Current Psychiatry

Like the “paradigm shift” Thomas Kuhn coined in his seminal book, The Structure of Scientific Revolutions,¹ paradigm shifts have been occurring at a breathless pace in psychiatry. Thanks to ongoing research, changes in the clinical standard of care for schizophrenia in the past 20 years are a case in point.

Old paradigm: Clozapine is ‘last resort’

Let’s take 1988 as a starting point. That’s when clozapine was “resurrected” as the only drug with proven efficacy in refractory schizophrenia after several first-generation antipsychotics (FGAs) had been tried.² However, because of its potentially fatal side effect (agranulocytosis), clozapine was designated as an absolute last-resort agent. It also was stigmatized for its many other side effects, including serious metabolic complications.

In the 1990s, several more-tolerable second-generation antipsychotics (SGAs) modeled after the clozapine receptor-binding paradigm with “broader efficacy” were launched and quickly became the standard of care. Then in 2000, the field was jolted by a meta-analysis claiming that SGAs are not superior to FGAs in either efficacy or tolerability.³ The 5-year Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, completed in 2004, confirmed that FGA and SGA discontinuation rates were not different,⁴ but it also showed that clozapine’s superior efficacy to FGAs also extended to SGAs.

Emerging research into neuroplasticity and neurogenesis later indicated that SGAs are neuroprotective, whereas FGAs are not.⁵ As a class, SGAs appeared to have repaired their tarnished image but still suffered from the fact that several are associated with metabolic syndrome risk factors,⁶ which are linked to early mortality.

New paradigm: Clozapine should be ‘first-line’

Then a report by Ray et al⁷ showing a significant increase in sudden cardiac death associated with both FGAs and SGAs appeared in January 2009. This put all antipsychotics in a negative light again. But in July 2009, a massive 11-year study by Tiihonen et al⁸ of 66,881 schizophrenia patients in Finland introduced yet another paradigm shift. It strongly suggested that clozapine was the safest antipsychotic, with the lowest mortality from all causes compared with any FGA or SGA, and that it should be considered as first-line treatment! That study also reported that mortality in antipsychotic-treated patients was lower than in untreated ones, which neutralized the cardiac death findings of Ray et al.

The greatest paradigm shift from the Tiihonen et al⁸ study is the stunning conclusion that clozapine should be a first-line antipsychotic, not a last resort for refractory patients. Clozapine has not only the highest efficacy (a very important outcome measure) but also the lowest mortality (death is the most important outcome measure in medicine!). Not a single practice guideline has ever recommended clozapine as a first-line antipsychotic. It is puzzling why the obesity, hyperglycemia, and hyperlipidemia observed with clozapine do not increase mortality. The low suicide rate with clozapine is not surprising, however, because clozapine received FDA approval for the treatment of suicidality in schizophrenia based on the InterSePT study.⁹

The bottom line: Evidence-based research leads to paradigm shifts in treatment that can shatter clinical dogmas. Stay tuned; ongoing psychiatric research will certainly generate new paradigms, and our patients will be better for it.

Like the “paradigm shift” Thomas Kuhn coined in his seminal book, The Structure of Scientific Revolutions,¹ paradigm shifts have been occurring at a breathless pace in psychiatry. Thanks to ongoing research, changes in the clinical standard of care for schizophrenia in the past 20 years are a case in point.

Old paradigm: Clozapine is ‘last resort’

Let’s take 1988 as a starting point. That’s when clozapine was “resurrected” as the only drug with proven efficacy in refractory schizophrenia after several first-generation antipsychotics (FGAs) had been tried.² However, because of its potentially fatal side effect (agranulocytosis), clozapine was designated as an absolute last-resort agent. It also was stigmatized for its many other side effects, including serious metabolic complications.

In the 1990s, several more-tolerable second-generation antipsychotics (SGAs) modeled after the clozapine receptor-binding paradigm with “broader efficacy” were launched and quickly became the standard of care. Then in 2000, the field was jolted by a meta-analysis claiming that SGAs are not superior to FGAs in either efficacy or tolerability.³ The 5-year Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, completed in 2004, confirmed that FGA and SGA discontinuation rates were not different,⁴ but it also showed that clozapine’s superior efficacy to FGAs also extended to SGAs.

Emerging research into neuroplasticity and neurogenesis later indicated that SGAs are neuroprotective, whereas FGAs are not.⁵ As a class, SGAs appeared to have repaired their tarnished image but still suffered from the fact that several are associated with metabolic syndrome risk factors,⁶ which are linked to early mortality.

New paradigm: Clozapine should be ‘first-line’

Then a report by Ray et al⁷ showing a significant increase in sudden cardiac death associated with both FGAs and SGAs appeared in January 2009. This put all antipsychotics in a negative light again. But in July 2009, a massive 11-year study by Tiihonen et al⁸ of 66,881 schizophrenia patients in Finland introduced yet another paradigm shift. It strongly suggested that clozapine was the safest antipsychotic, with the lowest mortality from all causes compared with any FGA or SGA, and that it should be considered as first-line treatment! That study also reported that mortality in antipsychotic-treated patients was lower than in untreated ones, which neutralized the cardiac death findings of Ray et al.

The greatest paradigm shift from the Tiihonen et al⁸ study is the stunning conclusion that clozapine should be a first-line antipsychotic, not a last resort for refractory patients. Clozapine has not only the highest efficacy (a very important outcome measure) but also the lowest mortality (death is the most important outcome measure in medicine!). Not a single practice guideline has ever recommended clozapine as a first-line antipsychotic. It is puzzling why the obesity, hyperglycemia, and hyperlipidemia observed with clozapine do not increase mortality. The low suicide rate with clozapine is not surprising, however, because clozapine received FDA approval for the treatment of suicidality in schizophrenia based on the InterSePT study.⁹

The bottom line: Evidence-based research leads to paradigm shifts in treatment that can shatter clinical dogmas. Stay tuned; ongoing psychiatric research will certainly generate new paradigms, and our patients will be better for it.

Like the “paradigm shift” Thomas Kuhn coined in his seminal book, The Structure of Scientific Revolutions,¹ paradigm shifts have been occurring at a breathless pace in psychiatry. Thanks to ongoing research, changes in the clinical standard of care for schizophrenia in the past 20 years are a case in point.

Old paradigm: Clozapine is ‘last resort’

Let’s take 1988 as a starting point. That’s when clozapine was “resurrected” as the only drug with proven efficacy in refractory schizophrenia after several first-generation antipsychotics (FGAs) had been tried.² However, because of its potentially fatal side effect (agranulocytosis), clozapine was designated as an absolute last-resort agent. It also was stigmatized for its many other side effects, including serious metabolic complications.

In the 1990s, several more-tolerable second-generation antipsychotics (SGAs) modeled after the clozapine receptor-binding paradigm with “broader efficacy” were launched and quickly became the standard of care. Then in 2000, the field was jolted by a meta-analysis claiming that SGAs are not superior to FGAs in either efficacy or tolerability.³ The 5-year Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, completed in 2004, confirmed that FGA and SGA discontinuation rates were not different,⁴ but it also showed that clozapine’s superior efficacy to FGAs also extended to SGAs.

Emerging research into neuroplasticity and neurogenesis later indicated that SGAs are neuroprotective, whereas FGAs are not.⁵ As a class, SGAs appeared to have repaired their tarnished image but still suffered from the fact that several are associated with metabolic syndrome risk factors,⁶ which are linked to early mortality.

New paradigm: Clozapine should be ‘first-line’

Then a report by Ray et al⁷ showing a significant increase in sudden cardiac death associated with both FGAs and SGAs appeared in January 2009. This put all antipsychotics in a negative light again. But in July 2009, a massive 11-year study by Tiihonen et al⁸ of 66,881 schizophrenia patients in Finland introduced yet another paradigm shift. It strongly suggested that clozapine was the safest antipsychotic, with the lowest mortality from all causes compared with any FGA or SGA, and that it should be considered as first-line treatment! That study also reported that mortality in antipsychotic-treated patients was lower than in untreated ones, which neutralized the cardiac death findings of Ray et al.

The greatest paradigm shift from the Tiihonen et al⁸ study is the stunning conclusion that clozapine should be a first-line antipsychotic, not a last resort for refractory patients. Clozapine has not only the highest efficacy (a very important outcome measure) but also the lowest mortality (death is the most important outcome measure in medicine!). Not a single practice guideline has ever recommended clozapine as a first-line antipsychotic. It is puzzling why the obesity, hyperglycemia, and hyperlipidemia observed with clozapine do not increase mortality. The low suicide rate with clozapine is not surprising, however, because clozapine received FDA approval for the treatment of suicidality in schizophrenia based on the InterSePT study.⁹

The bottom line: Evidence-based research leads to paradigm shifts in treatment that can shatter clinical dogmas. Stay tuned; ongoing psychiatric research will certainly generate new paradigms, and our patients will be better for it.

CASE: Unable to communicate

Mrs. A, age 44, is airlifted to the emergency room after a motor vehicle accident in which she was the restrained front seat passenger. She was on the way to a mental health follow-up appointment with her husband, who died on the scene, and 24-year-old son, who sustained multiple injuries. At the accident scene, Mrs. A was awake and responded to all questions by saying, “I don’t know.” No other history could be obtained. She was carrying documents from a local psychiatric facility that stated she had been discharged 1 month ago with a diagnosis of psychotic disorder, not otherwise specified (NOS). Her discharge medications were olanzapine, 15 mg at bedtime; escitalopram, 20 mg/d; lamotrigine, 100 mg/d; zolpidem, 10 mg as needed at bedtime; and diazepam, 5 mg tid.

Initial assessment reveals mild concussion, nondisplaced fractures of the left C7 and T1 transverse processes, and fracture of the posterior left first rib. Mrs. A is admitted to the trauma surgery service. Soon after, nurses report that Mrs. A is not able to report symptoms. Psychiatry service is consulted to evaluate her continued confusion and inability to communicate.

The authors’ observations

Mrs. A seems anxious because of my repeated attempts to communicate. Her affect is restricted, and her speech is limited to “I don’t know” but fluent. She does not appear to be responding to internal stimuli. Neurologic examination, including cranial nerves and reflexes, is normal. A chart review reveals that her psychiatric medications have been continued upon admission.

HISTORY: Always nervous

We contact Mrs. A’s son, who also was admitted to the hospital, for more information. He reports that his mother has a long history of “nerve problems,” which he describes as “crying and feeling sad and nervous.” He says Mrs. A’s mother also had these problems, and Mrs. A’s childhood was difficult (Table 1). Because of this condition, Mrs. A lives alone in a trailer next to the house where her husband and children live.

Mrs. A’s son said that she had a “nervous breakdown” a few months ago, was admitted to the local psychiatric facility, and since then had been saying only, “I don’t know.” She can communicate her wishes by pointing at “Yes” or “No” written on paper. At home, she can perform all activities of daily living (ADLs), including paying bills. He denies that his mother engages in drug abuse.

We obtain Mrs. A’s treatment records from the psychiatric facility and learn she was admitted with a history of confusion, auditory and visual hallucinations, and crying episodes. She had a history of noncompliance with outpatient medications, which included diazepam, duloxetine, and ziprasidone. Upon admission to that facility, Mrs. A was alert but disoriented to place and time. She answered questions slowly but was brief, sometimes incoherent, and having auditory and visual hallucinations.

During that hospitalization, clinicians established a working diagnosis of psychotic disorder, NOS. Mrs. A was noted to have a urinary tract infection, which they treated with amoxicillin/clavulanate. Ziprasidone was discontinued and olanzapine was started. Escitalopram and lamotrigine were added. Mrs. A’s hallucinations gradually resolved, and she was able to perform ADLs. However, she did not communicate much and started answering most questions with “I don’t know.” At discharge, she was sent home to the care of her sister and husband.

Since then, Mrs. A had been taking her medications regularly but did not show improvement in her speech or methods of communication.

The authors’ observations

Table 1

Mrs. A’s family and personal history of ‘nerve problems’

What is the cause of Mrs. A’s speech difficulties?

TREATMENT: An abbreviated stay

A week after admission, Mrs. A is deemed medically stable. Head CT reveals a small, calcified left parietal meningioma that did not correlate with her symptoms (Table 3). Brain MRI shows mild frontotemporal atrophy that was considered inconclusive evidence for a diagnosis of frontotemporal dementia; there is no evidence of infarction, tumors, or other enhancing lesions that may have explained Mrs. A’s symptoms. A 12-lead EEG shows no abnormalities, which rules out a seizure disorder.

Neurology consult rules out concussion syndrome. Over several different evaluations, Mrs. A is noted to follow commands, perform ADLs, and walk. She is able to write her name legibly but is unable to write anything else or to perform a clock-drawing test.

A speech pathology evaluation is requested. A speech pathologist diagnoses Mrs. A with expressive aphasia—impaired ability to speak and write—with some receptive component, meaning her ability to comprehend spoken words also is impaired.

Mrs. A’s speech status does not change, and she remains unable to communicate. She is discharged 10 days after admission with scheduled outpatient follow-up.

Table 3

Findings of Mrs. A’s neurologic testing

The authors’ observations

At discharge, it seemed likely that Mrs. A may have early symptoms of a neurodegenerative illness, such as frontotemporal dementia, or the aphasia may be a manifestation of chronic psychotic depression. We wanted to follow up with neuropsychological testing and PET scan before establishing a definitive psychiatric diagnosis and modifying the treatment plan.

Related resources

• The Academy of Aphasia. www.academyofaphasia.org.
  
• The National Aphasia Association. www.aphasia.org.
  

• Amoxicillin/clavulanate • Augmentin
  
• Diazepam • Valium
  
• Duloxetine • Cymbalta
  
• Escitalopram • Lexapro
  
• Lamotrigine • Lamictal
  
• Olanzapine • Zyprexa
  
• Ziprasidone • Geodon
  
• Zolpidem • Ambien
  

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

CASE: Unable to communicate

Mrs. A, age 44, is airlifted to the emergency room after a motor vehicle accident in which she was the restrained front seat passenger. She was on the way to a mental health follow-up appointment with her husband, who died on the scene, and 24-year-old son, who sustained multiple injuries. At the accident scene, Mrs. A was awake and responded to all questions by saying, “I don’t know.” No other history could be obtained. She was carrying documents from a local psychiatric facility that stated she had been discharged 1 month ago with a diagnosis of psychotic disorder, not otherwise specified (NOS). Her discharge medications were olanzapine, 15 mg at bedtime; escitalopram, 20 mg/d; lamotrigine, 100 mg/d; zolpidem, 10 mg as needed at bedtime; and diazepam, 5 mg tid.

Initial assessment reveals mild concussion, nondisplaced fractures of the left C7 and T1 transverse processes, and fracture of the posterior left first rib. Mrs. A is admitted to the trauma surgery service. Soon after, nurses report that Mrs. A is not able to report symptoms. Psychiatry service is consulted to evaluate her continued confusion and inability to communicate.

The authors’ observations

Mrs. A seems anxious because of my repeated attempts to communicate. Her affect is restricted, and her speech is limited to “I don’t know” but fluent. She does not appear to be responding to internal stimuli. Neurologic examination, including cranial nerves and reflexes, is normal. A chart review reveals that her psychiatric medications have been continued upon admission.

HISTORY: Always nervous

We contact Mrs. A’s son, who also was admitted to the hospital, for more information. He reports that his mother has a long history of “nerve problems,” which he describes as “crying and feeling sad and nervous.” He says Mrs. A’s mother also had these problems, and Mrs. A’s childhood was difficult (Table 1). Because of this condition, Mrs. A lives alone in a trailer next to the house where her husband and children live.

Mrs. A’s son said that she had a “nervous breakdown” a few months ago, was admitted to the local psychiatric facility, and since then had been saying only, “I don’t know.” She can communicate her wishes by pointing at “Yes” or “No” written on paper. At home, she can perform all activities of daily living (ADLs), including paying bills. He denies that his mother engages in drug abuse.

We obtain Mrs. A’s treatment records from the psychiatric facility and learn she was admitted with a history of confusion, auditory and visual hallucinations, and crying episodes. She had a history of noncompliance with outpatient medications, which included diazepam, duloxetine, and ziprasidone. Upon admission to that facility, Mrs. A was alert but disoriented to place and time. She answered questions slowly but was brief, sometimes incoherent, and having auditory and visual hallucinations.

During that hospitalization, clinicians established a working diagnosis of psychotic disorder, NOS. Mrs. A was noted to have a urinary tract infection, which they treated with amoxicillin/clavulanate. Ziprasidone was discontinued and olanzapine was started. Escitalopram and lamotrigine were added. Mrs. A’s hallucinations gradually resolved, and she was able to perform ADLs. However, she did not communicate much and started answering most questions with “I don’t know.” At discharge, she was sent home to the care of her sister and husband.

Since then, Mrs. A had been taking her medications regularly but did not show improvement in her speech or methods of communication.

The authors’ observations

Table 1

Mrs. A’s family and personal history of ‘nerve problems’

What is the cause of Mrs. A’s speech difficulties?

TREATMENT: An abbreviated stay

A week after admission, Mrs. A is deemed medically stable. Head CT reveals a small, calcified left parietal meningioma that did not correlate with her symptoms (Table 3). Brain MRI shows mild frontotemporal atrophy that was considered inconclusive evidence for a diagnosis of frontotemporal dementia; there is no evidence of infarction, tumors, or other enhancing lesions that may have explained Mrs. A’s symptoms. A 12-lead EEG shows no abnormalities, which rules out a seizure disorder.

Neurology consult rules out concussion syndrome. Over several different evaluations, Mrs. A is noted to follow commands, perform ADLs, and walk. She is able to write her name legibly but is unable to write anything else or to perform a clock-drawing test.

A speech pathology evaluation is requested. A speech pathologist diagnoses Mrs. A with expressive aphasia—impaired ability to speak and write—with some receptive component, meaning her ability to comprehend spoken words also is impaired.

Mrs. A’s speech status does not change, and she remains unable to communicate. She is discharged 10 days after admission with scheduled outpatient follow-up.

Table 3

Findings of Mrs. A’s neurologic testing

The authors’ observations

At discharge, it seemed likely that Mrs. A may have early symptoms of a neurodegenerative illness, such as frontotemporal dementia, or the aphasia may be a manifestation of chronic psychotic depression. We wanted to follow up with neuropsychological testing and PET scan before establishing a definitive psychiatric diagnosis and modifying the treatment plan.

Related resources

• The Academy of Aphasia. www.academyofaphasia.org.
  
• The National Aphasia Association. www.aphasia.org.
  

• Amoxicillin/clavulanate • Augmentin
  
• Diazepam • Valium
  
• Duloxetine • Cymbalta
  
• Escitalopram • Lexapro
  
• Lamotrigine • Lamictal
  
• Olanzapine • Zyprexa
  
• Ziprasidone • Geodon
  
• Zolpidem • Ambien
  

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

CASE: Unable to communicate

Mrs. A, age 44, is airlifted to the emergency room after a motor vehicle accident in which she was the restrained front seat passenger. She was on the way to a mental health follow-up appointment with her husband, who died on the scene, and 24-year-old son, who sustained multiple injuries. At the accident scene, Mrs. A was awake and responded to all questions by saying, “I don’t know.” No other history could be obtained. She was carrying documents from a local psychiatric facility that stated she had been discharged 1 month ago with a diagnosis of psychotic disorder, not otherwise specified (NOS). Her discharge medications were olanzapine, 15 mg at bedtime; escitalopram, 20 mg/d; lamotrigine, 100 mg/d; zolpidem, 10 mg as needed at bedtime; and diazepam, 5 mg tid.

Initial assessment reveals mild concussion, nondisplaced fractures of the left C7 and T1 transverse processes, and fracture of the posterior left first rib. Mrs. A is admitted to the trauma surgery service. Soon after, nurses report that Mrs. A is not able to report symptoms. Psychiatry service is consulted to evaluate her continued confusion and inability to communicate.

The authors’ observations

Mrs. A seems anxious because of my repeated attempts to communicate. Her affect is restricted, and her speech is limited to “I don’t know” but fluent. She does not appear to be responding to internal stimuli. Neurologic examination, including cranial nerves and reflexes, is normal. A chart review reveals that her psychiatric medications have been continued upon admission.

HISTORY: Always nervous

We contact Mrs. A’s son, who also was admitted to the hospital, for more information. He reports that his mother has a long history of “nerve problems,” which he describes as “crying and feeling sad and nervous.” He says Mrs. A’s mother also had these problems, and Mrs. A’s childhood was difficult (Table 1). Because of this condition, Mrs. A lives alone in a trailer next to the house where her husband and children live.

Mrs. A’s son said that she had a “nervous breakdown” a few months ago, was admitted to the local psychiatric facility, and since then had been saying only, “I don’t know.” She can communicate her wishes by pointing at “Yes” or “No” written on paper. At home, she can perform all activities of daily living (ADLs), including paying bills. He denies that his mother engages in drug abuse.

We obtain Mrs. A’s treatment records from the psychiatric facility and learn she was admitted with a history of confusion, auditory and visual hallucinations, and crying episodes. She had a history of noncompliance with outpatient medications, which included diazepam, duloxetine, and ziprasidone. Upon admission to that facility, Mrs. A was alert but disoriented to place and time. She answered questions slowly but was brief, sometimes incoherent, and having auditory and visual hallucinations.

During that hospitalization, clinicians established a working diagnosis of psychotic disorder, NOS. Mrs. A was noted to have a urinary tract infection, which they treated with amoxicillin/clavulanate. Ziprasidone was discontinued and olanzapine was started. Escitalopram and lamotrigine were added. Mrs. A’s hallucinations gradually resolved, and she was able to perform ADLs. However, she did not communicate much and started answering most questions with “I don’t know.” At discharge, she was sent home to the care of her sister and husband.

Since then, Mrs. A had been taking her medications regularly but did not show improvement in her speech or methods of communication.

The authors’ observations

Table 1

Mrs. A’s family and personal history of ‘nerve problems’

What is the cause of Mrs. A’s speech difficulties?

TREATMENT: An abbreviated stay

A week after admission, Mrs. A is deemed medically stable. Head CT reveals a small, calcified left parietal meningioma that did not correlate with her symptoms (Table 3). Brain MRI shows mild frontotemporal atrophy that was considered inconclusive evidence for a diagnosis of frontotemporal dementia; there is no evidence of infarction, tumors, or other enhancing lesions that may have explained Mrs. A’s symptoms. A 12-lead EEG shows no abnormalities, which rules out a seizure disorder.

Neurology consult rules out concussion syndrome. Over several different evaluations, Mrs. A is noted to follow commands, perform ADLs, and walk. She is able to write her name legibly but is unable to write anything else or to perform a clock-drawing test.

A speech pathology evaluation is requested. A speech pathologist diagnoses Mrs. A with expressive aphasia—impaired ability to speak and write—with some receptive component, meaning her ability to comprehend spoken words also is impaired.

Mrs. A’s speech status does not change, and she remains unable to communicate. She is discharged 10 days after admission with scheduled outpatient follow-up.

Table 3

Findings of Mrs. A’s neurologic testing

The authors’ observations

At discharge, it seemed likely that Mrs. A may have early symptoms of a neurodegenerative illness, such as frontotemporal dementia, or the aphasia may be a manifestation of chronic psychotic depression. We wanted to follow up with neuropsychological testing and PET scan before establishing a definitive psychiatric diagnosis and modifying the treatment plan.

Related resources

• The Academy of Aphasia. www.academyofaphasia.org.
  
• The National Aphasia Association. www.aphasia.org.
  

• Amoxicillin/clavulanate • Augmentin
  
• Diazepam • Valium
  
• Duloxetine • Cymbalta
  
• Escitalopram • Lexapro
  
• Lamotrigine • Lamictal
  
• Olanzapine • Zyprexa
  
• Ziprasidone • Geodon
  
• Zolpidem • Ambien
  

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

Comment on this article

What is it about dissociative identity disorder (DID) that makes it a polarizing diagnosis? Why does it split professionals into believers and nonbelievers, stirring up heated debates, high emotions, and fervor similar to what we see in religion?

The DID controversy is likely to continue beyond the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), slated for publication in 2012. Proponents and opponents claim to have the upper hand in arguments about the validity of the DID diagnosis and benefits vs harm of treatment. This article examines the logic of previous and new arguments.

1. The fallacy of equal-footing arguments

When 301 board-certified U.S. psychiatrists were surveyed in 1999 about their attitudes toward DSM-IV dissociative disorders diagnoses:

• 35% had no reservations about DID
• 43% were skeptical
• 15% indicated the diagnosis should not be included in the DSM.¹

Only 21% believed there was strong evidence for DID’s scientific validity. On balance, published papers appear skeptical about DID’s core components: dissociative amnesia and recovered-memory therapy.²

DID skeptics are sometimes accused of “denial” or “reluctance” to accept this diagnosis. Informed skepticism is acceptable—even encouraged—in making a diagnosis of malingering, factitious disorder, some personality disorders, substance abuse, and psychotic states, to name a few. Why is informed skepticism about DID frowned on?

In medical and surgical specialties, informed skepticism is encouraged so that the practitioner challenges his or her assumptions about a possible diagnosis through a methodical process of inclusion, exclusion, and hypothesis testing. I argue that little or no skepticism is substandard practice, if not negligence.

Bertrand Russell’s celestial teapot parable (Box 1)³ exposed the fallacy of equal-footing arguments (ie, in any debate or argument that has 2 sides, the 2 sides are not necessarily on equal footing). Russell’s argument is valid for any belief system relying on faith. Now that DID is in the “ancient book” (DSM-IV), the burden of proof by some magical logic has shifted to “nonbelievers.” In law that is called precedent, but law is even less scientific than psychiatry and not the best example to follow. A mistake made 100 years ago is still a mistake.

Box 1

2. Illogic of causation

Piper and Merskey’s extensive literature review^4,5 examined the presumed association between DID and childhood abuse (mostly sexual). They found:

• no proof that DID results from childhood trauma or that DID cases in children are almost never reported
• “consistent evidence of blatant iatrogenesis” in the practice of some DID proponents.

One can easily turn the logic around by claiming that a DID diagnosis causes memories of childhood sexual abuse.

As for patients’ presumed reluctance to report childhood abuse, I witnessed in every one of my 15 alleged cases of DID (all female) not reluctance but a strong tendency to flaunt their diagnosis and symptoms and an eagerness to re-tell their stories with graphic detail, usually unprovoked. Patients with a DID diagnosis seem to have a “powerful vested interest”—to borrow Paul McHugh’s expression⁶—in sustaining the DID diagnosis, symptoms, behaviors, and therapy as an end in itself.

DID proponents acknowledge that iatrogenic artifacts may exist in the diagnosis and treatment. However, they almost immediately insinuate that DID patients’ “subtle defensive strategies” generate these artifacts. Greaves’ discussion of multiple personality disorder⁷ acknowledged that overdiagnosis may be driven by therapists’ desire to “attain narcissistic gratification at ‘having a multiple [sic] of their own’” but blamed this on “neophytes.”

3. Tautology in DID’s definition

DSM-IV’s criterion A for DID is in fact a definition: “the presence of 2 or more distinct identities or personality states (each with its own relatively enduring pattern of perceiving, relating to, and thinking about the environment and self).”⁸ Together, criteria A and B show circularity and redundancy. If A is met, then B must be met because “a person’s behavior” is part of her or his identity and personality state, which was established in A.

Tautology is a major shortcoming of the descriptive system for psychopathology in general. Of greater clinical value are observing a patient’s actions, listening to his or her words, learning his or her history, studying his or her expressions, and noting his or her relationships.⁹

4. Bewitchment by language

Psychiatrists could spend hours over strong cups of coffee arguing the meanings of terms such as “dissociation,” “presence,” “identity,” “personality state,” etc. Psychiatry has been targeted unfairly regarding where it falls on the subjectivity-objectivity axis, but it has not fared that differently from other medical specialties.¹⁰ Psychiatry, however, depends much more on language.

Consider slippery terms such as personality, identity, self, dissociation, integration, alters, ego, ego states, trance states, personality states, unconscious, etc. Lack of precision, variability in use of words and their meaning, and variability in understanding the concept that these terms try to communicate make speaking a common language extremely difficult. To borrow from Wittgenstein, psychiatrists’ intellect is bewitched by language.¹¹

Words fail to communicate experiences such as the taste of red wine or the feeling of sand beneath bare feet. It is almost futile to try to define dissociation, identity, personality states, etc., using words or even pictures. More definitions and agreement on stricter definitions would not provide greater clarity or solve the problem of first-person authority.

An example is found in DID’s criterion B: “at least 2 of these identities or personality states recurrently take control of the person’s behavior” [italics mine]. “Possession” seems to be a fitting word! Whether it is an alter or the devil taking control is a technicality. Even more acceptable would be possessed by inconsolable anger, possessed by fierce jealousy, possessed by lust, possessed by hatred and vengeance, possessed by and obsessed with love, possessed by cocaine, etc.

Dissociation is used to describe so many things that it has become almost meaningless (Table). I refer not only to definitional imprecision but also to a lack of consensus on the nature of the concept itself.

The word “control” is another term on whose meaning almost no 2 psychiatrists agree. Consensus on definitions is elusive when words become divorced from the concepts they were intended to describe.

Table

A meaningless word? ‘Dissociation’ is used to describe many things

5. Validity of first-person authority

The skeptic’s attempt to investigate a subjective phenomena—especially DID—is bound to break on the rocks of the first-person authority, to borrow Donald Davidson’s words.⁹ To support reliability and validity of the diagnosis, dissociation researchers rely on “scales” and “instruments” to give the impression of objectivity, empiricism, and “science” hard at work. However, a quick look at some of the questions on these “instruments” reveals their assault on reason and intellect (Box 2).¹²

Proponents who claim DID is “sufficiently validated for inclusion in the current and future versions of DSM” are to be commended for adding “much more research is needed in several areas.”¹³ Piper and Merskey’s review^4,5 concluded that DID could not be reliably diagnosed.

Box 2

6. Does a DID diagnosis do harm?

Webster’s¹⁴ defines iatrogenic as: “Resulting from the activity of a physician. Originally applied to a disorder or disorders inadvertently induced in the patient by the manner of the physician’s examination, discussion, or treatment, it now applies to any condition occurring in a patient as result of medical treatment, such as a drug reaction.”

A DID diagnosis has been blamed for misdiagnosis of other entities,¹⁵ patient mismanagement,¹⁶ and inadequate treatment of depression.¹⁷ Even when DID is treated with the best of intentions, undesired negative effects may result from psychotherapy, and some patients experience worsening of symptoms and/or deterioration of functioning.^18,19

In Creating Hysteria, Acocella²⁰ cites examples of harm done to [alleged DID] patients and their families, including 2 high-profile cases under the care of a member of the DSM-IV work group on dissociation.

7. How is self-deception possible?

The ability to self-deceive has advantages and disadvantages,²¹ and widespread deception is possible. Richard Dawkins’s The God Delusion,²² Christopher Hitchens’s God is Not Great,²³ and Michael Shermer’s Why People Believe Weird Things²⁴ are recent exposés of how self-deception and deception by charismatic figures occurs despite the progress “reason” has made.

As with other belief systems that become entrenched in the face of criticism, DID proponents accuse critics of denial, reluctance, and adopting “defense[s] against dealing with the reality of child abuse in North America.”²⁰ One wonders why just North America! Why not Africa, with its children in Sudan, Somalia, Zimbabwe—to name a few—enduring enough abuse to spread around the world several times over?

Proponents also allege that part of the reason for “professionals’ reluctance” to embrace DID is the “subtle presentation of the symptoms.”²⁵ In other words, it is not reluctance; it is ignorance, with the insinuation that nonbelievers or skeptics are not smart enough to pick up on the subtle clinical presentation. I can’t see why professionals would be ignorant when it comes to dissociation as opposed to schizophrenia, depression, bipolar disorder, and almost all DSM-IV disorders. Why this selective ignorance exists remains unexplained.

8. Experts and conflict of interest

DSM-V’s guidelines on conflict of interest are very welcome. One hopes conflict of interest does not refer only to financial relationships with pharmaceutical companies. Conflicts of interest can exert unseen influence, which—if made clear—would have a direct bearing of the reliability and trustworthiness of the published literature. Strong adherents have a lot to gain from perpetuating DID. Nonbelievers, skeptics, and opponents would gain nothing if DID disappeared from DSM today or in 2012.

The first potential conflict of interest for DID “experts” is financial gain. For example, a psychologist saw 1 of my patients (before I came to the scene) for 5 years for 3 sessions a week (2 for adult alters and 1 for childhood alters), with annual earnings of nearly $20,000. A self-declared expert would need only 10 patients to be better off than most psychiatrists.

The second potential conflict of interest is personal gain in the form of narcissistic gratification, as mentioned above. Although DID proponents blame neophytes, “teachers” are no less prone to narcissistic gratification. Under this umbrella falls the DID experts’ interest in recognition, fame, and easily acquired expertise. One may argue that self-arrogated expertise in this realm is much ado about nothing.

The third potential conflict of interest is the very process of becoming an “expert.” The bias of this process is evident because if one does not accept a priori the presence of DID, he or she will never be admitted to the exclusive club of “DID experts.” To attain the status of authority or expert on this subject, one must be a believer. Otherwise, how would one claim to have diagnosed and treated hundreds of DID cases? It is a feedback loop that can’t be broken.

Related resources

• Borch-Jacobsen M. Making minds and madness: from hysteria to depression. New York, NY: Cambridge University Press; 2009.
• Memory and reality. False Memory Syndrome Foundation. www.fmsfonline.org.

Disclosure

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

Comment on this article

What is it about dissociative identity disorder (DID) that makes it a polarizing diagnosis? Why does it split professionals into believers and nonbelievers, stirring up heated debates, high emotions, and fervor similar to what we see in religion?

The DID controversy is likely to continue beyond the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), slated for publication in 2012. Proponents and opponents claim to have the upper hand in arguments about the validity of the DID diagnosis and benefits vs harm of treatment. This article examines the logic of previous and new arguments.

1. The fallacy of equal-footing arguments

When 301 board-certified U.S. psychiatrists were surveyed in 1999 about their attitudes toward DSM-IV dissociative disorders diagnoses:

• 35% had no reservations about DID
• 43% were skeptical
• 15% indicated the diagnosis should not be included in the DSM.¹

Only 21% believed there was strong evidence for DID’s scientific validity. On balance, published papers appear skeptical about DID’s core components: dissociative amnesia and recovered-memory therapy.²

DID skeptics are sometimes accused of “denial” or “reluctance” to accept this diagnosis. Informed skepticism is acceptable—even encouraged—in making a diagnosis of malingering, factitious disorder, some personality disorders, substance abuse, and psychotic states, to name a few. Why is informed skepticism about DID frowned on?

In medical and surgical specialties, informed skepticism is encouraged so that the practitioner challenges his or her assumptions about a possible diagnosis through a methodical process of inclusion, exclusion, and hypothesis testing. I argue that little or no skepticism is substandard practice, if not negligence.

Bertrand Russell’s celestial teapot parable (Box 1)³ exposed the fallacy of equal-footing arguments (ie, in any debate or argument that has 2 sides, the 2 sides are not necessarily on equal footing). Russell’s argument is valid for any belief system relying on faith. Now that DID is in the “ancient book” (DSM-IV), the burden of proof by some magical logic has shifted to “nonbelievers.” In law that is called precedent, but law is even less scientific than psychiatry and not the best example to follow. A mistake made 100 years ago is still a mistake.

Box 1

2. Illogic of causation

Piper and Merskey’s extensive literature review^4,5 examined the presumed association between DID and childhood abuse (mostly sexual). They found:

• no proof that DID results from childhood trauma or that DID cases in children are almost never reported
• “consistent evidence of blatant iatrogenesis” in the practice of some DID proponents.

One can easily turn the logic around by claiming that a DID diagnosis causes memories of childhood sexual abuse.

As for patients’ presumed reluctance to report childhood abuse, I witnessed in every one of my 15 alleged cases of DID (all female) not reluctance but a strong tendency to flaunt their diagnosis and symptoms and an eagerness to re-tell their stories with graphic detail, usually unprovoked. Patients with a DID diagnosis seem to have a “powerful vested interest”—to borrow Paul McHugh’s expression⁶—in sustaining the DID diagnosis, symptoms, behaviors, and therapy as an end in itself.

DID proponents acknowledge that iatrogenic artifacts may exist in the diagnosis and treatment. However, they almost immediately insinuate that DID patients’ “subtle defensive strategies” generate these artifacts. Greaves’ discussion of multiple personality disorder⁷ acknowledged that overdiagnosis may be driven by therapists’ desire to “attain narcissistic gratification at ‘having a multiple [sic] of their own’” but blamed this on “neophytes.”

3. Tautology in DID’s definition

DSM-IV’s criterion A for DID is in fact a definition: “the presence of 2 or more distinct identities or personality states (each with its own relatively enduring pattern of perceiving, relating to, and thinking about the environment and self).”⁸ Together, criteria A and B show circularity and redundancy. If A is met, then B must be met because “a person’s behavior” is part of her or his identity and personality state, which was established in A.

Tautology is a major shortcoming of the descriptive system for psychopathology in general. Of greater clinical value are observing a patient’s actions, listening to his or her words, learning his or her history, studying his or her expressions, and noting his or her relationships.⁹

4. Bewitchment by language

Psychiatrists could spend hours over strong cups of coffee arguing the meanings of terms such as “dissociation,” “presence,” “identity,” “personality state,” etc. Psychiatry has been targeted unfairly regarding where it falls on the subjectivity-objectivity axis, but it has not fared that differently from other medical specialties.¹⁰ Psychiatry, however, depends much more on language.

Consider slippery terms such as personality, identity, self, dissociation, integration, alters, ego, ego states, trance states, personality states, unconscious, etc. Lack of precision, variability in use of words and their meaning, and variability in understanding the concept that these terms try to communicate make speaking a common language extremely difficult. To borrow from Wittgenstein, psychiatrists’ intellect is bewitched by language.¹¹

Words fail to communicate experiences such as the taste of red wine or the feeling of sand beneath bare feet. It is almost futile to try to define dissociation, identity, personality states, etc., using words or even pictures. More definitions and agreement on stricter definitions would not provide greater clarity or solve the problem of first-person authority.

An example is found in DID’s criterion B: “at least 2 of these identities or personality states recurrently take control of the person’s behavior” [italics mine]. “Possession” seems to be a fitting word! Whether it is an alter or the devil taking control is a technicality. Even more acceptable would be possessed by inconsolable anger, possessed by fierce jealousy, possessed by lust, possessed by hatred and vengeance, possessed by and obsessed with love, possessed by cocaine, etc.

Dissociation is used to describe so many things that it has become almost meaningless (Table). I refer not only to definitional imprecision but also to a lack of consensus on the nature of the concept itself.

The word “control” is another term on whose meaning almost no 2 psychiatrists agree. Consensus on definitions is elusive when words become divorced from the concepts they were intended to describe.

Table

A meaningless word? ‘Dissociation’ is used to describe many things

5. Validity of first-person authority

The skeptic’s attempt to investigate a subjective phenomena—especially DID—is bound to break on the rocks of the first-person authority, to borrow Donald Davidson’s words.⁹ To support reliability and validity of the diagnosis, dissociation researchers rely on “scales” and “instruments” to give the impression of objectivity, empiricism, and “science” hard at work. However, a quick look at some of the questions on these “instruments” reveals their assault on reason and intellect (Box 2).¹²

Proponents who claim DID is “sufficiently validated for inclusion in the current and future versions of DSM” are to be commended for adding “much more research is needed in several areas.”¹³ Piper and Merskey’s review^4,5 concluded that DID could not be reliably diagnosed.

Box 2

6. Does a DID diagnosis do harm?

Webster’s¹⁴ defines iatrogenic as: “Resulting from the activity of a physician. Originally applied to a disorder or disorders inadvertently induced in the patient by the manner of the physician’s examination, discussion, or treatment, it now applies to any condition occurring in a patient as result of medical treatment, such as a drug reaction.”

A DID diagnosis has been blamed for misdiagnosis of other entities,¹⁵ patient mismanagement,¹⁶ and inadequate treatment of depression.¹⁷ Even when DID is treated with the best of intentions, undesired negative effects may result from psychotherapy, and some patients experience worsening of symptoms and/or deterioration of functioning.^18,19

In Creating Hysteria, Acocella²⁰ cites examples of harm done to [alleged DID] patients and their families, including 2 high-profile cases under the care of a member of the DSM-IV work group on dissociation.

7. How is self-deception possible?

The ability to self-deceive has advantages and disadvantages,²¹ and widespread deception is possible. Richard Dawkins’s The God Delusion,²² Christopher Hitchens’s God is Not Great,²³ and Michael Shermer’s Why People Believe Weird Things²⁴ are recent exposés of how self-deception and deception by charismatic figures occurs despite the progress “reason” has made.

As with other belief systems that become entrenched in the face of criticism, DID proponents accuse critics of denial, reluctance, and adopting “defense[s] against dealing with the reality of child abuse in North America.”²⁰ One wonders why just North America! Why not Africa, with its children in Sudan, Somalia, Zimbabwe—to name a few—enduring enough abuse to spread around the world several times over?

Proponents also allege that part of the reason for “professionals’ reluctance” to embrace DID is the “subtle presentation of the symptoms.”²⁵ In other words, it is not reluctance; it is ignorance, with the insinuation that nonbelievers or skeptics are not smart enough to pick up on the subtle clinical presentation. I can’t see why professionals would be ignorant when it comes to dissociation as opposed to schizophrenia, depression, bipolar disorder, and almost all DSM-IV disorders. Why this selective ignorance exists remains unexplained.

8. Experts and conflict of interest

DSM-V’s guidelines on conflict of interest are very welcome. One hopes conflict of interest does not refer only to financial relationships with pharmaceutical companies. Conflicts of interest can exert unseen influence, which—if made clear—would have a direct bearing of the reliability and trustworthiness of the published literature. Strong adherents have a lot to gain from perpetuating DID. Nonbelievers, skeptics, and opponents would gain nothing if DID disappeared from DSM today or in 2012.

The first potential conflict of interest for DID “experts” is financial gain. For example, a psychologist saw 1 of my patients (before I came to the scene) for 5 years for 3 sessions a week (2 for adult alters and 1 for childhood alters), with annual earnings of nearly $20,000. A self-declared expert would need only 10 patients to be better off than most psychiatrists.

The second potential conflict of interest is personal gain in the form of narcissistic gratification, as mentioned above. Although DID proponents blame neophytes, “teachers” are no less prone to narcissistic gratification. Under this umbrella falls the DID experts’ interest in recognition, fame, and easily acquired expertise. One may argue that self-arrogated expertise in this realm is much ado about nothing.

The third potential conflict of interest is the very process of becoming an “expert.” The bias of this process is evident because if one does not accept a priori the presence of DID, he or she will never be admitted to the exclusive club of “DID experts.” To attain the status of authority or expert on this subject, one must be a believer. Otherwise, how would one claim to have diagnosed and treated hundreds of DID cases? It is a feedback loop that can’t be broken.

Related resources

• Borch-Jacobsen M. Making minds and madness: from hysteria to depression. New York, NY: Cambridge University Press; 2009.
• Memory and reality. False Memory Syndrome Foundation. www.fmsfonline.org.

Disclosure

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

Comment on this article

What is it about dissociative identity disorder (DID) that makes it a polarizing diagnosis? Why does it split professionals into believers and nonbelievers, stirring up heated debates, high emotions, and fervor similar to what we see in religion?

The DID controversy is likely to continue beyond the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), slated for publication in 2012. Proponents and opponents claim to have the upper hand in arguments about the validity of the DID diagnosis and benefits vs harm of treatment. This article examines the logic of previous and new arguments.

1. The fallacy of equal-footing arguments

When 301 board-certified U.S. psychiatrists were surveyed in 1999 about their attitudes toward DSM-IV dissociative disorders diagnoses:

• 35% had no reservations about DID
• 43% were skeptical
• 15% indicated the diagnosis should not be included in the DSM.¹

Only 21% believed there was strong evidence for DID’s scientific validity. On balance, published papers appear skeptical about DID’s core components: dissociative amnesia and recovered-memory therapy.²

DID skeptics are sometimes accused of “denial” or “reluctance” to accept this diagnosis. Informed skepticism is acceptable—even encouraged—in making a diagnosis of malingering, factitious disorder, some personality disorders, substance abuse, and psychotic states, to name a few. Why is informed skepticism about DID frowned on?

In medical and surgical specialties, informed skepticism is encouraged so that the practitioner challenges his or her assumptions about a possible diagnosis through a methodical process of inclusion, exclusion, and hypothesis testing. I argue that little or no skepticism is substandard practice, if not negligence.

Bertrand Russell’s celestial teapot parable (Box 1)³ exposed the fallacy of equal-footing arguments (ie, in any debate or argument that has 2 sides, the 2 sides are not necessarily on equal footing). Russell’s argument is valid for any belief system relying on faith. Now that DID is in the “ancient book” (DSM-IV), the burden of proof by some magical logic has shifted to “nonbelievers.” In law that is called precedent, but law is even less scientific than psychiatry and not the best example to follow. A mistake made 100 years ago is still a mistake.

Box 1

2. Illogic of causation

Piper and Merskey’s extensive literature review^4,5 examined the presumed association between DID and childhood abuse (mostly sexual). They found:

• no proof that DID results from childhood trauma or that DID cases in children are almost never reported
• “consistent evidence of blatant iatrogenesis” in the practice of some DID proponents.

One can easily turn the logic around by claiming that a DID diagnosis causes memories of childhood sexual abuse.

As for patients’ presumed reluctance to report childhood abuse, I witnessed in every one of my 15 alleged cases of DID (all female) not reluctance but a strong tendency to flaunt their diagnosis and symptoms and an eagerness to re-tell their stories with graphic detail, usually unprovoked. Patients with a DID diagnosis seem to have a “powerful vested interest”—to borrow Paul McHugh’s expression⁶—in sustaining the DID diagnosis, symptoms, behaviors, and therapy as an end in itself.

DID proponents acknowledge that iatrogenic artifacts may exist in the diagnosis and treatment. However, they almost immediately insinuate that DID patients’ “subtle defensive strategies” generate these artifacts. Greaves’ discussion of multiple personality disorder⁷ acknowledged that overdiagnosis may be driven by therapists’ desire to “attain narcissistic gratification at ‘having a multiple [sic] of their own’” but blamed this on “neophytes.”

3. Tautology in DID’s definition

DSM-IV’s criterion A for DID is in fact a definition: “the presence of 2 or more distinct identities or personality states (each with its own relatively enduring pattern of perceiving, relating to, and thinking about the environment and self).”⁸ Together, criteria A and B show circularity and redundancy. If A is met, then B must be met because “a person’s behavior” is part of her or his identity and personality state, which was established in A.

Tautology is a major shortcoming of the descriptive system for psychopathology in general. Of greater clinical value are observing a patient’s actions, listening to his or her words, learning his or her history, studying his or her expressions, and noting his or her relationships.⁹

4. Bewitchment by language

Psychiatrists could spend hours over strong cups of coffee arguing the meanings of terms such as “dissociation,” “presence,” “identity,” “personality state,” etc. Psychiatry has been targeted unfairly regarding where it falls on the subjectivity-objectivity axis, but it has not fared that differently from other medical specialties.¹⁰ Psychiatry, however, depends much more on language.

Consider slippery terms such as personality, identity, self, dissociation, integration, alters, ego, ego states, trance states, personality states, unconscious, etc. Lack of precision, variability in use of words and their meaning, and variability in understanding the concept that these terms try to communicate make speaking a common language extremely difficult. To borrow from Wittgenstein, psychiatrists’ intellect is bewitched by language.¹¹

Words fail to communicate experiences such as the taste of red wine or the feeling of sand beneath bare feet. It is almost futile to try to define dissociation, identity, personality states, etc., using words or even pictures. More definitions and agreement on stricter definitions would not provide greater clarity or solve the problem of first-person authority.

An example is found in DID’s criterion B: “at least 2 of these identities or personality states recurrently take control of the person’s behavior” [italics mine]. “Possession” seems to be a fitting word! Whether it is an alter or the devil taking control is a technicality. Even more acceptable would be possessed by inconsolable anger, possessed by fierce jealousy, possessed by lust, possessed by hatred and vengeance, possessed by and obsessed with love, possessed by cocaine, etc.

Dissociation is used to describe so many things that it has become almost meaningless (Table). I refer not only to definitional imprecision but also to a lack of consensus on the nature of the concept itself.

The word “control” is another term on whose meaning almost no 2 psychiatrists agree. Consensus on definitions is elusive when words become divorced from the concepts they were intended to describe.

Table

A meaningless word? ‘Dissociation’ is used to describe many things

5. Validity of first-person authority

The skeptic’s attempt to investigate a subjective phenomena—especially DID—is bound to break on the rocks of the first-person authority, to borrow Donald Davidson’s words.⁹ To support reliability and validity of the diagnosis, dissociation researchers rely on “scales” and “instruments” to give the impression of objectivity, empiricism, and “science” hard at work. However, a quick look at some of the questions on these “instruments” reveals their assault on reason and intellect (Box 2).¹²

Proponents who claim DID is “sufficiently validated for inclusion in the current and future versions of DSM” are to be commended for adding “much more research is needed in several areas.”¹³ Piper and Merskey’s review^4,5 concluded that DID could not be reliably diagnosed.

Box 2

6. Does a DID diagnosis do harm?

Webster’s¹⁴ defines iatrogenic as: “Resulting from the activity of a physician. Originally applied to a disorder or disorders inadvertently induced in the patient by the manner of the physician’s examination, discussion, or treatment, it now applies to any condition occurring in a patient as result of medical treatment, such as a drug reaction.”

A DID diagnosis has been blamed for misdiagnosis of other entities,¹⁵ patient mismanagement,¹⁶ and inadequate treatment of depression.¹⁷ Even when DID is treated with the best of intentions, undesired negative effects may result from psychotherapy, and some patients experience worsening of symptoms and/or deterioration of functioning.^18,19

In Creating Hysteria, Acocella²⁰ cites examples of harm done to [alleged DID] patients and their families, including 2 high-profile cases under the care of a member of the DSM-IV work group on dissociation.

7. How is self-deception possible?

The ability to self-deceive has advantages and disadvantages,²¹ and widespread deception is possible. Richard Dawkins’s The God Delusion,²² Christopher Hitchens’s God is Not Great,²³ and Michael Shermer’s Why People Believe Weird Things²⁴ are recent exposés of how self-deception and deception by charismatic figures occurs despite the progress “reason” has made.

As with other belief systems that become entrenched in the face of criticism, DID proponents accuse critics of denial, reluctance, and adopting “defense[s] against dealing with the reality of child abuse in North America.”²⁰ One wonders why just North America! Why not Africa, with its children in Sudan, Somalia, Zimbabwe—to name a few—enduring enough abuse to spread around the world several times over?

Proponents also allege that part of the reason for “professionals’ reluctance” to embrace DID is the “subtle presentation of the symptoms.”²⁵ In other words, it is not reluctance; it is ignorance, with the insinuation that nonbelievers or skeptics are not smart enough to pick up on the subtle clinical presentation. I can’t see why professionals would be ignorant when it comes to dissociation as opposed to schizophrenia, depression, bipolar disorder, and almost all DSM-IV disorders. Why this selective ignorance exists remains unexplained.

8. Experts and conflict of interest

DSM-V’s guidelines on conflict of interest are very welcome. One hopes conflict of interest does not refer only to financial relationships with pharmaceutical companies. Conflicts of interest can exert unseen influence, which—if made clear—would have a direct bearing of the reliability and trustworthiness of the published literature. Strong adherents have a lot to gain from perpetuating DID. Nonbelievers, skeptics, and opponents would gain nothing if DID disappeared from DSM today or in 2012.

The first potential conflict of interest for DID “experts” is financial gain. For example, a psychologist saw 1 of my patients (before I came to the scene) for 5 years for 3 sessions a week (2 for adult alters and 1 for childhood alters), with annual earnings of nearly $20,000. A self-declared expert would need only 10 patients to be better off than most psychiatrists.

The second potential conflict of interest is personal gain in the form of narcissistic gratification, as mentioned above. Although DID proponents blame neophytes, “teachers” are no less prone to narcissistic gratification. Under this umbrella falls the DID experts’ interest in recognition, fame, and easily acquired expertise. One may argue that self-arrogated expertise in this realm is much ado about nothing.

The third potential conflict of interest is the very process of becoming an “expert.” The bias of this process is evident because if one does not accept a priori the presence of DID, he or she will never be admitted to the exclusive club of “DID experts.” To attain the status of authority or expert on this subject, one must be a believer. Otherwise, how would one claim to have diagnosed and treated hundreds of DID cases? It is a feedback loop that can’t be broken.

Related resources

• Borch-Jacobsen M. Making minds and madness: from hysteria to depression. New York, NY: Cambridge University Press; 2009.
• Memory and reality. False Memory Syndrome Foundation. www.fmsfonline.org.

Disclosure

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

Comment on this article

Mrs. S, age 34, worked as an office manager with responsibilities for more than 40 employees for 5 years. Starting in her mid 20s she had repeated periods of depression, binge drinking, and risk-taking that were treated ineffectively with antidepressants. Ultimately, she was fired from her job.

Eventually Mrs. S was diagnosed as bipolar and over time responded well to a mood-stabilizing regimen. She now desires to return to work, both for financial reasons and for the sense of accomplishment that comes from working. Initially, personnel managers review her résumé and tell her she would be bored by the routine nature of entry-level positions, or they offer her jobs with major responsibilities. She accepts a high-level position but soon leaves, feeling overwhelmed by the stress.

Bipolar disorder’s long-term course presents a therapeutic challenge when patients desire to remain employed, seek temporary or permanent disability status, or—most commonly—attempt to return to employment after a period of inability to work. As the experience of Mrs. S illustrates, previous capabilities that appear higher than the person’s present or recent work experience are a key issue to address in interpersonal therapy.

Evidence-based research is informative, but ultimately you must apply judgment and flexibility in setting and revising goals with the bipolar individual. Attention to the disorder’s core characteristics can help you equip patients for work that contributes to their pursuit of health.

Obstacles to employment

Role function. Bipolar disorder impairs family and social function in approximately one-half of persons with this diagnosis, a higher impairment rate than in persons with major depression.¹

Cognitive function. Bipolar disorder patients have subtle sustained impairments in cognitive function, particularly working memory.^2,3 These deficits—although generally much less severe than in persons with schizophrenia—contribute to workplace and educational difficulties.

Unstable mood. Some symptoms associated with elevated mood contribute to functional impairment. These are not limited to mania or hypomania but also can be prominent in mixed states and depression.

A study from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) found that two-thirds of 1,380 depressed bipolar I and II patients had ?1 concomitant symptoms principally associated with manic states. The most prominent were distractibility, pressured speech and thoughts, risky behavior, and agitation.⁴ Each of these—or, more often, all of these—can interfere with work responsibilities.

Circadian rhythm pattern. Sleep disturbances in bipolar disorder differ from those associated with other medical conditions. Bipolar patients’ tendency to increase their activity and interests in the evening may keep them awake into the early morning hours. Insufficient sleep and impaired daytime cognition and alertness related to idio syncratic circadian rhythms can interfere with job requirements.⁵ The structure of employment can help many bipolar patients maintain effective sleep patterns as well as waking activities (Box 1).

Some individuals recognize their disturbed activity pattern, but many view it simply as the way they approach a day. For the latter group, a sustained treatment effort is needed to help them recognize the adverse consequences of the pattern and develop a more effective daily routine.

Adverse treatment effects. Although important, this core medical issue is not central to the interpersonal focus of this article. The simple tolerability objective in prescribing medications—and less frequently therapies such as electroconvulsive treatment—is to avoid dosages that impair concentration, alertness, or motor speed and accuracy. Similarly, avoid medications that can cause physical changes noticeable to others—such as tremor, sleepiness, or significant weight gain—or adjust dosages to eliminate these side effects.

Box 1

Bipolar symptom domains

Anxiety is recognized as a separate and major domain in bipolar psychopathology,⁶ contributing strongly to poor outcomes. Although anxiety is somewhat more predominant in depression and mixed states, it is common in manic and recovered bipolar states as well.

Social anxiety and panic states appear to be most specifically associated with bipolar disorder.⁷ Because these types of anxiety entail excessive fearful responses, psychotherapeutic techniques including extinction approaches can be helpful.

Depression in bipolar disorder tends to manifest as slowed motor and cognitive function, which is likely to be evident in work situations. Additionally, loss of social interests—one of the most common and severe aspects of depression in bipolar disorders—is likely to be evident to coworkers and to negatively impact work effectiveness.

Irritability occurs most frequently in mixed bipolar states but also is characteristic of—though generally less intense in—depressed and manic clinical states. Even when strictly internal and subjective, irritability can reduce an individual’s confidence and work effectiveness. Expressed irritability, from minor annoyances to explosive outbursts, can have serious employment consequences, including termination.

Manic symptoms. The impulsivity that is common in bipolar mania can interfere with work. Acting without considering consequences, taking undue risks, or reaching conclusions on inadequate information can cause problems, including physical harm to self or coworkers. Excessive talking—usually associated with internally recognized racing thoughts—can be a nuisance when mild or problematic if it interferes with customer or coworker interactions.

Hyperactivity and increased energy may be perceived as behaviors that facilitate productivity at work (Box 2).^8-10 The adaptive characteristics of many hypomanic states are infrequent or absent in depressive, manic, and mixed manic clinical states, however.

Psychosis is principally associated with manic episodes, but it can be a component of any symptomatic clinical state. Delusional ideas or persecutory thoughts are rarely compatible with a work environment, in part because of potential risks to others.

Box 2

Componential treatment

Bipolar disorder’s multiple symptom domains suggest a componential approach to treatment. It may be useful to convey this concept metaphorically to the patient. When working on a jigsaw puzzle, a section that has been put together can be largely left intact and attention turned to other sections of the puzzle. Similarly, once a particular bipolar component is well managed—whether via medication, lifestyle, attitudes, or combinations of these—that symptom is likely to remain stable, barring a new insult/stressor (such as a medical condition requiring drugs that interfere with the bipolar regimen).

If mood stabilizers control risky behavior, impulsivity, and affective lability, the regimen generally will remain effective. If residual or new problems develop in another area (such as anxiety, sleep cycle, or irritability), choose drug regimens and psychoeducation approaches that are compatible with the mood-stabilizing plan. This attitude toward treatment:

• is reassuring to most patients, who come to see a new or recurring problem in one domain as not inherently a harbinger of complete relapse
• can reduce patient- or clinician-initiated deletions and additions of medications in a regimen that has been established as effective.

Autobiographical accounts of persons with bipolar disorders can be useful in educating patients about the considerations presented here. Actress Patty Duke made these observations in describing the gradual development of an effective treatment for her severe bipolar disorder:

I work at not flying off the handle…and I’m much better at it. My general medical bills dropped by $50,000 a year since my bipolar diagnosis and treatment. Until then, I was always in the hospital for some phantom illness. I was there with real symptoms born of depression. I haven’t been in the hospital since I was diagnosed.

My recovery from manic-depression has been an evolution, not a sudden miracle. For someone who spent 50% of her life screaming and yelling about something, I am now down to, say, 5%.¹¹

Psychosocial factors to consider

Stigma in the workplace. Although most coworkers are tolerant of and fair-minded about the functional difficulties common in symptomatic bipolar disorder, some will have biased, inaccurate views about psychiatric conditions. Advise bipolar individuals to make case-by-case decisions about whether to provide personal information to other employees and, if so, how much.

As with most medical conditions, the default choice will be to not discuss personal information in the workplace. Some coworkers, however, might appreciate learning of the bipolar condition (for example, a supervisor who seems empathic to an employee’s seeming stressed state).

Realistic expectations. Most clinicians recognize that relief from a syndromal bipolar state is achieved more quickly than a sustained recovered status in which symptoms are minimal. Attaining functional capacity in a normal range also lags, both in time and in the proportion of persons who ever achieve sustained good function.¹² Patients, their families, and often employers may have unrealistic expectations about early resumption of work after a depressive or manic episode resolves.

Ethnic considerations. Some literature suggests ethnic differences in the initial presentation of bipolar disorder, with more severe manifestations in some populations particularly if psychosis is a component symptom.¹³ Additionally, some cultural views about stigma from illness can add to patients’ or family members’ reluctance to re-enter the workplace.

Socioeconomic status. Sometimes bipolar illness puts out of reach the occupational activities that an individual has previously undertaken or that are characteristic of the family’s experience and expectations. Resistance to a change in self-concept can add to the difficulty in successfully moving a patient to consider employment that is more routinized and less intellectual or decisional in nature (Box 3).¹⁴

Divergence in education vs work status. Persons with bipolar disorders often have substantial divergence between high educational attainment and lower work performance. When this is the case, all or most of the factors reviewed in this article probably have contributed. Mrs. S’s experience illustrates this aspect of our care for persons with bipolar disorders.

Box 3

CASE CONTINUED: Finding a new balance

After leaving the stressful high-level job, Mrs. S next resolved to limit her search to half-time positions and took a job with limited responsibilities in a bookstore. Her work productivity was outstanding, but she became easily flustered when asked to assume additional responsibilities. Some of these required quick learning of new skills in inventory re-supply or interacting with dissatisfied customers.

As she became more confident and less fearful of being fired, Mrs. S talked with 2 supervisors about her illness management. This halted their well-intentioned efforts to promote her, based on their perception of her as talented and engaging.

Attention to these workplace issues took up approximately half of the time in her regular psychiatric appointments for more than 1 year. Through this process, Mrs. S developed increasingly effective insight into the complex mix of her accomplishments and resilience on one hand and her fluctuating social and vocational impairment on the other. She also recognized that subsyndromal symptoms continued at times, despite her overall good functional state. These insights and her greater self-confidence helped Mrs. S resolve and manage the divergences in her own and others’ perceptions of her capabilities and potential.

Related Resource

• Coping with depression or bipolar disorder at your job (patient information). Depression and Bipolar Support Alliance. www.dbsalliance.org/site/PageServer?pagename=Employment_Information.

Disclosure

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

Comment on this article

Mrs. S, age 34, worked as an office manager with responsibilities for more than 40 employees for 5 years. Starting in her mid 20s she had repeated periods of depression, binge drinking, and risk-taking that were treated ineffectively with antidepressants. Ultimately, she was fired from her job.

Eventually Mrs. S was diagnosed as bipolar and over time responded well to a mood-stabilizing regimen. She now desires to return to work, both for financial reasons and for the sense of accomplishment that comes from working. Initially, personnel managers review her résumé and tell her she would be bored by the routine nature of entry-level positions, or they offer her jobs with major responsibilities. She accepts a high-level position but soon leaves, feeling overwhelmed by the stress.

Bipolar disorder’s long-term course presents a therapeutic challenge when patients desire to remain employed, seek temporary or permanent disability status, or—most commonly—attempt to return to employment after a period of inability to work. As the experience of Mrs. S illustrates, previous capabilities that appear higher than the person’s present or recent work experience are a key issue to address in interpersonal therapy.

Evidence-based research is informative, but ultimately you must apply judgment and flexibility in setting and revising goals with the bipolar individual. Attention to the disorder’s core characteristics can help you equip patients for work that contributes to their pursuit of health.

Obstacles to employment

Role function. Bipolar disorder impairs family and social function in approximately one-half of persons with this diagnosis, a higher impairment rate than in persons with major depression.¹

Cognitive function. Bipolar disorder patients have subtle sustained impairments in cognitive function, particularly working memory.^2,3 These deficits—although generally much less severe than in persons with schizophrenia—contribute to workplace and educational difficulties.

Unstable mood. Some symptoms associated with elevated mood contribute to functional impairment. These are not limited to mania or hypomania but also can be prominent in mixed states and depression.

A study from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) found that two-thirds of 1,380 depressed bipolar I and II patients had ?1 concomitant symptoms principally associated with manic states. The most prominent were distractibility, pressured speech and thoughts, risky behavior, and agitation.⁴ Each of these—or, more often, all of these—can interfere with work responsibilities.

Circadian rhythm pattern. Sleep disturbances in bipolar disorder differ from those associated with other medical conditions. Bipolar patients’ tendency to increase their activity and interests in the evening may keep them awake into the early morning hours. Insufficient sleep and impaired daytime cognition and alertness related to idio syncratic circadian rhythms can interfere with job requirements.⁵ The structure of employment can help many bipolar patients maintain effective sleep patterns as well as waking activities (Box 1).

Some individuals recognize their disturbed activity pattern, but many view it simply as the way they approach a day. For the latter group, a sustained treatment effort is needed to help them recognize the adverse consequences of the pattern and develop a more effective daily routine.

Adverse treatment effects. Although important, this core medical issue is not central to the interpersonal focus of this article. The simple tolerability objective in prescribing medications—and less frequently therapies such as electroconvulsive treatment—is to avoid dosages that impair concentration, alertness, or motor speed and accuracy. Similarly, avoid medications that can cause physical changes noticeable to others—such as tremor, sleepiness, or significant weight gain—or adjust dosages to eliminate these side effects.

Box 1

Bipolar symptom domains

Anxiety is recognized as a separate and major domain in bipolar psychopathology,⁶ contributing strongly to poor outcomes. Although anxiety is somewhat more predominant in depression and mixed states, it is common in manic and recovered bipolar states as well.

Social anxiety and panic states appear to be most specifically associated with bipolar disorder.⁷ Because these types of anxiety entail excessive fearful responses, psychotherapeutic techniques including extinction approaches can be helpful.

Depression in bipolar disorder tends to manifest as slowed motor and cognitive function, which is likely to be evident in work situations. Additionally, loss of social interests—one of the most common and severe aspects of depression in bipolar disorders—is likely to be evident to coworkers and to negatively impact work effectiveness.

Irritability occurs most frequently in mixed bipolar states but also is characteristic of—though generally less intense in—depressed and manic clinical states. Even when strictly internal and subjective, irritability can reduce an individual’s confidence and work effectiveness. Expressed irritability, from minor annoyances to explosive outbursts, can have serious employment consequences, including termination.

Manic symptoms. The impulsivity that is common in bipolar mania can interfere with work. Acting without considering consequences, taking undue risks, or reaching conclusions on inadequate information can cause problems, including physical harm to self or coworkers. Excessive talking—usually associated with internally recognized racing thoughts—can be a nuisance when mild or problematic if it interferes with customer or coworker interactions.

Hyperactivity and increased energy may be perceived as behaviors that facilitate productivity at work (Box 2).^8-10 The adaptive characteristics of many hypomanic states are infrequent or absent in depressive, manic, and mixed manic clinical states, however.

Psychosis is principally associated with manic episodes, but it can be a component of any symptomatic clinical state. Delusional ideas or persecutory thoughts are rarely compatible with a work environment, in part because of potential risks to others.

Box 2

Componential treatment

Bipolar disorder’s multiple symptom domains suggest a componential approach to treatment. It may be useful to convey this concept metaphorically to the patient. When working on a jigsaw puzzle, a section that has been put together can be largely left intact and attention turned to other sections of the puzzle. Similarly, once a particular bipolar component is well managed—whether via medication, lifestyle, attitudes, or combinations of these—that symptom is likely to remain stable, barring a new insult/stressor (such as a medical condition requiring drugs that interfere with the bipolar regimen).

If mood stabilizers control risky behavior, impulsivity, and affective lability, the regimen generally will remain effective. If residual or new problems develop in another area (such as anxiety, sleep cycle, or irritability), choose drug regimens and psychoeducation approaches that are compatible with the mood-stabilizing plan. This attitude toward treatment:

• is reassuring to most patients, who come to see a new or recurring problem in one domain as not inherently a harbinger of complete relapse
• can reduce patient- or clinician-initiated deletions and additions of medications in a regimen that has been established as effective.

Autobiographical accounts of persons with bipolar disorders can be useful in educating patients about the considerations presented here. Actress Patty Duke made these observations in describing the gradual development of an effective treatment for her severe bipolar disorder:

I work at not flying off the handle…and I’m much better at it. My general medical bills dropped by $50,000 a year since my bipolar diagnosis and treatment. Until then, I was always in the hospital for some phantom illness. I was there with real symptoms born of depression. I haven’t been in the hospital since I was diagnosed.

My recovery from manic-depression has been an evolution, not a sudden miracle. For someone who spent 50% of her life screaming and yelling about something, I am now down to, say, 5%.¹¹

Psychosocial factors to consider

Stigma in the workplace. Although most coworkers are tolerant of and fair-minded about the functional difficulties common in symptomatic bipolar disorder, some will have biased, inaccurate views about psychiatric conditions. Advise bipolar individuals to make case-by-case decisions about whether to provide personal information to other employees and, if so, how much.

As with most medical conditions, the default choice will be to not discuss personal information in the workplace. Some coworkers, however, might appreciate learning of the bipolar condition (for example, a supervisor who seems empathic to an employee’s seeming stressed state).

Realistic expectations. Most clinicians recognize that relief from a syndromal bipolar state is achieved more quickly than a sustained recovered status in which symptoms are minimal. Attaining functional capacity in a normal range also lags, both in time and in the proportion of persons who ever achieve sustained good function.¹² Patients, their families, and often employers may have unrealistic expectations about early resumption of work after a depressive or manic episode resolves.

Ethnic considerations. Some literature suggests ethnic differences in the initial presentation of bipolar disorder, with more severe manifestations in some populations particularly if psychosis is a component symptom.¹³ Additionally, some cultural views about stigma from illness can add to patients’ or family members’ reluctance to re-enter the workplace.

Socioeconomic status. Sometimes bipolar illness puts out of reach the occupational activities that an individual has previously undertaken or that are characteristic of the family’s experience and expectations. Resistance to a change in self-concept can add to the difficulty in successfully moving a patient to consider employment that is more routinized and less intellectual or decisional in nature (Box 3).¹⁴

Divergence in education vs work status. Persons with bipolar disorders often have substantial divergence between high educational attainment and lower work performance. When this is the case, all or most of the factors reviewed in this article probably have contributed. Mrs. S’s experience illustrates this aspect of our care for persons with bipolar disorders.

Box 3

CASE CONTINUED: Finding a new balance

After leaving the stressful high-level job, Mrs. S next resolved to limit her search to half-time positions and took a job with limited responsibilities in a bookstore. Her work productivity was outstanding, but she became easily flustered when asked to assume additional responsibilities. Some of these required quick learning of new skills in inventory re-supply or interacting with dissatisfied customers.

As she became more confident and less fearful of being fired, Mrs. S talked with 2 supervisors about her illness management. This halted their well-intentioned efforts to promote her, based on their perception of her as talented and engaging.

Attention to these workplace issues took up approximately half of the time in her regular psychiatric appointments for more than 1 year. Through this process, Mrs. S developed increasingly effective insight into the complex mix of her accomplishments and resilience on one hand and her fluctuating social and vocational impairment on the other. She also recognized that subsyndromal symptoms continued at times, despite her overall good functional state. These insights and her greater self-confidence helped Mrs. S resolve and manage the divergences in her own and others’ perceptions of her capabilities and potential.

Related Resource

• Coping with depression or bipolar disorder at your job (patient information). Depression and Bipolar Support Alliance. www.dbsalliance.org/site/PageServer?pagename=Employment_Information.

Disclosure

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

Comment on this article

Mrs. S, age 34, worked as an office manager with responsibilities for more than 40 employees for 5 years. Starting in her mid 20s she had repeated periods of depression, binge drinking, and risk-taking that were treated ineffectively with antidepressants. Ultimately, she was fired from her job.

Eventually Mrs. S was diagnosed as bipolar and over time responded well to a mood-stabilizing regimen. She now desires to return to work, both for financial reasons and for the sense of accomplishment that comes from working. Initially, personnel managers review her résumé and tell her she would be bored by the routine nature of entry-level positions, or they offer her jobs with major responsibilities. She accepts a high-level position but soon leaves, feeling overwhelmed by the stress.

Bipolar disorder’s long-term course presents a therapeutic challenge when patients desire to remain employed, seek temporary or permanent disability status, or—most commonly—attempt to return to employment after a period of inability to work. As the experience of Mrs. S illustrates, previous capabilities that appear higher than the person’s present or recent work experience are a key issue to address in interpersonal therapy.

Evidence-based research is informative, but ultimately you must apply judgment and flexibility in setting and revising goals with the bipolar individual. Attention to the disorder’s core characteristics can help you equip patients for work that contributes to their pursuit of health.

Obstacles to employment

Role function. Bipolar disorder impairs family and social function in approximately one-half of persons with this diagnosis, a higher impairment rate than in persons with major depression.¹

Cognitive function. Bipolar disorder patients have subtle sustained impairments in cognitive function, particularly working memory.^2,3 These deficits—although generally much less severe than in persons with schizophrenia—contribute to workplace and educational difficulties.

Unstable mood. Some symptoms associated with elevated mood contribute to functional impairment. These are not limited to mania or hypomania but also can be prominent in mixed states and depression.

A study from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) found that two-thirds of 1,380 depressed bipolar I and II patients had ?1 concomitant symptoms principally associated with manic states. The most prominent were distractibility, pressured speech and thoughts, risky behavior, and agitation.⁴ Each of these—or, more often, all of these—can interfere with work responsibilities.

Circadian rhythm pattern. Sleep disturbances in bipolar disorder differ from those associated with other medical conditions. Bipolar patients’ tendency to increase their activity and interests in the evening may keep them awake into the early morning hours. Insufficient sleep and impaired daytime cognition and alertness related to idio syncratic circadian rhythms can interfere with job requirements.⁵ The structure of employment can help many bipolar patients maintain effective sleep patterns as well as waking activities (Box 1).

Some individuals recognize their disturbed activity pattern, but many view it simply as the way they approach a day. For the latter group, a sustained treatment effort is needed to help them recognize the adverse consequences of the pattern and develop a more effective daily routine.

Adverse treatment effects. Although important, this core medical issue is not central to the interpersonal focus of this article. The simple tolerability objective in prescribing medications—and less frequently therapies such as electroconvulsive treatment—is to avoid dosages that impair concentration, alertness, or motor speed and accuracy. Similarly, avoid medications that can cause physical changes noticeable to others—such as tremor, sleepiness, or significant weight gain—or adjust dosages to eliminate these side effects.

Box 1

Bipolar symptom domains

Anxiety is recognized as a separate and major domain in bipolar psychopathology,⁶ contributing strongly to poor outcomes. Although anxiety is somewhat more predominant in depression and mixed states, it is common in manic and recovered bipolar states as well.

Social anxiety and panic states appear to be most specifically associated with bipolar disorder.⁷ Because these types of anxiety entail excessive fearful responses, psychotherapeutic techniques including extinction approaches can be helpful.

Depression in bipolar disorder tends to manifest as slowed motor and cognitive function, which is likely to be evident in work situations. Additionally, loss of social interests—one of the most common and severe aspects of depression in bipolar disorders—is likely to be evident to coworkers and to negatively impact work effectiveness.

Irritability occurs most frequently in mixed bipolar states but also is characteristic of—though generally less intense in—depressed and manic clinical states. Even when strictly internal and subjective, irritability can reduce an individual’s confidence and work effectiveness. Expressed irritability, from minor annoyances to explosive outbursts, can have serious employment consequences, including termination.

Manic symptoms. The impulsivity that is common in bipolar mania can interfere with work. Acting without considering consequences, taking undue risks, or reaching conclusions on inadequate information can cause problems, including physical harm to self or coworkers. Excessive talking—usually associated with internally recognized racing thoughts—can be a nuisance when mild or problematic if it interferes with customer or coworker interactions.

Hyperactivity and increased energy may be perceived as behaviors that facilitate productivity at work (Box 2).^8-10 The adaptive characteristics of many hypomanic states are infrequent or absent in depressive, manic, and mixed manic clinical states, however.

Psychosis is principally associated with manic episodes, but it can be a component of any symptomatic clinical state. Delusional ideas or persecutory thoughts are rarely compatible with a work environment, in part because of potential risks to others.

Box 2

Componential treatment

Bipolar disorder’s multiple symptom domains suggest a componential approach to treatment. It may be useful to convey this concept metaphorically to the patient. When working on a jigsaw puzzle, a section that has been put together can be largely left intact and attention turned to other sections of the puzzle. Similarly, once a particular bipolar component is well managed—whether via medication, lifestyle, attitudes, or combinations of these—that symptom is likely to remain stable, barring a new insult/stressor (such as a medical condition requiring drugs that interfere with the bipolar regimen).

If mood stabilizers control risky behavior, impulsivity, and affective lability, the regimen generally will remain effective. If residual or new problems develop in another area (such as anxiety, sleep cycle, or irritability), choose drug regimens and psychoeducation approaches that are compatible with the mood-stabilizing plan. This attitude toward treatment:

• is reassuring to most patients, who come to see a new or recurring problem in one domain as not inherently a harbinger of complete relapse
• can reduce patient- or clinician-initiated deletions and additions of medications in a regimen that has been established as effective.

Autobiographical accounts of persons with bipolar disorders can be useful in educating patients about the considerations presented here. Actress Patty Duke made these observations in describing the gradual development of an effective treatment for her severe bipolar disorder:

I work at not flying off the handle…and I’m much better at it. My general medical bills dropped by $50,000 a year since my bipolar diagnosis and treatment. Until then, I was always in the hospital for some phantom illness. I was there with real symptoms born of depression. I haven’t been in the hospital since I was diagnosed.

My recovery from manic-depression has been an evolution, not a sudden miracle. For someone who spent 50% of her life screaming and yelling about something, I am now down to, say, 5%.¹¹

Psychosocial factors to consider

Stigma in the workplace. Although most coworkers are tolerant of and fair-minded about the functional difficulties common in symptomatic bipolar disorder, some will have biased, inaccurate views about psychiatric conditions. Advise bipolar individuals to make case-by-case decisions about whether to provide personal information to other employees and, if so, how much.

As with most medical conditions, the default choice will be to not discuss personal information in the workplace. Some coworkers, however, might appreciate learning of the bipolar condition (for example, a supervisor who seems empathic to an employee’s seeming stressed state).

Realistic expectations. Most clinicians recognize that relief from a syndromal bipolar state is achieved more quickly than a sustained recovered status in which symptoms are minimal. Attaining functional capacity in a normal range also lags, both in time and in the proportion of persons who ever achieve sustained good function.¹² Patients, their families, and often employers may have unrealistic expectations about early resumption of work after a depressive or manic episode resolves.

Ethnic considerations. Some literature suggests ethnic differences in the initial presentation of bipolar disorder, with more severe manifestations in some populations particularly if psychosis is a component symptom.¹³ Additionally, some cultural views about stigma from illness can add to patients’ or family members’ reluctance to re-enter the workplace.

Socioeconomic status. Sometimes bipolar illness puts out of reach the occupational activities that an individual has previously undertaken or that are characteristic of the family’s experience and expectations. Resistance to a change in self-concept can add to the difficulty in successfully moving a patient to consider employment that is more routinized and less intellectual or decisional in nature (Box 3).¹⁴

Divergence in education vs work status. Persons with bipolar disorders often have substantial divergence between high educational attainment and lower work performance. When this is the case, all or most of the factors reviewed in this article probably have contributed. Mrs. S’s experience illustrates this aspect of our care for persons with bipolar disorders.

Box 3

CASE CONTINUED: Finding a new balance

After leaving the stressful high-level job, Mrs. S next resolved to limit her search to half-time positions and took a job with limited responsibilities in a bookstore. Her work productivity was outstanding, but she became easily flustered when asked to assume additional responsibilities. Some of these required quick learning of new skills in inventory re-supply or interacting with dissatisfied customers.

As she became more confident and less fearful of being fired, Mrs. S talked with 2 supervisors about her illness management. This halted their well-intentioned efforts to promote her, based on their perception of her as talented and engaging.

Attention to these workplace issues took up approximately half of the time in her regular psychiatric appointments for more than 1 year. Through this process, Mrs. S developed increasingly effective insight into the complex mix of her accomplishments and resilience on one hand and her fluctuating social and vocational impairment on the other. She also recognized that subsyndromal symptoms continued at times, despite her overall good functional state. These insights and her greater self-confidence helped Mrs. S resolve and manage the divergences in her own and others’ perceptions of her capabilities and potential.

Related Resource

• Coping with depression or bipolar disorder at your job (patient information). Depression and Bipolar Support Alliance. www.dbsalliance.org/site/PageServer?pagename=Employment_Information.

Disclosure

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

Comment on this article

In a psychiatric clinic, Dr. B treats Ms. D, a single 28-year-old, for depression. She has multiple pain and gastrointestinal complaints that have responded poorly to treatment, morbid obesity, chronic tiredness, irritability, and Cluster B personality traits. Ms. D is lonely, unemployed, and seems to be in perpetual crisis. She states “unless someone does something to make this better, I just might kill myself.” She blames Dr. B for failing to adequately treat her depression; he has tried many medications to no avail. In psychotherapy sessions, Ms. D complains instead of examining methods for improvement, and she does not complete psychotherapy homework. She is extremely passive in her approach to getting better.

Ms. D asks Dr. B fill out the necessary paperwork so she can qualify for disability. Dr. B informs her that he will not do so because he believes she is capable of employment and that receiving disability would make her less likely to improve. Ms. D and her parents file letters of complaint about Dr. B to the supervisor of the psychiatric clinic for lack of treatment efficacy and for not supporting her disability claim. Dr. B dreads seeing Ms. D on his appointment list, and realizes she repulses him.

Although “the difficult patient” is not a diagnosis or specific clinical entity, clinicians universally struggle with such patients and have an immediate sense of shared experience when describing the phenomenon. In primary care, O’Dowd¹ aptly described this type of patient as the “heartsink” patient, meaning the practitioner often feels exasperation, defeat, or dislike when he or she sees the patient’s name on the schedule.

This article discusses the literature on this topic and provides strategies for dealing with difficult patients in psychiatric practice.

Patient characteristics

Most published reports of difficult patients involve descriptive case series or physician accounts, most often describing patients presenting in nonpsychiatric specialties, including family practice, emergency medicine, rheumatology, gastroenterology, plastic surgery, and dentistry, among others.^2-7

In a survey of physicians in 4 primary care clinics, subjects rated 96 (15%) of 627 adult patients as “difficult.”⁸ Difficult patients were significantly more likely than others to have a mental disorder ( Table 1 ).⁸ They also had more functional impairment, higher health care utilization, and lower satisfaction with care.

A separate primary care clinic study found uncannily similar results—physicians rated 74 (15%) of 500 new walk-in patients as “difficult.”⁹ Compared with other patients, the difficult patients had:

• higher rates of psychiatric illness, somatization (>5 somatic complaints), and more severe symptoms
  
• poorer functional status, more unmet expectations, less satisfaction with care, and higher use of health services.
  

Fewer articles on difficult patients have been published in psychiatric literature, although some commonalities have emerged ( Box ).^10-12 Often suffering from chronic conditions without well-defined treatment endpoints, difficult patients do worse clinically, have higher use of health services, and are less happy with their care than other patients.

Difficult patients challenge our competence as physicians and evoke personal distress. Physicians with less job satisfaction, less clinical experience, less training in counseling, and a poor attitude toward psychosocial problems are more likely to perceive a patient as difficult.^13,14

Table 1

Common psychiatric disorders in difficult patients

Survival strategies for clinicians

Eight strategies can help improve your care of difficult patients ( Table 2 ).

Table 2

8 strategies for managing difficult patients

2. Develop empathy. Empathy is identification with and understanding of why a person feels, thinks, and acts as he or she does. The best way to develop empathy for a difficult patient is to learn about him or her firsthand—directly from the patient, not from reading chart notes or from information passed among colleagues.

Learning about the patient firsthand means shifting from sign-and-symptom gathering to performing a genuine inquiry about how the person thinks or feels, including interests, loves, or background. Challenging clinical circumstances—such as seeing a patient in a busy emergency department or during a 15-minute medication check—can make this difficult. In some cases, however, the time needed to establish empathy can be surprisingly brief.

The more patients feel that the psychiatrist is “on their level,” the less likely they are to project internalized anguish or impulsively act on conflicted feelings.

3. Seek out supervision or consultation. You can gain new perspectives by taking a “step back” and looking at the case with a colleague. Seeking out consultation also allows you to decompress by “getting it off your chest.” Supervision often allows clinicians to develop:

• empathy toward a difficult patient
  
• increased energy and creativity in subsequent sessions.
  

5. Lower treatment goals. The nature of difficult patients makes complete “cures” a rarity. A psychiatrist whose goal is to substantially help a patient may become chronically frustrated and feel inadequate in the face of a patient’s perpetual suffering. The clinician sometimes reacts by developing therapeutic nihilism and withdrawing energy from the case. The patient, of course, senses this and increases his or her general distress level, which intensifies the negative interaction.

By lowering goals—for example, aiming for stabilization rather than improvement—you can feel less like a failure and be more relaxed. A relaxed clinician is more tolerant and in a better position to help the patient. Other lowered goals might be to reduce harm from impulsive or dangerous behaviors instead of eliminating them or better coping with symptoms rather than symptom remission.

7. Use ‘plussing.’ Because we experience dread with difficult patients, clinicians often avoid, refrain from, or simply don’t see opportunities to use positive comments and acknowledgements (“plussing”) when they arise. Most patients (as well as clinicians) want to be liked, and small compliments—when genuinely and appropriately placed—sometimes can make a huge difference in patients’ willingness to cope or try new things.

This technique might allow you to see the humorous side of yourself as the hardworking, well-intentioned yet ineffectual psychiatrist. You don’t know how the story will unfold, but you can accept this as you would in any other unfinished novel.

CASE CONTINUED: A more effective approach

Dr. B realizes Ms. D is a difficult patient for him and takes the case into supervision. He is stunned when he is unable to answer several of his supervisor’s questions about Ms. D, including “What was her upbringing like?” and “What are her strengths or interests?” He realizes he knows little about Ms. D and becomes aware that he has focused most of their sessions on either fixing her immediate and never-ending crises or defending himself.

The supervisor points out that Dr. B’s lack of empathy for Ms. D keeps him from helping her—being anxious and defensive makes him less likely to be supportive or creative. Dr. B feels better after the supervision session. He experiences some catharsis and develops a plan to improve the situation.

Dr. B structures the next session to get to know Ms. D better. He mentally decompresses the treatment timeline and refocuses on the need to develop empathy instead of attempting to ameliorate symptoms. Dr. B begins by letting Ms. D know he wants to help her but doesn’t know much about her. She initially rejects his attempts at empathic communication, but with gentle persistence he learns about her upbringing and interests. Dr. B is able to genuinely compliment her on coping with previous traumas and begins to better understand her strengths. Over the next several weeks, Ms. D seems more able to accept supportive interventions and eventually begins a part-time job.

Related resources

• Colson DB. Difficult patients in extended psychiatric hospitalization: a research perspective on the patient, staff, and team. Psychiatry. 1990;53(4):369-382.
  
• Koekkoek B, van Meijel B, Hutschemaekers G. “Difficult patients” in mental health care: a review. Psychiatr Serv. 2006;57:795-802.
  

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

Comment on this article

In a psychiatric clinic, Dr. B treats Ms. D, a single 28-year-old, for depression. She has multiple pain and gastrointestinal complaints that have responded poorly to treatment, morbid obesity, chronic tiredness, irritability, and Cluster B personality traits. Ms. D is lonely, unemployed, and seems to be in perpetual crisis. She states “unless someone does something to make this better, I just might kill myself.” She blames Dr. B for failing to adequately treat her depression; he has tried many medications to no avail. In psychotherapy sessions, Ms. D complains instead of examining methods for improvement, and she does not complete psychotherapy homework. She is extremely passive in her approach to getting better.

Ms. D asks Dr. B fill out the necessary paperwork so she can qualify for disability. Dr. B informs her that he will not do so because he believes she is capable of employment and that receiving disability would make her less likely to improve. Ms. D and her parents file letters of complaint about Dr. B to the supervisor of the psychiatric clinic for lack of treatment efficacy and for not supporting her disability claim. Dr. B dreads seeing Ms. D on his appointment list, and realizes she repulses him.

Although “the difficult patient” is not a diagnosis or specific clinical entity, clinicians universally struggle with such patients and have an immediate sense of shared experience when describing the phenomenon. In primary care, O’Dowd¹ aptly described this type of patient as the “heartsink” patient, meaning the practitioner often feels exasperation, defeat, or dislike when he or she sees the patient’s name on the schedule.

This article discusses the literature on this topic and provides strategies for dealing with difficult patients in psychiatric practice.

Patient characteristics

Most published reports of difficult patients involve descriptive case series or physician accounts, most often describing patients presenting in nonpsychiatric specialties, including family practice, emergency medicine, rheumatology, gastroenterology, plastic surgery, and dentistry, among others.^2-7

In a survey of physicians in 4 primary care clinics, subjects rated 96 (15%) of 627 adult patients as “difficult.”⁸ Difficult patients were significantly more likely than others to have a mental disorder ( Table 1 ).⁸ They also had more functional impairment, higher health care utilization, and lower satisfaction with care.

A separate primary care clinic study found uncannily similar results—physicians rated 74 (15%) of 500 new walk-in patients as “difficult.”⁹ Compared with other patients, the difficult patients had:

• higher rates of psychiatric illness, somatization (>5 somatic complaints), and more severe symptoms
  
• poorer functional status, more unmet expectations, less satisfaction with care, and higher use of health services.
  

Fewer articles on difficult patients have been published in psychiatric literature, although some commonalities have emerged ( Box ).^10-12 Often suffering from chronic conditions without well-defined treatment endpoints, difficult patients do worse clinically, have higher use of health services, and are less happy with their care than other patients.

Difficult patients challenge our competence as physicians and evoke personal distress. Physicians with less job satisfaction, less clinical experience, less training in counseling, and a poor attitude toward psychosocial problems are more likely to perceive a patient as difficult.^13,14

Table 1

Common psychiatric disorders in difficult patients

Survival strategies for clinicians

Eight strategies can help improve your care of difficult patients ( Table 2 ).

Table 2

8 strategies for managing difficult patients

2. Develop empathy. Empathy is identification with and understanding of why a person feels, thinks, and acts as he or she does. The best way to develop empathy for a difficult patient is to learn about him or her firsthand—directly from the patient, not from reading chart notes or from information passed among colleagues.

Learning about the patient firsthand means shifting from sign-and-symptom gathering to performing a genuine inquiry about how the person thinks or feels, including interests, loves, or background. Challenging clinical circumstances—such as seeing a patient in a busy emergency department or during a 15-minute medication check—can make this difficult. In some cases, however, the time needed to establish empathy can be surprisingly brief.

The more patients feel that the psychiatrist is “on their level,” the less likely they are to project internalized anguish or impulsively act on conflicted feelings.

3. Seek out supervision or consultation. You can gain new perspectives by taking a “step back” and looking at the case with a colleague. Seeking out consultation also allows you to decompress by “getting it off your chest.” Supervision often allows clinicians to develop:

• empathy toward a difficult patient
  
• increased energy and creativity in subsequent sessions.
  

5. Lower treatment goals. The nature of difficult patients makes complete “cures” a rarity. A psychiatrist whose goal is to substantially help a patient may become chronically frustrated and feel inadequate in the face of a patient’s perpetual suffering. The clinician sometimes reacts by developing therapeutic nihilism and withdrawing energy from the case. The patient, of course, senses this and increases his or her general distress level, which intensifies the negative interaction.

By lowering goals—for example, aiming for stabilization rather than improvement—you can feel less like a failure and be more relaxed. A relaxed clinician is more tolerant and in a better position to help the patient. Other lowered goals might be to reduce harm from impulsive or dangerous behaviors instead of eliminating them or better coping with symptoms rather than symptom remission.

7. Use ‘plussing.’ Because we experience dread with difficult patients, clinicians often avoid, refrain from, or simply don’t see opportunities to use positive comments and acknowledgements (“plussing”) when they arise. Most patients (as well as clinicians) want to be liked, and small compliments—when genuinely and appropriately placed—sometimes can make a huge difference in patients’ willingness to cope or try new things.

This technique might allow you to see the humorous side of yourself as the hardworking, well-intentioned yet ineffectual psychiatrist. You don’t know how the story will unfold, but you can accept this as you would in any other unfinished novel.

CASE CONTINUED: A more effective approach

Dr. B realizes Ms. D is a difficult patient for him and takes the case into supervision. He is stunned when he is unable to answer several of his supervisor’s questions about Ms. D, including “What was her upbringing like?” and “What are her strengths or interests?” He realizes he knows little about Ms. D and becomes aware that he has focused most of their sessions on either fixing her immediate and never-ending crises or defending himself.

The supervisor points out that Dr. B’s lack of empathy for Ms. D keeps him from helping her—being anxious and defensive makes him less likely to be supportive or creative. Dr. B feels better after the supervision session. He experiences some catharsis and develops a plan to improve the situation.

Dr. B structures the next session to get to know Ms. D better. He mentally decompresses the treatment timeline and refocuses on the need to develop empathy instead of attempting to ameliorate symptoms. Dr. B begins by letting Ms. D know he wants to help her but doesn’t know much about her. She initially rejects his attempts at empathic communication, but with gentle persistence he learns about her upbringing and interests. Dr. B is able to genuinely compliment her on coping with previous traumas and begins to better understand her strengths. Over the next several weeks, Ms. D seems more able to accept supportive interventions and eventually begins a part-time job.

Related resources

• Colson DB. Difficult patients in extended psychiatric hospitalization: a research perspective on the patient, staff, and team. Psychiatry. 1990;53(4):369-382.
  
• Koekkoek B, van Meijel B, Hutschemaekers G. “Difficult patients” in mental health care: a review. Psychiatr Serv. 2006;57:795-802.
  

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

Comment on this article

In a psychiatric clinic, Dr. B treats Ms. D, a single 28-year-old, for depression. She has multiple pain and gastrointestinal complaints that have responded poorly to treatment, morbid obesity, chronic tiredness, irritability, and Cluster B personality traits. Ms. D is lonely, unemployed, and seems to be in perpetual crisis. She states “unless someone does something to make this better, I just might kill myself.” She blames Dr. B for failing to adequately treat her depression; he has tried many medications to no avail. In psychotherapy sessions, Ms. D complains instead of examining methods for improvement, and she does not complete psychotherapy homework. She is extremely passive in her approach to getting better.

Ms. D asks Dr. B fill out the necessary paperwork so she can qualify for disability. Dr. B informs her that he will not do so because he believes she is capable of employment and that receiving disability would make her less likely to improve. Ms. D and her parents file letters of complaint about Dr. B to the supervisor of the psychiatric clinic for lack of treatment efficacy and for not supporting her disability claim. Dr. B dreads seeing Ms. D on his appointment list, and realizes she repulses him.

Although “the difficult patient” is not a diagnosis or specific clinical entity, clinicians universally struggle with such patients and have an immediate sense of shared experience when describing the phenomenon. In primary care, O’Dowd¹ aptly described this type of patient as the “heartsink” patient, meaning the practitioner often feels exasperation, defeat, or dislike when he or she sees the patient’s name on the schedule.

This article discusses the literature on this topic and provides strategies for dealing with difficult patients in psychiatric practice.

Patient characteristics

Most published reports of difficult patients involve descriptive case series or physician accounts, most often describing patients presenting in nonpsychiatric specialties, including family practice, emergency medicine, rheumatology, gastroenterology, plastic surgery, and dentistry, among others.^2-7

In a survey of physicians in 4 primary care clinics, subjects rated 96 (15%) of 627 adult patients as “difficult.”⁸ Difficult patients were significantly more likely than others to have a mental disorder ( Table 1 ).⁸ They also had more functional impairment, higher health care utilization, and lower satisfaction with care.

A separate primary care clinic study found uncannily similar results—physicians rated 74 (15%) of 500 new walk-in patients as “difficult.”⁹ Compared with other patients, the difficult patients had:

• higher rates of psychiatric illness, somatization (>5 somatic complaints), and more severe symptoms
  
• poorer functional status, more unmet expectations, less satisfaction with care, and higher use of health services.
  

Fewer articles on difficult patients have been published in psychiatric literature, although some commonalities have emerged ( Box ).^10-12 Often suffering from chronic conditions without well-defined treatment endpoints, difficult patients do worse clinically, have higher use of health services, and are less happy with their care than other patients.

Difficult patients challenge our competence as physicians and evoke personal distress. Physicians with less job satisfaction, less clinical experience, less training in counseling, and a poor attitude toward psychosocial problems are more likely to perceive a patient as difficult.^13,14

Table 1

Common psychiatric disorders in difficult patients

Survival strategies for clinicians

Eight strategies can help improve your care of difficult patients ( Table 2 ).

Table 2

8 strategies for managing difficult patients

2. Develop empathy. Empathy is identification with and understanding of why a person feels, thinks, and acts as he or she does. The best way to develop empathy for a difficult patient is to learn about him or her firsthand—directly from the patient, not from reading chart notes or from information passed among colleagues.

Learning about the patient firsthand means shifting from sign-and-symptom gathering to performing a genuine inquiry about how the person thinks or feels, including interests, loves, or background. Challenging clinical circumstances—such as seeing a patient in a busy emergency department or during a 15-minute medication check—can make this difficult. In some cases, however, the time needed to establish empathy can be surprisingly brief.

The more patients feel that the psychiatrist is “on their level,” the less likely they are to project internalized anguish or impulsively act on conflicted feelings.

3. Seek out supervision or consultation. You can gain new perspectives by taking a “step back” and looking at the case with a colleague. Seeking out consultation also allows you to decompress by “getting it off your chest.” Supervision often allows clinicians to develop:

• empathy toward a difficult patient
  
• increased energy and creativity in subsequent sessions.
  

5. Lower treatment goals. The nature of difficult patients makes complete “cures” a rarity. A psychiatrist whose goal is to substantially help a patient may become chronically frustrated and feel inadequate in the face of a patient’s perpetual suffering. The clinician sometimes reacts by developing therapeutic nihilism and withdrawing energy from the case. The patient, of course, senses this and increases his or her general distress level, which intensifies the negative interaction.

By lowering goals—for example, aiming for stabilization rather than improvement—you can feel less like a failure and be more relaxed. A relaxed clinician is more tolerant and in a better position to help the patient. Other lowered goals might be to reduce harm from impulsive or dangerous behaviors instead of eliminating them or better coping with symptoms rather than symptom remission.

7. Use ‘plussing.’ Because we experience dread with difficult patients, clinicians often avoid, refrain from, or simply don’t see opportunities to use positive comments and acknowledgements (“plussing”) when they arise. Most patients (as well as clinicians) want to be liked, and small compliments—when genuinely and appropriately placed—sometimes can make a huge difference in patients’ willingness to cope or try new things.

This technique might allow you to see the humorous side of yourself as the hardworking, well-intentioned yet ineffectual psychiatrist. You don’t know how the story will unfold, but you can accept this as you would in any other unfinished novel.

CASE CONTINUED: A more effective approach

Dr. B realizes Ms. D is a difficult patient for him and takes the case into supervision. He is stunned when he is unable to answer several of his supervisor’s questions about Ms. D, including “What was her upbringing like?” and “What are her strengths or interests?” He realizes he knows little about Ms. D and becomes aware that he has focused most of their sessions on either fixing her immediate and never-ending crises or defending himself.

The supervisor points out that Dr. B’s lack of empathy for Ms. D keeps him from helping her—being anxious and defensive makes him less likely to be supportive or creative. Dr. B feels better after the supervision session. He experiences some catharsis and develops a plan to improve the situation.

Dr. B structures the next session to get to know Ms. D better. He mentally decompresses the treatment timeline and refocuses on the need to develop empathy instead of attempting to ameliorate symptoms. Dr. B begins by letting Ms. D know he wants to help her but doesn’t know much about her. She initially rejects his attempts at empathic communication, but with gentle persistence he learns about her upbringing and interests. Dr. B is able to genuinely compliment her on coping with previous traumas and begins to better understand her strengths. Over the next several weeks, Ms. D seems more able to accept supportive interventions and eventually begins a part-time job.

Related resources

• Colson DB. Difficult patients in extended psychiatric hospitalization: a research perspective on the patient, staff, and team. Psychiatry. 1990;53(4):369-382.
  
• Koekkoek B, van Meijel B, Hutschemaekers G. “Difficult patients” in mental health care: a review. Psychiatr Serv. 2006;57:795-802.
  

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

The Mini-Mental State Examination (MMSE) is widely used in psychiatry and throughout the medical community to evaluate a patient’s cognitive status. The MMSE score is the common language for communicating a patient’s cognitive level among psychiatrists, primary care physicians, social workers, nursing staff, psychologists, long-term care and assisted living facility staff, and insurance companies.

Although the MMSE is highly useful and should continue to be used as a cognitive screening instrument, in some clinical situations time is too limited to allow a full assessment, which could take up to 30 minutes. In my clinical experience, I’ve discovered I can estimate the MMSE score range for a patient I suspect has dementia by asking 2 simple questions.

What is your date of birth (DOB)? When a patient cannot accurately state his or her complete DOB, usually the MMSE is ≤10, indicating severe dementia. Often this observation has been confirmed when another clinician later would do a complete MMSE and return a score close to one I predicted. DOB is a highly personal piece of information that an individual should be able to provide quickly and directly. If a patient is unable to give this information, consider the rest of the patient’s history to be inaccurate and check with collateral sources such as family or close friends.

Can you name 10 vegetables? If a patient is unable to list 10 vegetables—for example, if he or she cannot name 10 vegetables within a minute, repeats them, or mixes them up with fruits or other foods—the MMSE range usually is between 10 to 20, indicating moderate dementia. Instead of vegetables, you can ask your patient to name animals, fruits, or familiar items in other categories.

Clinical value. These 2 bedside questions do not take the place of performing a full MMSE or another established cognitive screen, such as the Montreal Cognitive Assessment¹ or the Mini-Cog.² My quick assessment—which has not been validated by research—is merely a tip that in certain situations may help you get a rough estimate of a patient’s cognitive status.

The Mini-Mental State Examination (MMSE) is widely used in psychiatry and throughout the medical community to evaluate a patient’s cognitive status. The MMSE score is the common language for communicating a patient’s cognitive level among psychiatrists, primary care physicians, social workers, nursing staff, psychologists, long-term care and assisted living facility staff, and insurance companies.

Although the MMSE is highly useful and should continue to be used as a cognitive screening instrument, in some clinical situations time is too limited to allow a full assessment, which could take up to 30 minutes. In my clinical experience, I’ve discovered I can estimate the MMSE score range for a patient I suspect has dementia by asking 2 simple questions.

What is your date of birth (DOB)? When a patient cannot accurately state his or her complete DOB, usually the MMSE is ≤10, indicating severe dementia. Often this observation has been confirmed when another clinician later would do a complete MMSE and return a score close to one I predicted. DOB is a highly personal piece of information that an individual should be able to provide quickly and directly. If a patient is unable to give this information, consider the rest of the patient’s history to be inaccurate and check with collateral sources such as family or close friends.

Can you name 10 vegetables? If a patient is unable to list 10 vegetables—for example, if he or she cannot name 10 vegetables within a minute, repeats them, or mixes them up with fruits or other foods—the MMSE range usually is between 10 to 20, indicating moderate dementia. Instead of vegetables, you can ask your patient to name animals, fruits, or familiar items in other categories.

Clinical value. These 2 bedside questions do not take the place of performing a full MMSE or another established cognitive screen, such as the Montreal Cognitive Assessment¹ or the Mini-Cog.² My quick assessment—which has not been validated by research—is merely a tip that in certain situations may help you get a rough estimate of a patient’s cognitive status.

The Mini-Mental State Examination (MMSE) is widely used in psychiatry and throughout the medical community to evaluate a patient’s cognitive status. The MMSE score is the common language for communicating a patient’s cognitive level among psychiatrists, primary care physicians, social workers, nursing staff, psychologists, long-term care and assisted living facility staff, and insurance companies.

Although the MMSE is highly useful and should continue to be used as a cognitive screening instrument, in some clinical situations time is too limited to allow a full assessment, which could take up to 30 minutes. In my clinical experience, I’ve discovered I can estimate the MMSE score range for a patient I suspect has dementia by asking 2 simple questions.

What is your date of birth (DOB)? When a patient cannot accurately state his or her complete DOB, usually the MMSE is ≤10, indicating severe dementia. Often this observation has been confirmed when another clinician later would do a complete MMSE and return a score close to one I predicted. DOB is a highly personal piece of information that an individual should be able to provide quickly and directly. If a patient is unable to give this information, consider the rest of the patient’s history to be inaccurate and check with collateral sources such as family or close friends.

Can you name 10 vegetables? If a patient is unable to list 10 vegetables—for example, if he or she cannot name 10 vegetables within a minute, repeats them, or mixes them up with fruits or other foods—the MMSE range usually is between 10 to 20, indicating moderate dementia. Instead of vegetables, you can ask your patient to name animals, fruits, or familiar items in other categories.

Clinical value. These 2 bedside questions do not take the place of performing a full MMSE or another established cognitive screen, such as the Montreal Cognitive Assessment¹ or the Mini-Cog.² My quick assessment—which has not been validated by research—is merely a tip that in certain situations may help you get a rough estimate of a patient’s cognitive status.

Comment on this article

Ms. G, age 56, presents with the chief complaint of “depression.” Review of symptoms reveals 6 months of depressed mood, anhedonia, tearfulness, 30-pound weight gain, low energy, and bilateral ankle edema. Her psychiatrist orders a thyroid stimulating hormone (TSH) level, which shows 9.51 mU/L (normal range 0.35 to 4.94 mU/L), indicating hypothyroidism. After 1 month of treatment with levothyroxine, Ms. G’s mood symptoms and edema resolve and her weight stabilizes.

A patient who comes to you for treatment of depression might also present with physical symptoms (such as, fatigue, nausea, balance problems, etc.) that could point to a medical illness. Endocrine, neurologic, infectious, and malignant processes (Table 1) and vitamin deficiencies (Table 2) could be causing your patient’s depression. To help differentiate various etiologies of depressive symptoms, we review common medical causes of depression, their distinguishing characteristics, and pertinent treatment issues.

DSM-IV-TR considers major depression secondary to a general medical condition to be diagnostically separate from a major depressive episode. When considering nonpsychiatric causes of depression, begin with a thorough medical history including current and past medications (Table 3),^1-7 illicit substance use, review of systems, and a detailed neurologic exam.

Table 1

Medical conditions with evidence of causing depression

Table 2

Vitamin deficiencies that can lead to depression

Table 3

Medications that may be linked to depressive symptoms

Endocrine disorders

Hypothyroidism increases a patient’s risk of a mood disorder 7-fold, compared with the general population.⁸

Signs and symptoms. Patients with hypothyroidism may complain of constipation, thinning hair, dry skin, edema, sensitivity to cold, goiter, thyroid nodule, or hoarse voice. Symptoms such as fatigue, weight gain, and sleep disturbance overlap with depressive symptoms. A TSH value >4.94 mU/L indicates hypothyroidism and warrants referral to a primary care provider or endocrinologist.

Although the pathophysiology is unclear, 1 study found elevated thyroid peroxide antibodies in depressed postmenopausal women who had abnormal thyroid function tests, suggesting an autoimmune link between depression and hypothyroidism.⁹ In another study, 2.5% of depressed patients had abnormal serum TSH or thyroxine levels indicating hypothyroidism.¹⁰ Thyroid hormones have been used to augment treatment of refractory depression.¹¹

Hyperparathyroidism. “Moans, groans, stones, and psychiatric overtones” describes the constellation of hyperparathyroidism symptoms. As serum calcium levels rise, mood and physical symptoms worsen (Table 4).

Signs and symptoms. Elevated serum calcium (normal range 8.7 to 10.7 mg/dL) and parathyroid hormone (PTH) levels support the diagnosis. Depressive symptoms may diminish or even resolve when calcium levels return to normal after parathyroidectomy.¹²

Cushing’s syndrome (CS). As many as 80% of patients exhibit depressive symptoms when CS is active.¹³

Signs and symptoms. Distinguishing CS symptoms include:

• hirsutism
• truncal obesity
• acne
• hypertension
• facial flushing
• purple striae.

Elevated serum cortisol, the condition’s hallmark, may be caused by pituitary adenomas, adrenal tumors or hyperplasia, or ectopic adrenocorticotropic hormone secretion. The most common cause is exogenous administration of glucocorticoids. A dexamethasone suppression test or 24-hour urine cortisol confirms CS diagnosis.

Depressed CS patients often experience poor concentration, early morning waking, and decreased libido. Compared with nondepressed individuals with CS, those with depression tend to be older (average age 37.5) and more likely to be female, have more severe CS-related symptoms, and exhibit higher urine cortisol levels at diagnosis (average 1.694 pmol/L).^14,15

Antidepressants typically will not resolve depression in patients with CS unless you also correct the hypercorticalism.¹⁶

Addison’s disease (AD). Major depressive disorder is >2 times more prevalent in AD patients compared with matched controls.¹⁷

Signs and symptoms. Hyperpigmentation, salt cravings, low blood pressure, nausea, and vomiting are AD hallmarks. AD patients present with fatigue, vegetative symptoms, weight loss, and weakness that mimics a major depressive episode.

AD is caused by damage to the adrenal cortex. These patients do not have enough of the mineralocorticoid aldosterone, which maintains sodium and potassium balance and regulates blood pressure via the renin-angiotensin-aldosterone pathway. Decreased morning serum cortisol level, hyponatremia, and hyperkalemia confirm the diagnosis. AD can be serious—possibly fatal—so prompt referral to an endocrinologist is warranted.

Table 4

Clinical symptoms of hyperparathyroidism

Neurologic disorders

Stroke. Post-stroke depressive symptoms generally do not differ from endogenous depression. Apathy, catastrophic reactions, hyper emotionalism, and diurnal mood variations are more prevalent in stroke patients,¹⁸ although some of these features have been noted in other neurologic conditions.

Signs and symptoms. Look for depression onset or a change in existing depression symptoms that occurs in the context of a clinically apparent stroke.¹⁹ Antidepressants such as serotonin reuptake inhibitors may relieve post-stroke depression.

Seizures. Depressive symptoms could appear before or after a seizure or may be the clinical presentation of a simple or complex partial seizure.¹

Signs and symptoms. Episodic, short-lived depression that resolves rapidly may warrant a seizure evaluation. Prodromal depressive symptoms such as irritability, depression, fear, or anger²⁰ may precede a seizure by 1 to 3 days and could improve after the seizure.

Caused by a simple partial seizure, ictal depression is characterized by guilt, anhedonia, or sudden-onset suicidal ideation without an environmental trigger. Symptoms are fairly short-lived, lasting from a few hours to a few days.⁵

Depressive symptoms also may develop minutes before a complex partial seizure or a secondarily generalized seizure.² Mood changes typically are brief, stereotypical, and associated with other ictal phenomena. Interictal depression involves mild chronic symptoms similar to dysthymia. Postictal depression may last for several days.

Prodromal and ictal depression often improve when antiepileptic therapy reduces seizure frequency.

Huntington’s disease (HD) is a hereditary chorea caused by expanded trinucleotide repeats and characterized by abnormal movements, cognitive impairment, and neuropsychiatric symptoms. The suicide rate among HD patients is 4 times higher than in the general population.²¹

Signs and symptoms. Depression concurrent with neurologic symptoms such as chorea or dystonia may warrant an HD evaluation. Patients may present with psychiatric complaints such as depression, apathy, insomnia, or anxiety that may coincide with or precede other neurologic symptoms.²² Mood-congruent delusions and auditory hallucinations also have been reported.²³ In one study, 98% of HD patients exhibited psychiatric symptoms—including dysphoria, agitation, irritability, apathy, and anxiety—that occurred irrespective of cognitive or motor symptoms.²⁴

Research into the cause of HD’s neuropsychiatric symptoms has focused on abnormalities in frontostriatal brain circuitry.²⁵ Depressive symptoms might respond to any class of antidepressant.

Wilson’s disease—caused by copper accumulation in the liver and basal ganglia—is characterized by degenerative changes in the brain, liver disease, and golden-brown or green Kayser-Fleischer rings in the cornea.

Signs and symptoms. Hepatic symptoms include hepatomegaly, hepatitis, and cirrhosis. Psychiatric symptoms—which include personality changes, depression, irritability, and psychosis—may occur alone or concurrent with neurologic symptoms such as tremor or dystonia.²⁶ Neuropsychiatric symptoms—the initial presentation in up to one-third of Wilson’s disease patients—may respond to anticopper therapies.²⁶

Multiple sclerosis (MS). Up to 50% of MS patients experience depression, although it is unclear if symptoms are caused by the disease or the impact of having a progressive chronic illness.

Signs and symptoms. MS may cause weakness, visual loss, incontinence, paresthesias, and speech disturbances. MS symptoms such as fatigue, insomnia, and poor concentration overlap with DSM-IV-TR criteria for major depression. Depressive symptoms may worsen during disease flare-ups and with advanced neurologic disease.

Depression may be more prevalent in MS patients with brain lesions compared with those with spinal cord lesions.²⁹ Imaging studies indicate that depressed MS patients are more likely to have hyperintense lesions in the left inferior frontal regions of the brain and greater atrophy of the left anterior temporal region,³⁰ indicating that the disease may play a role in depressive symptoms.

Parkinson’s disease (PD). Nearly one-half of PD patients experience depression, which recent research suggests is related to neuroanatomic degeneration and not a reaction to having the illness.³¹

Signs and symptoms. Because PD can present with sleep disturbances, bradykinesia, restricted range of facial expression, and apathy, it initially might be mistaken for a depressive disorder.

Other neurologic disorders. Depression in Alzheimer’s disease typically involves prominent anhedonia, irritability, apathy, and anxiety, rather than suicidal ideation and guilt.³² In traumatic brain injury, the most common psychiatric disturbance is a depressive syndrome resembling endogenous depression.³² Progressive supranuclear palsy—a degenerative disorder of the basal ganglia, brainstem, and cerebellar nuclei—is associated with cognitive impairments and personality changes and may present as depression.³³

Infectious disease

Human immunodeficiency virus (HIV). Depression affects 22% to 45% of HIV patients, particularly women, homosexual men, intravenous drug users, and patients with a history of depression.³⁴ The cause of depression in HIV infection is unclear because studies are complicated by factors such as:

• social stigma and isolation associated with HIV
• side effects (such as fatigue) of antiretroviral medications
• comorbid opportunistic CNS infections, such as tuberculosis or cryptococcal meningitis
• the virus itself, which is known to affect the brain.³⁵

Certain sociodemographic factors are associated with depression in HIV patients, but Gibbie et al³⁶ found that CD4 count and viral load are not. This suggests that HIV does not directly cause depression, although research is ongoing. Comorbid substance dependence and AIDS-related dementia can complicate the clinical picture.

The depressive syndrome in patients with HIV typically does not precede the diagnosis of HIV. Diagnosing depression in HIV patients—regardless of the cause—is crucial because of its effect on quality of life, productivity, medication adherence, and mortality.³⁷

West Nile virus. Among the one-third of patients who report new-onset depression after West Nile infection, 75% experience mild-to-severe depression as measured on a depression scale.³⁸ Studies of depression in West Nile virus infection are complicated by recall bias, illness-related disability, and fatigue that interferes with psychiatric assessment. Similar to HIV, a depression diagnosis typically is made following a known West Nile virus infection.

Lyme disease. More than one-third of patients diagnosed with post-Lyme syndrome—chronic symptoms that persist after antibiotic treatment—will have depression during their lifetime.³⁹ One report that attempted to determine a causal relationship between Lyme disease and depression found a similar lifetime incidence of depression in those with Lyme disease and in the general population. Even so, the incidence of depression doubled in this sample after the onset of Lyme disease. Studies of this relationship are confounded by other effects of Lyme disease, small numbers of subjects, and recall bias.

Signs and symptoms. Exposure to ticks, cranial nerve involvement, arthralgias, memory deficits, and psychotic depression may suggest Lyme disease.

Creutzfeldt-Jakob disease is a rare prion disease that can be genetic, spontaneous, or acquired via contaminated beef, corneal transplants, or dural transplants. Patients may present with cognitive impairment, fatigue, emotional lability, and depression.

Signs and symptoms include changes in the brain seen on an MRI, rapid physical and mental decline, and myoclonus and ataxia signs that occur late in the disease. Depression caused by this incurable disease often fails to respond to treatment.

Neurosyphilis patients may experience personality changes, irritability, psychosis, and decreased self-care, which may be interpreted as anhedonia or depressed mood.

Signs and symptoms. Common physical signs include dysarthria, hyperreflexia, cognitive decline, hallucinations, tremor, tabes dorsalis, and Argyll Robertson pupils. Neurosyphilis is confirmed by positive venereal disease research laboratory test of cerebrospinal fluid and treated with high-dose penicillin. Consensus is lacking on the role of psychotropic medications for the management of psychiatric symptoms.⁴⁰

Hepatitis C patients have a higher lifetime prevalence of major depression compared with controls.⁴¹ Although evidence does not support a causal link between hepatitis C infection and depression, anecdotal reports persist.⁴² Studies of comorbid depression and hepatitis C are complicated by hepatic encephalopathy, fatigue, medication side effects, and social and economic factors associated with hepatitis C. Physical symptoms include decreased appetite, fatigue, fever, nausea, vomiting, abdominal pain, clay-colored stool, joint pain, and jaundice.

Interferon (IFN) treatment for chronic, active hepatitis C has been associated with increased depressive symptoms and suicidal behavior. In a study of 31 hepatitis C patients, 23% experienced depressive episodes concurrent with IFN alfa treatment.⁴³ Depressive symptoms seem to be related to dose and treatment duration and may take several weeks to develop.

Malignancy

Cancer patients often report depressive symptoms, although a causal relationship between malignancy and depression remains unclear. Some evidence suggests that pancreatic cancer and paraneoplastic syndromes can cause depression. In a retrospective study, depression preceded a pancreatic cancer diagnosis more often than with other gastrointestinal or non-gastrointestinal cancers.⁴⁴ Typically, depression starts >1 year before the cancer is discovered. It is unclear, however, if the cancer leads to depression or depression predisposes a person to pancreatic cancer.

Signs and symptoms. New-onset depression, dramatic unintended weight loss, and predominant sleep disturbance warrant further evaluation for malignancy. In patients diagnosed with cancer, depressive symptoms may be caused by reactive depression, an acute stress reaction, or adjustment disorder with depressed mood.

Paraneoplastic syndromes can cause depression, behavior and personality changes, and memory deficits.⁴⁵ These syndromes are commonly found in breast, lung, and testicular cancer, all of which might not be discovered when psychiatric symptoms develop.⁴⁶

The immune system’s reaction to cancer produces antibodies that attack the nervous system. Diagnosis of the resulting limbic encephalitis thought to underlie psychiatric symptoms is by CSF-positive antibodies (anti-Yo antibodies, anti-Ma2 antibodies, or anti-Hu) and abnormalities in brain MRI. Psychiatric symptoms often improve when the underlying malignancy is treated.

Related resources

• Blumenfield M, Strain JJ. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams, & Wilkins; 2006.
• Ferrando SJ, Freyberg Z. Neuropsychiatric aspects of infectious diseases. Crit Care Clin. 2008;24:889-919.

Drug brand names

• Bupropion • Wellbutrin, Zyban
• Felbamate • Felbatol
• Interferon alfa • Intron, Roferon
• Interferon beta • Avonex, Rebif
• Isotretinoin • Accutane
• Levetiracetam • Keppra
• Phenytoin • Dilantin
• Primidone • Mysoline
• Propranolol • Inderal
• Tiagabine • Gabitril Roferon
• Topiramate • Topamax
• Verapamil • Isoptin
• Vigabatrin • Sabril
• Varenicline • Chantix

Disclosures

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

Dr. Rado receives research support from Eli Lilly and Company, Neuronetics, and Otsuka, and is a speaker for Eli Lilly and Company.

Comment on this article

Ms. G, age 56, presents with the chief complaint of “depression.” Review of symptoms reveals 6 months of depressed mood, anhedonia, tearfulness, 30-pound weight gain, low energy, and bilateral ankle edema. Her psychiatrist orders a thyroid stimulating hormone (TSH) level, which shows 9.51 mU/L (normal range 0.35 to 4.94 mU/L), indicating hypothyroidism. After 1 month of treatment with levothyroxine, Ms. G’s mood symptoms and edema resolve and her weight stabilizes.

A patient who comes to you for treatment of depression might also present with physical symptoms (such as, fatigue, nausea, balance problems, etc.) that could point to a medical illness. Endocrine, neurologic, infectious, and malignant processes (Table 1) and vitamin deficiencies (Table 2) could be causing your patient’s depression. To help differentiate various etiologies of depressive symptoms, we review common medical causes of depression, their distinguishing characteristics, and pertinent treatment issues.

DSM-IV-TR considers major depression secondary to a general medical condition to be diagnostically separate from a major depressive episode. When considering nonpsychiatric causes of depression, begin with a thorough medical history including current and past medications (Table 3),^1-7 illicit substance use, review of systems, and a detailed neurologic exam.

Table 1

Medical conditions with evidence of causing depression

Table 2

Vitamin deficiencies that can lead to depression

Table 3

Medications that may be linked to depressive symptoms

Endocrine disorders

Hypothyroidism increases a patient’s risk of a mood disorder 7-fold, compared with the general population.⁸

Signs and symptoms. Patients with hypothyroidism may complain of constipation, thinning hair, dry skin, edema, sensitivity to cold, goiter, thyroid nodule, or hoarse voice. Symptoms such as fatigue, weight gain, and sleep disturbance overlap with depressive symptoms. A TSH value >4.94 mU/L indicates hypothyroidism and warrants referral to a primary care provider or endocrinologist.

Although the pathophysiology is unclear, 1 study found elevated thyroid peroxide antibodies in depressed postmenopausal women who had abnormal thyroid function tests, suggesting an autoimmune link between depression and hypothyroidism.⁹ In another study, 2.5% of depressed patients had abnormal serum TSH or thyroxine levels indicating hypothyroidism.¹⁰ Thyroid hormones have been used to augment treatment of refractory depression.¹¹

Hyperparathyroidism. “Moans, groans, stones, and psychiatric overtones” describes the constellation of hyperparathyroidism symptoms. As serum calcium levels rise, mood and physical symptoms worsen (Table 4).

Signs and symptoms. Elevated serum calcium (normal range 8.7 to 10.7 mg/dL) and parathyroid hormone (PTH) levels support the diagnosis. Depressive symptoms may diminish or even resolve when calcium levels return to normal after parathyroidectomy.¹²

Cushing’s syndrome (CS). As many as 80% of patients exhibit depressive symptoms when CS is active.¹³

Signs and symptoms. Distinguishing CS symptoms include:

• hirsutism
• truncal obesity
• acne
• hypertension
• facial flushing
• purple striae.

Elevated serum cortisol, the condition’s hallmark, may be caused by pituitary adenomas, adrenal tumors or hyperplasia, or ectopic adrenocorticotropic hormone secretion. The most common cause is exogenous administration of glucocorticoids. A dexamethasone suppression test or 24-hour urine cortisol confirms CS diagnosis.

Depressed CS patients often experience poor concentration, early morning waking, and decreased libido. Compared with nondepressed individuals with CS, those with depression tend to be older (average age 37.5) and more likely to be female, have more severe CS-related symptoms, and exhibit higher urine cortisol levels at diagnosis (average 1.694 pmol/L).^14,15

Antidepressants typically will not resolve depression in patients with CS unless you also correct the hypercorticalism.¹⁶

Addison’s disease (AD). Major depressive disorder is >2 times more prevalent in AD patients compared with matched controls.¹⁷

Signs and symptoms. Hyperpigmentation, salt cravings, low blood pressure, nausea, and vomiting are AD hallmarks. AD patients present with fatigue, vegetative symptoms, weight loss, and weakness that mimics a major depressive episode.

AD is caused by damage to the adrenal cortex. These patients do not have enough of the mineralocorticoid aldosterone, which maintains sodium and potassium balance and regulates blood pressure via the renin-angiotensin-aldosterone pathway. Decreased morning serum cortisol level, hyponatremia, and hyperkalemia confirm the diagnosis. AD can be serious—possibly fatal—so prompt referral to an endocrinologist is warranted.

Table 4

Clinical symptoms of hyperparathyroidism

Neurologic disorders

Stroke. Post-stroke depressive symptoms generally do not differ from endogenous depression. Apathy, catastrophic reactions, hyper emotionalism, and diurnal mood variations are more prevalent in stroke patients,¹⁸ although some of these features have been noted in other neurologic conditions.

Signs and symptoms. Look for depression onset or a change in existing depression symptoms that occurs in the context of a clinically apparent stroke.¹⁹ Antidepressants such as serotonin reuptake inhibitors may relieve post-stroke depression.

Seizures. Depressive symptoms could appear before or after a seizure or may be the clinical presentation of a simple or complex partial seizure.¹

Signs and symptoms. Episodic, short-lived depression that resolves rapidly may warrant a seizure evaluation. Prodromal depressive symptoms such as irritability, depression, fear, or anger²⁰ may precede a seizure by 1 to 3 days and could improve after the seizure.

Caused by a simple partial seizure, ictal depression is characterized by guilt, anhedonia, or sudden-onset suicidal ideation without an environmental trigger. Symptoms are fairly short-lived, lasting from a few hours to a few days.⁵

Depressive symptoms also may develop minutes before a complex partial seizure or a secondarily generalized seizure.² Mood changes typically are brief, stereotypical, and associated with other ictal phenomena. Interictal depression involves mild chronic symptoms similar to dysthymia. Postictal depression may last for several days.

Prodromal and ictal depression often improve when antiepileptic therapy reduces seizure frequency.

Huntington’s disease (HD) is a hereditary chorea caused by expanded trinucleotide repeats and characterized by abnormal movements, cognitive impairment, and neuropsychiatric symptoms. The suicide rate among HD patients is 4 times higher than in the general population.²¹

Signs and symptoms. Depression concurrent with neurologic symptoms such as chorea or dystonia may warrant an HD evaluation. Patients may present with psychiatric complaints such as depression, apathy, insomnia, or anxiety that may coincide with or precede other neurologic symptoms.²² Mood-congruent delusions and auditory hallucinations also have been reported.²³ In one study, 98% of HD patients exhibited psychiatric symptoms—including dysphoria, agitation, irritability, apathy, and anxiety—that occurred irrespective of cognitive or motor symptoms.²⁴

Research into the cause of HD’s neuropsychiatric symptoms has focused on abnormalities in frontostriatal brain circuitry.²⁵ Depressive symptoms might respond to any class of antidepressant.

Wilson’s disease—caused by copper accumulation in the liver and basal ganglia—is characterized by degenerative changes in the brain, liver disease, and golden-brown or green Kayser-Fleischer rings in the cornea.

Signs and symptoms. Hepatic symptoms include hepatomegaly, hepatitis, and cirrhosis. Psychiatric symptoms—which include personality changes, depression, irritability, and psychosis—may occur alone or concurrent with neurologic symptoms such as tremor or dystonia.²⁶ Neuropsychiatric symptoms—the initial presentation in up to one-third of Wilson’s disease patients—may respond to anticopper therapies.²⁶

Multiple sclerosis (MS). Up to 50% of MS patients experience depression, although it is unclear if symptoms are caused by the disease or the impact of having a progressive chronic illness.

Signs and symptoms. MS may cause weakness, visual loss, incontinence, paresthesias, and speech disturbances. MS symptoms such as fatigue, insomnia, and poor concentration overlap with DSM-IV-TR criteria for major depression. Depressive symptoms may worsen during disease flare-ups and with advanced neurologic disease.

Depression may be more prevalent in MS patients with brain lesions compared with those with spinal cord lesions.²⁹ Imaging studies indicate that depressed MS patients are more likely to have hyperintense lesions in the left inferior frontal regions of the brain and greater atrophy of the left anterior temporal region,³⁰ indicating that the disease may play a role in depressive symptoms.

Parkinson’s disease (PD). Nearly one-half of PD patients experience depression, which recent research suggests is related to neuroanatomic degeneration and not a reaction to having the illness.³¹

Signs and symptoms. Because PD can present with sleep disturbances, bradykinesia, restricted range of facial expression, and apathy, it initially might be mistaken for a depressive disorder.

Other neurologic disorders. Depression in Alzheimer’s disease typically involves prominent anhedonia, irritability, apathy, and anxiety, rather than suicidal ideation and guilt.³² In traumatic brain injury, the most common psychiatric disturbance is a depressive syndrome resembling endogenous depression.³² Progressive supranuclear palsy—a degenerative disorder of the basal ganglia, brainstem, and cerebellar nuclei—is associated with cognitive impairments and personality changes and may present as depression.³³

Infectious disease

Human immunodeficiency virus (HIV). Depression affects 22% to 45% of HIV patients, particularly women, homosexual men, intravenous drug users, and patients with a history of depression.³⁴ The cause of depression in HIV infection is unclear because studies are complicated by factors such as:

• social stigma and isolation associated with HIV
• side effects (such as fatigue) of antiretroviral medications
• comorbid opportunistic CNS infections, such as tuberculosis or cryptococcal meningitis
• the virus itself, which is known to affect the brain.³⁵

Certain sociodemographic factors are associated with depression in HIV patients, but Gibbie et al³⁶ found that CD4 count and viral load are not. This suggests that HIV does not directly cause depression, although research is ongoing. Comorbid substance dependence and AIDS-related dementia can complicate the clinical picture.

The depressive syndrome in patients with HIV typically does not precede the diagnosis of HIV. Diagnosing depression in HIV patients—regardless of the cause—is crucial because of its effect on quality of life, productivity, medication adherence, and mortality.³⁷

West Nile virus. Among the one-third of patients who report new-onset depression after West Nile infection, 75% experience mild-to-severe depression as measured on a depression scale.³⁸ Studies of depression in West Nile virus infection are complicated by recall bias, illness-related disability, and fatigue that interferes with psychiatric assessment. Similar to HIV, a depression diagnosis typically is made following a known West Nile virus infection.

Lyme disease. More than one-third of patients diagnosed with post-Lyme syndrome—chronic symptoms that persist after antibiotic treatment—will have depression during their lifetime.³⁹ One report that attempted to determine a causal relationship between Lyme disease and depression found a similar lifetime incidence of depression in those with Lyme disease and in the general population. Even so, the incidence of depression doubled in this sample after the onset of Lyme disease. Studies of this relationship are confounded by other effects of Lyme disease, small numbers of subjects, and recall bias.

Signs and symptoms. Exposure to ticks, cranial nerve involvement, arthralgias, memory deficits, and psychotic depression may suggest Lyme disease.

Creutzfeldt-Jakob disease is a rare prion disease that can be genetic, spontaneous, or acquired via contaminated beef, corneal transplants, or dural transplants. Patients may present with cognitive impairment, fatigue, emotional lability, and depression.

Signs and symptoms include changes in the brain seen on an MRI, rapid physical and mental decline, and myoclonus and ataxia signs that occur late in the disease. Depression caused by this incurable disease often fails to respond to treatment.

Neurosyphilis patients may experience personality changes, irritability, psychosis, and decreased self-care, which may be interpreted as anhedonia or depressed mood.

Signs and symptoms. Common physical signs include dysarthria, hyperreflexia, cognitive decline, hallucinations, tremor, tabes dorsalis, and Argyll Robertson pupils. Neurosyphilis is confirmed by positive venereal disease research laboratory test of cerebrospinal fluid and treated with high-dose penicillin. Consensus is lacking on the role of psychotropic medications for the management of psychiatric symptoms.⁴⁰

Hepatitis C patients have a higher lifetime prevalence of major depression compared with controls.⁴¹ Although evidence does not support a causal link between hepatitis C infection and depression, anecdotal reports persist.⁴² Studies of comorbid depression and hepatitis C are complicated by hepatic encephalopathy, fatigue, medication side effects, and social and economic factors associated with hepatitis C. Physical symptoms include decreased appetite, fatigue, fever, nausea, vomiting, abdominal pain, clay-colored stool, joint pain, and jaundice.

Interferon (IFN) treatment for chronic, active hepatitis C has been associated with increased depressive symptoms and suicidal behavior. In a study of 31 hepatitis C patients, 23% experienced depressive episodes concurrent with IFN alfa treatment.⁴³ Depressive symptoms seem to be related to dose and treatment duration and may take several weeks to develop.

Malignancy

Cancer patients often report depressive symptoms, although a causal relationship between malignancy and depression remains unclear. Some evidence suggests that pancreatic cancer and paraneoplastic syndromes can cause depression. In a retrospective study, depression preceded a pancreatic cancer diagnosis more often than with other gastrointestinal or non-gastrointestinal cancers.⁴⁴ Typically, depression starts >1 year before the cancer is discovered. It is unclear, however, if the cancer leads to depression or depression predisposes a person to pancreatic cancer.

Signs and symptoms. New-onset depression, dramatic unintended weight loss, and predominant sleep disturbance warrant further evaluation for malignancy. In patients diagnosed with cancer, depressive symptoms may be caused by reactive depression, an acute stress reaction, or adjustment disorder with depressed mood.

Paraneoplastic syndromes can cause depression, behavior and personality changes, and memory deficits.⁴⁵ These syndromes are commonly found in breast, lung, and testicular cancer, all of which might not be discovered when psychiatric symptoms develop.⁴⁶

The immune system’s reaction to cancer produces antibodies that attack the nervous system. Diagnosis of the resulting limbic encephalitis thought to underlie psychiatric symptoms is by CSF-positive antibodies (anti-Yo antibodies, anti-Ma2 antibodies, or anti-Hu) and abnormalities in brain MRI. Psychiatric symptoms often improve when the underlying malignancy is treated.

Related resources

• Blumenfield M, Strain JJ. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams, & Wilkins; 2006.
• Ferrando SJ, Freyberg Z. Neuropsychiatric aspects of infectious diseases. Crit Care Clin. 2008;24:889-919.

Drug brand names

• Bupropion • Wellbutrin, Zyban
• Felbamate • Felbatol
• Interferon alfa • Intron, Roferon
• Interferon beta • Avonex, Rebif
• Isotretinoin • Accutane
• Levetiracetam • Keppra
• Phenytoin • Dilantin
• Primidone • Mysoline
• Propranolol • Inderal
• Tiagabine • Gabitril Roferon
• Topiramate • Topamax
• Verapamil • Isoptin
• Vigabatrin • Sabril
• Varenicline • Chantix

Disclosures

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

Dr. Rado receives research support from Eli Lilly and Company, Neuronetics, and Otsuka, and is a speaker for Eli Lilly and Company.

Comment on this article

Ms. G, age 56, presents with the chief complaint of “depression.” Review of symptoms reveals 6 months of depressed mood, anhedonia, tearfulness, 30-pound weight gain, low energy, and bilateral ankle edema. Her psychiatrist orders a thyroid stimulating hormone (TSH) level, which shows 9.51 mU/L (normal range 0.35 to 4.94 mU/L), indicating hypothyroidism. After 1 month of treatment with levothyroxine, Ms. G’s mood symptoms and edema resolve and her weight stabilizes.

A patient who comes to you for treatment of depression might also present with physical symptoms (such as, fatigue, nausea, balance problems, etc.) that could point to a medical illness. Endocrine, neurologic, infectious, and malignant processes (Table 1) and vitamin deficiencies (Table 2) could be causing your patient’s depression. To help differentiate various etiologies of depressive symptoms, we review common medical causes of depression, their distinguishing characteristics, and pertinent treatment issues.

DSM-IV-TR considers major depression secondary to a general medical condition to be diagnostically separate from a major depressive episode. When considering nonpsychiatric causes of depression, begin with a thorough medical history including current and past medications (Table 3),^1-7 illicit substance use, review of systems, and a detailed neurologic exam.

Table 1

Medical conditions with evidence of causing depression

Table 2

Vitamin deficiencies that can lead to depression

Table 3

Medications that may be linked to depressive symptoms

Endocrine disorders

Hypothyroidism increases a patient’s risk of a mood disorder 7-fold, compared with the general population.⁸

Signs and symptoms. Patients with hypothyroidism may complain of constipation, thinning hair, dry skin, edema, sensitivity to cold, goiter, thyroid nodule, or hoarse voice. Symptoms such as fatigue, weight gain, and sleep disturbance overlap with depressive symptoms. A TSH value >4.94 mU/L indicates hypothyroidism and warrants referral to a primary care provider or endocrinologist.

Although the pathophysiology is unclear, 1 study found elevated thyroid peroxide antibodies in depressed postmenopausal women who had abnormal thyroid function tests, suggesting an autoimmune link between depression and hypothyroidism.⁹ In another study, 2.5% of depressed patients had abnormal serum TSH or thyroxine levels indicating hypothyroidism.¹⁰ Thyroid hormones have been used to augment treatment of refractory depression.¹¹

Hyperparathyroidism. “Moans, groans, stones, and psychiatric overtones” describes the constellation of hyperparathyroidism symptoms. As serum calcium levels rise, mood and physical symptoms worsen (Table 4).

Signs and symptoms. Elevated serum calcium (normal range 8.7 to 10.7 mg/dL) and parathyroid hormone (PTH) levels support the diagnosis. Depressive symptoms may diminish or even resolve when calcium levels return to normal after parathyroidectomy.¹²

Cushing’s syndrome (CS). As many as 80% of patients exhibit depressive symptoms when CS is active.¹³

Signs and symptoms. Distinguishing CS symptoms include:

• hirsutism
• truncal obesity
• acne
• hypertension
• facial flushing
• purple striae.

Elevated serum cortisol, the condition’s hallmark, may be caused by pituitary adenomas, adrenal tumors or hyperplasia, or ectopic adrenocorticotropic hormone secretion. The most common cause is exogenous administration of glucocorticoids. A dexamethasone suppression test or 24-hour urine cortisol confirms CS diagnosis.

Depressed CS patients often experience poor concentration, early morning waking, and decreased libido. Compared with nondepressed individuals with CS, those with depression tend to be older (average age 37.5) and more likely to be female, have more severe CS-related symptoms, and exhibit higher urine cortisol levels at diagnosis (average 1.694 pmol/L).^14,15

Antidepressants typically will not resolve depression in patients with CS unless you also correct the hypercorticalism.¹⁶

Addison’s disease (AD). Major depressive disorder is >2 times more prevalent in AD patients compared with matched controls.¹⁷

Signs and symptoms. Hyperpigmentation, salt cravings, low blood pressure, nausea, and vomiting are AD hallmarks. AD patients present with fatigue, vegetative symptoms, weight loss, and weakness that mimics a major depressive episode.

AD is caused by damage to the adrenal cortex. These patients do not have enough of the mineralocorticoid aldosterone, which maintains sodium and potassium balance and regulates blood pressure via the renin-angiotensin-aldosterone pathway. Decreased morning serum cortisol level, hyponatremia, and hyperkalemia confirm the diagnosis. AD can be serious—possibly fatal—so prompt referral to an endocrinologist is warranted.

Table 4

Clinical symptoms of hyperparathyroidism

Neurologic disorders

Stroke. Post-stroke depressive symptoms generally do not differ from endogenous depression. Apathy, catastrophic reactions, hyper emotionalism, and diurnal mood variations are more prevalent in stroke patients,¹⁸ although some of these features have been noted in other neurologic conditions.

Signs and symptoms. Look for depression onset or a change in existing depression symptoms that occurs in the context of a clinically apparent stroke.¹⁹ Antidepressants such as serotonin reuptake inhibitors may relieve post-stroke depression.

Seizures. Depressive symptoms could appear before or after a seizure or may be the clinical presentation of a simple or complex partial seizure.¹

Signs and symptoms. Episodic, short-lived depression that resolves rapidly may warrant a seizure evaluation. Prodromal depressive symptoms such as irritability, depression, fear, or anger²⁰ may precede a seizure by 1 to 3 days and could improve after the seizure.

Caused by a simple partial seizure, ictal depression is characterized by guilt, anhedonia, or sudden-onset suicidal ideation without an environmental trigger. Symptoms are fairly short-lived, lasting from a few hours to a few days.⁵

Depressive symptoms also may develop minutes before a complex partial seizure or a secondarily generalized seizure.² Mood changes typically are brief, stereotypical, and associated with other ictal phenomena. Interictal depression involves mild chronic symptoms similar to dysthymia. Postictal depression may last for several days.

Prodromal and ictal depression often improve when antiepileptic therapy reduces seizure frequency.

Huntington’s disease (HD) is a hereditary chorea caused by expanded trinucleotide repeats and characterized by abnormal movements, cognitive impairment, and neuropsychiatric symptoms. The suicide rate among HD patients is 4 times higher than in the general population.²¹

Signs and symptoms. Depression concurrent with neurologic symptoms such as chorea or dystonia may warrant an HD evaluation. Patients may present with psychiatric complaints such as depression, apathy, insomnia, or anxiety that may coincide with or precede other neurologic symptoms.²² Mood-congruent delusions and auditory hallucinations also have been reported.²³ In one study, 98% of HD patients exhibited psychiatric symptoms—including dysphoria, agitation, irritability, apathy, and anxiety—that occurred irrespective of cognitive or motor symptoms.²⁴

Research into the cause of HD’s neuropsychiatric symptoms has focused on abnormalities in frontostriatal brain circuitry.²⁵ Depressive symptoms might respond to any class of antidepressant.

Wilson’s disease—caused by copper accumulation in the liver and basal ganglia—is characterized by degenerative changes in the brain, liver disease, and golden-brown or green Kayser-Fleischer rings in the cornea.

Signs and symptoms. Hepatic symptoms include hepatomegaly, hepatitis, and cirrhosis. Psychiatric symptoms—which include personality changes, depression, irritability, and psychosis—may occur alone or concurrent with neurologic symptoms such as tremor or dystonia.²⁶ Neuropsychiatric symptoms—the initial presentation in up to one-third of Wilson’s disease patients—may respond to anticopper therapies.²⁶

Multiple sclerosis (MS). Up to 50% of MS patients experience depression, although it is unclear if symptoms are caused by the disease or the impact of having a progressive chronic illness.

Signs and symptoms. MS may cause weakness, visual loss, incontinence, paresthesias, and speech disturbances. MS symptoms such as fatigue, insomnia, and poor concentration overlap with DSM-IV-TR criteria for major depression. Depressive symptoms may worsen during disease flare-ups and with advanced neurologic disease.

Depression may be more prevalent in MS patients with brain lesions compared with those with spinal cord lesions.²⁹ Imaging studies indicate that depressed MS patients are more likely to have hyperintense lesions in the left inferior frontal regions of the brain and greater atrophy of the left anterior temporal region,³⁰ indicating that the disease may play a role in depressive symptoms.

Parkinson’s disease (PD). Nearly one-half of PD patients experience depression, which recent research suggests is related to neuroanatomic degeneration and not a reaction to having the illness.³¹

Signs and symptoms. Because PD can present with sleep disturbances, bradykinesia, restricted range of facial expression, and apathy, it initially might be mistaken for a depressive disorder.

Other neurologic disorders. Depression in Alzheimer’s disease typically involves prominent anhedonia, irritability, apathy, and anxiety, rather than suicidal ideation and guilt.³² In traumatic brain injury, the most common psychiatric disturbance is a depressive syndrome resembling endogenous depression.³² Progressive supranuclear palsy—a degenerative disorder of the basal ganglia, brainstem, and cerebellar nuclei—is associated with cognitive impairments and personality changes and may present as depression.³³

Infectious disease

Human immunodeficiency virus (HIV). Depression affects 22% to 45% of HIV patients, particularly women, homosexual men, intravenous drug users, and patients with a history of depression.³⁴ The cause of depression in HIV infection is unclear because studies are complicated by factors such as:

• social stigma and isolation associated with HIV
• side effects (such as fatigue) of antiretroviral medications
• comorbid opportunistic CNS infections, such as tuberculosis or cryptococcal meningitis
• the virus itself, which is known to affect the brain.³⁵

Certain sociodemographic factors are associated with depression in HIV patients, but Gibbie et al³⁶ found that CD4 count and viral load are not. This suggests that HIV does not directly cause depression, although research is ongoing. Comorbid substance dependence and AIDS-related dementia can complicate the clinical picture.

The depressive syndrome in patients with HIV typically does not precede the diagnosis of HIV. Diagnosing depression in HIV patients—regardless of the cause—is crucial because of its effect on quality of life, productivity, medication adherence, and mortality.³⁷

West Nile virus. Among the one-third of patients who report new-onset depression after West Nile infection, 75% experience mild-to-severe depression as measured on a depression scale.³⁸ Studies of depression in West Nile virus infection are complicated by recall bias, illness-related disability, and fatigue that interferes with psychiatric assessment. Similar to HIV, a depression diagnosis typically is made following a known West Nile virus infection.

Lyme disease. More than one-third of patients diagnosed with post-Lyme syndrome—chronic symptoms that persist after antibiotic treatment—will have depression during their lifetime.³⁹ One report that attempted to determine a causal relationship between Lyme disease and depression found a similar lifetime incidence of depression in those with Lyme disease and in the general population. Even so, the incidence of depression doubled in this sample after the onset of Lyme disease. Studies of this relationship are confounded by other effects of Lyme disease, small numbers of subjects, and recall bias.

Signs and symptoms. Exposure to ticks, cranial nerve involvement, arthralgias, memory deficits, and psychotic depression may suggest Lyme disease.

Creutzfeldt-Jakob disease is a rare prion disease that can be genetic, spontaneous, or acquired via contaminated beef, corneal transplants, or dural transplants. Patients may present with cognitive impairment, fatigue, emotional lability, and depression.

Signs and symptoms include changes in the brain seen on an MRI, rapid physical and mental decline, and myoclonus and ataxia signs that occur late in the disease. Depression caused by this incurable disease often fails to respond to treatment.

Neurosyphilis patients may experience personality changes, irritability, psychosis, and decreased self-care, which may be interpreted as anhedonia or depressed mood.

Signs and symptoms. Common physical signs include dysarthria, hyperreflexia, cognitive decline, hallucinations, tremor, tabes dorsalis, and Argyll Robertson pupils. Neurosyphilis is confirmed by positive venereal disease research laboratory test of cerebrospinal fluid and treated with high-dose penicillin. Consensus is lacking on the role of psychotropic medications for the management of psychiatric symptoms.⁴⁰

Hepatitis C patients have a higher lifetime prevalence of major depression compared with controls.⁴¹ Although evidence does not support a causal link between hepatitis C infection and depression, anecdotal reports persist.⁴² Studies of comorbid depression and hepatitis C are complicated by hepatic encephalopathy, fatigue, medication side effects, and social and economic factors associated with hepatitis C. Physical symptoms include decreased appetite, fatigue, fever, nausea, vomiting, abdominal pain, clay-colored stool, joint pain, and jaundice.

Interferon (IFN) treatment for chronic, active hepatitis C has been associated with increased depressive symptoms and suicidal behavior. In a study of 31 hepatitis C patients, 23% experienced depressive episodes concurrent with IFN alfa treatment.⁴³ Depressive symptoms seem to be related to dose and treatment duration and may take several weeks to develop.

Malignancy

Cancer patients often report depressive symptoms, although a causal relationship between malignancy and depression remains unclear. Some evidence suggests that pancreatic cancer and paraneoplastic syndromes can cause depression. In a retrospective study, depression preceded a pancreatic cancer diagnosis more often than with other gastrointestinal or non-gastrointestinal cancers.⁴⁴ Typically, depression starts >1 year before the cancer is discovered. It is unclear, however, if the cancer leads to depression or depression predisposes a person to pancreatic cancer.

Signs and symptoms. New-onset depression, dramatic unintended weight loss, and predominant sleep disturbance warrant further evaluation for malignancy. In patients diagnosed with cancer, depressive symptoms may be caused by reactive depression, an acute stress reaction, or adjustment disorder with depressed mood.

Paraneoplastic syndromes can cause depression, behavior and personality changes, and memory deficits.⁴⁵ These syndromes are commonly found in breast, lung, and testicular cancer, all of which might not be discovered when psychiatric symptoms develop.⁴⁶

The immune system’s reaction to cancer produces antibodies that attack the nervous system. Diagnosis of the resulting limbic encephalitis thought to underlie psychiatric symptoms is by CSF-positive antibodies (anti-Yo antibodies, anti-Ma2 antibodies, or anti-Hu) and abnormalities in brain MRI. Psychiatric symptoms often improve when the underlying malignancy is treated.

Related resources

• Blumenfield M, Strain JJ. Psychosomatic medicine. Philadelphia, PA: Lippincott, Williams, & Wilkins; 2006.
• Ferrando SJ, Freyberg Z. Neuropsychiatric aspects of infectious diseases. Crit Care Clin. 2008;24:889-919.

Drug brand names

• Bupropion • Wellbutrin, Zyban
• Felbamate • Felbatol
• Interferon alfa • Intron, Roferon
• Interferon beta • Avonex, Rebif
• Isotretinoin • Accutane
• Levetiracetam • Keppra
• Phenytoin • Dilantin
• Primidone • Mysoline
• Propranolol • Inderal
• Tiagabine • Gabitril Roferon
• Topiramate • Topamax
• Verapamil • Isoptin
• Vigabatrin • Sabril
• Varenicline • Chantix

Disclosures

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

Dr. Rado receives research support from Eli Lilly and Company, Neuronetics, and Otsuka, and is a speaker for Eli Lilly and Company.