoms with SSRIs, a recent prospective study found no significant worsening of PD symptoms during treatment with citalopram, fluoxetine, fluvoxamine, or sertraline.¹⁹ Co-administration of an SSRI with selegiline is not absolutely contraindicated, but the combination does carry a very small risk of development of serotonin syndrome.^1,5

Box 1

Data are even more scant on the safe use of other antidepressants in PD. Electroconvulsive therapy has been proven helpful in refractory cases and sometimes results in transient motor symptom improvement.^1,5,12 While clinical experience suggests that psychotherapy frequently helps, no extensive controlled studies exist. One small study suggests the efficacy of structured cognitive psychotherapy.²⁰

Anxiety. No studies have examined the treatment of anxiety in PD patients. Given the extremely high comorbidity of anxiety with depression, antidepressants should probably be considered as a first-line pharmacotherapy. Benzodiazepines should be used cautiously, as they increase the risk of falls, sedation, and confusion in older patients. One small controlled study found that buspirone was well tolerated in PD patients at low dosages (10 to 40 mg/d), but anxiety did not improve. At high dosages (100 mg/d), anxiety worsened.²¹

Psychosis. Data on use of antipsychotic agents in PD are also limited, but some evidence supports their use in treating PD-related psychotic symptoms. While conventional antipsychotics can help control psychosis, the potential is high for worsening of parkinsonian symptoms due to D2 receptor blockade.

Among the atypical antipsychotics, clozapine has been most extensively studied in PD and has been shown in open and double-blind trials to be effective and well tolerated at low dosages (6.25 to 50 mg/d). A limited number of open studies of some of the newer atypicals have been performed. While extreme caution must be used in comparing data from these studies due to highly variable dosing and other study design issues, clozapine and quetiapine appear to be the agents best tolerated by PD patients.^12,18,22 Initial antipsychotic dosing should be low and escalation cautious—regardless of the agent chosen—because of the dose-related potential for worsening of parkinsonian symptoms, sedation, and orthostatic hypotension.

A team approach to treatment

Because psychiatric and PD symptoms and treatments are closely interrelated, the psychiatrist, neurologist, patient, and caregiver must collaborate for the best therapeutic result. A simplistic approach to treatment can result in a catastrophic downward spiral in patient functioning.

Often, compromises must be made between optimal control of parkinsonian and psychiatric symptoms to achieve the best overall patient function. Patients and caregivers must be counseled about possible psychiatric symptoms associated with PD and antiparkinsonian therapy, as well as the potential for adverse effects from psychiatric medications. With this knowledge, patients and caregivers can help assess the severity of symptoms and set treatment priorities, depending on how symptoms may be affecting the patient’s level of functioning. For example, if an effective antiparkinsonian regimen has triggered infrequent, nondistressing hallucinations with preserved insight, intervention may not be required beyond patient and caregiver education (Box 2).

Patient workup. When intervention is required for psychiatric symptoms, it should begin with careful neurologic evaluation. Triggering factors such as infections (commonly urinary tract infections and pneumonia), metabolic disorders (hyperglycemia, hypothyroidism), subdural hematomas (if the patient is falling), and drug interactions should be ruled out or appropriately addressed.

Next, try to sequentially eliminate antiparkinsonian medications until the psychosis resolves or motor function worsens.²³ Because of considerable overlap between PD symptoms and depression (psychomotor retardation, fatigue, and anergia), optimizing PD therapy sometimes can result in substantial psychiatric improvement. Some evidence also suggests that the dopamine agonist pramipexole may be effective in treating both PD and depression.⁵

When psychiatric medications are necessary for depression, anxiety, or psychosis, carefully review target symptoms, treatment expectations, and possible adverse effects with the patient and caregiver. Keep in mind the progressive nature of PD and, in addition to frequent monitoring, educate and encourage caregivers to immediately report any suspected adverse effects.

Any motor function deterioration should trigger a re-evaluation of psychotropic medications before you presume that the patient’s PD is progressing. Because antiparkinsonian drug regimens change over time, review the patient’s medications at each appointment, and alert patients and caregivers to potential psychiatric complications of any new medication.

Caregiver treatment In addition to treating the patient, it is important to monitor the impact of psychiatric symptoms and PD on the patient’s caregiver. Frequently assess whether the caregiver and patient have adequate social supports, and address any emerging needs. Useful interventions include caregiver counseling, referrals to support groups, and respite care.²⁴

Box 2

Related resources

• Parkinson’s Disease Foundation: http://www.pdf.org
• American Parkinson Disease Association: http://apdaparkinson.com
• National Parkinson Foundation: http://www.parkinson.org
• Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease 2001: treatment guidelines. Neurology 2001;56:5(suppl):S1-S88.

Drug brand names

• Alprazolam • Xanax
• Amantadine • Symmetrel
• Benztropine • Cogentin
• Biperiden • Akineton
• Buspirone • Buspar
• Carbidopa-levodopa • Sinemet
• Citalopram • Celexa
• Clozapine • Clozaril
• Entacapone • Comtan
• Fluvoxamine • Luvox
• Hyoscyamine • Levsin
• Paroxetine • Paxil
• Pergolide • Permax
• Pramipexole • Mirapex
• Ropinirole • Requip
• Selegeline • Eldepryl
• Sertraline • Zoloft
• Tolcapone • Tasmar
• Trihexyphenidyl • Artane
• Trifluoperazine • Stelazine

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

A growing body of evidence suggests that psychiatrists have much to offer patients with severe irritable bowel syndrome (IBS). Behavioral and psychotherapeutic approaches are showing promise in relieving both GI and mood disturbances.

Treating patients with IBS with medications designed to influence only gut function can be frustrating. Those with refractory symptoms may be extremely sensitive to drug side effects, and they often report that medical management worsens or does not improve their symptoms. They experiment with alternative medicines and wander from physician to physician in a disappointing search for a “cure.”

Let’s look at evidence on the efficacy of individual and group behavioral therapies, hypnotherapy, biofeedback, and combination medical and behavioral treatment.

Psychotherapeutic approaches

IBS is a common gastrointestinal disorder that is characterized by abdominal discomfort and changes in bowel habits (Boxes 1 and 2). Patients with severe IBS symptoms often bring significant psychological impairment and psychosocial trauma to clinical encounters.^1,2 They respond poorly to standard medical management, and evidence supporting the efficacy of medical treatments for IBS remains weak.^3,4

Box 1

In 1983, the first controlled trial of psychodynamic psychotherapy for IBS showed dramatic reductions in symptoms.⁵ A subsequent series of high-quality articles in the early 1990s also showed that interpersonal psychotherapy (with greater interaction between therapist and patient) could significantly decrease IBS symptoms.

Persistent improvement. In one randomized controlled trial,⁶ 102 patients with IBS received either standard medical treatment or 10 hours of dynamically oriented individual psychotherapy in combination with standard medical treatment. After 3 months, patients who received psychotherapy showed significantly greater improvement in somatic symptoms and emotional well-being, compared with those who received medical treatment only.

Interestingly, this difference persisted 1 year after the study ended. GI symptoms and the emotional well-being of patients who received combination therapy continued to improve, whereas the physical and emotional status of those who received only standard medical treatment deteriorated.

In a second study,⁷ 101 patients with severe IBS symptoms continued to receive medical treatment but were randomly divided into two groups:

• Study subjects received 8 hours of dynamically oriented psychotherapy.
• Control patients met with a psychiatrist who engaged in “supportive listening” but delivered no psychotherapy. This strategy was adopted to control for the effect of the psychiatrist’s presence.

Assessments included patients’ self-reports of symptoms, ratings of GI symptoms by the treating gastroenterologists, and measures of depression, anxiety, and health care utilization. Patients who received psychotherapy reported significant improvements in bowel symptoms (e.g., diarrhea, constipation, bloating, and abdominal pain). Likewise, the gastroenterologist who rated patients’ GI symptoms felt that those who received psychotherapy improved significantly across the entire spectrum of GI symptoms. The improvements were maintained at 1-year follow-up.

By comparison, the control patients reported worsening symptoms, as did subjects who dropped out. Patients who received psychotherapy also made significantly fewer outpatient visits to gastroenterologists, compared with controls (p<0.001).

Cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT) is emerging as a major psychotherapeutic tool for treating mood disorders, anxiety disorders, and somatic syndromes associated with psychosocial distress. CBT also is showing promise for patients with moderate to severe IBS and those with IBS and concomitant anxiety or mood disorders. Studies consistently show that CBT is superior to standard medical management or the use of support groups or other behavioral treatments alone.

Reduced symptoms. In an early trial of CBT, 17 patients with IBS experienced significantly less abdominal pain and diarrhea after participating in a program of progressive relaxation, education about bowel functioning, use of thermal biofeedback, and stress coping techniques based on CBT. Overall, 64% of the patients improved.⁸

The same investigators then assigned 90 patients to 12 sessions of CBT, given over 8 weeks with or without meditation and biofeedback. Patients with axis I psychiatric diagnoses tended to respond poorly to CBT. The authors concluded that a careful pretreatment psychological workup is important to identify patients with IBS who would benefit most from CBT.⁹

As a follow-up, these investigators randomly assigned 20 patients to intensive individualized CBT (10 sessions over 8 weeks) or 8 weeks of daily GI symptom monitoring. Patients who received CBT had significantly fewer GI symptoms than did the symptom-monitoring group (p = 0.005). With CBT, 80% improved clinically, compared with only 10% in the control group. Improvements in the CBT group persisted at 3 months’ follow-up. Improved GI symptoms also were correlated with increased positive thoughts and reduced negative automatic thoughts (i.e., negative self-image).¹⁰

Box 2

Group therapy. In a study of group rather than individualized CBT, 45 patients with severe IBS symptoms were randomly assigned to either a group CBT module (n = 25) or a waiting list control group (n = 20). Patients received eight 2-hour group CBT sessions over 3 months, then were followed an average of 2.25 years. Their abdominal pain, number of successful coping behavioral strategies, and avoidance of negative situations improved significantly—compared with the waiting list controls—and persisted during follow-up. The authors concluded that group CBT is effective for alleviating IBS symptoms and improving patients’ coping strategies.¹¹

CBT vs. support groups. In a study comparing the effectiveness of CBT and an IBS self-help support group, 34 patients were randomly assigned to:

• individualized CBT (study group)
• a self-help support group
• or a symptom-monitoring waiting list (control group).

Each group was followed for 8 weeks. GI symptoms were reduced significantly in patients who received individualized CBT, compared with the support group or controls. Anxiety and depression in the CBT group also remained significantly improved 3 months later, compared with both other groups.¹²

Group psychotherapy

Group psychotherapy for IBS treatment can be more cost-effective than individual therapy, but its success depends on whether patients accept a group format. Data on the use of group psychotherapeutic approaches are largely favorable.

As described previously, one study demonstrated that group CBT reduced abdominal pain and diarrhea and improved symptoms overall.¹¹ In another study, 20 patients with refractory IBS underwent 6 weeks of group behavioral and didactic psychotherapy. GI symptoms, dysphoria, and psychological distress improved significantly in all patients, and their interpersonal sensitivity and hostility were reduced. These improvements persisted 6 months later.¹²

A recent review suggests that cognitive-behavioral group psychotherapy may be highly effective in patients with IBS. These authors concluded that CBT can improve patients’ mood and other emotional symptoms, reduce their pain, and improve well-being and coping ability.¹⁴

Hypnotherapy

Researchers in Manchester, UK, have shown excellent results with hypnotherapy for patients with severe refractory IBS. Although their data seem to have established the ability of hypnotherapy to improve the GI and non-GI symptoms of IBS, corroborating evidence is needed from other centers. In this regard, some preliminary evidence is emerging.

Manchester group. In the first trial by the Manchester group, 30 patients received seven half-hour sessions of hypnotherapy (study group) or supportive psychotherapy and placebo (control group). Patients who received hypnotherapy also were given a tape for home autohypnosis after the third session.

Patients who received hypnotherapy improved dramatically in all GI symptoms— including abdominal pain, bloating, and bowel habits—and in their sense of well-being. This effect persisted 3 months later. The control patients’ abdominal pain, bloating, and well-being improved somewhat, but their bowel habits did not improve.¹⁵

The same investigators then studied 30 patients with IBS to assess the effect of hypnotherapy on rectal physiology. Fifteen patients received hypnotherapy, and 15 received relaxation exercises. Rectal sensitivity was measured using anorectal manometry at the start and finish of the intervention.

For patients with diarrhea-predominant IBS, rectal sensitivity was significantly reduced during hypnosis and after the full course of hypnotherapy, compared with controls (p<0.05). In patients with constipation-predominant IBS, a trend towards normalized rectal sensitivity did not reach statistical significance. The investigators concluded that symptomatic improvement of IBS after hypnotherapy may be related to changes in visceral sensitivity of the colon.¹⁶

These investigators later studied changes in distal colonic motility in 18 patients undergoing hypnotherapy for IBS. As the patients’ hypnotically induced anger or excitement increased, colonic motility decreased significantly (p<0.01) The investigators concluded that hypnosis may be a useful tool to investigate the effects of emotion on physiologic function.¹⁷

Using more contemporary outcome measures and diagnostic criteria, these investigators later showed that hypnotherapy significantly improved:

• IBS symptoms (abdominal pain and bloating, bowel habit, nausea, flatulence, urinary symptoms, lethargy, backache, and dyspareunia)
• quality of life (psychological and physical well-being, mood, locus of control, and work attitude).

Patients treated with hypnosis also took less time away from work (p = 0.02) and visited their physicians less often (p = 0.056), compared with controls.¹⁸

Other hypnosis studies. In the United States, another group randomly assigned 12 patients to gut-directed hypnotherapy or symptom monitoring. Subjects were matched by concurrent psychiatric diagnosis, susceptibility to hypnosis, and demographic features.

In findings similar to those of the Manchester group, primary IBS symptoms (abdominal pain, constipation, and flatulence) of patients who received hypnotherapy improved more than those of controls (p = 0.016). Anxiety, as measured by the Spielberger State-Trait Anxiety Inventory (STAXI), also decreased significantly. Treatment-induced gains were well-maintained 2 months later. No significant correlation was found between initial sensitivity to hypnosis and subsequent response to hypnotherapy. A positive relationship was seen between the presence of psychiatric diagnoses and overall levels of improvement.

This study suggests that hypnotherapy can be useful for treating IBS and can be easily adapted to different clinical settings and treatment populations.¹⁹ A similar study using gut-directed hypnotherapy found significant improvement in 27 IBS patients treated with short-term hypnosis, and symptom improvement persisted after treatment.²⁰

Biofeedback

The role of biofeedback in IBS treatment remains ill-defined. To be considered as a treatment option, biofeedback must meet or exceed the benefits being achieved with psychotherapy, hypnotherapy, and other behavioral approaches.

In gastroenterology, biofeedback has been used mainly to treat constipation and specifically for outlet constipation due to pelvic floor dysfunction. Anorectal probes to measure rectal pressure in the resting state and during defecation can reveal a pattern of pelvic floor dysfunction. Studies have demonstrated up to 67% improvement in constipation symptoms using biofeedback. Use of anorectal biofeedback in adults with IBS also appears promising, but more controlled trials are needed.²¹

Anorectal biofeedback has also been used effectively to treat fecal incontinence in children and adults, achieving success rates of 70% or better. In IBS, however, the benefit of biofeedback is less clear. Studies of multicomponent treatment—combining biofeedback with CBT techniques—suggest improvement rates in the 50 to 60% range. However, these findings need to be compared with other treatments for IBS.

Combination treatment

Medical treatment of IBS is progressing. Antidepressant therapy, particularly using tricyclics, has shown moderate benefit.²² Newer medications such as alosetron and tegaserod, which modulate serotonin metabolism in the gut, have been developed. Alosetron and tegaserod have shown significantly greater efficacy compared with placebo for treatment of women with the diarrhea-predominant and constipation-predominant types of IBS, respectively.

Alosetron was voluntarily withdrawn from clinical use in 2000 because of reports of serious GI events associated with its use, including ischemic colitis in a small number of patients (about 3 women in 1,000). Because of the drug’s efficacy in IBS, however, the FDA recently approved its rerelease with a restricted indication—it is to be used only in women with severe diarrhea-predominant IBS who have not responded to conventional IBS treatment. The drug’s manufacturer also is implementing a risk management plan designed to reduce the potential for serious GI side effects.

Table

PSYCHOTHERAPY AS TREATMENT FOR IRRITABLE BOWEL SYNDROME

Tegaserod, a serotonin-4 receptor (5HT4) agonist, was approved by the FDA in July. It is indicated for short-term treatment of women with IBS whose primary bowel symptom is constipation.

Combination therapy—medical management plus psychotherapy—may represent the future of IBS treatment (Table). This approach was examined recently in a randomized study of 24 IBS patients who received standard medical treatment alone or in combination with behavioral therapy. The behavioral component included patient education, helping patients shape a plausible model for their illness, progressive muscle relaxation, cognitive coping strategies, problem-solving education, and assertiveness and social skills training. All patients were treated in 10 individual therapy sessions of approximately 1 hour each by one of two psychotherapists across 10 weeks.

Compared with medical treatment alone, patients treated with combination therapy showed significantly improved GI symptoms (p < 0.001) and psychological symptoms (p = 0.01) in terms of both patient report and objective psychological measures. Outcomes are enhanced for patients with severe IBS, the investigators concluded, when behavioral therapy is added to thoughtful medical management.²³

Related resource

• International Foundation for Functional Gastrointestinal Disorders. www.iffgd.org

Drug brand names

• Alosetron • Lotronex
• Tegaserod • Zelnorm

Disclosure

The author reports that he serves as a consultant to Novartis Pharmaceuticals Corp. He reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

A growing body of evidence suggests that psychiatrists have much to offer patients with severe irritable bowel syndrome (IBS). Behavioral and psychotherapeutic approaches are showing promise in relieving both GI and mood disturbances.

Treating patients with IBS with medications designed to influence only gut function can be frustrating. Those with refractory symptoms may be extremely sensitive to drug side effects, and they often report that medical management worsens or does not improve their symptoms. They experiment with alternative medicines and wander from physician to physician in a disappointing search for a “cure.”

Let’s look at evidence on the efficacy of individual and group behavioral therapies, hypnotherapy, biofeedback, and combination medical and behavioral treatment.

Psychotherapeutic approaches

IBS is a common gastrointestinal disorder that is characterized by abdominal discomfort and changes in bowel habits (Boxes 1 and 2). Patients with severe IBS symptoms often bring significant psychological impairment and psychosocial trauma to clinical encounters.^1,2 They respond poorly to standard medical management, and evidence supporting the efficacy of medical treatments for IBS remains weak.^3,4

Box 1

In 1983, the first controlled trial of psychodynamic psychotherapy for IBS showed dramatic reductions in symptoms.⁵ A subsequent series of high-quality articles in the early 1990s also showed that interpersonal psychotherapy (with greater interaction between therapist and patient) could significantly decrease IBS symptoms.

Persistent improvement. In one randomized controlled trial,⁶ 102 patients with IBS received either standard medical treatment or 10 hours of dynamically oriented individual psychotherapy in combination with standard medical treatment. After 3 months, patients who received psychotherapy showed significantly greater improvement in somatic symptoms and emotional well-being, compared with those who received medical treatment only.

Interestingly, this difference persisted 1 year after the study ended. GI symptoms and the emotional well-being of patients who received combination therapy continued to improve, whereas the physical and emotional status of those who received only standard medical treatment deteriorated.

In a second study,⁷ 101 patients with severe IBS symptoms continued to receive medical treatment but were randomly divided into two groups:

• Study subjects received 8 hours of dynamically oriented psychotherapy.
• Control patients met with a psychiatrist who engaged in “supportive listening” but delivered no psychotherapy. This strategy was adopted to control for the effect of the psychiatrist’s presence.

Assessments included patients’ self-reports of symptoms, ratings of GI symptoms by the treating gastroenterologists, and measures of depression, anxiety, and health care utilization. Patients who received psychotherapy reported significant improvements in bowel symptoms (e.g., diarrhea, constipation, bloating, and abdominal pain). Likewise, the gastroenterologist who rated patients’ GI symptoms felt that those who received psychotherapy improved significantly across the entire spectrum of GI symptoms. The improvements were maintained at 1-year follow-up.

By comparison, the control patients reported worsening symptoms, as did subjects who dropped out. Patients who received psychotherapy also made significantly fewer outpatient visits to gastroenterologists, compared with controls (p<0.001).

Cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT) is emerging as a major psychotherapeutic tool for treating mood disorders, anxiety disorders, and somatic syndromes associated with psychosocial distress. CBT also is showing promise for patients with moderate to severe IBS and those with IBS and concomitant anxiety or mood disorders. Studies consistently show that CBT is superior to standard medical management or the use of support groups or other behavioral treatments alone.

Reduced symptoms. In an early trial of CBT, 17 patients with IBS experienced significantly less abdominal pain and diarrhea after participating in a program of progressive relaxation, education about bowel functioning, use of thermal biofeedback, and stress coping techniques based on CBT. Overall, 64% of the patients improved.⁸

The same investigators then assigned 90 patients to 12 sessions of CBT, given over 8 weeks with or without meditation and biofeedback. Patients with axis I psychiatric diagnoses tended to respond poorly to CBT. The authors concluded that a careful pretreatment psychological workup is important to identify patients with IBS who would benefit most from CBT.⁹

As a follow-up, these investigators randomly assigned 20 patients to intensive individualized CBT (10 sessions over 8 weeks) or 8 weeks of daily GI symptom monitoring. Patients who received CBT had significantly fewer GI symptoms than did the symptom-monitoring group (p = 0.005). With CBT, 80% improved clinically, compared with only 10% in the control group. Improvements in the CBT group persisted at 3 months’ follow-up. Improved GI symptoms also were correlated with increased positive thoughts and reduced negative automatic thoughts (i.e., negative self-image).¹⁰

Box 2

Group therapy. In a study of group rather than individualized CBT, 45 patients with severe IBS symptoms were randomly assigned to either a group CBT module (n = 25) or a waiting list control group (n = 20). Patients received eight 2-hour group CBT sessions over 3 months, then were followed an average of 2.25 years. Their abdominal pain, number of successful coping behavioral strategies, and avoidance of negative situations improved significantly—compared with the waiting list controls—and persisted during follow-up. The authors concluded that group CBT is effective for alleviating IBS symptoms and improving patients’ coping strategies.¹¹

CBT vs. support groups. In a study comparing the effectiveness of CBT and an IBS self-help support group, 34 patients were randomly assigned to:

• individualized CBT (study group)
• a self-help support group
• or a symptom-monitoring waiting list (control group).

Each group was followed for 8 weeks. GI symptoms were reduced significantly in patients who received individualized CBT, compared with the support group or controls. Anxiety and depression in the CBT group also remained significantly improved 3 months later, compared with both other groups.¹²

Group psychotherapy

Group psychotherapy for IBS treatment can be more cost-effective than individual therapy, but its success depends on whether patients accept a group format. Data on the use of group psychotherapeutic approaches are largely favorable.

As described previously, one study demonstrated that group CBT reduced abdominal pain and diarrhea and improved symptoms overall.¹¹ In another study, 20 patients with refractory IBS underwent 6 weeks of group behavioral and didactic psychotherapy. GI symptoms, dysphoria, and psychological distress improved significantly in all patients, and their interpersonal sensitivity and hostility were reduced. These improvements persisted 6 months later.¹²

A recent review suggests that cognitive-behavioral group psychotherapy may be highly effective in patients with IBS. These authors concluded that CBT can improve patients’ mood and other emotional symptoms, reduce their pain, and improve well-being and coping ability.¹⁴

Hypnotherapy

Researchers in Manchester, UK, have shown excellent results with hypnotherapy for patients with severe refractory IBS. Although their data seem to have established the ability of hypnotherapy to improve the GI and non-GI symptoms of IBS, corroborating evidence is needed from other centers. In this regard, some preliminary evidence is emerging.

Manchester group. In the first trial by the Manchester group, 30 patients received seven half-hour sessions of hypnotherapy (study group) or supportive psychotherapy and placebo (control group). Patients who received hypnotherapy also were given a tape for home autohypnosis after the third session.

Patients who received hypnotherapy improved dramatically in all GI symptoms— including abdominal pain, bloating, and bowel habits—and in their sense of well-being. This effect persisted 3 months later. The control patients’ abdominal pain, bloating, and well-being improved somewhat, but their bowel habits did not improve.¹⁵

The same investigators then studied 30 patients with IBS to assess the effect of hypnotherapy on rectal physiology. Fifteen patients received hypnotherapy, and 15 received relaxation exercises. Rectal sensitivity was measured using anorectal manometry at the start and finish of the intervention.

For patients with diarrhea-predominant IBS, rectal sensitivity was significantly reduced during hypnosis and after the full course of hypnotherapy, compared with controls (p<0.05). In patients with constipation-predominant IBS, a trend towards normalized rectal sensitivity did not reach statistical significance. The investigators concluded that symptomatic improvement of IBS after hypnotherapy may be related to changes in visceral sensitivity of the colon.¹⁶

These investigators later studied changes in distal colonic motility in 18 patients undergoing hypnotherapy for IBS. As the patients’ hypnotically induced anger or excitement increased, colonic motility decreased significantly (p<0.01) The investigators concluded that hypnosis may be a useful tool to investigate the effects of emotion on physiologic function.¹⁷

Using more contemporary outcome measures and diagnostic criteria, these investigators later showed that hypnotherapy significantly improved:

• IBS symptoms (abdominal pain and bloating, bowel habit, nausea, flatulence, urinary symptoms, lethargy, backache, and dyspareunia)
• quality of life (psychological and physical well-being, mood, locus of control, and work attitude).

Patients treated with hypnosis also took less time away from work (p = 0.02) and visited their physicians less often (p = 0.056), compared with controls.¹⁸

Other hypnosis studies. In the United States, another group randomly assigned 12 patients to gut-directed hypnotherapy or symptom monitoring. Subjects were matched by concurrent psychiatric diagnosis, susceptibility to hypnosis, and demographic features.

In findings similar to those of the Manchester group, primary IBS symptoms (abdominal pain, constipation, and flatulence) of patients who received hypnotherapy improved more than those of controls (p = 0.016). Anxiety, as measured by the Spielberger State-Trait Anxiety Inventory (STAXI), also decreased significantly. Treatment-induced gains were well-maintained 2 months later. No significant correlation was found between initial sensitivity to hypnosis and subsequent response to hypnotherapy. A positive relationship was seen between the presence of psychiatric diagnoses and overall levels of improvement.

This study suggests that hypnotherapy can be useful for treating IBS and can be easily adapted to different clinical settings and treatment populations.¹⁹ A similar study using gut-directed hypnotherapy found significant improvement in 27 IBS patients treated with short-term hypnosis, and symptom improvement persisted after treatment.²⁰

Biofeedback

The role of biofeedback in IBS treatment remains ill-defined. To be considered as a treatment option, biofeedback must meet or exceed the benefits being achieved with psychotherapy, hypnotherapy, and other behavioral approaches.

In gastroenterology, biofeedback has been used mainly to treat constipation and specifically for outlet constipation due to pelvic floor dysfunction. Anorectal probes to measure rectal pressure in the resting state and during defecation can reveal a pattern of pelvic floor dysfunction. Studies have demonstrated up to 67% improvement in constipation symptoms using biofeedback. Use of anorectal biofeedback in adults with IBS also appears promising, but more controlled trials are needed.²¹

Anorectal biofeedback has also been used effectively to treat fecal incontinence in children and adults, achieving success rates of 70% or better. In IBS, however, the benefit of biofeedback is less clear. Studies of multicomponent treatment—combining biofeedback with CBT techniques—suggest improvement rates in the 50 to 60% range. However, these findings need to be compared with other treatments for IBS.

Combination treatment

Medical treatment of IBS is progressing. Antidepressant therapy, particularly using tricyclics, has shown moderate benefit.²² Newer medications such as alosetron and tegaserod, which modulate serotonin metabolism in the gut, have been developed. Alosetron and tegaserod have shown significantly greater efficacy compared with placebo for treatment of women with the diarrhea-predominant and constipation-predominant types of IBS, respectively.

Alosetron was voluntarily withdrawn from clinical use in 2000 because of reports of serious GI events associated with its use, including ischemic colitis in a small number of patients (about 3 women in 1,000). Because of the drug’s efficacy in IBS, however, the FDA recently approved its rerelease with a restricted indication—it is to be used only in women with severe diarrhea-predominant IBS who have not responded to conventional IBS treatment. The drug’s manufacturer also is implementing a risk management plan designed to reduce the potential for serious GI side effects.

Table

PSYCHOTHERAPY AS TREATMENT FOR IRRITABLE BOWEL SYNDROME

Tegaserod, a serotonin-4 receptor (5HT4) agonist, was approved by the FDA in July. It is indicated for short-term treatment of women with IBS whose primary bowel symptom is constipation.

Combination therapy—medical management plus psychotherapy—may represent the future of IBS treatment (Table). This approach was examined recently in a randomized study of 24 IBS patients who received standard medical treatment alone or in combination with behavioral therapy. The behavioral component included patient education, helping patients shape a plausible model for their illness, progressive muscle relaxation, cognitive coping strategies, problem-solving education, and assertiveness and social skills training. All patients were treated in 10 individual therapy sessions of approximately 1 hour each by one of two psychotherapists across 10 weeks.

Compared with medical treatment alone, patients treated with combination therapy showed significantly improved GI symptoms (p < 0.001) and psychological symptoms (p = 0.01) in terms of both patient report and objective psychological measures. Outcomes are enhanced for patients with severe IBS, the investigators concluded, when behavioral therapy is added to thoughtful medical management.²³

Related resource

• International Foundation for Functional Gastrointestinal Disorders. www.iffgd.org

Drug brand names

• Alosetron • Lotronex
• Tegaserod • Zelnorm

Disclosure

The author reports that he serves as a consultant to Novartis Pharmaceuticals Corp. He reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

A growing body of evidence suggests that psychiatrists have much to offer patients with severe irritable bowel syndrome (IBS). Behavioral and psychotherapeutic approaches are showing promise in relieving both GI and mood disturbances.

Treating patients with IBS with medications designed to influence only gut function can be frustrating. Those with refractory symptoms may be extremely sensitive to drug side effects, and they often report that medical management worsens or does not improve their symptoms. They experiment with alternative medicines and wander from physician to physician in a disappointing search for a “cure.”

Let’s look at evidence on the efficacy of individual and group behavioral therapies, hypnotherapy, biofeedback, and combination medical and behavioral treatment.

Psychotherapeutic approaches

IBS is a common gastrointestinal disorder that is characterized by abdominal discomfort and changes in bowel habits (Boxes 1 and 2). Patients with severe IBS symptoms often bring significant psychological impairment and psychosocial trauma to clinical encounters.^1,2 They respond poorly to standard medical management, and evidence supporting the efficacy of medical treatments for IBS remains weak.^3,4

Box 1

In 1983, the first controlled trial of psychodynamic psychotherapy for IBS showed dramatic reductions in symptoms.⁵ A subsequent series of high-quality articles in the early 1990s also showed that interpersonal psychotherapy (with greater interaction between therapist and patient) could significantly decrease IBS symptoms.

Persistent improvement. In one randomized controlled trial,⁶ 102 patients with IBS received either standard medical treatment or 10 hours of dynamically oriented individual psychotherapy in combination with standard medical treatment. After 3 months, patients who received psychotherapy showed significantly greater improvement in somatic symptoms and emotional well-being, compared with those who received medical treatment only.

Interestingly, this difference persisted 1 year after the study ended. GI symptoms and the emotional well-being of patients who received combination therapy continued to improve, whereas the physical and emotional status of those who received only standard medical treatment deteriorated.

In a second study,⁷ 101 patients with severe IBS symptoms continued to receive medical treatment but were randomly divided into two groups:

• Study subjects received 8 hours of dynamically oriented psychotherapy.
• Control patients met with a psychiatrist who engaged in “supportive listening” but delivered no psychotherapy. This strategy was adopted to control for the effect of the psychiatrist’s presence.

Assessments included patients’ self-reports of symptoms, ratings of GI symptoms by the treating gastroenterologists, and measures of depression, anxiety, and health care utilization. Patients who received psychotherapy reported significant improvements in bowel symptoms (e.g., diarrhea, constipation, bloating, and abdominal pain). Likewise, the gastroenterologist who rated patients’ GI symptoms felt that those who received psychotherapy improved significantly across the entire spectrum of GI symptoms. The improvements were maintained at 1-year follow-up.

By comparison, the control patients reported worsening symptoms, as did subjects who dropped out. Patients who received psychotherapy also made significantly fewer outpatient visits to gastroenterologists, compared with controls (p<0.001).

Cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT) is emerging as a major psychotherapeutic tool for treating mood disorders, anxiety disorders, and somatic syndromes associated with psychosocial distress. CBT also is showing promise for patients with moderate to severe IBS and those with IBS and concomitant anxiety or mood disorders. Studies consistently show that CBT is superior to standard medical management or the use of support groups or other behavioral treatments alone.

Reduced symptoms. In an early trial of CBT, 17 patients with IBS experienced significantly less abdominal pain and diarrhea after participating in a program of progressive relaxation, education about bowel functioning, use of thermal biofeedback, and stress coping techniques based on CBT. Overall, 64% of the patients improved.⁸

The same investigators then assigned 90 patients to 12 sessions of CBT, given over 8 weeks with or without meditation and biofeedback. Patients with axis I psychiatric diagnoses tended to respond poorly to CBT. The authors concluded that a careful pretreatment psychological workup is important to identify patients with IBS who would benefit most from CBT.⁹

As a follow-up, these investigators randomly assigned 20 patients to intensive individualized CBT (10 sessions over 8 weeks) or 8 weeks of daily GI symptom monitoring. Patients who received CBT had significantly fewer GI symptoms than did the symptom-monitoring group (p = 0.005). With CBT, 80% improved clinically, compared with only 10% in the control group. Improvements in the CBT group persisted at 3 months’ follow-up. Improved GI symptoms also were correlated with increased positive thoughts and reduced negative automatic thoughts (i.e., negative self-image).¹⁰

Box 2

Group therapy. In a study of group rather than individualized CBT, 45 patients with severe IBS symptoms were randomly assigned to either a group CBT module (n = 25) or a waiting list control group (n = 20). Patients received eight 2-hour group CBT sessions over 3 months, then were followed an average of 2.25 years. Their abdominal pain, number of successful coping behavioral strategies, and avoidance of negative situations improved significantly—compared with the waiting list controls—and persisted during follow-up. The authors concluded that group CBT is effective for alleviating IBS symptoms and improving patients’ coping strategies.¹¹

CBT vs. support groups. In a study comparing the effectiveness of CBT and an IBS self-help support group, 34 patients were randomly assigned to:

• individualized CBT (study group)
• a self-help support group
• or a symptom-monitoring waiting list (control group).

Each group was followed for 8 weeks. GI symptoms were reduced significantly in patients who received individualized CBT, compared with the support group or controls. Anxiety and depression in the CBT group also remained significantly improved 3 months later, compared with both other groups.¹²

Group psychotherapy

Group psychotherapy for IBS treatment can be more cost-effective than individual therapy, but its success depends on whether patients accept a group format. Data on the use of group psychotherapeutic approaches are largely favorable.

As described previously, one study demonstrated that group CBT reduced abdominal pain and diarrhea and improved symptoms overall.¹¹ In another study, 20 patients with refractory IBS underwent 6 weeks of group behavioral and didactic psychotherapy. GI symptoms, dysphoria, and psychological distress improved significantly in all patients, and their interpersonal sensitivity and hostility were reduced. These improvements persisted 6 months later.¹²

A recent review suggests that cognitive-behavioral group psychotherapy may be highly effective in patients with IBS. These authors concluded that CBT can improve patients’ mood and other emotional symptoms, reduce their pain, and improve well-being and coping ability.¹⁴

Hypnotherapy

Researchers in Manchester, UK, have shown excellent results with hypnotherapy for patients with severe refractory IBS. Although their data seem to have established the ability of hypnotherapy to improve the GI and non-GI symptoms of IBS, corroborating evidence is needed from other centers. In this regard, some preliminary evidence is emerging.

Manchester group. In the first trial by the Manchester group, 30 patients received seven half-hour sessions of hypnotherapy (study group) or supportive psychotherapy and placebo (control group). Patients who received hypnotherapy also were given a tape for home autohypnosis after the third session.

Patients who received hypnotherapy improved dramatically in all GI symptoms— including abdominal pain, bloating, and bowel habits—and in their sense of well-being. This effect persisted 3 months later. The control patients’ abdominal pain, bloating, and well-being improved somewhat, but their bowel habits did not improve.¹⁵

The same investigators then studied 30 patients with IBS to assess the effect of hypnotherapy on rectal physiology. Fifteen patients received hypnotherapy, and 15 received relaxation exercises. Rectal sensitivity was measured using anorectal manometry at the start and finish of the intervention.

For patients with diarrhea-predominant IBS, rectal sensitivity was significantly reduced during hypnosis and after the full course of hypnotherapy, compared with controls (p<0.05). In patients with constipation-predominant IBS, a trend towards normalized rectal sensitivity did not reach statistical significance. The investigators concluded that symptomatic improvement of IBS after hypnotherapy may be related to changes in visceral sensitivity of the colon.¹⁶

These investigators later studied changes in distal colonic motility in 18 patients undergoing hypnotherapy for IBS. As the patients’ hypnotically induced anger or excitement increased, colonic motility decreased significantly (p<0.01) The investigators concluded that hypnosis may be a useful tool to investigate the effects of emotion on physiologic function.¹⁷

Using more contemporary outcome measures and diagnostic criteria, these investigators later showed that hypnotherapy significantly improved:

• IBS symptoms (abdominal pain and bloating, bowel habit, nausea, flatulence, urinary symptoms, lethargy, backache, and dyspareunia)
• quality of life (psychological and physical well-being, mood, locus of control, and work attitude).

Patients treated with hypnosis also took less time away from work (p = 0.02) and visited their physicians less often (p = 0.056), compared with controls.¹⁸

Other hypnosis studies. In the United States, another group randomly assigned 12 patients to gut-directed hypnotherapy or symptom monitoring. Subjects were matched by concurrent psychiatric diagnosis, susceptibility to hypnosis, and demographic features.

In findings similar to those of the Manchester group, primary IBS symptoms (abdominal pain, constipation, and flatulence) of patients who received hypnotherapy improved more than those of controls (p = 0.016). Anxiety, as measured by the Spielberger State-Trait Anxiety Inventory (STAXI), also decreased significantly. Treatment-induced gains were well-maintained 2 months later. No significant correlation was found between initial sensitivity to hypnosis and subsequent response to hypnotherapy. A positive relationship was seen between the presence of psychiatric diagnoses and overall levels of improvement.

This study suggests that hypnotherapy can be useful for treating IBS and can be easily adapted to different clinical settings and treatment populations.¹⁹ A similar study using gut-directed hypnotherapy found significant improvement in 27 IBS patients treated with short-term hypnosis, and symptom improvement persisted after treatment.²⁰

Biofeedback

The role of biofeedback in IBS treatment remains ill-defined. To be considered as a treatment option, biofeedback must meet or exceed the benefits being achieved with psychotherapy, hypnotherapy, and other behavioral approaches.

In gastroenterology, biofeedback has been used mainly to treat constipation and specifically for outlet constipation due to pelvic floor dysfunction. Anorectal probes to measure rectal pressure in the resting state and during defecation can reveal a pattern of pelvic floor dysfunction. Studies have demonstrated up to 67% improvement in constipation symptoms using biofeedback. Use of anorectal biofeedback in adults with IBS also appears promising, but more controlled trials are needed.²¹

Anorectal biofeedback has also been used effectively to treat fecal incontinence in children and adults, achieving success rates of 70% or better. In IBS, however, the benefit of biofeedback is less clear. Studies of multicomponent treatment—combining biofeedback with CBT techniques—suggest improvement rates in the 50 to 60% range. However, these findings need to be compared with other treatments for IBS.

Combination treatment

Medical treatment of IBS is progressing. Antidepressant therapy, particularly using tricyclics, has shown moderate benefit.²² Newer medications such as alosetron and tegaserod, which modulate serotonin metabolism in the gut, have been developed. Alosetron and tegaserod have shown significantly greater efficacy compared with placebo for treatment of women with the diarrhea-predominant and constipation-predominant types of IBS, respectively.

Alosetron was voluntarily withdrawn from clinical use in 2000 because of reports of serious GI events associated with its use, including ischemic colitis in a small number of patients (about 3 women in 1,000). Because of the drug’s efficacy in IBS, however, the FDA recently approved its rerelease with a restricted indication—it is to be used only in women with severe diarrhea-predominant IBS who have not responded to conventional IBS treatment. The drug’s manufacturer also is implementing a risk management plan designed to reduce the potential for serious GI side effects.

Table

PSYCHOTHERAPY AS TREATMENT FOR IRRITABLE BOWEL SYNDROME

Tegaserod, a serotonin-4 receptor (5HT4) agonist, was approved by the FDA in July. It is indicated for short-term treatment of women with IBS whose primary bowel symptom is constipation.

Combination therapy—medical management plus psychotherapy—may represent the future of IBS treatment (Table). This approach was examined recently in a randomized study of 24 IBS patients who received standard medical treatment alone or in combination with behavioral therapy. The behavioral component included patient education, helping patients shape a plausible model for their illness, progressive muscle relaxation, cognitive coping strategies, problem-solving education, and assertiveness and social skills training. All patients were treated in 10 individual therapy sessions of approximately 1 hour each by one of two psychotherapists across 10 weeks.

Compared with medical treatment alone, patients treated with combination therapy showed significantly improved GI symptoms (p < 0.001) and psychological symptoms (p = 0.01) in terms of both patient report and objective psychological measures. Outcomes are enhanced for patients with severe IBS, the investigators concluded, when behavioral therapy is added to thoughtful medical management.²³

Related resource

• International Foundation for Functional Gastrointestinal Disorders. www.iffgd.org

Drug brand names

• Alosetron • Lotronex
• Tegaserod • Zelnorm

Disclosure

The author reports that he serves as a consultant to Novartis Pharmaceuticals Corp. He reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Roughly 50 million adult Americans have hypertension.¹ Chances are some of them are—or soon will be—under your care.

Hypertension is common among patients with psychiatric disorders, particularly in those with chronic mental conditions.² Medication-associated weight gain and other reactions to psychotropics, drug-drug interactions, lack of exercise, adverse dietary habits, and pre-existing medical conditions all predispose psychiatric patients to hypertension.

Yet hypertension often goes undetected in psychiatric patients. Hypertension many times is asymptomatic—about 50% of all people with the disorder don’t even know they have it.³ Some symptoms of uncontrolled hypertension—fatigue, headache, palpitations, and dizziness—are also associated with many psychiatric disorders. As a result, psychiatrists may attempt to manage the symptoms but miss the hypertension.

Psychiatrists need to be alert for hypertension, either as a possible contributing factor to a mental disorder or as a potential side effect of a psychiatric disorder or treatment. The following diagnostic and treatment strategies will help you detect and manage this common condition.

Causes of hypertension in mental illness

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure defines elevated blood pressure as 140 mm Hg systolic and/or 90 mm Hg diastolic. The diagnosis of hypertension should be based on the average of two or more blood pressure readings at each of two or more visits after initial screening.

All patients with elevated blood pressure have an underlying physiologic abnormality that is causing their hypertension. The disorder falls within the following two categories:

• essential hypertension, emanating from an unknown cause
• secondary hypertension, resulting from an underlying, discoverable, often treatable cause.

Researchers have speculated that certain psychiatric disorders might cause, or be risk factors for, hypertension. Anxiety or panic disorders have been associated with acute (and perhaps chronic) blood pressure elevations.² Some research suggests that patients with alexithymia are at risk for developing hypertension.⁴

Other studies suggest that hypertensive patients with certain psychological disorders (e.g., depression) or social factors (e.g., substance abuse) are less likely than nonaffected patients to self-report the presence of hypertension and less likely to receive medical attention for it.⁵

Psychiatric drugs also may affect blood pressure by one of two mechanisms:

• Pharmacodynamic—direct effects at the site of action (e.g., receptors) via physiologic mechanisms (Table 1). For example, amphetamines act directly on the sympathetic nervous system to elevate blood pressure.
• Pharmacokinetic—indirect effects on blood pressure via drug/drug interactions that alter the absorption, distribution, metabolism, or clearance of antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, and salt intake restrictions can raise lithium levels. The calcium-channel blockers verapamil and diltiazem can unpredictably increase or decrease lithium levels, but the combination generally is safe. Verapamil also raises tricyclic antidepressant levels. Monoamine oxidase inhibitors (MAOIs) used in tandem with the antihypertensive reserpine can cause hypomania. Beta-blocker levels are increased when used in concert with selective serotonin reuptake inhibitors. Use of carbamazepine with calcium-channel blockers can elevate carbamazapine levels and diminish the effectiveness of the calcium-channel blocker.

Table 1

POSSIBLE PHARMACODYNAMIC EFFECTS OFPSYCHIATRIC MEDICATIONS ON BLOOD PRESSURE

Symptoms, complications of high blood pressure

Symptoms that may be associated with high blood pressure include headaches, dizziness, lightheadedness, fatigue, palpitations, and chest discomfort. Patients may also experience symptoms secondary to end-organ damage (e.g., shortness of breath from congestive heart failure).

Most people, however, experience no symptoms when their blood pressure is elevated. This is one reason most people with hypertension do not adequately control their blood pressure.

Aside from the long-term end-organ damage caused by persistently elevated blood pressure, hypertension also has been found to cause psychiatric disorders, though not directly. For example, post-MI depression is well-recognized. Hypertension may also cause multi-infarct dementia with resultant depression, paranoia, or other psychotic features.

The psychological burden of having chronic and usually incurable (though controllable) hypertension may worsen depression or anxiety disorders. Patients with a chronic psychiatric illness generally have a higher incidence of chronic medical problems.

Likewise, patients with chronic medical disorders have a higher incidence of psychiatric complaints.⁶

Patient evaluation

When evaluating the patient with elevated blood pressure, it is important to:

• detect and confirm hypertension
• detect target-organ disease (e.g., renal damage or congestive heart failure)
• identify other cardiovascular risk factors (e.g., diabetes mellitus, hyperlipidemia, obesity)
• identify secondary causes of hypertension, such as endocrine abnormalities (e.g., hyperaldosteronism, thyroid disorders), kidney disease, obstructive sleep apnea, and response to medications.

Table 2

ANTIHYPERTENSIVE MEDICATIONS AND SIDE EFFECTS

A thorough history and physical examination should be performed to assess these four areas. Routine laboratory testing for the hypertensive patient should include a urinalysis, a complete blood count, an assessment of blood chemistries (potassium, sodium, creatinine, fasting glucose, fasting lipid profile), and a 12-lead electrocardiogram.

Treating hypertension

Many medications are used to treat hypertension. Most classes of antihypertensive agents have been shown to be about equally effective in lowering blood pressure.

All other factors being equal, the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) recommends initial treatment with a diuretic or beta-blocker. These classes of drugs have been shown to significantly reduce overall hypertension-related mortality.

Most patients with hypertension—particularly the elderly, patients with diabetes mellitus, and those with renal disease—will need two or more agents to control their blood pressure. Avoid prescribing agents that may worsen an existing condition (e.g., beta-blockers may worsen bronchospasm in patients with asthma). Use agents that may help improve comorbid conditions (e.g., beta-blockers have been shown to reduce mortality in patients with previous MI).

Box

Potential side effects, some of which mimic or are commonly found in psychiatric disorders, must be considered when choosing an antihypertensive agent. Table 2 lists nine classes of antihypertensives and some associated side effects. Also consider the agent’s cost, convenience of administration, direct-to-consumer advertising, and the patient’s age or race. For example, beta-blockers tend to be less effective in black or elderly patients than in other demographic groups.

Nonpharmacologic hypertension management emphasizes weight reduction, moderation of alcohol intake, regular aerobic exercise, dietary restriction of sodium, and smoking cessation. Most studies of these behavioral interventions have demonstrated a short-term benefit in decreasing blood pressure, but long-term adherence to them is disappointing. Relaxation therapies and biofeedback have been advocated for hypertension, but proof of their efficacy is lacking.⁷

As more is learned about genetic and other causes of hypertension, more-effective treatments for hypertension could become available (Box).

Treating high-risk groups

Special considerations apply to two patient groups with a high prevalence of hypertension—those age 65 and older and those with diabetes.

Older patients. Treatment benefits are more pronounced in patients age 65 or older because of their greater absolute risk for cardiovascular events. Also, systolic blood pressures increase with aging as the arterial tree becomes progressively less distensible.

Older patients often will require more than one drug to control their blood pressure. The initial dosages should be low and gradually titrated upward as needed. To minimize side effects, use smaller doses of multiple agents that are well tolerated instead of high-dose monotherapy.

A diuretic is often recommended as initial treatment for older patients, though a long-acting dihydropyridine calcium-channel blocker is a reasonable alternative. An ACE inhibitor is recommended for older patients with diabetes, systolic congestive heart failure, or previous MI. An alpha blocker should not be used as initial therapy for hypertension in the elderly because of relative lack of efficacy in preventing cardiovascular events.

Patients with diabetes. Aggressive blood pressure control is especially important in the patient with diabetes, which is the leading cause of end-stage renal disease. Most patients with diabetes also have hypertension—which accelerates their renal disease as well as cardiovascular disease. Blood pressure control goals significantly below 140/90 mm Hg are recommended (120 to 135 mm Hg systolic, 80 to 85 mm Hg diastolic) if diabetes is present.

ACE inhibitors or angiotensin receptor blockers are preferred for initial treatment of hypertension in diabetes, especially if proteinuria is present. Some authorities feel the level of blood pressure control in diabetes is more important than the agent(s) chosen to achieve that control. Most patients with hypertension and diabetes are not controlled on a single antihypertensive drug, and a diuretic is often added.

Psychological aspects of hypertension management

The diagnosis of hypertension and a resulting perception of loss of health or longevity may trigger a grief reaction in some patients.

Several psychological aspects to hypertension treatment make it difficult to achieve long-term control. Patients may become discouraged as dosages are increased and more medications are added. Asymptomatic patients may have no incentive to control their blood pressure. Many report, “I don’t feel any better” when their blood pressure comes down.

Because the goal of hypertension therapy is control rather than cure, the patient must commit to long-term treatment. Lifestyle changes such as dietary sodium restriction, smoking cessation, and weight loss may be difficult to achieve, especially for patients already dealing with a psychiatric disorder.

Also, the cost of treatment—the price of medications and initial and follow-up laboratory studies, plus the expense of follow-up office visits (possibly requiring time off work)—may be high.

Psychiatrists can help by offering moral support and encouraging patients to manage their medical problems, risk factors, and overall health. Psychiatrists can also educate patients on the importance of blood pressure control in preventing cardiovascular morbidity and mortality.

Brief cognitive-behaviorial therapy can identify the individual’s state of change (precontemplation, contemplation, preparation, action, or maintenance). Process techniques (such as consciousness-raising, commitment, or self-reevaluation) appropriate to the stage of change may then be employed.

For example, a patient in the precontemplation stage may resist returning to his or her primary care doctor to begin treatment for high blood pressure, employing such reasoning as, “I can’t afford those expensive office visits, and the medications would cost too much anyway.”

The psychiatrist might then apply consciousness-raising to motivate the patient: “How serious do you think it is to have high blood pressure that isn’t controlled? Are you aware that many people with high blood pressure are treated by means other than medications, or that many blood pressure medications are inexpensive?”

Providing relaxation techniques or a 12-week course of buproprion also can enhance the efficacy of smoking cessation efforts.

Related resources

• Drugs for hypertension. The Medical Letter 2001;43(1099):17-22.
• Some drugs that cause psychiatric symptoms. The Medical Letter 1998;40(1020):21-4.
• Hypertension—Journal of the American Heart Association. http://hyper.ahajournals.org/
• National Heart, Lung, and Blood institute’s Cardiovascular information site. http://www.nhlbi.nih.gov/health/public/heart/index.htm#hbp

Drug brand names

• Bupropion • Wellbutrin
• Guanadrel • Hylorel
• Lisinopril • Prinivil, Zestril
• Losartan • Hyzaar
• Ramipril • Altace
• Reserpine • Diutensen-R
• Valsartan • Diovan
• Venlafaxine • Effexor
• (Numerous other drugs mentioned in this article are available generically)

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.