Current Psychiatry

You need a printout now, but you’re at a meeting, in a hotel, or at the hospital. What do you do?

Printers have become more compact and versatile, and numerous remote printing solutions exist with more on the way. This article reviews the options to help you print anytime, anywhere.

Portable printers

HP and Canon make inkjet printers that weigh approximately 4 lbs but are portable and compatible with most systems. These printers can be connected to your notebook via a USB or parallel port cable, or wirelessly with Bluetooth or infrared. Built with high-resolution inkjet nozzles, portable printers provide sharp printouts and can even print photos (although this can quickly drain their small ink cartridges).

By contrast, the Psyber Psychiatry, December 2003). WiFi makes printing from your hotel room relatively easy.

Psyber Psychiatry, December 2004).

First, make sure the program you used to create the document is compatible with the business center’s computers. Because most business centers use the free Adobe document reader, your best bet is to convert the file to Adobe PDF, which maintains its format. Use PDFCreator or PrimoPDF to convert the file; both are free and work on Windows computers. Mac users can download the Mac-Net Freeware PDF file creator.

The future

Imagine a pocket-size device that prints onto a blank page as you move it across.

PrintDreams is developing such a device using its random-movement printing technology (RMPT). PrintDreams reports that the scanning device can print any document with 100% accuracy, though it seems best suited to text. The device is still a year or two from reaching the mainstream; PrintDreams is licensing its technology to other printer manufacturers.

Also, don’t be surprised if cellular phones one day have the capability to print e-mail attachments using Bluetooth or general packet radio service (GPRS), a very fast data transfer protocol on a GSM network.

Disclosure

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

You need a printout now, but you’re at a meeting, in a hotel, or at the hospital. What do you do?

Printers have become more compact and versatile, and numerous remote printing solutions exist with more on the way. This article reviews the options to help you print anytime, anywhere.

Portable printers

HP and Canon make inkjet printers that weigh approximately 4 lbs but are portable and compatible with most systems. These printers can be connected to your notebook via a USB or parallel port cable, or wirelessly with Bluetooth or infrared. Built with high-resolution inkjet nozzles, portable printers provide sharp printouts and can even print photos (although this can quickly drain their small ink cartridges).

By contrast, the Psyber Psychiatry, December 2003). WiFi makes printing from your hotel room relatively easy.

Psyber Psychiatry, December 2004).

First, make sure the program you used to create the document is compatible with the business center’s computers. Because most business centers use the free Adobe document reader, your best bet is to convert the file to Adobe PDF, which maintains its format. Use PDFCreator or PrimoPDF to convert the file; both are free and work on Windows computers. Mac users can download the Mac-Net Freeware PDF file creator.

The future

Imagine a pocket-size device that prints onto a blank page as you move it across.

PrintDreams is developing such a device using its random-movement printing technology (RMPT). PrintDreams reports that the scanning device can print any document with 100% accuracy, though it seems best suited to text. The device is still a year or two from reaching the mainstream; PrintDreams is licensing its technology to other printer manufacturers.

Also, don’t be surprised if cellular phones one day have the capability to print e-mail attachments using Bluetooth or general packet radio service (GPRS), a very fast data transfer protocol on a GSM network.

Disclosure

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

You need a printout now, but you’re at a meeting, in a hotel, or at the hospital. What do you do?

Printers have become more compact and versatile, and numerous remote printing solutions exist with more on the way. This article reviews the options to help you print anytime, anywhere.

Portable printers

HP and Canon make inkjet printers that weigh approximately 4 lbs but are portable and compatible with most systems. These printers can be connected to your notebook via a USB or parallel port cable, or wirelessly with Bluetooth or infrared. Built with high-resolution inkjet nozzles, portable printers provide sharp printouts and can even print photos (although this can quickly drain their small ink cartridges).

By contrast, the Psyber Psychiatry, December 2003). WiFi makes printing from your hotel room relatively easy.

Psyber Psychiatry, December 2004).

First, make sure the program you used to create the document is compatible with the business center’s computers. Because most business centers use the free Adobe document reader, your best bet is to convert the file to Adobe PDF, which maintains its format. Use PDFCreator or PrimoPDF to convert the file; both are free and work on Windows computers. Mac users can download the Mac-Net Freeware PDF file creator.

The future

Imagine a pocket-size device that prints onto a blank page as you move it across.

PrintDreams is developing such a device using its random-movement printing technology (RMPT). PrintDreams reports that the scanning device can print any document with 100% accuracy, though it seems best suited to text. The device is still a year or two from reaching the mainstream; PrintDreams is licensing its technology to other printer manufacturers.

Also, don’t be surprised if cellular phones one day have the capability to print e-mail attachments using Bluetooth or general packet radio service (GPRS), a very fast data transfer protocol on a GSM network.

Disclosure

Dr. Luo reports no financial relationship with any company whose products are mentioned in this article. The opinions expressed by Dr. Luo in this column are his own and do not necessarily reflect those of Current Psychiatry.

Wernicke’s encephalopathy is often missed in clinical practice.¹ Left untreated, the alcohol-induced amnestic disorder can progress to Korsakoff’s syndrome, a form of permanent short-term memory loss from which four out of five patients do not recover.²

Why Wernicke’s is missed

Lesions in the medial dorsal nucleus of the thalamus, hippocampus, and mammillary bodies cause signs and symptoms of Wernicke’s. Associated psychotic symptoms—including delusions, confusion, agitation, blunted to apathetic affect, and confabulation—may incorrectly suggest delirium tremens, alcohol-induced psychosis, delusional disorder, or dementia.

Key features of Wernicke’s are remembered with the acronym CANON:

Clouded consciousness with impaired orientation and inability to sustain attention to environmental stimuli.

Ataxia, primarily affecting gait

Nystagmus, mainly horizontal

Ophthalmoplegia accompanied by lateral orbital palsy and gaze palsy, which is usually bilateral. Anisocoria and a sluggish reaction to light also are present.

Neuropathy, mainly peripheral.

Early recognition and treatment is essential as early-stage Wernicke’s responds rapidly to parenteral thiamine, 100 mg/d for 5 to 7 days. Oral thiamine, 100 mg two to three times daily, is then given for 1 to 2 weeks.

Wernicke’s encephalopathy is often missed in clinical practice.¹ Left untreated, the alcohol-induced amnestic disorder can progress to Korsakoff’s syndrome, a form of permanent short-term memory loss from which four out of five patients do not recover.²

Why Wernicke’s is missed

Lesions in the medial dorsal nucleus of the thalamus, hippocampus, and mammillary bodies cause signs and symptoms of Wernicke’s. Associated psychotic symptoms—including delusions, confusion, agitation, blunted to apathetic affect, and confabulation—may incorrectly suggest delirium tremens, alcohol-induced psychosis, delusional disorder, or dementia.

Key features of Wernicke’s are remembered with the acronym CANON:

Clouded consciousness with impaired orientation and inability to sustain attention to environmental stimuli.

Ataxia, primarily affecting gait

Nystagmus, mainly horizontal

Ophthalmoplegia accompanied by lateral orbital palsy and gaze palsy, which is usually bilateral. Anisocoria and a sluggish reaction to light also are present.

Neuropathy, mainly peripheral.

Early recognition and treatment is essential as early-stage Wernicke’s responds rapidly to parenteral thiamine, 100 mg/d for 5 to 7 days. Oral thiamine, 100 mg two to three times daily, is then given for 1 to 2 weeks.

Wernicke’s encephalopathy is often missed in clinical practice.¹ Left untreated, the alcohol-induced amnestic disorder can progress to Korsakoff’s syndrome, a form of permanent short-term memory loss from which four out of five patients do not recover.²

Why Wernicke’s is missed

Lesions in the medial dorsal nucleus of the thalamus, hippocampus, and mammillary bodies cause signs and symptoms of Wernicke’s. Associated psychotic symptoms—including delusions, confusion, agitation, blunted to apathetic affect, and confabulation—may incorrectly suggest delirium tremens, alcohol-induced psychosis, delusional disorder, or dementia.

Key features of Wernicke’s are remembered with the acronym CANON:

Clouded consciousness with impaired orientation and inability to sustain attention to environmental stimuli.

Ataxia, primarily affecting gait

Nystagmus, mainly horizontal

Ophthalmoplegia accompanied by lateral orbital palsy and gaze palsy, which is usually bilateral. Anisocoria and a sluggish reaction to light also are present.

Neuropathy, mainly peripheral.

Early recognition and treatment is essential as early-stage Wernicke’s responds rapidly to parenteral thiamine, 100 mg/d for 5 to 7 days. Oral thiamine, 100 mg two to three times daily, is then given for 1 to 2 weeks.

Compulsive hoarders collect useless things—most often newspapers, magazines, old clothing, bags, books, mail, notes, and lists, according to this month’s article by Jamie Feusner, MD, and Sanjaya Saxena, MD, of the UCLA Neuropsychiatric Institute.

Initially I thought I didn’t save all of those items since I don’t save old clothes and bags. Then I remembered the closetful of clothes that don’t fit me. I lost weight last year, but—playing the odds—these clothes may fit me again someday and I hesitate to discard them. I also remembered all those APA-logo scientific meeting tote bags I haven’t thrown away.

These may be small obsessive-compulsive signs compared with my hoarding of medical journals. To my amazement, I have more than 2,000 journals in my office. I haven’t looked at more than a handful and probably didn’t read most when I received them. Why do I keep them? Could I have “problems with information processing, obsessional anxiety, and avoiding decisions” that Drs. Feusner and Saxena suggest as targets for psychotherapeutic intervention?

Maybe it’s rational to keep these journals in case I want to look something up, but then why save Current Psychiatry? Its full text is available online.

My best explanation is that old journals are an interior design element. William Morris, the 19th century designer and proponent of the arts and crafts movement, counseled: “Have nothing in your homes that you do not know to be useful or believe to be beautiful.”

Old journals may be visual clutter, but they are beautiful to me because they remind me that psychiatric treatments are backed by decades of study and research. When I wonder if I know anything at all (you have those moments, don’t you?), glancing at my shelves of journals reassures me and gives me courage to continue the perpetually astonishing unknown that is clinical practice.

Compulsive hoarders collect useless things—most often newspapers, magazines, old clothing, bags, books, mail, notes, and lists, according to this month’s article by Jamie Feusner, MD, and Sanjaya Saxena, MD, of the UCLA Neuropsychiatric Institute.

Initially I thought I didn’t save all of those items since I don’t save old clothes and bags. Then I remembered the closetful of clothes that don’t fit me. I lost weight last year, but—playing the odds—these clothes may fit me again someday and I hesitate to discard them. I also remembered all those APA-logo scientific meeting tote bags I haven’t thrown away.

These may be small obsessive-compulsive signs compared with my hoarding of medical journals. To my amazement, I have more than 2,000 journals in my office. I haven’t looked at more than a handful and probably didn’t read most when I received them. Why do I keep them? Could I have “problems with information processing, obsessional anxiety, and avoiding decisions” that Drs. Feusner and Saxena suggest as targets for psychotherapeutic intervention?

Maybe it’s rational to keep these journals in case I want to look something up, but then why save Current Psychiatry? Its full text is available online.

My best explanation is that old journals are an interior design element. William Morris, the 19th century designer and proponent of the arts and crafts movement, counseled: “Have nothing in your homes that you do not know to be useful or believe to be beautiful.”

Old journals may be visual clutter, but they are beautiful to me because they remind me that psychiatric treatments are backed by decades of study and research. When I wonder if I know anything at all (you have those moments, don’t you?), glancing at my shelves of journals reassures me and gives me courage to continue the perpetually astonishing unknown that is clinical practice.

Compulsive hoarders collect useless things—most often newspapers, magazines, old clothing, bags, books, mail, notes, and lists, according to this month’s article by Jamie Feusner, MD, and Sanjaya Saxena, MD, of the UCLA Neuropsychiatric Institute.

Initially I thought I didn’t save all of those items since I don’t save old clothes and bags. Then I remembered the closetful of clothes that don’t fit me. I lost weight last year, but—playing the odds—these clothes may fit me again someday and I hesitate to discard them. I also remembered all those APA-logo scientific meeting tote bags I haven’t thrown away.

These may be small obsessive-compulsive signs compared with my hoarding of medical journals. To my amazement, I have more than 2,000 journals in my office. I haven’t looked at more than a handful and probably didn’t read most when I received them. Why do I keep them? Could I have “problems with information processing, obsessional anxiety, and avoiding decisions” that Drs. Feusner and Saxena suggest as targets for psychotherapeutic intervention?

Maybe it’s rational to keep these journals in case I want to look something up, but then why save Current Psychiatry? Its full text is available online.

My best explanation is that old journals are an interior design element. William Morris, the 19th century designer and proponent of the arts and crafts movement, counseled: “Have nothing in your homes that you do not know to be useful or believe to be beautiful.”

Old journals may be visual clutter, but they are beautiful to me because they remind me that psychiatric treatments are backed by decades of study and research. When I wonder if I know anything at all (you have those moments, don’t you?), glancing at my shelves of journals reassures me and gives me courage to continue the perpetually astonishing unknown that is clinical practice.

Because 40% of individuals with a psychotic prodrome develop schizophrenia, detecting and preventing this transition could improve many patients’ lives. Unfortunately:

• psychotic prodrome lacks clear-cut symptoms and is difficult to identify
  
• little evidence exists to help clinicians select psychotropics and decide how long to use them
  
• treating all prodromal patients would expose those who never develop psychosis to the risk of psychotropics’ side effects.
  

How, then, can psychiatrists help patients who present with possible prodromal symptoms? Based on research and our experience, this article describes the psychotic prodrome and offers a pragmatic, evidence-based approach to diagnosis and treatment.

WHAT CAUSES PSYCHOTIC CONVERSION?

Reduced gray matter volumes in certain brain regions may be associated with conversion to psychosis (Box 1). Stress also may play a role; elevated stress-reactive cortisol levels are associated with positive symptom severity in the prodrome.¹ Other factors being investigated include obstetric complications at birth, maternal age >30, premorbid schizotypal personality disorder, and impaired olfaction.

Symptoms. Nearly 80% of patients with schizophrenia experience a psychotic prodrome that lasts a few months to several years.² Common features include:

• gradual worsening of perceptual disturbance
  
• referential thinking
  
• paranoia
  
• mild cognitive deficits
  
• mood lability
  
• impulsivity
  
• suicidality
  
• declining social function and academic performance.^3,4
  

A premorbid phase often precedes the prodrome, with symptoms such as impaired attention, soft neurologic signs, and subtle social deficits. These changes may be harbingers of the prodrome but are too nonspecific to be diagnostic. Other functional impairments—including anxiety, depression, drug abuse, and psychosocial factors such as school stress—may mimic schizophrenic prodrome.

Prognosis. Studies of patients’ first schizophrenia episodes suggest that prodrome duration may predict outcome. A longer prodrome is thought to indicate a poor prognosis,⁶ such as in patients who wait a year before seeking treatment.⁷ A review of 22 studies of first-episode psychosis found early psychosocial and pharmacologic interventions improved long-term prognosis, and medication discontinuation predicted more-severe and chronic disease.⁸

Box 1

Pioneering work by McGorry et al¹⁰ identified an “ultra high-risk group” with a psychotic conversion rate of 40% to 60%. These patients present with three symptom patterns:

• attenuated positive symptoms
  
• brief intermittent psychotic episodes
  
• genetic risk and recent deterioration syndrome (Table 1).
  

3 patient groups considered at ‘ultra high risk’ to develop schizophrenia

The Edinburgh High Risk Study of 162 individuals ages 16 to 25 showed more marked psychopathology in those with at least two close relatives with schizophrenia, compared with control groups. A direct correlation was seen between genetic liability and poor neurocognitive performance.¹¹

PRODROME RATING SCALES

Researchers are using outcome measures to diagnose prodromal symptoms and assess their severity. Operational, validated assessment tools include:

• Bonn Scale for the Assessment of Basic Symptoms (BSABS): captures subtle changes in thinking, feeling, and perception.
  
• Schizophrenia Prediction Instrument for Adults (SPI-A): defines prepsychotic deviations and rates symptoms that are subjectively experienced by the patient.
  
• Comprehensive Assessment of At Risk Mental State (CAARMS): defines ultra high-risk criteria and incorporates eight dimensions of psychopathology.
  
• Scale of Prodromal Symptoms (SOPS): rates psychosis severity. When embedded within the Structured Interview for Prodromal Syndromes (SIPS), the SOPS determines the presence or absence of psychosis and predicts progression to psychopathology.
  
• Criteria for Prodromal Symptoms (COPS): defines ultra high-risk categories.
  
• Presence of Psychosis Scale (POPS): rates severity, intensity, and duration of positive prodromal symptoms.¹²
  

PROPHYLACTIC ANTIPSYCHOTICS?

Atypical antipsychotics may be the standard of care for patients with a first psychotic episode, but this intervention is based on few double-blind controlled trials. Not surprisingly, only a handful of studies have examined antipsychotic therapy for the prodrome’s less clear-cut symptoms.

Risperidone. An 8- to 12-week open-label study in adolescents with first- and second-degree relatives with schizophrenia¹³ included four prodromal and six first-episode psychosis patients who met criteria for a cluster A personality disorder. Risperidone, 1.0 mg/d and 1.8 mg/d, respectively, improved thought disorder and attention symptoms, as measured with the Child Behavior Checklist. Verbal memory improved minimally, and no medication side effects were reported.

An open-label observational study¹⁴ identified four middle-aged subjects with a genetic risk of schizophrenia who reported negative symptoms and neurocognitive deficits. Risperidone, started at 0.25 mg/d and gradually increased to a maximum of 2 mg/d, improved negative symptoms, attention, and working memory. Mild side effects including tremors, sedation, dry mouth, and anxiety symptoms were reported.

An open-label, randomized, comparator trial¹⁵ examined psychotic transition rates in 59 subjects (mean age, 20) who met ultra high-risk criteria. They received:

• a needs-based intervention (NBI) comprising case management, psychotropics excluding antipsychotics, and supportive psychotherapy
  
• or a specific preventive intervention (SPI) that included risperidone, 1 to 2 mg/d, and a modified cognitive-behavioral therapy (CBT).
  

Should you intervene with patients in suspected psychotic prodrome?

At 12-months’ follow-up, another 3 SPI patients who had been partially adherent or non-adherent to antipsychotic therapy had converted to psychosis. For adherent SPI patients, protection against conversion appeared to persist for 6 months after risperidone therapy ended. All medication side effects were mild and transient.

Table 3

Psychotic prodrome: Unanswered clinical questions

In the first year, 11 of 29 placebo-group patients and 5 of 31 receiving olanzapine converted to psychosis. Among patients receiving no treatment in the second year, 2 of 8 former placebo patients and 3 of 9 former olanzapine patients converted to psychosis.

Discontinuation rates were 35% and 28%, respectively. Compared with the placebo group, patients taking olanzapine experienced greater weight gain, suggesting that risks associated with antipsychotic therapy may exceed unproven benefits in this population.

Discussion. Little information exists on using quetiapine, ziprasidone, or aripiprazole in prodromal patients. As cited above, preliminary studies with risperidone and olanzapine suggest that these agents may improve several domains of psychotic prodrome. The evidence does not support firm conclusions, however, given the trials’ small sample sizes and brief duration.

The prevalence of obesity and metabolic syndrome in patients with schizophrenia and the added metabolic risks associated with atypical antipsychotics make their use during the prodrome controversial. Weighing the potential advantages and disadvantages (Table 2), we consider antipsychotics to be the last resort after psychosocial interventions have failed to improve prodromal symptoms.

Low-dose atypical antipsychotics may be warranted for some patients, but their use requires stringent monitoring of:

• weight and waist circumference
  
• vital signs
  
• metabolic parameters such as fasting blood glucose and lipid profile
  
• abnormal involuntary movements
  
• prolactin elevations.
  

OTHER THERAPIES

Antidepressants. Researchers are also exploring the efficacy of using antidepressants and anxiolytics in the prodromal phase. The only published naturalistic study of adolescents found antidepressants alone or in combination with mood stabilizers or anxiolytics to be as effective as atypical antipsychotics in treating prodromal symptoms.¹⁷ A more substantial study is ongoing.

Psychotherapy. For patients with a suspected psychotic prodrome, nondrug strategies may help minimize functional and cognitive impairments, ease distress, and improve coping skills.

CBT has been shown to reduce psychotic progression over 12 months.¹⁸ Use CBT to help patients cope with the illness while focusing on:

• symptom monitoring
  
• premorbid and present functioning
  
• establishing a therapeutic alliance
  
• assessing the patient’s experience of psychosis and any thought distortions.
  

‘REAL WORLD’ EARLY INTERVENTION

Patients with prodromal symptoms are often referred to psychiatrists by family members, primary care physicians, or other mental health professionals. They tend to be young adults, and a few may present in their teens. Most are experiencing behavioral changes such as social isolation, feeling suspicious, perceptual disturbances, depression, and/or anxiety symptoms that seem abnormal but fall short of DSM-IV criteria for schizophrenia diagnosis.

Many clinical questions about schizophrenia’s prodromal phase remain unanswered (Table 3). Our primary aim is to adequately assess these patients and provide treatment and follow-up, taking into account:

• the individual’s presentation
  
• risks and benefits of available interventions.
  

Box 2

Consider atypical antipsychotics for patients with distressing psychotic symptoms, rapidly deteriorating function, increased agitation, and safety risks. Consider antidepressant and/or anxiolytic therapy for depression and anxiety, respectively.

Discuss at length with patients and families the risks and benefits of pharmacologic treatments. When clinically appropriate, cautiously discontinue or taper any medication with patients’ consent, while monitoring for side effects and symptoms.

Related resources

• Issue devoted to early prodrome research. SchizophrBull 2003;29(4):621-879.
  
• Diagnostic and therapeutic intervention during psychotic prodrome. CNS Spectrums 2004;9(8):578-606.
  
• PRIME (Prevention through Risk Identification, Management & Education) Research Clinic. Department of Psychiatry, Yale University. http://info.med.yale.edu/psych/prime/pintro.html.
  
• Youth Mental Health Update. Schizophrenia: New strategies for early detection and treatment. RAPP Clinic, Zucker Hillside Hospital, Glen Oaks, NY. http://schoolnet.lij.edu/eshare/files/rapp.html
  

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

Dr. Narasimhan receives research support from Eli Lilly and Co. and Janssen Pharmaceutica and is a speaker or consultant for Eli Lilly and Co., Pfizer Inc., and Abbott Laboratories.

Dr. Buckley receives research support from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Co., Eli Lilly and Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., Pfizer Inc., and Solvay Pharmaceuticals. He is a consultant to and/or speaker for Abbott Laboratories, Alamo Pharmaceuticals, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Co., Eli Lilly and Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., Pfizer Inc., and Pharmstar.

Because 40% of individuals with a psychotic prodrome develop schizophrenia, detecting and preventing this transition could improve many patients’ lives. Unfortunately:

• psychotic prodrome lacks clear-cut symptoms and is difficult to identify
  
• little evidence exists to help clinicians select psychotropics and decide how long to use them
  
• treating all prodromal patients would expose those who never develop psychosis to the risk of psychotropics’ side effects.
  

How, then, can psychiatrists help patients who present with possible prodromal symptoms? Based on research and our experience, this article describes the psychotic prodrome and offers a pragmatic, evidence-based approach to diagnosis and treatment.

WHAT CAUSES PSYCHOTIC CONVERSION?

Reduced gray matter volumes in certain brain regions may be associated with conversion to psychosis (Box 1). Stress also may play a role; elevated stress-reactive cortisol levels are associated with positive symptom severity in the prodrome.¹ Other factors being investigated include obstetric complications at birth, maternal age >30, premorbid schizotypal personality disorder, and impaired olfaction.

Symptoms. Nearly 80% of patients with schizophrenia experience a psychotic prodrome that lasts a few months to several years.² Common features include:

• gradual worsening of perceptual disturbance
  
• referential thinking
  
• paranoia
  
• mild cognitive deficits
  
• mood lability
  
• impulsivity
  
• suicidality
  
• declining social function and academic performance.^3,4
  

A premorbid phase often precedes the prodrome, with symptoms such as impaired attention, soft neurologic signs, and subtle social deficits. These changes may be harbingers of the prodrome but are too nonspecific to be diagnostic. Other functional impairments—including anxiety, depression, drug abuse, and psychosocial factors such as school stress—may mimic schizophrenic prodrome.

Prognosis. Studies of patients’ first schizophrenia episodes suggest that prodrome duration may predict outcome. A longer prodrome is thought to indicate a poor prognosis,⁶ such as in patients who wait a year before seeking treatment.⁷ A review of 22 studies of first-episode psychosis found early psychosocial and pharmacologic interventions improved long-term prognosis, and medication discontinuation predicted more-severe and chronic disease.⁸

Box 1

Pioneering work by McGorry et al¹⁰ identified an “ultra high-risk group” with a psychotic conversion rate of 40% to 60%. These patients present with three symptom patterns:

• attenuated positive symptoms
  
• brief intermittent psychotic episodes
  
• genetic risk and recent deterioration syndrome (Table 1).
  

3 patient groups considered at ‘ultra high risk’ to develop schizophrenia

The Edinburgh High Risk Study of 162 individuals ages 16 to 25 showed more marked psychopathology in those with at least two close relatives with schizophrenia, compared with control groups. A direct correlation was seen between genetic liability and poor neurocognitive performance.¹¹

PRODROME RATING SCALES

Researchers are using outcome measures to diagnose prodromal symptoms and assess their severity. Operational, validated assessment tools include:

• Bonn Scale for the Assessment of Basic Symptoms (BSABS): captures subtle changes in thinking, feeling, and perception.
  
• Schizophrenia Prediction Instrument for Adults (SPI-A): defines prepsychotic deviations and rates symptoms that are subjectively experienced by the patient.
  
• Comprehensive Assessment of At Risk Mental State (CAARMS): defines ultra high-risk criteria and incorporates eight dimensions of psychopathology.
  
• Scale of Prodromal Symptoms (SOPS): rates psychosis severity. When embedded within the Structured Interview for Prodromal Syndromes (SIPS), the SOPS determines the presence or absence of psychosis and predicts progression to psychopathology.
  
• Criteria for Prodromal Symptoms (COPS): defines ultra high-risk categories.
  
• Presence of Psychosis Scale (POPS): rates severity, intensity, and duration of positive prodromal symptoms.¹²
  

PROPHYLACTIC ANTIPSYCHOTICS?

Atypical antipsychotics may be the standard of care for patients with a first psychotic episode, but this intervention is based on few double-blind controlled trials. Not surprisingly, only a handful of studies have examined antipsychotic therapy for the prodrome’s less clear-cut symptoms.

Risperidone. An 8- to 12-week open-label study in adolescents with first- and second-degree relatives with schizophrenia¹³ included four prodromal and six first-episode psychosis patients who met criteria for a cluster A personality disorder. Risperidone, 1.0 mg/d and 1.8 mg/d, respectively, improved thought disorder and attention symptoms, as measured with the Child Behavior Checklist. Verbal memory improved minimally, and no medication side effects were reported.

An open-label observational study¹⁴ identified four middle-aged subjects with a genetic risk of schizophrenia who reported negative symptoms and neurocognitive deficits. Risperidone, started at 0.25 mg/d and gradually increased to a maximum of 2 mg/d, improved negative symptoms, attention, and working memory. Mild side effects including tremors, sedation, dry mouth, and anxiety symptoms were reported.

An open-label, randomized, comparator trial¹⁵ examined psychotic transition rates in 59 subjects (mean age, 20) who met ultra high-risk criteria. They received:

• a needs-based intervention (NBI) comprising case management, psychotropics excluding antipsychotics, and supportive psychotherapy
  
• or a specific preventive intervention (SPI) that included risperidone, 1 to 2 mg/d, and a modified cognitive-behavioral therapy (CBT).
  

Should you intervene with patients in suspected psychotic prodrome?

At 12-months’ follow-up, another 3 SPI patients who had been partially adherent or non-adherent to antipsychotic therapy had converted to psychosis. For adherent SPI patients, protection against conversion appeared to persist for 6 months after risperidone therapy ended. All medication side effects were mild and transient.

Table 3

Psychotic prodrome: Unanswered clinical questions

In the first year, 11 of 29 placebo-group patients and 5 of 31 receiving olanzapine converted to psychosis. Among patients receiving no treatment in the second year, 2 of 8 former placebo patients and 3 of 9 former olanzapine patients converted to psychosis.

Discontinuation rates were 35% and 28%, respectively. Compared with the placebo group, patients taking olanzapine experienced greater weight gain, suggesting that risks associated with antipsychotic therapy may exceed unproven benefits in this population.

Discussion. Little information exists on using quetiapine, ziprasidone, or aripiprazole in prodromal patients. As cited above, preliminary studies with risperidone and olanzapine suggest that these agents may improve several domains of psychotic prodrome. The evidence does not support firm conclusions, however, given the trials’ small sample sizes and brief duration.

The prevalence of obesity and metabolic syndrome in patients with schizophrenia and the added metabolic risks associated with atypical antipsychotics make their use during the prodrome controversial. Weighing the potential advantages and disadvantages (Table 2), we consider antipsychotics to be the last resort after psychosocial interventions have failed to improve prodromal symptoms.

Low-dose atypical antipsychotics may be warranted for some patients, but their use requires stringent monitoring of:

• weight and waist circumference
  
• vital signs
  
• metabolic parameters such as fasting blood glucose and lipid profile
  
• abnormal involuntary movements
  
• prolactin elevations.
  

OTHER THERAPIES

Antidepressants. Researchers are also exploring the efficacy of using antidepressants and anxiolytics in the prodromal phase. The only published naturalistic study of adolescents found antidepressants alone or in combination with mood stabilizers or anxiolytics to be as effective as atypical antipsychotics in treating prodromal symptoms.¹⁷ A more substantial study is ongoing.

Psychotherapy. For patients with a suspected psychotic prodrome, nondrug strategies may help minimize functional and cognitive impairments, ease distress, and improve coping skills.

CBT has been shown to reduce psychotic progression over 12 months.¹⁸ Use CBT to help patients cope with the illness while focusing on:

• symptom monitoring
  
• premorbid and present functioning
  
• establishing a therapeutic alliance
  
• assessing the patient’s experience of psychosis and any thought distortions.
  

‘REAL WORLD’ EARLY INTERVENTION

Patients with prodromal symptoms are often referred to psychiatrists by family members, primary care physicians, or other mental health professionals. They tend to be young adults, and a few may present in their teens. Most are experiencing behavioral changes such as social isolation, feeling suspicious, perceptual disturbances, depression, and/or anxiety symptoms that seem abnormal but fall short of DSM-IV criteria for schizophrenia diagnosis.

Many clinical questions about schizophrenia’s prodromal phase remain unanswered (Table 3). Our primary aim is to adequately assess these patients and provide treatment and follow-up, taking into account:

• the individual’s presentation
  
• risks and benefits of available interventions.
  

Box 2

Consider atypical antipsychotics for patients with distressing psychotic symptoms, rapidly deteriorating function, increased agitation, and safety risks. Consider antidepressant and/or anxiolytic therapy for depression and anxiety, respectively.

Discuss at length with patients and families the risks and benefits of pharmacologic treatments. When clinically appropriate, cautiously discontinue or taper any medication with patients’ consent, while monitoring for side effects and symptoms.

Related resources

• Issue devoted to early prodrome research. SchizophrBull 2003;29(4):621-879.
  
• Diagnostic and therapeutic intervention during psychotic prodrome. CNS Spectrums 2004;9(8):578-606.
  
• PRIME (Prevention through Risk Identification, Management & Education) Research Clinic. Department of Psychiatry, Yale University. http://info.med.yale.edu/psych/prime/pintro.html.
  
• Youth Mental Health Update. Schizophrenia: New strategies for early detection and treatment. RAPP Clinic, Zucker Hillside Hospital, Glen Oaks, NY. http://schoolnet.lij.edu/eshare/files/rapp.html
  

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

Dr. Narasimhan receives research support from Eli Lilly and Co. and Janssen Pharmaceutica and is a speaker or consultant for Eli Lilly and Co., Pfizer Inc., and Abbott Laboratories.

Dr. Buckley receives research support from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Co., Eli Lilly and Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., Pfizer Inc., and Solvay Pharmaceuticals. He is a consultant to and/or speaker for Abbott Laboratories, Alamo Pharmaceuticals, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Co., Eli Lilly and Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., Pfizer Inc., and Pharmstar.

Because 40% of individuals with a psychotic prodrome develop schizophrenia, detecting and preventing this transition could improve many patients’ lives. Unfortunately:

• psychotic prodrome lacks clear-cut symptoms and is difficult to identify
  
• little evidence exists to help clinicians select psychotropics and decide how long to use them
  
• treating all prodromal patients would expose those who never develop psychosis to the risk of psychotropics’ side effects.
  

How, then, can psychiatrists help patients who present with possible prodromal symptoms? Based on research and our experience, this article describes the psychotic prodrome and offers a pragmatic, evidence-based approach to diagnosis and treatment.

WHAT CAUSES PSYCHOTIC CONVERSION?

Reduced gray matter volumes in certain brain regions may be associated with conversion to psychosis (Box 1). Stress also may play a role; elevated stress-reactive cortisol levels are associated with positive symptom severity in the prodrome.¹ Other factors being investigated include obstetric complications at birth, maternal age >30, premorbid schizotypal personality disorder, and impaired olfaction.

Symptoms. Nearly 80% of patients with schizophrenia experience a psychotic prodrome that lasts a few months to several years.² Common features include:

• gradual worsening of perceptual disturbance
  
• referential thinking
  
• paranoia
  
• mild cognitive deficits
  
• mood lability
  
• impulsivity
  
• suicidality
  
• declining social function and academic performance.^3,4
  

A premorbid phase often precedes the prodrome, with symptoms such as impaired attention, soft neurologic signs, and subtle social deficits. These changes may be harbingers of the prodrome but are too nonspecific to be diagnostic. Other functional impairments—including anxiety, depression, drug abuse, and psychosocial factors such as school stress—may mimic schizophrenic prodrome.

Prognosis. Studies of patients’ first schizophrenia episodes suggest that prodrome duration may predict outcome. A longer prodrome is thought to indicate a poor prognosis,⁶ such as in patients who wait a year before seeking treatment.⁷ A review of 22 studies of first-episode psychosis found early psychosocial and pharmacologic interventions improved long-term prognosis, and medication discontinuation predicted more-severe and chronic disease.⁸

Box 1

Pioneering work by McGorry et al¹⁰ identified an “ultra high-risk group” with a psychotic conversion rate of 40% to 60%. These patients present with three symptom patterns:

• attenuated positive symptoms
  
• brief intermittent psychotic episodes
  
• genetic risk and recent deterioration syndrome (Table 1).
  

3 patient groups considered at ‘ultra high risk’ to develop schizophrenia

The Edinburgh High Risk Study of 162 individuals ages 16 to 25 showed more marked psychopathology in those with at least two close relatives with schizophrenia, compared with control groups. A direct correlation was seen between genetic liability and poor neurocognitive performance.¹¹

PRODROME RATING SCALES

Researchers are using outcome measures to diagnose prodromal symptoms and assess their severity. Operational, validated assessment tools include:

• Bonn Scale for the Assessment of Basic Symptoms (BSABS): captures subtle changes in thinking, feeling, and perception.
  
• Schizophrenia Prediction Instrument for Adults (SPI-A): defines prepsychotic deviations and rates symptoms that are subjectively experienced by the patient.
  
• Comprehensive Assessment of At Risk Mental State (CAARMS): defines ultra high-risk criteria and incorporates eight dimensions of psychopathology.
  
• Scale of Prodromal Symptoms (SOPS): rates psychosis severity. When embedded within the Structured Interview for Prodromal Syndromes (SIPS), the SOPS determines the presence or absence of psychosis and predicts progression to psychopathology.
  
• Criteria for Prodromal Symptoms (COPS): defines ultra high-risk categories.
  
• Presence of Psychosis Scale (POPS): rates severity, intensity, and duration of positive prodromal symptoms.¹²
  

PROPHYLACTIC ANTIPSYCHOTICS?

Atypical antipsychotics may be the standard of care for patients with a first psychotic episode, but this intervention is based on few double-blind controlled trials. Not surprisingly, only a handful of studies have examined antipsychotic therapy for the prodrome’s less clear-cut symptoms.

Risperidone. An 8- to 12-week open-label study in adolescents with first- and second-degree relatives with schizophrenia¹³ included four prodromal and six first-episode psychosis patients who met criteria for a cluster A personality disorder. Risperidone, 1.0 mg/d and 1.8 mg/d, respectively, improved thought disorder and attention symptoms, as measured with the Child Behavior Checklist. Verbal memory improved minimally, and no medication side effects were reported.

An open-label observational study¹⁴ identified four middle-aged subjects with a genetic risk of schizophrenia who reported negative symptoms and neurocognitive deficits. Risperidone, started at 0.25 mg/d and gradually increased to a maximum of 2 mg/d, improved negative symptoms, attention, and working memory. Mild side effects including tremors, sedation, dry mouth, and anxiety symptoms were reported.

An open-label, randomized, comparator trial¹⁵ examined psychotic transition rates in 59 subjects (mean age, 20) who met ultra high-risk criteria. They received:

• a needs-based intervention (NBI) comprising case management, psychotropics excluding antipsychotics, and supportive psychotherapy
  
• or a specific preventive intervention (SPI) that included risperidone, 1 to 2 mg/d, and a modified cognitive-behavioral therapy (CBT).
  

Should you intervene with patients in suspected psychotic prodrome?

At 12-months’ follow-up, another 3 SPI patients who had been partially adherent or non-adherent to antipsychotic therapy had converted to psychosis. For adherent SPI patients, protection against conversion appeared to persist for 6 months after risperidone therapy ended. All medication side effects were mild and transient.

Table 3

Psychotic prodrome: Unanswered clinical questions

In the first year, 11 of 29 placebo-group patients and 5 of 31 receiving olanzapine converted to psychosis. Among patients receiving no treatment in the second year, 2 of 8 former placebo patients and 3 of 9 former olanzapine patients converted to psychosis.

Discontinuation rates were 35% and 28%, respectively. Compared with the placebo group, patients taking olanzapine experienced greater weight gain, suggesting that risks associated with antipsychotic therapy may exceed unproven benefits in this population.

Discussion. Little information exists on using quetiapine, ziprasidone, or aripiprazole in prodromal patients. As cited above, preliminary studies with risperidone and olanzapine suggest that these agents may improve several domains of psychotic prodrome. The evidence does not support firm conclusions, however, given the trials’ small sample sizes and brief duration.

The prevalence of obesity and metabolic syndrome in patients with schizophrenia and the added metabolic risks associated with atypical antipsychotics make their use during the prodrome controversial. Weighing the potential advantages and disadvantages (Table 2), we consider antipsychotics to be the last resort after psychosocial interventions have failed to improve prodromal symptoms.

Low-dose atypical antipsychotics may be warranted for some patients, but their use requires stringent monitoring of:

• weight and waist circumference
  
• vital signs
  
• metabolic parameters such as fasting blood glucose and lipid profile
  
• abnormal involuntary movements
  
• prolactin elevations.
  

OTHER THERAPIES

Antidepressants. Researchers are also exploring the efficacy of using antidepressants and anxiolytics in the prodromal phase. The only published naturalistic study of adolescents found antidepressants alone or in combination with mood stabilizers or anxiolytics to be as effective as atypical antipsychotics in treating prodromal symptoms.¹⁷ A more substantial study is ongoing.

Psychotherapy. For patients with a suspected psychotic prodrome, nondrug strategies may help minimize functional and cognitive impairments, ease distress, and improve coping skills.

CBT has been shown to reduce psychotic progression over 12 months.¹⁸ Use CBT to help patients cope with the illness while focusing on:

• symptom monitoring
  
• premorbid and present functioning
  
• establishing a therapeutic alliance
  
• assessing the patient’s experience of psychosis and any thought distortions.
  

‘REAL WORLD’ EARLY INTERVENTION

Patients with prodromal symptoms are often referred to psychiatrists by family members, primary care physicians, or other mental health professionals. They tend to be young adults, and a few may present in their teens. Most are experiencing behavioral changes such as social isolation, feeling suspicious, perceptual disturbances, depression, and/or anxiety symptoms that seem abnormal but fall short of DSM-IV criteria for schizophrenia diagnosis.

Many clinical questions about schizophrenia’s prodromal phase remain unanswered (Table 3). Our primary aim is to adequately assess these patients and provide treatment and follow-up, taking into account:

• the individual’s presentation
  
• risks and benefits of available interventions.
  

Box 2

Consider atypical antipsychotics for patients with distressing psychotic symptoms, rapidly deteriorating function, increased agitation, and safety risks. Consider antidepressant and/or anxiolytic therapy for depression and anxiety, respectively.

Discuss at length with patients and families the risks and benefits of pharmacologic treatments. When clinically appropriate, cautiously discontinue or taper any medication with patients’ consent, while monitoring for side effects and symptoms.

Related resources

• Issue devoted to early prodrome research. SchizophrBull 2003;29(4):621-879.
  
• Diagnostic and therapeutic intervention during psychotic prodrome. CNS Spectrums 2004;9(8):578-606.
  
• PRIME (Prevention through Risk Identification, Management & Education) Research Clinic. Department of Psychiatry, Yale University. http://info.med.yale.edu/psych/prime/pintro.html.
  
• Youth Mental Health Update. Schizophrenia: New strategies for early detection and treatment. RAPP Clinic, Zucker Hillside Hospital, Glen Oaks, NY. http://schoolnet.lij.edu/eshare/files/rapp.html
  

• Aripiprazole • Abilify
  
• Olanzapine • Zyprexa
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Ziprasidone • Geodon
  

Dr. Narasimhan receives research support from Eli Lilly and Co. and Janssen Pharmaceutica and is a speaker or consultant for Eli Lilly and Co., Pfizer Inc., and Abbott Laboratories.

Dr. Buckley receives research support from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Co., Eli Lilly and Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., Pfizer Inc., and Solvay Pharmaceuticals. He is a consultant to and/or speaker for Abbott Laboratories, Alamo Pharmaceuticals, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Co., Eli Lilly and Co., Janssen Pharmaceutica, Novartis Pharmaceuticals Corp., Pfizer Inc., and Pharmstar.

HISTORY: LIFE AT HOME

For nearly 10 years Mr. P, age 50, has had episodes of shortness of breath, increasing perspiration, and faintness that occur 2 to 3 times a month, usually when he’s out of the house. Fearing his legs will give out in public, he never goes out except to shop with his wife.

Once a welder for an aircraft company, he has been unable to work for 6 years. He worries incessantly about his medical expenses, and smokes 1 pack of cigarettes per day to help control the anxiety.

Baseline laboratory tests reveal a low-density lipoprotein cholesterol level of 199 mg/dL, exceeding the optimal range by 100 mg/dL. Total cholesterol is 288 mg/dL and triglycerides are 244 mg/dL. Thyroid stimulating hormone, liver function, renal function, serum electrolytes, and serum glucose are normal. Mr. P meets DSM-IV-TR criteria for panic disorder with agoraphobia and is started on citalopram, 20 mg/d.

At follow-up 2 weeks later, Mr. P complains that the citalopram is causing ‘aches and pains’ in his back and legs, so we switch to controlled-release paroxetine, 12.5 mg/d, which we found in clinical practice to be more tolerable than immediate-release paroxetine. After 2 weeks, he says he cannot tolerate the paroxetine because of ‘body aches.’

At Mr. P’s insistence, we switch to alprazolam, 0.5 mg tid, although his desire to start taking alprazolam makes us suspect that he might be trying to obtain this benzodiazepine for illicit use.

Neuropsychological tests—including a diagnostic interview, Minnesota Multiphasic Personality Inventory, and Millon Clinical Multiaxial Inventory—are ordered after Mr. P’s third visit. He seems guarded when answering questions about himself during these interviews. He acknowledges having severe physical symptoms but appears unwilling to accept a psychiatric diagnosis for them.

The authors’ observations

Panic disorder is usually chronic and can cause considerable morbidity. DSM-IV-TR criteria for panic disorder include recurrent or unexpected panic attacks and persistent fear of additional attacks and their implications and consequences.¹ Panic disorder can also lead to social problems including unemployment, financial dependence, and substance abuse or dependence.²

Mr. P’s anxiety, shortness of breath, faintness, and profuse sweating during episodes match DSM-IV-TR criteria for panic attacks (Table 1). His ruminative and obsessive attitude toward his physical problems does not suggest somatoform disorder because he also thinks obsessively about other issues, such as his medical expenses.

We will watch for signs of prescription drug abuse, including premature requests for refills, use of multiple pharmacies, or complaints of lost prescription or medication.³

FURTHER HISTORY: FAINT MEMORY

Mr. P first sought medical help in 1996 after fainting at home while standing up. A few weeks later he experienced sudden dizziness, faintness, and perspiration while shopping with his wife. During that episode, he said, he barely made it out of the store before passing out in his truck. His wife described him as ‘pale and gray’ and rushed him to the emergency room. The ER physician suspected that Mr. P suffered a ‘convulsive episode’ and ordered testing. Results of awake and sleep EEG and head MRI were normal. Laboratory work revealed a positive antinuclear antibody (ANA) and rheumatoid factor (RF), suggesting pulmonary vasculitis.

Table 1

DSM-IV-TR criteria for panic attack

Two years and 17 doctors later, Mr. P’s physical symptoms persisted. He stopped working and began collecting disability insurance benefits. Frustrated over the lack of a definitive diagnosis, he then went 6 years without seeing a doctor.

TREATMENT: INTENSE ‘PANIC’

Mr. P has been coming to our clinic for 8 months. He takes 0.5 mg of alprazolam twice daily—less frequently than prescribed—and has never prematurely requested a refill, so prescription abuse is ruled out. He joins a fibromyalgia support group but laments that his symptoms differ from those of other group members. During follow-up visits, he continues to focus on his somatic symptoms.

During a routine visit, Mr. P tells us that he recently suffered an intense ‘panic’ episode—consisting of shortness of breath, dizziness, diaphoresis, chest pain, palpitations, and near syncope—less than 15 minutes after he started clearing brush in his backyard. We notice marked clubbing on Mr. P’s fingers, a physical sign seen in congenital heart disease, infective endocarditis, pulmonary fibrosis, and numerous other diseases.⁴

The clubbing prompts us to ask about his occupational history in detail, as work-related exposure to chemicals or fumes may result in pulmonary fibrosis. We then learn that for approximately 20 years before joining the aircraft company, Mr. P welded without wearing protective equipment—all that time inhaling noxious fumes while working.

We refer Mr. P to an internist, who finds clubbing of the fingers, decreased breath sounds, and increased pulmonic second heart sound (P2) on auscultation. The internist then orders:

• ECG, which reveals right axis deviation, incomplete right bundle branch block, and right ventricular hypertrophy (RVH)
  
• Pulmonary function tests, which show decreased diffusing capacity. Subsequent heart catheterization reveals RVH and concentric left ventricular hypertrophy.
  

The authors’ observations

Panic attacks often mimic symptoms of cardiac or pulmonary disease. By the same token, symptoms of an underlying cardiac or pulmonary disease can be mistaken for panic disorder, particularly in patients whose past episodes appear to meet DSM-IV-TR panic attack criteria (Table 2).⁵

Table 2

Panic attack symptoms that may suggest a cardiopulmonary disease

To avoid unnecessary referrals, psychiatrists need to quickly and accurately discern:

• when a medical problem is causing the patient’s symptoms
  
• how far to carry the medical evaluation, particularly for patients with palpitations, chest pain, or shortness of breath.
  

Also, a psychiatric patient whose mental disorder or comorbid axis II pathology compromises speech or cognitive function may have trouble communicating potentially serious medical problems to other clinicians. Mr. P’s guarded demeanor and obsession toward his physical problems may have kept him from accurately describing his symptoms in a clinical setting. Alternately, he might have misinterpreted his pulmonologist’s explanation of pulmonary fibrosis, thus believing the disorder was not serious.

Finally, patients with panic disorder are more aware of their heartbeats and physiologic responses than are persons without panic disorder,⁸ thus further complicating diagnosis.

UNCOVERING A MEDICAL CAUSE

Suspect an underlying heart or lung problem when panic symptoms affect breathing or resemble a heart attack.

Check for predisposing risk factors for cardiac disease. Ask the patient detailed questions about past and current medical problems, including:

• smoking
  
• hyperlipidemia
  
• diabetes
  
• heart problems
  
• pulmonary disease
  
• family history of any medical problems
  
• work-related exposure to any metal that may increase risk of cardiopulmonary disease.
  

Review medical treatment history. Mentally ill persons are more likely than those without a mental illness to receive inadequate general medical and preventative care.⁹ Patient, provider, and health care system issues—such as lack of insurance or the patient’s inability to recognize or describe symptoms—may impede medical care delivery to the mentally ill.⁹

Review overall history. A deeper look into Mr. P’s work and diagnostic history uncovered numerous possible causes of right heart failure, including:

• pulmonary fibrosis secondary to inhalational injury
  
• possible pulmonary vasculitis as indicated by his positive ANA and RF.
  

FOLLOW-UP: A PANIC-FREE FUTURE

Over the next 4 weeks, Mr. P has stopped taking alprazolam and begins to understand that his episodes were secondary to cardiopulmonary dysfunction. No longer afraid of developing a panic attack, he is going out more often.

Mr. P recently told us that he started a part-time job, decreased his smoking to a half pack/day, and has a plan to quit smoking completely. He adds that he is using his CPAP machine regularly and has remained free of panic-like episodes. He limits physical exertion to avoid cardiopulmonary symptoms.

Related resources

• Raj A, Sheehan DV. Medical evaluation of panic attacks. J Clin Psychiatry 1987;48:309-13.
  
• Jones DR, Macias C, Barreira PJ, et al. Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness. Psychiatr Serv 2004;55:1250-7.
  

• Alprazolam • Xanax
  
• Citalopram • Celexa
  
• Paroxetine • Paxil
  

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

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

HISTORY: LIFE AT HOME

For nearly 10 years Mr. P, age 50, has had episodes of shortness of breath, increasing perspiration, and faintness that occur 2 to 3 times a month, usually when he’s out of the house. Fearing his legs will give out in public, he never goes out except to shop with his wife.

Once a welder for an aircraft company, he has been unable to work for 6 years. He worries incessantly about his medical expenses, and smokes 1 pack of cigarettes per day to help control the anxiety.

Baseline laboratory tests reveal a low-density lipoprotein cholesterol level of 199 mg/dL, exceeding the optimal range by 100 mg/dL. Total cholesterol is 288 mg/dL and triglycerides are 244 mg/dL. Thyroid stimulating hormone, liver function, renal function, serum electrolytes, and serum glucose are normal. Mr. P meets DSM-IV-TR criteria for panic disorder with agoraphobia and is started on citalopram, 20 mg/d.

At follow-up 2 weeks later, Mr. P complains that the citalopram is causing ‘aches and pains’ in his back and legs, so we switch to controlled-release paroxetine, 12.5 mg/d, which we found in clinical practice to be more tolerable than immediate-release paroxetine. After 2 weeks, he says he cannot tolerate the paroxetine because of ‘body aches.’

At Mr. P’s insistence, we switch to alprazolam, 0.5 mg tid, although his desire to start taking alprazolam makes us suspect that he might be trying to obtain this benzodiazepine for illicit use.

Neuropsychological tests—including a diagnostic interview, Minnesota Multiphasic Personality Inventory, and Millon Clinical Multiaxial Inventory—are ordered after Mr. P’s third visit. He seems guarded when answering questions about himself during these interviews. He acknowledges having severe physical symptoms but appears unwilling to accept a psychiatric diagnosis for them.

The authors’ observations

Panic disorder is usually chronic and can cause considerable morbidity. DSM-IV-TR criteria for panic disorder include recurrent or unexpected panic attacks and persistent fear of additional attacks and their implications and consequences.¹ Panic disorder can also lead to social problems including unemployment, financial dependence, and substance abuse or dependence.²

Mr. P’s anxiety, shortness of breath, faintness, and profuse sweating during episodes match DSM-IV-TR criteria for panic attacks (Table 1). His ruminative and obsessive attitude toward his physical problems does not suggest somatoform disorder because he also thinks obsessively about other issues, such as his medical expenses.

We will watch for signs of prescription drug abuse, including premature requests for refills, use of multiple pharmacies, or complaints of lost prescription or medication.³

FURTHER HISTORY: FAINT MEMORY

Mr. P first sought medical help in 1996 after fainting at home while standing up. A few weeks later he experienced sudden dizziness, faintness, and perspiration while shopping with his wife. During that episode, he said, he barely made it out of the store before passing out in his truck. His wife described him as ‘pale and gray’ and rushed him to the emergency room. The ER physician suspected that Mr. P suffered a ‘convulsive episode’ and ordered testing. Results of awake and sleep EEG and head MRI were normal. Laboratory work revealed a positive antinuclear antibody (ANA) and rheumatoid factor (RF), suggesting pulmonary vasculitis.

Table 1

DSM-IV-TR criteria for panic attack

Two years and 17 doctors later, Mr. P’s physical symptoms persisted. He stopped working and began collecting disability insurance benefits. Frustrated over the lack of a definitive diagnosis, he then went 6 years without seeing a doctor.

TREATMENT: INTENSE ‘PANIC’

Mr. P has been coming to our clinic for 8 months. He takes 0.5 mg of alprazolam twice daily—less frequently than prescribed—and has never prematurely requested a refill, so prescription abuse is ruled out. He joins a fibromyalgia support group but laments that his symptoms differ from those of other group members. During follow-up visits, he continues to focus on his somatic symptoms.

During a routine visit, Mr. P tells us that he recently suffered an intense ‘panic’ episode—consisting of shortness of breath, dizziness, diaphoresis, chest pain, palpitations, and near syncope—less than 15 minutes after he started clearing brush in his backyard. We notice marked clubbing on Mr. P’s fingers, a physical sign seen in congenital heart disease, infective endocarditis, pulmonary fibrosis, and numerous other diseases.⁴

The clubbing prompts us to ask about his occupational history in detail, as work-related exposure to chemicals or fumes may result in pulmonary fibrosis. We then learn that for approximately 20 years before joining the aircraft company, Mr. P welded without wearing protective equipment—all that time inhaling noxious fumes while working.

We refer Mr. P to an internist, who finds clubbing of the fingers, decreased breath sounds, and increased pulmonic second heart sound (P2) on auscultation. The internist then orders:

• ECG, which reveals right axis deviation, incomplete right bundle branch block, and right ventricular hypertrophy (RVH)
  
• Pulmonary function tests, which show decreased diffusing capacity. Subsequent heart catheterization reveals RVH and concentric left ventricular hypertrophy.
  

The authors’ observations

Panic attacks often mimic symptoms of cardiac or pulmonary disease. By the same token, symptoms of an underlying cardiac or pulmonary disease can be mistaken for panic disorder, particularly in patients whose past episodes appear to meet DSM-IV-TR panic attack criteria (Table 2).⁵

Table 2

Panic attack symptoms that may suggest a cardiopulmonary disease

To avoid unnecessary referrals, psychiatrists need to quickly and accurately discern:

• when a medical problem is causing the patient’s symptoms
  
• how far to carry the medical evaluation, particularly for patients with palpitations, chest pain, or shortness of breath.
  

Also, a psychiatric patient whose mental disorder or comorbid axis II pathology compromises speech or cognitive function may have trouble communicating potentially serious medical problems to other clinicians. Mr. P’s guarded demeanor and obsession toward his physical problems may have kept him from accurately describing his symptoms in a clinical setting. Alternately, he might have misinterpreted his pulmonologist’s explanation of pulmonary fibrosis, thus believing the disorder was not serious.

Finally, patients with panic disorder are more aware of their heartbeats and physiologic responses than are persons without panic disorder,⁸ thus further complicating diagnosis.

UNCOVERING A MEDICAL CAUSE

Suspect an underlying heart or lung problem when panic symptoms affect breathing or resemble a heart attack.

Check for predisposing risk factors for cardiac disease. Ask the patient detailed questions about past and current medical problems, including:

• smoking
  
• hyperlipidemia
  
• diabetes
  
• heart problems
  
• pulmonary disease
  
• family history of any medical problems
  
• work-related exposure to any metal that may increase risk of cardiopulmonary disease.
  

Review medical treatment history. Mentally ill persons are more likely than those without a mental illness to receive inadequate general medical and preventative care.⁹ Patient, provider, and health care system issues—such as lack of insurance or the patient’s inability to recognize or describe symptoms—may impede medical care delivery to the mentally ill.⁹

Review overall history. A deeper look into Mr. P’s work and diagnostic history uncovered numerous possible causes of right heart failure, including:

• pulmonary fibrosis secondary to inhalational injury
  
• possible pulmonary vasculitis as indicated by his positive ANA and RF.
  

FOLLOW-UP: A PANIC-FREE FUTURE

Over the next 4 weeks, Mr. P has stopped taking alprazolam and begins to understand that his episodes were secondary to cardiopulmonary dysfunction. No longer afraid of developing a panic attack, he is going out more often.

Mr. P recently told us that he started a part-time job, decreased his smoking to a half pack/day, and has a plan to quit smoking completely. He adds that he is using his CPAP machine regularly and has remained free of panic-like episodes. He limits physical exertion to avoid cardiopulmonary symptoms.

Related resources

• Raj A, Sheehan DV. Medical evaluation of panic attacks. J Clin Psychiatry 1987;48:309-13.
  
• Jones DR, Macias C, Barreira PJ, et al. Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness. Psychiatr Serv 2004;55:1250-7.
  

• Alprazolam • Xanax
  
• Citalopram • Celexa
  
• Paroxetine • Paxil
  

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

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

HISTORY: LIFE AT HOME

For nearly 10 years Mr. P, age 50, has had episodes of shortness of breath, increasing perspiration, and faintness that occur 2 to 3 times a month, usually when he’s out of the house. Fearing his legs will give out in public, he never goes out except to shop with his wife.

Once a welder for an aircraft company, he has been unable to work for 6 years. He worries incessantly about his medical expenses, and smokes 1 pack of cigarettes per day to help control the anxiety.

Baseline laboratory tests reveal a low-density lipoprotein cholesterol level of 199 mg/dL, exceeding the optimal range by 100 mg/dL. Total cholesterol is 288 mg/dL and triglycerides are 244 mg/dL. Thyroid stimulating hormone, liver function, renal function, serum electrolytes, and serum glucose are normal. Mr. P meets DSM-IV-TR criteria for panic disorder with agoraphobia and is started on citalopram, 20 mg/d.

At follow-up 2 weeks later, Mr. P complains that the citalopram is causing ‘aches and pains’ in his back and legs, so we switch to controlled-release paroxetine, 12.5 mg/d, which we found in clinical practice to be more tolerable than immediate-release paroxetine. After 2 weeks, he says he cannot tolerate the paroxetine because of ‘body aches.’

At Mr. P’s insistence, we switch to alprazolam, 0.5 mg tid, although his desire to start taking alprazolam makes us suspect that he might be trying to obtain this benzodiazepine for illicit use.

Neuropsychological tests—including a diagnostic interview, Minnesota Multiphasic Personality Inventory, and Millon Clinical Multiaxial Inventory—are ordered after Mr. P’s third visit. He seems guarded when answering questions about himself during these interviews. He acknowledges having severe physical symptoms but appears unwilling to accept a psychiatric diagnosis for them.

The authors’ observations

Panic disorder is usually chronic and can cause considerable morbidity. DSM-IV-TR criteria for panic disorder include recurrent or unexpected panic attacks and persistent fear of additional attacks and their implications and consequences.¹ Panic disorder can also lead to social problems including unemployment, financial dependence, and substance abuse or dependence.²

Mr. P’s anxiety, shortness of breath, faintness, and profuse sweating during episodes match DSM-IV-TR criteria for panic attacks (Table 1). His ruminative and obsessive attitude toward his physical problems does not suggest somatoform disorder because he also thinks obsessively about other issues, such as his medical expenses.

We will watch for signs of prescription drug abuse, including premature requests for refills, use of multiple pharmacies, or complaints of lost prescription or medication.³

FURTHER HISTORY: FAINT MEMORY

Mr. P first sought medical help in 1996 after fainting at home while standing up. A few weeks later he experienced sudden dizziness, faintness, and perspiration while shopping with his wife. During that episode, he said, he barely made it out of the store before passing out in his truck. His wife described him as ‘pale and gray’ and rushed him to the emergency room. The ER physician suspected that Mr. P suffered a ‘convulsive episode’ and ordered testing. Results of awake and sleep EEG and head MRI were normal. Laboratory work revealed a positive antinuclear antibody (ANA) and rheumatoid factor (RF), suggesting pulmonary vasculitis.

Table 1

DSM-IV-TR criteria for panic attack

Two years and 17 doctors later, Mr. P’s physical symptoms persisted. He stopped working and began collecting disability insurance benefits. Frustrated over the lack of a definitive diagnosis, he then went 6 years without seeing a doctor.

TREATMENT: INTENSE ‘PANIC’

Mr. P has been coming to our clinic for 8 months. He takes 0.5 mg of alprazolam twice daily—less frequently than prescribed—and has never prematurely requested a refill, so prescription abuse is ruled out. He joins a fibromyalgia support group but laments that his symptoms differ from those of other group members. During follow-up visits, he continues to focus on his somatic symptoms.

During a routine visit, Mr. P tells us that he recently suffered an intense ‘panic’ episode—consisting of shortness of breath, dizziness, diaphoresis, chest pain, palpitations, and near syncope—less than 15 minutes after he started clearing brush in his backyard. We notice marked clubbing on Mr. P’s fingers, a physical sign seen in congenital heart disease, infective endocarditis, pulmonary fibrosis, and numerous other diseases.⁴

The clubbing prompts us to ask about his occupational history in detail, as work-related exposure to chemicals or fumes may result in pulmonary fibrosis. We then learn that for approximately 20 years before joining the aircraft company, Mr. P welded without wearing protective equipment—all that time inhaling noxious fumes while working.

We refer Mr. P to an internist, who finds clubbing of the fingers, decreased breath sounds, and increased pulmonic second heart sound (P2) on auscultation. The internist then orders:

• ECG, which reveals right axis deviation, incomplete right bundle branch block, and right ventricular hypertrophy (RVH)
  
• Pulmonary function tests, which show decreased diffusing capacity. Subsequent heart catheterization reveals RVH and concentric left ventricular hypertrophy.
  

The authors’ observations

Panic attacks often mimic symptoms of cardiac or pulmonary disease. By the same token, symptoms of an underlying cardiac or pulmonary disease can be mistaken for panic disorder, particularly in patients whose past episodes appear to meet DSM-IV-TR panic attack criteria (Table 2).⁵

Table 2

Panic attack symptoms that may suggest a cardiopulmonary disease

To avoid unnecessary referrals, psychiatrists need to quickly and accurately discern:

• when a medical problem is causing the patient’s symptoms
  
• how far to carry the medical evaluation, particularly for patients with palpitations, chest pain, or shortness of breath.
  

Also, a psychiatric patient whose mental disorder or comorbid axis II pathology compromises speech or cognitive function may have trouble communicating potentially serious medical problems to other clinicians. Mr. P’s guarded demeanor and obsession toward his physical problems may have kept him from accurately describing his symptoms in a clinical setting. Alternately, he might have misinterpreted his pulmonologist’s explanation of pulmonary fibrosis, thus believing the disorder was not serious.

Finally, patients with panic disorder are more aware of their heartbeats and physiologic responses than are persons without panic disorder,⁸ thus further complicating diagnosis.

UNCOVERING A MEDICAL CAUSE

Suspect an underlying heart or lung problem when panic symptoms affect breathing or resemble a heart attack.

Check for predisposing risk factors for cardiac disease. Ask the patient detailed questions about past and current medical problems, including:

• smoking
  
• hyperlipidemia
  
• diabetes
  
• heart problems
  
• pulmonary disease
  
• family history of any medical problems
  
• work-related exposure to any metal that may increase risk of cardiopulmonary disease.
  

Review medical treatment history. Mentally ill persons are more likely than those without a mental illness to receive inadequate general medical and preventative care.⁹ Patient, provider, and health care system issues—such as lack of insurance or the patient’s inability to recognize or describe symptoms—may impede medical care delivery to the mentally ill.⁹

Review overall history. A deeper look into Mr. P’s work and diagnostic history uncovered numerous possible causes of right heart failure, including:

• pulmonary fibrosis secondary to inhalational injury
  
• possible pulmonary vasculitis as indicated by his positive ANA and RF.
  

FOLLOW-UP: A PANIC-FREE FUTURE

Over the next 4 weeks, Mr. P has stopped taking alprazolam and begins to understand that his episodes were secondary to cardiopulmonary dysfunction. No longer afraid of developing a panic attack, he is going out more often.

Mr. P recently told us that he started a part-time job, decreased his smoking to a half pack/day, and has a plan to quit smoking completely. He adds that he is using his CPAP machine regularly and has remained free of panic-like episodes. He limits physical exertion to avoid cardiopulmonary symptoms.

Related resources

• Raj A, Sheehan DV. Medical evaluation of panic attacks. J Clin Psychiatry 1987;48:309-13.
  
• Jones DR, Macias C, Barreira PJ, et al. Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness. Psychiatr Serv 2004;55:1250-7.
  

• Alprazolam • Xanax
  
• Citalopram • Celexa
  
• Paroxetine • Paxil
  

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

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

Compulsive hoarding behavior is considered notoriously difficult to treat, but targeting its characteristic symptoms with medication and psychotherapy can be successful. This article provides a guide for the psychiatrist—alone or with a cognitive-behavioral therapist—to diagnose compulsive hoarding syndrome and help patients overcome the anxieties that fuel its symptoms.

WHAT IS COMPULSIVE HOARDING?

Hoarders acquire and are unable to discard items that others consider of little use or value.¹ They most often save newspapers, magazines, old clothing, bags, books, mail, notes, and lists. Hoarding and saving behaviors occur in nonclinical populations and with other neuropsychiatric disorders—schizophrenia, dementia, eating disorders, mental retardation—but are most often found in persons with obsessive-compulsive disorder (OCD).

OCD is a heterogeneous clinical entity with several major symptom domains:^2,3

• aggressive, sexual, and religious obsessions with checking compulsions
  
• symmetry/order obsessions with ordering, arranging, and repeating compulsions
  
• contamination obsessions with washing and cleaning compulsions
  
• hoarding and saving symptoms.
  

ASSESSMENT AND TREATMENT PLANNING

To manage compulsive hoarding syndrome, begin with a thorough neuropsychiatric evaluation:

• Rule out primary psychotic disorders, dementia, and other cognitive impairments and neurologic disorders.
  
• Rule out primary major depression, as clutter and self-neglect may be caused by amotivation, low energy, or hopelessness.
  
• Determine if the patient has OCD.
  

Amount of clutter. Living areas may be so cluttered that sleeping in a bed, sitting on chairs, or preparing food on a kitchen counter are impossible. How much of the home is cluttered? How much floor and counter space is usable? Are rooms unusable or inaccessible because of clutter? Can the patient use the laundry, prepare food in the kitchen, use the shower, toilet, etc.?

Health or safety hazards. Huge piles of papers can be a fire hazard. Clutter may be blocking the exits. Collected items may extend beyond patients’ homes to their cars, garages, storage lockers, and even storage areas owned by friends and family.

Beliefs about possessions. Compulsive hoarders often have distorted feelings about their possessions. They may over-buy or impulsively purchase items they feel have emotional or monetary value. They may consider the items extensions of themselves and suffer grief-like loss when discarding things.⁷

Some collect free items—flyers, coupons, newspapers, discarded goods—hoping to save money or be prepared “just in case” the item is ever needed. This may represent unattainable expectations of perfection, needing to maintain preparedness for every possible contingency. Hoarders often believe they have poor memory and have catastrophic fears of what might happen if they forget something. Thus, their desire to keep their possessions in sight is strong.¹⁷

Information processing deficits. Because of anxieties about making mistakes, most hoarders have great difficulty making decisions.¹⁸ It is easier to not decide than to suffer the consequences of a “wrong” decision. To gauge this behavior, ask patients how long routine decisions take them and which decisions they procrastinate or avoid.

Compulsive hoarders often have trouble categorizing possessions;^6,7 because every item feels unique, they create a special category for each one and resist storing items together.

Table 1

Proposed criteria to diagnose obsessive-compulsive hoarding*

Avoidance behaviors are a hallmark of the compulsive hoarding syndrome. To avoid deciding to discard items, they put them in a box, garage, rented storage facility, etc. They may also avoid routine decision-making tasks that could lead to making a mistake.

Daily functioning. Hoarders may take a long time to do even small chores, such as taking an hour to pay one bill. An inordinate amount of time may be spent “churning”—moving items from one pile to another but never discarding any item or establishing a consistent system or organization.

Medication compliance. Compulsive hoarders often forget to take medications or take them at inappropriate times. They may lose their medications in the clutter.

Insight. Hoarders often have little awareness of how their behavior and clutter affect their lives.¹⁹ They minimize the clutter in their homes and its health and safety risks. Insight can fluctuate over time and needs to be assessed repeatedly during treatment.

Table 2

Assessing a patient with compulsive hoarding symptoms

Cognitive behavioral therapy for compulsive hoarding

Motivation. Like insight, motivation can fluctuate over time. Patients usually must work tremendously hard to adhere to treatment. To support these efforts, we periodically review with patients compulsive hoarding’s negative effects and the activities they would enjoy—such as improved relationships, greater work capacity, hobbies—if overcoming this behavior allowed them more time and space.

Rating scales. The symptom checklist of the Yale-Brown Obsessive-Compulsive Scale (YBOCS)²¹ contains two items for hoarding obsessions and compulsions but none for avoidance behaviors, which are prominent with compulsive hoarding. The Saving Inventory-Revised²² is a validated, 23-item self-report measure of clutter, difficulty discarding, and excessive acquisition, which distinguishes compulsive hoarders, nonhoarding OCD patients, and normal controls.

TREATMENT

The compulsive hoarder’s problems will not be solved by someone else throwing away or organizing his or her possessions. These actions often anger patients, who see them as intrusive and a loss of control.

In our experience, family members’ attempts to intervene can disrupt relationships and worsen hoarders’ social withdrawal. “Taking over” also does not help the patient create a sustainable system for keeping clutter-free.

Algorithm

Medication treatment for compulsive hoarding*

Psychotherapy. Exposure and response prevention (ERP) focuses on preventing incoming clutter, discarding, organizing, and relapse prevention (Table 3).²³ Start treatment by explaining compulsive hoarding syndrome to patients as having problems with information processing, obsessional anxiety, and avoiding decisions.

Preventing incoming clutter. Before you focus on discarding, patients must stop incoming clutter; otherwise, it will come in as fast as it goes out. We ask patients to keep a daily log of every item they acquire or buy to build their awareness of what triggers their behavior.

Discarding. To desensitize over time, we repeatedly expose patients to the anxiety, sadness, or anger they feel when discarding items and making decisions. We encourage them to provoke their anxiety by throwing away as many items as possible, keeping only necessary items.

We support ERP with cognitive restructuring, prompting patients to reframe their obsessive fears about losing something necessary or valuable. By thinking through the consequences of discarding their clutter, they challenge their erroneous beliefs that dire consequences will occur.

Organizing. When patients decide they must keep an item, ask them to immediately identify a specific place and deadline to store it. After an area is cleared, patients must keep it clear and use it for its intended purpose. Most patients need training in time management, scheduling, and prioritizing.

Relapse prevention. Replace hoarding behaviors with more-adaptive, healthy behaviors. Teach patients to create a realistic schedule that includes time for chores, eating and sleeping, CBT homework, and recreation. Treatment goals are to:

• extinguish obsessional fears and compulsive saving behaviors
  
• teach lasting organizational and decision-making skills, thereby reducing relapse risk.
  

Medications. No controlled studies have examined whether any medications are effective for compulsive hoarding syndrome. The treatment strategies and algorithm described here are based on our clinical experience, controlled trials of OCD patients, and limited OCD studies secondarily examining hoarders’ specific treatment responses.

Selective serotonin reuptake inhibitors (SSRIs) may be less effective for compulsive hoarding than for other compulsive behaviors.^14,27 Nevertheless, SSRIs may help alleviate hoarders’ core symptoms, other OCD symptoms, depression, and anxiety. For hoarding treatment to be effective, comorbid disorders must be treated and stabilized.

Several studies of SSRI use in OCD patients have shown modest improvements in compulsive hoarders:

• In a descriptive study of patients with compulsive hoarding, 1 of 18 (6%) patients had a “marked” response to at least one SSRI trial. The others showed a partial response,¹⁷ with YBOCS scores decreasing by at least 25% in approximately 50% of this group.
  
• When 17 OCD patients with hoarding symptoms were treated with paroxetine, CBT, or placebo, 18% responded to active treatment. Response was defined as a 40% reduction on YBOCS scores and “very much” or “much” improved on the Clinical Global Impression Scale (CGI).¹⁴
  

Atypical antipsychotics may be effective for OCD symptoms that do not respond adequately to SSRIs.²⁹ Conventional antipsychotics are also effective adjuncts to SSRIs—particularly for patients with coexisting tic or psychotic disorders³⁰—but consider the potential for extrapyramidal side effects and tardive dyskinesia.

We find that stimulants help some compulsive hoarders, particularly those with comorbid ADHD, other attentional problems, low motivation, or lethargy. Mood stabilizers are necessary to treat comorbid bipolar disorder, cyclothymia, and impulsivity.

Related resources

• Saxena S, Maidment K. Treatment of compulsive hoarding. J Clin Psychol 2004;60(11):1143-54.
  
• UCLA OCD Intensive Treatment Program. For information on research studies contact Karron Maidment (310) 794-7305 or visit www.mentalhealth.ucla.edu/projects/anxiety/ocdintensivetreatment.htm.
  
• Compulsive hoarding project. Institute of Living Anxiety Disorders Center, Hartford Hospital. http://instituteofliving.org/adc/compulsive_hoarding.htm
  
• Obsessive Compulsive Foundation compulsive hoarding Web site. http://www.ocfoundation.org/1005/index.html
  
• Neziroglu F, Bubrick J, Yaryura-Tobias JA. Overcoming compulsive hoarding. Oakland, CA: New Harbinger Publications, 2004.
  

• Citalopram • Celexa
  
• Clomipramine • Anafranil
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Fluvoxamine • Luvox
  
• Olanzapine • Zyprexa
  
• Paroxetine • Paxil
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Sertraline • Zoloft
  
• Venlafaxine • Effexor
  

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

Compulsive hoarding behavior is considered notoriously difficult to treat, but targeting its characteristic symptoms with medication and psychotherapy can be successful. This article provides a guide for the psychiatrist—alone or with a cognitive-behavioral therapist—to diagnose compulsive hoarding syndrome and help patients overcome the anxieties that fuel its symptoms.

WHAT IS COMPULSIVE HOARDING?

Hoarders acquire and are unable to discard items that others consider of little use or value.¹ They most often save newspapers, magazines, old clothing, bags, books, mail, notes, and lists. Hoarding and saving behaviors occur in nonclinical populations and with other neuropsychiatric disorders—schizophrenia, dementia, eating disorders, mental retardation—but are most often found in persons with obsessive-compulsive disorder (OCD).

OCD is a heterogeneous clinical entity with several major symptom domains:^2,3

• aggressive, sexual, and religious obsessions with checking compulsions
  
• symmetry/order obsessions with ordering, arranging, and repeating compulsions
  
• contamination obsessions with washing and cleaning compulsions
  
• hoarding and saving symptoms.
  

ASSESSMENT AND TREATMENT PLANNING

To manage compulsive hoarding syndrome, begin with a thorough neuropsychiatric evaluation:

• Rule out primary psychotic disorders, dementia, and other cognitive impairments and neurologic disorders.
  
• Rule out primary major depression, as clutter and self-neglect may be caused by amotivation, low energy, or hopelessness.
  
• Determine if the patient has OCD.
  

Amount of clutter. Living areas may be so cluttered that sleeping in a bed, sitting on chairs, or preparing food on a kitchen counter are impossible. How much of the home is cluttered? How much floor and counter space is usable? Are rooms unusable or inaccessible because of clutter? Can the patient use the laundry, prepare food in the kitchen, use the shower, toilet, etc.?

Health or safety hazards. Huge piles of papers can be a fire hazard. Clutter may be blocking the exits. Collected items may extend beyond patients’ homes to their cars, garages, storage lockers, and even storage areas owned by friends and family.

Beliefs about possessions. Compulsive hoarders often have distorted feelings about their possessions. They may over-buy or impulsively purchase items they feel have emotional or monetary value. They may consider the items extensions of themselves and suffer grief-like loss when discarding things.⁷

Some collect free items—flyers, coupons, newspapers, discarded goods—hoping to save money or be prepared “just in case” the item is ever needed. This may represent unattainable expectations of perfection, needing to maintain preparedness for every possible contingency. Hoarders often believe they have poor memory and have catastrophic fears of what might happen if they forget something. Thus, their desire to keep their possessions in sight is strong.¹⁷

Information processing deficits. Because of anxieties about making mistakes, most hoarders have great difficulty making decisions.¹⁸ It is easier to not decide than to suffer the consequences of a “wrong” decision. To gauge this behavior, ask patients how long routine decisions take them and which decisions they procrastinate or avoid.

Compulsive hoarders often have trouble categorizing possessions;^6,7 because every item feels unique, they create a special category for each one and resist storing items together.

Table 1

Proposed criteria to diagnose obsessive-compulsive hoarding*

Avoidance behaviors are a hallmark of the compulsive hoarding syndrome. To avoid deciding to discard items, they put them in a box, garage, rented storage facility, etc. They may also avoid routine decision-making tasks that could lead to making a mistake.

Daily functioning. Hoarders may take a long time to do even small chores, such as taking an hour to pay one bill. An inordinate amount of time may be spent “churning”—moving items from one pile to another but never discarding any item or establishing a consistent system or organization.

Medication compliance. Compulsive hoarders often forget to take medications or take them at inappropriate times. They may lose their medications in the clutter.

Insight. Hoarders often have little awareness of how their behavior and clutter affect their lives.¹⁹ They minimize the clutter in their homes and its health and safety risks. Insight can fluctuate over time and needs to be assessed repeatedly during treatment.

Table 2

Assessing a patient with compulsive hoarding symptoms

Cognitive behavioral therapy for compulsive hoarding

Motivation. Like insight, motivation can fluctuate over time. Patients usually must work tremendously hard to adhere to treatment. To support these efforts, we periodically review with patients compulsive hoarding’s negative effects and the activities they would enjoy—such as improved relationships, greater work capacity, hobbies—if overcoming this behavior allowed them more time and space.

Rating scales. The symptom checklist of the Yale-Brown Obsessive-Compulsive Scale (YBOCS)²¹ contains two items for hoarding obsessions and compulsions but none for avoidance behaviors, which are prominent with compulsive hoarding. The Saving Inventory-Revised²² is a validated, 23-item self-report measure of clutter, difficulty discarding, and excessive acquisition, which distinguishes compulsive hoarders, nonhoarding OCD patients, and normal controls.

TREATMENT

The compulsive hoarder’s problems will not be solved by someone else throwing away or organizing his or her possessions. These actions often anger patients, who see them as intrusive and a loss of control.

In our experience, family members’ attempts to intervene can disrupt relationships and worsen hoarders’ social withdrawal. “Taking over” also does not help the patient create a sustainable system for keeping clutter-free.

Algorithm

Medication treatment for compulsive hoarding*

Psychotherapy. Exposure and response prevention (ERP) focuses on preventing incoming clutter, discarding, organizing, and relapse prevention (Table 3).²³ Start treatment by explaining compulsive hoarding syndrome to patients as having problems with information processing, obsessional anxiety, and avoiding decisions.

Preventing incoming clutter. Before you focus on discarding, patients must stop incoming clutter; otherwise, it will come in as fast as it goes out. We ask patients to keep a daily log of every item they acquire or buy to build their awareness of what triggers their behavior.

Discarding. To desensitize over time, we repeatedly expose patients to the anxiety, sadness, or anger they feel when discarding items and making decisions. We encourage them to provoke their anxiety by throwing away as many items as possible, keeping only necessary items.

We support ERP with cognitive restructuring, prompting patients to reframe their obsessive fears about losing something necessary or valuable. By thinking through the consequences of discarding their clutter, they challenge their erroneous beliefs that dire consequences will occur.

Organizing. When patients decide they must keep an item, ask them to immediately identify a specific place and deadline to store it. After an area is cleared, patients must keep it clear and use it for its intended purpose. Most patients need training in time management, scheduling, and prioritizing.

Relapse prevention. Replace hoarding behaviors with more-adaptive, healthy behaviors. Teach patients to create a realistic schedule that includes time for chores, eating and sleeping, CBT homework, and recreation. Treatment goals are to:

• extinguish obsessional fears and compulsive saving behaviors
  
• teach lasting organizational and decision-making skills, thereby reducing relapse risk.
  

Medications. No controlled studies have examined whether any medications are effective for compulsive hoarding syndrome. The treatment strategies and algorithm described here are based on our clinical experience, controlled trials of OCD patients, and limited OCD studies secondarily examining hoarders’ specific treatment responses.

Selective serotonin reuptake inhibitors (SSRIs) may be less effective for compulsive hoarding than for other compulsive behaviors.^14,27 Nevertheless, SSRIs may help alleviate hoarders’ core symptoms, other OCD symptoms, depression, and anxiety. For hoarding treatment to be effective, comorbid disorders must be treated and stabilized.

Several studies of SSRI use in OCD patients have shown modest improvements in compulsive hoarders:

• In a descriptive study of patients with compulsive hoarding, 1 of 18 (6%) patients had a “marked” response to at least one SSRI trial. The others showed a partial response,¹⁷ with YBOCS scores decreasing by at least 25% in approximately 50% of this group.
  
• When 17 OCD patients with hoarding symptoms were treated with paroxetine, CBT, or placebo, 18% responded to active treatment. Response was defined as a 40% reduction on YBOCS scores and “very much” or “much” improved on the Clinical Global Impression Scale (CGI).¹⁴
  

Atypical antipsychotics may be effective for OCD symptoms that do not respond adequately to SSRIs.²⁹ Conventional antipsychotics are also effective adjuncts to SSRIs—particularly for patients with coexisting tic or psychotic disorders³⁰—but consider the potential for extrapyramidal side effects and tardive dyskinesia.

We find that stimulants help some compulsive hoarders, particularly those with comorbid ADHD, other attentional problems, low motivation, or lethargy. Mood stabilizers are necessary to treat comorbid bipolar disorder, cyclothymia, and impulsivity.

Related resources

• Saxena S, Maidment K. Treatment of compulsive hoarding. J Clin Psychol 2004;60(11):1143-54.
  
• UCLA OCD Intensive Treatment Program. For information on research studies contact Karron Maidment (310) 794-7305 or visit www.mentalhealth.ucla.edu/projects/anxiety/ocdintensivetreatment.htm.
  
• Compulsive hoarding project. Institute of Living Anxiety Disorders Center, Hartford Hospital. http://instituteofliving.org/adc/compulsive_hoarding.htm
  
• Obsessive Compulsive Foundation compulsive hoarding Web site. http://www.ocfoundation.org/1005/index.html
  
• Neziroglu F, Bubrick J, Yaryura-Tobias JA. Overcoming compulsive hoarding. Oakland, CA: New Harbinger Publications, 2004.
  

• Citalopram • Celexa
  
• Clomipramine • Anafranil
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Fluvoxamine • Luvox
  
• Olanzapine • Zyprexa
  
• Paroxetine • Paxil
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Sertraline • Zoloft
  
• Venlafaxine • Effexor
  

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

Compulsive hoarding behavior is considered notoriously difficult to treat, but targeting its characteristic symptoms with medication and psychotherapy can be successful. This article provides a guide for the psychiatrist—alone or with a cognitive-behavioral therapist—to diagnose compulsive hoarding syndrome and help patients overcome the anxieties that fuel its symptoms.

WHAT IS COMPULSIVE HOARDING?

Hoarders acquire and are unable to discard items that others consider of little use or value.¹ They most often save newspapers, magazines, old clothing, bags, books, mail, notes, and lists. Hoarding and saving behaviors occur in nonclinical populations and with other neuropsychiatric disorders—schizophrenia, dementia, eating disorders, mental retardation—but are most often found in persons with obsessive-compulsive disorder (OCD).

OCD is a heterogeneous clinical entity with several major symptom domains:^2,3

• aggressive, sexual, and religious obsessions with checking compulsions
  
• symmetry/order obsessions with ordering, arranging, and repeating compulsions
  
• contamination obsessions with washing and cleaning compulsions
  
• hoarding and saving symptoms.
  

ASSESSMENT AND TREATMENT PLANNING

To manage compulsive hoarding syndrome, begin with a thorough neuropsychiatric evaluation:

• Rule out primary psychotic disorders, dementia, and other cognitive impairments and neurologic disorders.
  
• Rule out primary major depression, as clutter and self-neglect may be caused by amotivation, low energy, or hopelessness.
  
• Determine if the patient has OCD.
  

Amount of clutter. Living areas may be so cluttered that sleeping in a bed, sitting on chairs, or preparing food on a kitchen counter are impossible. How much of the home is cluttered? How much floor and counter space is usable? Are rooms unusable or inaccessible because of clutter? Can the patient use the laundry, prepare food in the kitchen, use the shower, toilet, etc.?

Health or safety hazards. Huge piles of papers can be a fire hazard. Clutter may be blocking the exits. Collected items may extend beyond patients’ homes to their cars, garages, storage lockers, and even storage areas owned by friends and family.

Beliefs about possessions. Compulsive hoarders often have distorted feelings about their possessions. They may over-buy or impulsively purchase items they feel have emotional or monetary value. They may consider the items extensions of themselves and suffer grief-like loss when discarding things.⁷

Some collect free items—flyers, coupons, newspapers, discarded goods—hoping to save money or be prepared “just in case” the item is ever needed. This may represent unattainable expectations of perfection, needing to maintain preparedness for every possible contingency. Hoarders often believe they have poor memory and have catastrophic fears of what might happen if they forget something. Thus, their desire to keep their possessions in sight is strong.¹⁷

Information processing deficits. Because of anxieties about making mistakes, most hoarders have great difficulty making decisions.¹⁸ It is easier to not decide than to suffer the consequences of a “wrong” decision. To gauge this behavior, ask patients how long routine decisions take them and which decisions they procrastinate or avoid.

Compulsive hoarders often have trouble categorizing possessions;^6,7 because every item feels unique, they create a special category for each one and resist storing items together.

Table 1

Proposed criteria to diagnose obsessive-compulsive hoarding*

Avoidance behaviors are a hallmark of the compulsive hoarding syndrome. To avoid deciding to discard items, they put them in a box, garage, rented storage facility, etc. They may also avoid routine decision-making tasks that could lead to making a mistake.

Daily functioning. Hoarders may take a long time to do even small chores, such as taking an hour to pay one bill. An inordinate amount of time may be spent “churning”—moving items from one pile to another but never discarding any item or establishing a consistent system or organization.

Medication compliance. Compulsive hoarders often forget to take medications or take them at inappropriate times. They may lose their medications in the clutter.

Insight. Hoarders often have little awareness of how their behavior and clutter affect their lives.¹⁹ They minimize the clutter in their homes and its health and safety risks. Insight can fluctuate over time and needs to be assessed repeatedly during treatment.

Table 2

Assessing a patient with compulsive hoarding symptoms

Cognitive behavioral therapy for compulsive hoarding

Motivation. Like insight, motivation can fluctuate over time. Patients usually must work tremendously hard to adhere to treatment. To support these efforts, we periodically review with patients compulsive hoarding’s negative effects and the activities they would enjoy—such as improved relationships, greater work capacity, hobbies—if overcoming this behavior allowed them more time and space.

Rating scales. The symptom checklist of the Yale-Brown Obsessive-Compulsive Scale (YBOCS)²¹ contains two items for hoarding obsessions and compulsions but none for avoidance behaviors, which are prominent with compulsive hoarding. The Saving Inventory-Revised²² is a validated, 23-item self-report measure of clutter, difficulty discarding, and excessive acquisition, which distinguishes compulsive hoarders, nonhoarding OCD patients, and normal controls.

TREATMENT

The compulsive hoarder’s problems will not be solved by someone else throwing away or organizing his or her possessions. These actions often anger patients, who see them as intrusive and a loss of control.

In our experience, family members’ attempts to intervene can disrupt relationships and worsen hoarders’ social withdrawal. “Taking over” also does not help the patient create a sustainable system for keeping clutter-free.

Algorithm

Medication treatment for compulsive hoarding*

Psychotherapy. Exposure and response prevention (ERP) focuses on preventing incoming clutter, discarding, organizing, and relapse prevention (Table 3).²³ Start treatment by explaining compulsive hoarding syndrome to patients as having problems with information processing, obsessional anxiety, and avoiding decisions.

Preventing incoming clutter. Before you focus on discarding, patients must stop incoming clutter; otherwise, it will come in as fast as it goes out. We ask patients to keep a daily log of every item they acquire or buy to build their awareness of what triggers their behavior.

Discarding. To desensitize over time, we repeatedly expose patients to the anxiety, sadness, or anger they feel when discarding items and making decisions. We encourage them to provoke their anxiety by throwing away as many items as possible, keeping only necessary items.

We support ERP with cognitive restructuring, prompting patients to reframe their obsessive fears about losing something necessary or valuable. By thinking through the consequences of discarding their clutter, they challenge their erroneous beliefs that dire consequences will occur.

Organizing. When patients decide they must keep an item, ask them to immediately identify a specific place and deadline to store it. After an area is cleared, patients must keep it clear and use it for its intended purpose. Most patients need training in time management, scheduling, and prioritizing.

Relapse prevention. Replace hoarding behaviors with more-adaptive, healthy behaviors. Teach patients to create a realistic schedule that includes time for chores, eating and sleeping, CBT homework, and recreation. Treatment goals are to:

• extinguish obsessional fears and compulsive saving behaviors
  
• teach lasting organizational and decision-making skills, thereby reducing relapse risk.
  

Medications. No controlled studies have examined whether any medications are effective for compulsive hoarding syndrome. The treatment strategies and algorithm described here are based on our clinical experience, controlled trials of OCD patients, and limited OCD studies secondarily examining hoarders’ specific treatment responses.

Selective serotonin reuptake inhibitors (SSRIs) may be less effective for compulsive hoarding than for other compulsive behaviors.^14,27 Nevertheless, SSRIs may help alleviate hoarders’ core symptoms, other OCD symptoms, depression, and anxiety. For hoarding treatment to be effective, comorbid disorders must be treated and stabilized.

Several studies of SSRI use in OCD patients have shown modest improvements in compulsive hoarders:

• In a descriptive study of patients with compulsive hoarding, 1 of 18 (6%) patients had a “marked” response to at least one SSRI trial. The others showed a partial response,¹⁷ with YBOCS scores decreasing by at least 25% in approximately 50% of this group.
  
• When 17 OCD patients with hoarding symptoms were treated with paroxetine, CBT, or placebo, 18% responded to active treatment. Response was defined as a 40% reduction on YBOCS scores and “very much” or “much” improved on the Clinical Global Impression Scale (CGI).¹⁴
  

Atypical antipsychotics may be effective for OCD symptoms that do not respond adequately to SSRIs.²⁹ Conventional antipsychotics are also effective adjuncts to SSRIs—particularly for patients with coexisting tic or psychotic disorders³⁰—but consider the potential for extrapyramidal side effects and tardive dyskinesia.

We find that stimulants help some compulsive hoarders, particularly those with comorbid ADHD, other attentional problems, low motivation, or lethargy. Mood stabilizers are necessary to treat comorbid bipolar disorder, cyclothymia, and impulsivity.

Related resources

• Saxena S, Maidment K. Treatment of compulsive hoarding. J Clin Psychol 2004;60(11):1143-54.
  
• UCLA OCD Intensive Treatment Program. For information on research studies contact Karron Maidment (310) 794-7305 or visit www.mentalhealth.ucla.edu/projects/anxiety/ocdintensivetreatment.htm.
  
• Compulsive hoarding project. Institute of Living Anxiety Disorders Center, Hartford Hospital. http://instituteofliving.org/adc/compulsive_hoarding.htm
  
• Obsessive Compulsive Foundation compulsive hoarding Web site. http://www.ocfoundation.org/1005/index.html
  
• Neziroglu F, Bubrick J, Yaryura-Tobias JA. Overcoming compulsive hoarding. Oakland, CA: New Harbinger Publications, 2004.
  

• Citalopram • Celexa
  
• Clomipramine • Anafranil
  
• Escitalopram • Lexapro
  
• Fluoxetine • Prozac
  
• Fluvoxamine • Luvox
  
• Olanzapine • Zyprexa
  
• Paroxetine • Paxil
  
• Quetiapine • Seroquel
  
• Risperidone • Risperdal
  
• Sertraline • Zoloft
  
• Venlafaxine • Effexor
  

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

Women with depression and polycystic ovary syndrome (PCOS) can be trapped in a vicious cycle of hormonal dysregulation. Treating these patients appropriately—with or without antidepressants—requires an understanding of their underlying metabolic disorder.

This article presents a case¹ that exemplifies the association between depression and PCOS (Box 1).^2-4 Based on our research and clinical experience, we offer recommendations to help you manage depression in patients with PCOS.

CHRONIC DEPRESSION WITH AMENORRHEA

Ms. K, age 30, presented for psychiatric evaluation of treatment-resistant recurrent major depression. Her symptoms included sad mood, sleep disturbance, decreased energy, anhedonia, poor concentration, and feelings of guilt and worthlessness. Her score of 28 on the Hamilton Rating Scale for Depression (HAM-D-21) indicated severe depression.

Box 1

This was Ms. K’s third episode of major depression, with the first two occurring at ages 24 and 26. She reported similar symptoms each time. Previous psychiatrists had tried a variety of antidepressants with no therapeutic benefit before she responded to citalopram, 40 mg/d, at age 27. With this selective serotonin reuptake inhibitor, her depressive symptoms resolved for >1 year, except for mild irritability and low mood the week before menses.

Her depressive symptoms returned, however, and her previous psychiatrist treated her for approximately 13 months with extended-release venlafaxine, 225 mg/d. When she remained depressed, she was referred to our clinic for evaluation. Based on her history, we could not determine whether she had become euthymic at age 27 or her symptoms had improved but still met criteria for a major depressive episode.

Ms. K reported having PCOS symptoms from age 19. These included amenorrhea since menarche, hirsutism, hair loss, alopecia, central fat distribution characteristic of PCOS, and male-pattern hair growth on her abdomen and thighs. She was not obese—with a body mass index (BMI) of approximately 25—but had gained 10 to 15 lbs while taking venlafaxine.

Ms. K had never been treated for PCOS but reported that her desire to become pregnant made her more concerned about her symptoms and possible infertility.

Diagnosis. PCOS is usually diagnosed using endocrinologic, clinical, and ultrasonographic criteria (Table 1). Obesity is not a presenting symptom in all women with PCOS. As with Ms. K, about 50% of patients have normal BMI.

Causes of depression in PCOS. Depressed mood in PCOS may be both physiologic and psychological:

• Hypothalamic, pituitary, and other end-organ system dysregulation occurs in both PCOS and affective disorders, which share clinical and biochemical markers including insulin resistance, obesity, and hyperandrogenism.
• PCOS’ clinical sequelae—hirsutism, acne, obesity, hormonal disturbances, fear of infertility, and psychological distress—may damage their self-esteem and female identity.

PCOS’ physical symptoms alone apparently do not account for patients’ worsened mood states. Weiner et al⁵ found that women with PCOS and free testosterone (FT) of 10 to 26 pg/mL (just above normal range) were more depressed than women without PCOS (FT <10 pg/mL) and women with PCOS and FT >26 pg/mL. Women with PCOS with the lower and higher FT levels had similar demographic profiles, but those with the highest FT levels were not the most depressed.

Similarly, in a study of 32 women with PCOS, we found no association between depression and other possibly distressing PCOS symptoms, including hirsutism, irregular menses, acne, or alopecia.⁴

Testosterone and mood disorders. Women such as Ms. K with hyperandrogenic syndromes are at increased risk for mood disorders.⁶ Many metabolic changes associated with PCOS—insulin resistance, obesity, and hyperandrogenism—are also described in patients with affective disorders. Our investigation of reproductive status in women with bipolar disorder found no clinical or biochemical evidence of PCOS with mood-stabilizer treatment. We did find that menstrual disturbances were common, however, and sometimes preceded bipolar disorder onset.⁷

Insulin resistance and depression. Others have linked insulin resistance and depression;⁸ depression has been shown to be associated with impaired insulin sensitivity and hyperinsulinemia.⁹ Depressed persons also tend to eat more sweets, drink more alcohol, exercise less, and sleep fewer hours than the nondepressed—all of which contribute to insulin sensitivity and insulin resistance.¹⁰

WHAT LINKS ENDOCRINE, MOOD DISORDERS?

Insulin and serotonin. Insulin affects central serotonin (5-HT) levels.¹¹ Thus, central 5-HT system dysregulation that causes depression might also affect peripheral insulin sensitivity—or vice versa.⁹

Tryptophan, a serotonin precursor, competes with other large neutral amino acids for access to the transport system that moves them across the blood-brain barrier. Insulin stimulates uptake of the competing amino acids—but not tryptophan—into muscle tissue. The resulting increased tryptophan ratio in plasma affords it greater access to the transport system to contribute toward serotonin synthesis. Insulin also promotes central catecholaminergic activity, perhaps by suppressing norepinephrine reuptake and prolonging its residence in the synaptic cleft.¹⁰

Table 1

Diagnostic signs of PCOS

Several studies have found that insulin resistance and hyperinsulinemia can resolve after depression recovery.^9,12 Because insulin resistance is a cardinal feature in PCOS pathophysiology,² insulin resistance may be a common link between depression and PCOS.

Weight gain and obesity also have been described in patients with affective disorders.¹³ Not known is whether the weight gain precedes the psychopathology or is caused by long-term exposure to drugs used to treat affective disorders.

Box 2

We reported a correlation between depression and BMI in women with PCOS.⁴ Depression might be independently associated with BMI, as weight gain and obesity are distressing symptoms associated with depression.¹⁴ However, we found no association between depression and other possibly distressing PCOS symptoms. Thus, the correlation between BMI and depression might more likely reflect the relationship between depression and insulin resistance, as degree of insulin resistance is known to correlate with BMI.

Elevated cortisol. Clearly, other factors—such as hypothalamus-pituitary-adrenal (HPA) axis dysfunction—are known to link affective and endocrine disorders. Hypercortisolemia can lead to both insulin resistance and obesity. Cortisol is one of the glucocorticoids the body secretes in response to stress to mobilize energy by increasing blood glucose levels. Early life stress and chronic emotional stress:

• can impair the negative feedback system that limits cortisol production during stress
• are associated with depression.

Approximately one-half of individuals with depression have elevated serum cortisol.¹⁰ Epidemiologic data show a positive correlation between cortisol levels and insulin resistance,¹⁵ and an association between HPA dysfunction and obesity has been described.¹⁶ Insulin can trigger androgen production by enhancing adrenal sensitivity to adrenocorticotrophic hormone (ACTH).¹⁷

CASE: IMPROVING INSULIN RESISTANCE

We referred Ms. K to an endocrinologist for PCOS evaluation and treatment. Her serum glucose and insulin levels were 83 mg/dL (normal range 70 to 125 mg/dL) and 19.0 uIU/mL (normal range <10 uIU/mL), respectively. These values indicated insulin resistance as determined by the homeostasis model assessment (HOMA) ratio (fasting insulin x fasting glucose/22.5). Values >3.2 indicate insulin resistance, and Ms. K had a HOMA ratio of 3.9. The endocrinologist recommended:

• metformin, starting at 850 mg/d and gradually increased to 2,550 mg/d
• spironolactone, 100 mg/d.

Metformin, a biguanide approved for treating for type 2 diabetes, inhibits hepatic glucose production and increases peripheral insulin sensitivity, but it does not modify pancreatic insulin secretion. It may decrease insulin resistance by reducing gut absorption of glucose, improving glucose uptake by tissues, and/or increasing the number of insulin receptors.¹⁸ In treating PCOS, metformin can:

• restore ovulation¹⁹
• decrease insulin resistance, acne, hirsutism, total and bioavailable testosterone, BMI, and waist-hip ratio.^20,21

Although the link between insulin resistance and depression is unclear, insulin is known to contribute to 5-HT synthesis by promoting tryptophan influx into the brain.²² Therefore, drugs used to treat insulin resistance—such as metformin and alpha lipoic acid²³—might be useful in treating depression.

Spironolactone, a mineralocorticoid receptor (MR) antagonist, reduces hirsutism in women with PCOS.²⁴ It also can decrease insulin resistance and fasting insulin levels in PCOS patients and reduce serum testosterone.²⁵

Evidence on treating mood disorders with hormonal agents such as spironolactone is scarce, although treatment-resistant depression has been reported to resolve with antiglucocorticoid use (Box 2).^25-31 Modulating HPA axis activity to treat affective disorders has been investigated.

CASE: GOING ANTIDEPRESSANT-FREE

At first, Ms. K said she wanted to continue taking venlafaxine with the PCOS treatment. After 2 weeks of combined therapy, however, she chose to stop the antidepressant after her depressive symptoms persisted, and her HAM-D-21 score remained at 28.

During the next 4 weeks, as we tapered off the venlafaxine, Ms. K’s HAM-D-21 score dropped to 7, indicating depressive symptom resolution. Despite slow venlafaxine titration, withdrawal symptoms of excessive crying, not feeling “present,” and tingling sensations occurred. Three days of fluoxetine, 20 mg/d, alleviated these symptoms.

Table 2

Insulin-sensitizing medications used to treat PCOS

We continued Ms. K’s treatment without antidepressants, and her mood continued to improve with metformin, 2,550 mg/d, and spironolactone, 100 mg/d.

TREATMENT RECOMMENDATIONS

PCOS therapy may take up to 6 months to resolve symptoms such as anovulation or hirsutism, but affective symptoms may improve during the first 6 weeks, as this case shows. Choosing medications to treat depression in patients such as Ms. K depends on whether their PCOS is being treated when they present for psychiatric evaluation.

Patient not being treated for PCOS. Refer her to an endocrinologist for PCOS treatment with an insulin-sensitizing medication, such as metformin (Table 2). Treating the insulin resistance associated with PCOS may also resolve the depression. PCOS drug therapy may also include antiandrogens such as spironolactone to treat hirsutism, male-pattern baldness, and acne. We suggest that spironolactone’s antiandrogen effects may help reduce depressive symptoms.

If your patient is not taking an antidepressant at presentation, try PCOS treatment first. If depressive symptoms persist after 3 months, consider adding an antidepressant. If your patient is taking an antidepressant at presentation but continues to be depressed, offer two options:

• taper off the antidepressant while starting PCOS treatment
• continue the antidepressant while starting PCOS treatment.

The first option allows you to try PCOS treatment alone. If the depression is caused by a common underlying pathophysiology—such as insulin resistance—treating PCOS alone may alleviate her depressive symptoms. Monitor for withdrawal symptoms, which may be minimized with a short-term SSRI, such as fluoxetine.

The second option may help patients who have responded to antidepressants in the past. Adjunctive PCOS treatment may “jump-start” the antidepressant response without withdrawal symptoms, but you will not be sure whether the antidepressant response was caused by PCOS therapy alone or the combination therapy.

Patient being treated for PCOS. Treat her with antidepressants, and consult with her endocrinologist to consider more-aggressive insulin-sensitizing medications, especially if she exhibits high levels of insulin resistance.

Other interventions that increase insulin sensitivity and improve glycemic control—such as improving dietary management and sleep habits, reducing alcohol consumption, and increasing physical activity—might have an antidepressant effect. Therefore, recommend these health practices to patients as adjuncts to drug therapies.

CASE: DEPRESSION IN REMISSION

At the 3-month follow-up visit, Ms. K scored zero on the HAM-D-21 scale. With metformin treatment, she had lost approximately 10 lbs and resumed menstruating approximately every 33 days. She reported experiencing low mood, decreased energy, and irritability during the week before her periods, but these symptoms resolved with menses onset.

Serum glucose was within normal range at 89 mg/dL, and serum insulin was 15.0 uIU/Ml. Her HOMA ratio had dropped to 2.8 (below the 3.2 cut-off for insulin resistance).

Ms. K’s endocrinologist monitored her spironolactone and metformin therapy for approximately 1 year, when she became pregnant.

Discussion. PCOS treatment duration depends on the patient’s response and her goals for therapy. Whether or not she continues PCOS treatment, her primary care physician or endocrinologist should continue to monitor her for insulin resistance’s metabolic consequences, including increased risk of type 2 diabetes and cardiovascular disease.

Related resources

• Legro RS, Winans EA. Overview of polycystic ovary syndrome and its relation to psychiatric illness and treatment. Current Psychiatry 2004;3(Dec[suppl]):12-20.
• The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004 Jan; 81(1):19-25.
• Polycystic ovary syndrome (patient information). The National Women’s Health Information Center. U.S. Department of Health and Human Services, Office on Women’s Health. Available at: http://www.4woman.gov/faq/pcos.htm. Accessed Jan. 13, 2005.

Drug brand names

• Citalopram • Celexa
• Fluoxetine • Prozac
• Ketoconazole • Nizoral
• Metformin • Glucophage
• Metyrapone • Metopirone
• Mifepristone • Mifiprex
• Pioglitazone • Actos
• Rosiglitazone • Avandia
• Spironolactone • Aldactone
• Venlafaxine • Effexor XR

Disclosures

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

Women with depression and polycystic ovary syndrome (PCOS) can be trapped in a vicious cycle of hormonal dysregulation. Treating these patients appropriately—with or without antidepressants—requires an understanding of their underlying metabolic disorder.

This article presents a case¹ that exemplifies the association between depression and PCOS (Box 1).^2-4 Based on our research and clinical experience, we offer recommendations to help you manage depression in patients with PCOS.

CHRONIC DEPRESSION WITH AMENORRHEA

Ms. K, age 30, presented for psychiatric evaluation of treatment-resistant recurrent major depression. Her symptoms included sad mood, sleep disturbance, decreased energy, anhedonia, poor concentration, and feelings of guilt and worthlessness. Her score of 28 on the Hamilton Rating Scale for Depression (HAM-D-21) indicated severe depression.

Box 1

This was Ms. K’s third episode of major depression, with the first two occurring at ages 24 and 26. She reported similar symptoms each time. Previous psychiatrists had tried a variety of antidepressants with no therapeutic benefit before she responded to citalopram, 40 mg/d, at age 27. With this selective serotonin reuptake inhibitor, her depressive symptoms resolved for >1 year, except for mild irritability and low mood the week before menses.

Her depressive symptoms returned, however, and her previous psychiatrist treated her for approximately 13 months with extended-release venlafaxine, 225 mg/d. When she remained depressed, she was referred to our clinic for evaluation. Based on her history, we could not determine whether she had become euthymic at age 27 or her symptoms had improved but still met criteria for a major depressive episode.

Ms. K reported having PCOS symptoms from age 19. These included amenorrhea since menarche, hirsutism, hair loss, alopecia, central fat distribution characteristic of PCOS, and male-pattern hair growth on her abdomen and thighs. She was not obese—with a body mass index (BMI) of approximately 25—but had gained 10 to 15 lbs while taking venlafaxine.

Ms. K had never been treated for PCOS but reported that her desire to become pregnant made her more concerned about her symptoms and possible infertility.

Diagnosis. PCOS is usually diagnosed using endocrinologic, clinical, and ultrasonographic criteria (Table 1). Obesity is not a presenting symptom in all women with PCOS. As with Ms. K, about 50% of patients have normal BMI.

Causes of depression in PCOS. Depressed mood in PCOS may be both physiologic and psychological:

• Hypothalamic, pituitary, and other end-organ system dysregulation occurs in both PCOS and affective disorders, which share clinical and biochemical markers including insulin resistance, obesity, and hyperandrogenism.
• PCOS’ clinical sequelae—hirsutism, acne, obesity, hormonal disturbances, fear of infertility, and psychological distress—may damage their self-esteem and female identity.

PCOS’ physical symptoms alone apparently do not account for patients’ worsened mood states. Weiner et al⁵ found that women with PCOS and free testosterone (FT) of 10 to 26 pg/mL (just above normal range) were more depressed than women without PCOS (FT <10 pg/mL) and women with PCOS and FT >26 pg/mL. Women with PCOS with the lower and higher FT levels had similar demographic profiles, but those with the highest FT levels were not the most depressed.

Similarly, in a study of 32 women with PCOS, we found no association between depression and other possibly distressing PCOS symptoms, including hirsutism, irregular menses, acne, or alopecia.⁴

Testosterone and mood disorders. Women such as Ms. K with hyperandrogenic syndromes are at increased risk for mood disorders.⁶ Many metabolic changes associated with PCOS—insulin resistance, obesity, and hyperandrogenism—are also described in patients with affective disorders. Our investigation of reproductive status in women with bipolar disorder found no clinical or biochemical evidence of PCOS with mood-stabilizer treatment. We did find that menstrual disturbances were common, however, and sometimes preceded bipolar disorder onset.⁷

Insulin resistance and depression. Others have linked insulin resistance and depression;⁸ depression has been shown to be associated with impaired insulin sensitivity and hyperinsulinemia.⁹ Depressed persons also tend to eat more sweets, drink more alcohol, exercise less, and sleep fewer hours than the nondepressed—all of which contribute to insulin sensitivity and insulin resistance.¹⁰

WHAT LINKS ENDOCRINE, MOOD DISORDERS?

Insulin and serotonin. Insulin affects central serotonin (5-HT) levels.¹¹ Thus, central 5-HT system dysregulation that causes depression might also affect peripheral insulin sensitivity—or vice versa.⁹

Tryptophan, a serotonin precursor, competes with other large neutral amino acids for access to the transport system that moves them across the blood-brain barrier. Insulin stimulates uptake of the competing amino acids—but not tryptophan—into muscle tissue. The resulting increased tryptophan ratio in plasma affords it greater access to the transport system to contribute toward serotonin synthesis. Insulin also promotes central catecholaminergic activity, perhaps by suppressing norepinephrine reuptake and prolonging its residence in the synaptic cleft.¹⁰

Table 1

Diagnostic signs of PCOS

Several studies have found that insulin resistance and hyperinsulinemia can resolve after depression recovery.^9,12 Because insulin resistance is a cardinal feature in PCOS pathophysiology,² insulin resistance may be a common link between depression and PCOS.

Weight gain and obesity also have been described in patients with affective disorders.¹³ Not known is whether the weight gain precedes the psychopathology or is caused by long-term exposure to drugs used to treat affective disorders.

Box 2

We reported a correlation between depression and BMI in women with PCOS.⁴ Depression might be independently associated with BMI, as weight gain and obesity are distressing symptoms associated with depression.¹⁴ However, we found no association between depression and other possibly distressing PCOS symptoms. Thus, the correlation between BMI and depression might more likely reflect the relationship between depression and insulin resistance, as degree of insulin resistance is known to correlate with BMI.

Elevated cortisol. Clearly, other factors—such as hypothalamus-pituitary-adrenal (HPA) axis dysfunction—are known to link affective and endocrine disorders. Hypercortisolemia can lead to both insulin resistance and obesity. Cortisol is one of the glucocorticoids the body secretes in response to stress to mobilize energy by increasing blood glucose levels. Early life stress and chronic emotional stress:

• can impair the negative feedback system that limits cortisol production during stress
• are associated with depression.

Approximately one-half of individuals with depression have elevated serum cortisol.¹⁰ Epidemiologic data show a positive correlation between cortisol levels and insulin resistance,¹⁵ and an association between HPA dysfunction and obesity has been described.¹⁶ Insulin can trigger androgen production by enhancing adrenal sensitivity to adrenocorticotrophic hormone (ACTH).¹⁷

CASE: IMPROVING INSULIN RESISTANCE

We referred Ms. K to an endocrinologist for PCOS evaluation and treatment. Her serum glucose and insulin levels were 83 mg/dL (normal range 70 to 125 mg/dL) and 19.0 uIU/mL (normal range <10 uIU/mL), respectively. These values indicated insulin resistance as determined by the homeostasis model assessment (HOMA) ratio (fasting insulin x fasting glucose/22.5). Values >3.2 indicate insulin resistance, and Ms. K had a HOMA ratio of 3.9. The endocrinologist recommended:

• metformin, starting at 850 mg/d and gradually increased to 2,550 mg/d
• spironolactone, 100 mg/d.

Metformin, a biguanide approved for treating for type 2 diabetes, inhibits hepatic glucose production and increases peripheral insulin sensitivity, but it does not modify pancreatic insulin secretion. It may decrease insulin resistance by reducing gut absorption of glucose, improving glucose uptake by tissues, and/or increasing the number of insulin receptors.¹⁸ In treating PCOS, metformin can:

• restore ovulation¹⁹
• decrease insulin resistance, acne, hirsutism, total and bioavailable testosterone, BMI, and waist-hip ratio.^20,21

Although the link between insulin resistance and depression is unclear, insulin is known to contribute to 5-HT synthesis by promoting tryptophan influx into the brain.²² Therefore, drugs used to treat insulin resistance—such as metformin and alpha lipoic acid²³—might be useful in treating depression.

Spironolactone, a mineralocorticoid receptor (MR) antagonist, reduces hirsutism in women with PCOS.²⁴ It also can decrease insulin resistance and fasting insulin levels in PCOS patients and reduce serum testosterone.²⁵

Evidence on treating mood disorders with hormonal agents such as spironolactone is scarce, although treatment-resistant depression has been reported to resolve with antiglucocorticoid use (Box 2).^25-31 Modulating HPA axis activity to treat affective disorders has been investigated.

CASE: GOING ANTIDEPRESSANT-FREE

At first, Ms. K said she wanted to continue taking venlafaxine with the PCOS treatment. After 2 weeks of combined therapy, however, she chose to stop the antidepressant after her depressive symptoms persisted, and her HAM-D-21 score remained at 28.

During the next 4 weeks, as we tapered off the venlafaxine, Ms. K’s HAM-D-21 score dropped to 7, indicating depressive symptom resolution. Despite slow venlafaxine titration, withdrawal symptoms of excessive crying, not feeling “present,” and tingling sensations occurred. Three days of fluoxetine, 20 mg/d, alleviated these symptoms.

Table 2

Insulin-sensitizing medications used to treat PCOS

We continued Ms. K’s treatment without antidepressants, and her mood continued to improve with metformin, 2,550 mg/d, and spironolactone, 100 mg/d.

TREATMENT RECOMMENDATIONS

PCOS therapy may take up to 6 months to resolve symptoms such as anovulation or hirsutism, but affective symptoms may improve during the first 6 weeks, as this case shows. Choosing medications to treat depression in patients such as Ms. K depends on whether their PCOS is being treated when they present for psychiatric evaluation.

Patient not being treated for PCOS. Refer her to an endocrinologist for PCOS treatment with an insulin-sensitizing medication, such as metformin (Table 2). Treating the insulin resistance associated with PCOS may also resolve the depression. PCOS drug therapy may also include antiandrogens such as spironolactone to treat hirsutism, male-pattern baldness, and acne. We suggest that spironolactone’s antiandrogen effects may help reduce depressive symptoms.

If your patient is not taking an antidepressant at presentation, try PCOS treatment first. If depressive symptoms persist after 3 months, consider adding an antidepressant. If your patient is taking an antidepressant at presentation but continues to be depressed, offer two options:

• taper off the antidepressant while starting PCOS treatment
• continue the antidepressant while starting PCOS treatment.

The first option allows you to try PCOS treatment alone. If the depression is caused by a common underlying pathophysiology—such as insulin resistance—treating PCOS alone may alleviate her depressive symptoms. Monitor for withdrawal symptoms, which may be minimized with a short-term SSRI, such as fluoxetine.

The second option may help patients who have responded to antidepressants in the past. Adjunctive PCOS treatment may “jump-start” the antidepressant response without withdrawal symptoms, but you will not be sure whether the antidepressant response was caused by PCOS therapy alone or the combination therapy.

Patient being treated for PCOS. Treat her with antidepressants, and consult with her endocrinologist to consider more-aggressive insulin-sensitizing medications, especially if she exhibits high levels of insulin resistance.

Other interventions that increase insulin sensitivity and improve glycemic control—such as improving dietary management and sleep habits, reducing alcohol consumption, and increasing physical activity—might have an antidepressant effect. Therefore, recommend these health practices to patients as adjuncts to drug therapies.

CASE: DEPRESSION IN REMISSION

At the 3-month follow-up visit, Ms. K scored zero on the HAM-D-21 scale. With metformin treatment, she had lost approximately 10 lbs and resumed menstruating approximately every 33 days. She reported experiencing low mood, decreased energy, and irritability during the week before her periods, but these symptoms resolved with menses onset.

Serum glucose was within normal range at 89 mg/dL, and serum insulin was 15.0 uIU/Ml. Her HOMA ratio had dropped to 2.8 (below the 3.2 cut-off for insulin resistance).

Ms. K’s endocrinologist monitored her spironolactone and metformin therapy for approximately 1 year, when she became pregnant.

Discussion. PCOS treatment duration depends on the patient’s response and her goals for therapy. Whether or not she continues PCOS treatment, her primary care physician or endocrinologist should continue to monitor her for insulin resistance’s metabolic consequences, including increased risk of type 2 diabetes and cardiovascular disease.

Related resources

• Legro RS, Winans EA. Overview of polycystic ovary syndrome and its relation to psychiatric illness and treatment. Current Psychiatry 2004;3(Dec[suppl]):12-20.
• The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004 Jan; 81(1):19-25.
• Polycystic ovary syndrome (patient information). The National Women’s Health Information Center. U.S. Department of Health and Human Services, Office on Women’s Health. Available at: http://www.4woman.gov/faq/pcos.htm. Accessed Jan. 13, 2005.

Drug brand names

• Citalopram • Celexa
• Fluoxetine • Prozac
• Ketoconazole • Nizoral
• Metformin • Glucophage
• Metyrapone • Metopirone
• Mifepristone • Mifiprex
• Pioglitazone • Actos
• Rosiglitazone • Avandia
• Spironolactone • Aldactone
• Venlafaxine • Effexor XR

Disclosures

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

Women with depression and polycystic ovary syndrome (PCOS) can be trapped in a vicious cycle of hormonal dysregulation. Treating these patients appropriately—with or without antidepressants—requires an understanding of their underlying metabolic disorder.

This article presents a case¹ that exemplifies the association between depression and PCOS (Box 1).^2-4 Based on our research and clinical experience, we offer recommendations to help you manage depression in patients with PCOS.

CHRONIC DEPRESSION WITH AMENORRHEA

Ms. K, age 30, presented for psychiatric evaluation of treatment-resistant recurrent major depression. Her symptoms included sad mood, sleep disturbance, decreased energy, anhedonia, poor concentration, and feelings of guilt and worthlessness. Her score of 28 on the Hamilton Rating Scale for Depression (HAM-D-21) indicated severe depression.

Box 1

This was Ms. K’s third episode of major depression, with the first two occurring at ages 24 and 26. She reported similar symptoms each time. Previous psychiatrists had tried a variety of antidepressants with no therapeutic benefit before she responded to citalopram, 40 mg/d, at age 27. With this selective serotonin reuptake inhibitor, her depressive symptoms resolved for >1 year, except for mild irritability and low mood the week before menses.

Her depressive symptoms returned, however, and her previous psychiatrist treated her for approximately 13 months with extended-release venlafaxine, 225 mg/d. When she remained depressed, she was referred to our clinic for evaluation. Based on her history, we could not determine whether she had become euthymic at age 27 or her symptoms had improved but still met criteria for a major depressive episode.

Ms. K reported having PCOS symptoms from age 19. These included amenorrhea since menarche, hirsutism, hair loss, alopecia, central fat distribution characteristic of PCOS, and male-pattern hair growth on her abdomen and thighs. She was not obese—with a body mass index (BMI) of approximately 25—but had gained 10 to 15 lbs while taking venlafaxine.

Ms. K had never been treated for PCOS but reported that her desire to become pregnant made her more concerned about her symptoms and possible infertility.

Diagnosis. PCOS is usually diagnosed using endocrinologic, clinical, and ultrasonographic criteria (Table 1). Obesity is not a presenting symptom in all women with PCOS. As with Ms. K, about 50% of patients have normal BMI.

Causes of depression in PCOS. Depressed mood in PCOS may be both physiologic and psychological:

• Hypothalamic, pituitary, and other end-organ system dysregulation occurs in both PCOS and affective disorders, which share clinical and biochemical markers including insulin resistance, obesity, and hyperandrogenism.
• PCOS’ clinical sequelae—hirsutism, acne, obesity, hormonal disturbances, fear of infertility, and psychological distress—may damage their self-esteem and female identity.

PCOS’ physical symptoms alone apparently do not account for patients’ worsened mood states. Weiner et al⁵ found that women with PCOS and free testosterone (FT) of 10 to 26 pg/mL (just above normal range) were more depressed than women without PCOS (FT <10 pg/mL) and women with PCOS and FT >26 pg/mL. Women with PCOS with the lower and higher FT levels had similar demographic profiles, but those with the highest FT levels were not the most depressed.

Similarly, in a study of 32 women with PCOS, we found no association between depression and other possibly distressing PCOS symptoms, including hirsutism, irregular menses, acne, or alopecia.⁴

Testosterone and mood disorders. Women such as Ms. K with hyperandrogenic syndromes are at increased risk for mood disorders.⁶ Many metabolic changes associated with PCOS—insulin resistance, obesity, and hyperandrogenism—are also described in patients with affective disorders. Our investigation of reproductive status in women with bipolar disorder found no clinical or biochemical evidence of PCOS with mood-stabilizer treatment. We did find that menstrual disturbances were common, however, and sometimes preceded bipolar disorder onset.⁷

Insulin resistance and depression. Others have linked insulin resistance and depression;⁸ depression has been shown to be associated with impaired insulin sensitivity and hyperinsulinemia.⁹ Depressed persons also tend to eat more sweets, drink more alcohol, exercise less, and sleep fewer hours than the nondepressed—all of which contribute to insulin sensitivity and insulin resistance.¹⁰

WHAT LINKS ENDOCRINE, MOOD DISORDERS?

Insulin and serotonin. Insulin affects central serotonin (5-HT) levels.¹¹ Thus, central 5-HT system dysregulation that causes depression might also affect peripheral insulin sensitivity—or vice versa.⁹

Tryptophan, a serotonin precursor, competes with other large neutral amino acids for access to the transport system that moves them across the blood-brain barrier. Insulin stimulates uptake of the competing amino acids—but not tryptophan—into muscle tissue. The resulting increased tryptophan ratio in plasma affords it greater access to the transport system to contribute toward serotonin synthesis. Insulin also promotes central catecholaminergic activity, perhaps by suppressing norepinephrine reuptake and prolonging its residence in the synaptic cleft.¹⁰

Table 1

Diagnostic signs of PCOS

Several studies have found that insulin resistance and hyperinsulinemia can resolve after depression recovery.^9,12 Because insulin resistance is a cardinal feature in PCOS pathophysiology,² insulin resistance may be a common link between depression and PCOS.

Weight gain and obesity also have been described in patients with affective disorders.¹³ Not known is whether the weight gain precedes the psychopathology or is caused by long-term exposure to drugs used to treat affective disorders.

Box 2

We reported a correlation between depression and BMI in women with PCOS.⁴ Depression might be independently associated with BMI, as weight gain and obesity are distressing symptoms associated with depression.¹⁴ However, we found no association between depression and other possibly distressing PCOS symptoms. Thus, the correlation between BMI and depression might more likely reflect the relationship between depression and insulin resistance, as degree of insulin resistance is known to correlate with BMI.

Elevated cortisol. Clearly, other factors—such as hypothalamus-pituitary-adrenal (HPA) axis dysfunction—are known to link affective and endocrine disorders. Hypercortisolemia can lead to both insulin resistance and obesity. Cortisol is one of the glucocorticoids the body secretes in response to stress to mobilize energy by increasing blood glucose levels. Early life stress and chronic emotional stress:

• can impair the negative feedback system that limits cortisol production during stress
• are associated with depression.

Approximately one-half of individuals with depression have elevated serum cortisol.¹⁰ Epidemiologic data show a positive correlation between cortisol levels and insulin resistance,¹⁵ and an association between HPA dysfunction and obesity has been described.¹⁶ Insulin can trigger androgen production by enhancing adrenal sensitivity to adrenocorticotrophic hormone (ACTH).¹⁷

CASE: IMPROVING INSULIN RESISTANCE

We referred Ms. K to an endocrinologist for PCOS evaluation and treatment. Her serum glucose and insulin levels were 83 mg/dL (normal range 70 to 125 mg/dL) and 19.0 uIU/mL (normal range <10 uIU/mL), respectively. These values indicated insulin resistance as determined by the homeostasis model assessment (HOMA) ratio (fasting insulin x fasting glucose/22.5). Values >3.2 indicate insulin resistance, and Ms. K had a HOMA ratio of 3.9. The endocrinologist recommended:

• metformin, starting at 850 mg/d and gradually increased to 2,550 mg/d
• spironolactone, 100 mg/d.

Metformin, a biguanide approved for treating for type 2 diabetes, inhibits hepatic glucose production and increases peripheral insulin sensitivity, but it does not modify pancreatic insulin secretion. It may decrease insulin resistance by reducing gut absorption of glucose, improving glucose uptake by tissues, and/or increasing the number of insulin receptors.¹⁸ In treating PCOS, metformin can:

• restore ovulation¹⁹
• decrease insulin resistance, acne, hirsutism, total and bioavailable testosterone, BMI, and waist-hip ratio.^20,21

Although the link between insulin resistance and depression is unclear, insulin is known to contribute to 5-HT synthesis by promoting tryptophan influx into the brain.²² Therefore, drugs used to treat insulin resistance—such as metformin and alpha lipoic acid²³—might be useful in treating depression.

Spironolactone, a mineralocorticoid receptor (MR) antagonist, reduces hirsutism in women with PCOS.²⁴ It also can decrease insulin resistance and fasting insulin levels in PCOS patients and reduce serum testosterone.²⁵

Evidence on treating mood disorders with hormonal agents such as spironolactone is scarce, although treatment-resistant depression has been reported to resolve with antiglucocorticoid use (Box 2).^25-31 Modulating HPA axis activity to treat affective disorders has been investigated.

CASE: GOING ANTIDEPRESSANT-FREE

At first, Ms. K said she wanted to continue taking venlafaxine with the PCOS treatment. After 2 weeks of combined therapy, however, she chose to stop the antidepressant after her depressive symptoms persisted, and her HAM-D-21 score remained at 28.

During the next 4 weeks, as we tapered off the venlafaxine, Ms. K’s HAM-D-21 score dropped to 7, indicating depressive symptom resolution. Despite slow venlafaxine titration, withdrawal symptoms of excessive crying, not feeling “present,” and tingling sensations occurred. Three days of fluoxetine, 20 mg/d, alleviated these symptoms.

Table 2

Insulin-sensitizing medications used to treat PCOS

We continued Ms. K’s treatment without antidepressants, and her mood continued to improve with metformin, 2,550 mg/d, and spironolactone, 100 mg/d.

TREATMENT RECOMMENDATIONS

PCOS therapy may take up to 6 months to resolve symptoms such as anovulation or hirsutism, but affective symptoms may improve during the first 6 weeks, as this case shows. Choosing medications to treat depression in patients such as Ms. K depends on whether their PCOS is being treated when they present for psychiatric evaluation.

Patient not being treated for PCOS. Refer her to an endocrinologist for PCOS treatment with an insulin-sensitizing medication, such as metformin (Table 2). Treating the insulin resistance associated with PCOS may also resolve the depression. PCOS drug therapy may also include antiandrogens such as spironolactone to treat hirsutism, male-pattern baldness, and acne. We suggest that spironolactone’s antiandrogen effects may help reduce depressive symptoms.

If your patient is not taking an antidepressant at presentation, try PCOS treatment first. If depressive symptoms persist after 3 months, consider adding an antidepressant. If your patient is taking an antidepressant at presentation but continues to be depressed, offer two options:

• taper off the antidepressant while starting PCOS treatment
• continue the antidepressant while starting PCOS treatment.

The first option allows you to try PCOS treatment alone. If the depression is caused by a common underlying pathophysiology—such as insulin resistance—treating PCOS alone may alleviate her depressive symptoms. Monitor for withdrawal symptoms, which may be minimized with a short-term SSRI, such as fluoxetine.

The second option may help patients who have responded to antidepressants in the past. Adjunctive PCOS treatment may “jump-start” the antidepressant response without withdrawal symptoms, but you will not be sure whether the antidepressant response was caused by PCOS therapy alone or the combination therapy.

Patient being treated for PCOS. Treat her with antidepressants, and consult with her endocrinologist to consider more-aggressive insulin-sensitizing medications, especially if she exhibits high levels of insulin resistance.

Other interventions that increase insulin sensitivity and improve glycemic control—such as improving dietary management and sleep habits, reducing alcohol consumption, and increasing physical activity—might have an antidepressant effect. Therefore, recommend these health practices to patients as adjuncts to drug therapies.

CASE: DEPRESSION IN REMISSION

At the 3-month follow-up visit, Ms. K scored zero on the HAM-D-21 scale. With metformin treatment, she had lost approximately 10 lbs and resumed menstruating approximately every 33 days. She reported experiencing low mood, decreased energy, and irritability during the week before her periods, but these symptoms resolved with menses onset.

Serum glucose was within normal range at 89 mg/dL, and serum insulin was 15.0 uIU/Ml. Her HOMA ratio had dropped to 2.8 (below the 3.2 cut-off for insulin resistance).

Ms. K’s endocrinologist monitored her spironolactone and metformin therapy for approximately 1 year, when she became pregnant.

Discussion. PCOS treatment duration depends on the patient’s response and her goals for therapy. Whether or not she continues PCOS treatment, her primary care physician or endocrinologist should continue to monitor her for insulin resistance’s metabolic consequences, including increased risk of type 2 diabetes and cardiovascular disease.

Related resources

• Legro RS, Winans EA. Overview of polycystic ovary syndrome and its relation to psychiatric illness and treatment. Current Psychiatry 2004;3(Dec[suppl]):12-20.
• The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004 Jan; 81(1):19-25.
• Polycystic ovary syndrome (patient information). The National Women’s Health Information Center. U.S. Department of Health and Human Services, Office on Women’s Health. Available at: http://www.4woman.gov/faq/pcos.htm. Accessed Jan. 13, 2005.

Drug brand names

• Citalopram • Celexa
• Fluoxetine • Prozac
• Ketoconazole • Nizoral
• Metformin • Glucophage
• Metyrapone • Metopirone
• Mifepristone • Mifiprex
• Pioglitazone • Actos
• Rosiglitazone • Avandia
• Spironolactone • Aldactone
• Venlafaxine • Effexor XR

Disclosures

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

Children with developmental problems and serious psychopathologies often do not fit neatly into DSM diagnoses.^1,2 These “diagnostically homeless” children—handicapped by hyperactivity, volcanic rages, extreme anxieties, and other complex problems—need assessment and treatment that address four domains of dysfunction:

• mood/anxiety problems
  
• possible psychosis
  
• language/thought disorder
  
• relationship/socialization problems.
  

This article offers snapshots of four children with undetermined diagnoses, explores the dilemma of treating such patients without knowing what they really have, and recommends a treatment approach to help them function better in school and at home.

WHO ARE THE ‘DIAGNOSTICALLY HOMELESS’?

Devon is 5. He is extremely hyperactive and impulsive, with a normal IQ but significant language delay. He exhibits little but not absent interest in peers and rages when changes are imposed on him.

Table 1

Criteria describing impairments in ‘diagnostically homeless’ children

Steven is 11, referred “to rule out bipolar disorder” and to evaluate hyperactivity, explosiveness, and nightmares. He didn’t speak until he was 22 months old. He worries that bad people are chasing him, fears skeletons under his bed, has nightmares of vampires, and believes that cartoon characters are real and that Sponge Bob is his protector. He says he sees “scary stuff” out of the corner of his eyes. He does not have a thought disorder; psychotic symptoms are more than an overactive imagination or anxiety.

Lauren, age 12, has been diagnosed with attention-deficit/hyperactivity disorder (ADHD) but now presents with withdrawn, depressed, and defiant behaviors. She is described as a “loner” who has never related well to other children. Lauren speaks about being tortured by her peers to the point of sounding paranoid. Her conversation is extremely circumstantial and rambling.

Richard, age 8, has motor coordination, attachment, and disinhibition problems. He hears voices telling him to do bad things, such as hurt people, steal things, and “break stuff.” He doesn’t mind the voices much, and they don’t pervade his life the way hallucinations do in schizophrenia.

Children such as these are common, and it is unclear whether they have a developmental disorder, the prodrome of a psychotic or mood disorder, or idiosyncratic personalities. They don’t meet criteria for many disorders, including autism, bipolar disorder, schizophrenia, and obsessive-compulsive disorder (OCD). They have more-extensive difficulties than those seen in ADHD, generalized anxiety disorder (GAD), or OCD.

Clinically, they are either forced into a category someone thinks they resemble (such as mania in Devon’s case) or are given a “not otherwise specified” (NOS) label (such as PDD NOS, psychosis NOS, or mood disorder NOS), the severity of which goes unacknowledged.

Problems with ‘NOS.’ Some might consider “NOS” a less-severe problem than a specific diagnosis, but these children are very impaired. They are excluded from treatment studies because they do not meet formal criteria for the designated disorder or they get included erroneously because the structured diagnostic interview doesn’t assess what they really have.

Meaningful psychoeducation for their parents is impossible because no Web site or book exists to help them help their child. Finally, no follow-up studies have been done of this group of children because no one can agree on a diagnosis. Small studies have addressed some of these concerns, but outcomes—not surprisingly—are wide-ranging.^3-6

NOS diagnoses also don’t adequately address children with marked anxiety, unusual fears, and perseverative behaviors who are socially clumsy but manage reciprocal social interaction. These children are substantially disabled by:

• attention difficulties
  
• mood dysregulation (including anxiety and/or manic symptoms)
  
• trouble with transitions/change
  
• motor problems (not infrequently)
  
• pragmatic language/social difficulties.