2 NAMES, 1 DISEASE: Does schizophrenia = psychotic bipolar disorder?

When a patient presents with psychotic symptoms, you might not recognize or pursue hints of bipolarity if you assume psychosis means schizophrenia. Yet psychotic bipolar disorder can explain every sign, symptom, course, and other characteristic traditionally assumed to indicate schizophrenia (Table 1). The literature, including recent genetic data,^1-6 marshals a persuasive argument that patients diagnosed with schizophrenia usually suffer from a psychotic bipolar disorder.

Consider here how a cascade of changing signs and symptoms, initially unrecognized, caused five sequential re-evaluations of one psychotic patient’s primary Axis I diagnosis. His case highlights why the correct initial diagnosis of the disease causing psychosis is essential to effective treatment.^4,7-9

Table 1

DSM-IV-TR criteria for schizophrenia vs. psychotic mood disorder

Schizophrenia diagnosis6	Seen in psychotic mood disorders
Criterion A
Hallucinations and delusions	50% to 80% explained by mood16,21
Paranoia	Hides grandiosity4
Catatonia	75% explained by mood7,8
Disorganized speech and behavior	All patients with moderate to severe mania1-5
Negative symptoms	All patients with moderate to severe depression4
Criterion B
Social and job dysfunction	All patients with moderate to severe bipolar disorder5,13
Criterion C
Chronic continuous symptoms	Patients can have psychotic symptoms continuously for 2 years to life5,6,13

Case: Carved in stone

Police officers carry Mr. C, age 30, into the emergency department. He is mentally disorganized and arrives in a rigid, catatonic posture. According to a neighbor, Mr. C was kneeling motionless on his mother’s front lawn, alternating between mutism and inappropriately loud, disorganized religious preaching. When his arm is lifted, it remains as placed. He is admitted to the acute care inpatient unit.

Mr. C’s most striking symptoms are catatonia and psychosis. Postural rigidity, waxy flexibility, and automatic obedience are characteristics of catatonia.^6-8 An organic cause is first considered, such as hyperthyroidism, cerebrovascular accident, cerebral neoplasm, head trauma, seizure disorder, dementia, neuroleptic malignant syndrome, pheochromocytoma, or—especially—intoxication from illegal drugs.⁷

While awaiting results from physical, mental status, and lab exams and imaging studies, staff assign him two admitting diagnoses: catatonic disorder due to a general medical condition and psychotic disorder not otherwise specified.⁶

Case: Inconclusive workup

Mr. C denies using illegal substances or alcohol, which his mother confirms. He has no history of seizures or other medical conditions. His distractibility prevents him from focusing on a formal mental status exam. Physical exam, urine drug screen, lab results, and imaging studies are unremarkable except for an admitting blood pressure of 145/95 mm Hg and pulse of 115 beats per minute. These readings normalize within 1 hour. IM haloperidol and lorazepam are given as needed for agitation, but physicians withhold scheduled medications to allow staff to observe his symptoms.

Organic causes of catatonia now seem less likely, though past use of drugs such as phencyclidine that can cause chronic psychosis cannot be ruled out. Schizophrenia is considered likely because catatonia is one of schizophrenia’s five core diagnostic symptoms.⁶ Catatonia can also be a symptom of bipolar disorder.^6-9 Staff make a preliminary diagnosis of schizophrenia, catatonic type.

Case: ‘Hit men are after me’

Staff observe Mr. C responding to threatening auditory hallucinations. His affect is “fearful to terrified.” He says he hears the voice of God warning him of danger and continuing a running commentary on his actions. He fears for his life because “hit men have been sent to kill me” and have “infiltrated” the inpatient ward. He does not eat, saying his food is poisoned. He says these beliefs have escalated over the past year.

Mr. C’s catatonic symptoms resolve overnight, but obtaining additional history is difficult because of his paranoia. He denies any history of bizarre behavior or past contact with mental health services. He claims not to be especially religious. He is unmarried and lives with his mother, is college-educated, but has held only menial jobs.

Inpatient staff shifts its diagnostic focus to functional disorders associated with auditory hallucinations, paranoid delusions, and gross disorganization. According to Schneider and the DSM-IV-TR,^6,10 hearing a voice “keeping up a running commentary on one’s behavior” is especially diagnostic of schizophrenia.

Because of the rapid resolution of his “catatonic” symptoms and prominence of paranoia, they change his diagnosis on day 2 to schizophrenia, paranoid type. Mr. C meets all diagnostic criteria for schizophrenia except one: the staff has overlooked and has not adequately excluded a psychotic mood disorder.

Case: A turn for the worse

That night, nursing staff find Mr. C naked and cowering in the fetal position in a corner of his room. He has smeared his feces on his face and in his hair and mouth. While being cleaned up, he suddenly begins quoting scripture in a loud, disorganized voice. His expressed thoughts are incomprehensible. He is given haloperidol and lorazepam immediately; oral haloperidol is continued at 10 mg bid.

 

Both Bleuler and Kraepelin concluded “coprophilia and coprophagia are unique to children and patients with schizophrenia.”^11,12 The DSM casebook cites Kraepelin’s description of a catatonic patient who “smeared feces about” as a “classic, textbook case” of schizophrenia.¹¹ The casebook goes on to say: “In the absence of any known general medical condition, the combination of coprophilia, disorganized speech, and catatonic behavior clearly indicates the diagnosis of schizophrenia.”

Mr. C shows each of these. Staff changes his diagnosis again—to schizophrenia, disorganized type, which carries a poor prognosis.^11,12

Case: Banking and ray guns

By day 5, Mr. C’s mental status is normalizing and his psychosis improving. He volunteers for a weekly student case conference. There, he reveals additional information that staff could have discovered at admission with more-focused questions.

He reports that 2 years earlier he suffered severe suicidal depression. Six months later, during a hypomanic episode, he began “toying with the idea” that he might become part owner of his local bank. He believes “the Secret Service decided to transfer ownership to me.”

His plans upon acquiring the bank include buying three houses and six cars valued at several million dollars and running for state governor. For weeks before admission, he did not need sleep, experienced an increase in energy and activities, and his mind was racing. His job seemed so “trivial” that he quit. Immediately before his hospital admission, his delusions intensified to include an “evil conspiracy” to murder him for ownership of the bank and he feared his execution was imminent.

He explains his catatonic behavior on the lawn by his belief that “hit men” hiding across the street aimed a “motion-detecting, heat-seeking ray gun” at him so that if he had “moved an inch,” he would die. He says the “feces incident” was an effort to get himself transferred to the state hospital, where he thought he would be safer because his present caretakers were “infiltrated.” He also says his mother received electroconvulsive therapy in her 20s.

These symptoms—especially the striking grandiosity, lack of need for sleep, racing thoughts, hallucinations and delusions—define a manic episode with psychotic features. Only one manic episode as described here is diagnostic of bipolar disorder, type I.^2,6,13 Staff changes his diagnosis to schizoaffective disorder, a compromise used to include patients with bipolar and psychotic (schizophrenic) features. Some authors contend schizoaffective disorder is psychotic bipolar disorder and not a separate disease.^3,4,9

Case: From SSRI to lithium

After 2 weeks, Mr. C is discharged on haloperidol, 5 mg bid, but no mood stabilizer. He receives follow-up care at a community mental health center. When he develops severe depressive symptoms 6 months after discharge, the attending psychiatrist starts him on a selective serotonin reuptake inhibitor (SSRI). Within 2 weeks, Mr. C switches from depression to a mixed, dysphoric mania. After the SSRI is discontinued and lithium is added to his haloperidol, his mood gradually stabilizes to moderate depression. He develops rigidity, masked faces, and a fine tremor in his hands.

About 10% of bipolar depressed patients given an antidepressant—especially without a mood stabilizer—switch to mania, and their cycle frequency increases.^2,13-15 A correct initial diagnosis and treatment with a mood stabilizer might have avoided Mr. C’s switch.

Mixed bipolar disorder with overlapping depressive and manic symptoms is often resistant to monotherapy, requiring two or more mood stabilizers such as lithium and an anticonvulsant.¹⁴ Without a mood-stabilizing combination, the mixed, rapid-cycling type of bipolar disorder is likely to progress, with more-rapid and more-severe episodes.^2,13-15 Adding lamotrigine, a mood stabilizer with antidepressant effects, can help.^2,14

Stopping the SSRI is correct, despite Mr. C’s severe depression, to avoid increasing the cycle frequency.^13-15 Some authors recommend tapering the antipsychotic, using it only as needed for psychotic features after psychosis has resolved.^14-17 Continuing antipsychotic drugs after psychosis has remitted increases rates of cycling to depression, depressive and extrapyramidal symptoms, and medication discontinuation.¹⁷ Lithium may have aggravated Mr. C’s antipsychotic-induced parkinsonism, but discontinuing haloperidol may have been the most therapeutic decision.

The community mental health staff changes his diagnosis again, this time to bipolar disorder, type I, mixed, severe with psychotic features. We concur that this is correct.

Case: A diagnostic step back

Two years later, Mr. C is working and continues to take lithium and haloperidol prescribed at the mental health center. His intermittent depressive episodes persist, but—apparently because he has not had another manic episode—the staff switches his diagnosis back to schizoaffective disorder.

We disagree with this change. A diagnosis of schizoaffective disorder precludes ideal pharmacotherapy for Mr. C’s rapid-cycling bipolar disorder and increases the risk of adverse drug effects and stigma. Persuasive evidence shows that schizoaffective disorder is psychotic bipolar disorder; there is no schizoaffective disorder (Box).^3,4,16-18

 

Box

Misdiagnosis of psychosis

Bipolar disorder can be missed when patients present with psychotic symptoms, but clinicians could have initially recognized Mr. C’s bipolar disorder. His diagnostic trail illustrates important points about psychotic presentations:

• Predominant psychotic symptoms can obscure mood disturbances.
  
• Mistakenly believing that psychosis means schizophrenia can jeopardize patient care.
  
• When paranoia and fear hide grandiosity, then mania—not schizophrenia—is likely.
  
• Psychotic mood disorders—not schizophrenia—cause functional psychosis; there is no schizophrenia (Box).
  
• Pursuing mood symptoms in psychotic presentations is critical in an initial diagnostic interview.
  

Questioning the concept that hallucinations, delusions, catatonia, and disorganization are specific to and diagnostic of schizophrenia is not new. In 1978, Pope and Lipinski compared symptoms, course, outcome, family history, and responses to lithium in bipolar disorder and schizophrenia.³ They and others find no symptom, group of symptoms, or course that differentiates schizophrenia from psychotic bipolar disorder.^{3-5,8,9,16,18,19} They conclude that most cases diagnosed as schizophrenia or schizoaffective disorder are misdiagnosed cases of bipolar illness, whereas others question the validity of schizophrenia.²⁰

Bipolar disorder has a broad spectrum of severity and course; it frequently reaches psychotic levels that can become chronic.^2,5,21 Psychotic symptoms of rigorously diagnosed bipolar patients can deteriorate until their overwhelming psychosis obscures bipolar symptoms.^5,6,13,21 Like most, if not all, acutely psychotic bipolar patients, Mr. C shows all diagnostic criteria for schizophrenia.^1-6,21

Patients with severe, psychotic bipolar disorder can stop responding to medication and suffer chronic deterioration without remission.^5,21 They can lose their jobs, families, friends, and health until they are homeless, hungry, sick, and psychotic. A deteriorating course such as this has typically defined the schizophrenic process, but this concept has been reassessed.^1-6,13,15

Most, but not all, bipolar type I patients experience psychosis. Mr. C’s bipolar symptoms were not initially obvious because of predominant psychosis and were revealed only with specific, focused questions. Without the student case conference, his diagnosis might have remained schizophrenia. His treatment would have remained substandard because of the conventional belief that schizophrenia requires lifelong antipsychotics, usually without mood stabilizers.

Our patient satisfied all DSM-IV-TR criteria for both schizophrenia and psychotic bipolar. Bleuler and Schneider would have diagnosed him as having schizophrenia because they thought all psychotic disorders were schizophrenic.^10,12 They were incorrect, as psychotic symptoms are common in patients with severe bipolar disorder.^1-6,13,22

Cinical implications

Our observations about this case suggest four important clinical questions:

• Do data justify diagnosing patients such as Mr. C with bipolar disorder and not schizophrenia?
  
• Do data substantiate either diagnosis as valid?
  
• Does the diagnosis matter?
  
• What is standard-of-care treatment for these patients?
  

Which diagnosis? No psychiatric disorder can be validated as rigorously as Koch’s postulates did for infectious diseases. To be considered scientifically grounded, a psychiatric illness must show one or more symptoms not found in any other disorder. Bipolar disorder meets this criterion; schizophrenia does not because the psychotic symptoms and chronic course used to diagnose it are not disease-specific. Psychotic symptoms are not diagnostic of bipolar disorder but define its severity.⁶

Evidence for validity? Bipolar disorder’s two extremes in mood and behavior are so different from those in persons without bipolar disorder or with any other condition that homogeneous bipolar populations can be identified and studied with confidence.^2,5,13,21 DSM-IV-TR diagnostic symptoms for bipolar disorder are unique (Table 2).

For a psychiatric disorder to be considered valid, patients must share other characteristics. Bipolar disorder has been validated as a specific disease by consistent genetic,^1,13,23,24 pharmacologic,^2,14,15 and epidemiologic¹ data accumulated across 30 years. The concordance for bipolar disorder in monozygotic twins is approximately 75%, and susceptibility loci for bipolar disorder are established.^23,24

Table 2

Characteristics indicating a mood disorder, not schizophrenia*

History	Past diagnosis or symptoms of a mood disorder; family history of mood disorder or alcoholism
Past medications	Lithium, valproic acid, or other mood stabilizers
Periods of uncharacteristic and excessive goal-directed activities	Political, religious, legal, sexual, business, criminal, medical, physical, spending, calling, writing, preaching, cleaning, planning, exercise
Presence of uncharacteristic emotions or conflict	Irritability, anger, violence, conflict with law enforcement, elation, grandiosity (paranoia), sadness, hopelessness, crying, suicidal ideation
Periods of appropriate affect	Smiles, laughs, cries, irritable, angry
Mood-congruent delusions and/or hallucinations	Consider grandiosity when there is paranoia and fear
Episodes of relatively normal function/remission; premorbid personality positive	Friends, dating, team sports, group activities, election to an office/title, club or gang memberships
Current social interactions	Enjoys a friendship, active interactions with spouse and own children, regular interactions with others
*Absence of any or all does not rule out mood disorder.

 

Does the diagnosis matter? Failing to make an accurate initial diagnosis can worsen the course of patients who present with psychosis (Table 3):

• Bipolar illness not treated with mood stabilizers progresses, with episodes becoming more frequent and severe.^2,14,15
  
• Antipsychotics are given longer and in higher dosages for schizophrenia than for psychotic bipolar disorder and tend to have more common, chronic, and disabling adverse effects than do antidepressants and mood stabilizers.^14,16
  
• Mr. C was given an antidepressant without mood stabilization, which is contraindicated in bipolar I disorder (especially mixed type) because the cycling rate increases.^2,14,15
  

Paranoia and fear often hide grandiosity that is diagnostic of bipolar disorder, but patients such as Mr. C focus on perceived threats to their lives, not their grandiose delusions. Admitting physicians listening to their paranoid complaints may overlook the grandiose source and the possibility of psychotic bipolar disorder. Mr. C’s manic grandiosity explains the motivation for each of his psychotic behaviors: paranoid delusions, catatonia, and coprophilia.

Several initial signs could have raised suspicion that Mr. C had psychotic bipolar disorder (Table 4). Standard-of-care treatment in psychotic patients is predicated on early and correct diagnosis. On the basis of the evidence and our experience, we recommend that you look for bipolar symptoms when a patient:

• presents for the first time with psychosis, and you rule out an organic cause
  
• is readmitted for treatment of psychotic symptoms after having been diagnosed with schizophrenia.
  

Table 3

Consequences of misdiagnosing psychotic mood disorder as schizophrenia

For patient Less likely to receive a mood stabilizer or antidepressant Without a mood stabilizer, cycles increase and occur more rapidly; symptoms worsen More likely to receive neuroleptics for life, increasing risk for severe and permanent side effects Greater stigma with schizophrenia Less likely to be employed More likely to receive disability for life More likely to “give up”
For clinician Increased risk of liability if patient given long-term neuroleptics instead of mood stabilizers develops tardive dyskinesia or commits suicide

Table 4

Mr. C’s symptoms that indicated bipolar disorder

Religiosity	Loud preaching and no past special interest in religion
Catatonia	Most frequently associated with bipolar disorder
Paranoia; fear	Usually hides grandiosity, which is diagnostic of mania
Distractibility	Could not stay focused in the diagnostic interview; showed ‘flight of ideas’
Pressured speech	Rapid, disorganized thoughts
Disorganization	Hallmark of mania; present in all patients with severe mania
Functional psychosis	If an organic cause is ruled out, a psychotic mood disorder is the most likely diagnosis
Trouble with the law	Police found patient disturbing neighborhood and escorted him to hospital
Patient history	Severe depression
Family history	Mother was treated for depression with ECT
ECT: electroconvulsive therapy

What is standard of care? Patients with psychotic mania warrant polypharmacy:

• an antipsychotic, with or without a benzodiazepine for sedation, to enhance ward safety and treat acute psychotic symptoms
  
• and a first-line mood stabilizer such as valproate, carbamazepine, lithium, or lamotrigine, followed by atypical antipsychotics.
  

Antidepressants appear to be contraindicated, even in psychotic bipolar depressed patients.^14,15 We suggest that you taper and discontinue the initial antipsychotic when psychotic symptoms resolve. Some data indicate that continuing antipsychotics in psychotic bipolar patients is detrimental after the psychosis has resolved.¹⁷ Medication-resistant cases may require two or three mood stabilizers and possibly an atypical antipsychotic.

The idea that “symptoms should be treated, not the diagnosis” is inaccurate and provides substandard care. When psychotic symptoms overwhelm and obscure bipolar symptoms, giving only antipsychotics is beyond standard of care.

Related resources

• Berrettini WH. Molecular linkage studies of bipolar disorders. Bipolar Disord 2001;3:276-83.
  
• Lake CR, Hurwitz N. Schizoaffective disorders are psychotic mood disorders; there are no schizoaffective disorders. Psychiatry Res 2006 (in press).
  
• Pope HG, Lipinski JF. Diagnosis in schizophrenia and manic-depressive illness, a reassessment of the specificity of “schizophrenic” symptoms in the light of current research. Arch Gen Psychiatry 1978;35:811-28.
  
• Post RM. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 1992;149:999-1010.
  

Drug brand names

• Haloperidol • Haldol
  
• Lamotrigine • Lamictal
  
• Lithium • Lithobid
  
• Lorazepam • Ativan
  
• Carbamazepine • Tegretol
  
• Valproate • Depakote
  

Disclosures

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

Acknowledgements

The patient described in this case report gave informed, written consent to interviews and to the anonymous publication of his treatment.

The authors thank Anita Swisher for technical assistance.

When a patient presents with psychotic symptoms, you might not recognize or pursue hints of bipolarity if you assume psychosis means schizophrenia. Yet psychotic bipolar disorder can explain every sign, symptom, course, and other characteristic traditionally assumed to indicate schizophrenia (Table 1). The literature, including recent genetic data,^1-6 marshals a persuasive argument that patients diagnosed with schizophrenia usually suffer from a psychotic bipolar disorder.

Consider here how a cascade of changing signs and symptoms, initially unrecognized, caused five sequential re-evaluations of one psychotic patient’s primary Axis I diagnosis. His case highlights why the correct initial diagnosis of the disease causing psychosis is essential to effective treatment.^4,7-9

Table 1

DSM-IV-TR criteria for schizophrenia vs. psychotic mood disorder

Schizophrenia diagnosis6	Seen in psychotic mood disorders
Criterion A
Hallucinations and delusions	50% to 80% explained by mood16,21
Paranoia	Hides grandiosity4
Catatonia	75% explained by mood7,8
Disorganized speech and behavior	All patients with moderate to severe mania1-5
Negative symptoms	All patients with moderate to severe depression4
Criterion B
Social and job dysfunction	All patients with moderate to severe bipolar disorder5,13
Criterion C
Chronic continuous symptoms	Patients can have psychotic symptoms continuously for 2 years to life5,6,13

Case: Carved in stone

Police officers carry Mr. C, age 30, into the emergency department. He is mentally disorganized and arrives in a rigid, catatonic posture. According to a neighbor, Mr. C was kneeling motionless on his mother’s front lawn, alternating between mutism and inappropriately loud, disorganized religious preaching. When his arm is lifted, it remains as placed. He is admitted to the acute care inpatient unit.

Mr. C’s most striking symptoms are catatonia and psychosis. Postural rigidity, waxy flexibility, and automatic obedience are characteristics of catatonia.^6-8 An organic cause is first considered, such as hyperthyroidism, cerebrovascular accident, cerebral neoplasm, head trauma, seizure disorder, dementia, neuroleptic malignant syndrome, pheochromocytoma, or—especially—intoxication from illegal drugs.⁷

While awaiting results from physical, mental status, and lab exams and imaging studies, staff assign him two admitting diagnoses: catatonic disorder due to a general medical condition and psychotic disorder not otherwise specified.⁶

Case: Inconclusive workup

Mr. C denies using illegal substances or alcohol, which his mother confirms. He has no history of seizures or other medical conditions. His distractibility prevents him from focusing on a formal mental status exam. Physical exam, urine drug screen, lab results, and imaging studies are unremarkable except for an admitting blood pressure of 145/95 mm Hg and pulse of 115 beats per minute. These readings normalize within 1 hour. IM haloperidol and lorazepam are given as needed for agitation, but physicians withhold scheduled medications to allow staff to observe his symptoms.

Organic causes of catatonia now seem less likely, though past use of drugs such as phencyclidine that can cause chronic psychosis cannot be ruled out. Schizophrenia is considered likely because catatonia is one of schizophrenia’s five core diagnostic symptoms.⁶ Catatonia can also be a symptom of bipolar disorder.^6-9 Staff make a preliminary diagnosis of schizophrenia, catatonic type.

Case: ‘Hit men are after me’

Staff observe Mr. C responding to threatening auditory hallucinations. His affect is “fearful to terrified.” He says he hears the voice of God warning him of danger and continuing a running commentary on his actions. He fears for his life because “hit men have been sent to kill me” and have “infiltrated” the inpatient ward. He does not eat, saying his food is poisoned. He says these beliefs have escalated over the past year.

Mr. C’s catatonic symptoms resolve overnight, but obtaining additional history is difficult because of his paranoia. He denies any history of bizarre behavior or past contact with mental health services. He claims not to be especially religious. He is unmarried and lives with his mother, is college-educated, but has held only menial jobs.

Inpatient staff shifts its diagnostic focus to functional disorders associated with auditory hallucinations, paranoid delusions, and gross disorganization. According to Schneider and the DSM-IV-TR,^6,10 hearing a voice “keeping up a running commentary on one’s behavior” is especially diagnostic of schizophrenia.

Because of the rapid resolution of his “catatonic” symptoms and prominence of paranoia, they change his diagnosis on day 2 to schizophrenia, paranoid type. Mr. C meets all diagnostic criteria for schizophrenia except one: the staff has overlooked and has not adequately excluded a psychotic mood disorder.

Case: A turn for the worse

That night, nursing staff find Mr. C naked and cowering in the fetal position in a corner of his room. He has smeared his feces on his face and in his hair and mouth. While being cleaned up, he suddenly begins quoting scripture in a loud, disorganized voice. His expressed thoughts are incomprehensible. He is given haloperidol and lorazepam immediately; oral haloperidol is continued at 10 mg bid.

 

Both Bleuler and Kraepelin concluded “coprophilia and coprophagia are unique to children and patients with schizophrenia.”^11,12 The DSM casebook cites Kraepelin’s description of a catatonic patient who “smeared feces about” as a “classic, textbook case” of schizophrenia.¹¹ The casebook goes on to say: “In the absence of any known general medical condition, the combination of coprophilia, disorganized speech, and catatonic behavior clearly indicates the diagnosis of schizophrenia.”

Mr. C shows each of these. Staff changes his diagnosis again—to schizophrenia, disorganized type, which carries a poor prognosis.^11,12

Case: Banking and ray guns

By day 5, Mr. C’s mental status is normalizing and his psychosis improving. He volunteers for a weekly student case conference. There, he reveals additional information that staff could have discovered at admission with more-focused questions.

He reports that 2 years earlier he suffered severe suicidal depression. Six months later, during a hypomanic episode, he began “toying with the idea” that he might become part owner of his local bank. He believes “the Secret Service decided to transfer ownership to me.”

His plans upon acquiring the bank include buying three houses and six cars valued at several million dollars and running for state governor. For weeks before admission, he did not need sleep, experienced an increase in energy and activities, and his mind was racing. His job seemed so “trivial” that he quit. Immediately before his hospital admission, his delusions intensified to include an “evil conspiracy” to murder him for ownership of the bank and he feared his execution was imminent.

He explains his catatonic behavior on the lawn by his belief that “hit men” hiding across the street aimed a “motion-detecting, heat-seeking ray gun” at him so that if he had “moved an inch,” he would die. He says the “feces incident” was an effort to get himself transferred to the state hospital, where he thought he would be safer because his present caretakers were “infiltrated.” He also says his mother received electroconvulsive therapy in her 20s.

These symptoms—especially the striking grandiosity, lack of need for sleep, racing thoughts, hallucinations and delusions—define a manic episode with psychotic features. Only one manic episode as described here is diagnostic of bipolar disorder, type I.^2,6,13 Staff changes his diagnosis to schizoaffective disorder, a compromise used to include patients with bipolar and psychotic (schizophrenic) features. Some authors contend schizoaffective disorder is psychotic bipolar disorder and not a separate disease.^3,4,9

Case: From SSRI to lithium

After 2 weeks, Mr. C is discharged on haloperidol, 5 mg bid, but no mood stabilizer. He receives follow-up care at a community mental health center. When he develops severe depressive symptoms 6 months after discharge, the attending psychiatrist starts him on a selective serotonin reuptake inhibitor (SSRI). Within 2 weeks, Mr. C switches from depression to a mixed, dysphoric mania. After the SSRI is discontinued and lithium is added to his haloperidol, his mood gradually stabilizes to moderate depression. He develops rigidity, masked faces, and a fine tremor in his hands.

About 10% of bipolar depressed patients given an antidepressant—especially without a mood stabilizer—switch to mania, and their cycle frequency increases.^2,13-15 A correct initial diagnosis and treatment with a mood stabilizer might have avoided Mr. C’s switch.

Mixed bipolar disorder with overlapping depressive and manic symptoms is often resistant to monotherapy, requiring two or more mood stabilizers such as lithium and an anticonvulsant.¹⁴ Without a mood-stabilizing combination, the mixed, rapid-cycling type of bipolar disorder is likely to progress, with more-rapid and more-severe episodes.^2,13-15 Adding lamotrigine, a mood stabilizer with antidepressant effects, can help.^2,14

Stopping the SSRI is correct, despite Mr. C’s severe depression, to avoid increasing the cycle frequency.^13-15 Some authors recommend tapering the antipsychotic, using it only as needed for psychotic features after psychosis has resolved.^14-17 Continuing antipsychotic drugs after psychosis has remitted increases rates of cycling to depression, depressive and extrapyramidal symptoms, and medication discontinuation.¹⁷ Lithium may have aggravated Mr. C’s antipsychotic-induced parkinsonism, but discontinuing haloperidol may have been the most therapeutic decision.

The community mental health staff changes his diagnosis again, this time to bipolar disorder, type I, mixed, severe with psychotic features. We concur that this is correct.

Case: A diagnostic step back

Two years later, Mr. C is working and continues to take lithium and haloperidol prescribed at the mental health center. His intermittent depressive episodes persist, but—apparently because he has not had another manic episode—the staff switches his diagnosis back to schizoaffective disorder.

We disagree with this change. A diagnosis of schizoaffective disorder precludes ideal pharmacotherapy for Mr. C’s rapid-cycling bipolar disorder and increases the risk of adverse drug effects and stigma. Persuasive evidence shows that schizoaffective disorder is psychotic bipolar disorder; there is no schizoaffective disorder (Box).^3,4,16-18

 

Box

Misdiagnosis of psychosis

Bipolar disorder can be missed when patients present with psychotic symptoms, but clinicians could have initially recognized Mr. C’s bipolar disorder. His diagnostic trail illustrates important points about psychotic presentations:

• Predominant psychotic symptoms can obscure mood disturbances.
  
• Mistakenly believing that psychosis means schizophrenia can jeopardize patient care.
  
• When paranoia and fear hide grandiosity, then mania—not schizophrenia—is likely.
  
• Psychotic mood disorders—not schizophrenia—cause functional psychosis; there is no schizophrenia (Box).
  
• Pursuing mood symptoms in psychotic presentations is critical in an initial diagnostic interview.
  

Questioning the concept that hallucinations, delusions, catatonia, and disorganization are specific to and diagnostic of schizophrenia is not new. In 1978, Pope and Lipinski compared symptoms, course, outcome, family history, and responses to lithium in bipolar disorder and schizophrenia.³ They and others find no symptom, group of symptoms, or course that differentiates schizophrenia from psychotic bipolar disorder.^{3-5,8,9,16,18,19} They conclude that most cases diagnosed as schizophrenia or schizoaffective disorder are misdiagnosed cases of bipolar illness, whereas others question the validity of schizophrenia.²⁰

Bipolar disorder has a broad spectrum of severity and course; it frequently reaches psychotic levels that can become chronic.^2,5,21 Psychotic symptoms of rigorously diagnosed bipolar patients can deteriorate until their overwhelming psychosis obscures bipolar symptoms.^5,6,13,21 Like most, if not all, acutely psychotic bipolar patients, Mr. C shows all diagnostic criteria for schizophrenia.^1-6,21

Patients with severe, psychotic bipolar disorder can stop responding to medication and suffer chronic deterioration without remission.^5,21 They can lose their jobs, families, friends, and health until they are homeless, hungry, sick, and psychotic. A deteriorating course such as this has typically defined the schizophrenic process, but this concept has been reassessed.^1-6,13,15

Most, but not all, bipolar type I patients experience psychosis. Mr. C’s bipolar symptoms were not initially obvious because of predominant psychosis and were revealed only with specific, focused questions. Without the student case conference, his diagnosis might have remained schizophrenia. His treatment would have remained substandard because of the conventional belief that schizophrenia requires lifelong antipsychotics, usually without mood stabilizers.

Our patient satisfied all DSM-IV-TR criteria for both schizophrenia and psychotic bipolar. Bleuler and Schneider would have diagnosed him as having schizophrenia because they thought all psychotic disorders were schizophrenic.^10,12 They were incorrect, as psychotic symptoms are common in patients with severe bipolar disorder.^1-6,13,22

Cinical implications

Our observations about this case suggest four important clinical questions:

• Do data justify diagnosing patients such as Mr. C with bipolar disorder and not schizophrenia?
  
• Do data substantiate either diagnosis as valid?
  
• Does the diagnosis matter?
  
• What is standard-of-care treatment for these patients?
  

Which diagnosis? No psychiatric disorder can be validated as rigorously as Koch’s postulates did for infectious diseases. To be considered scientifically grounded, a psychiatric illness must show one or more symptoms not found in any other disorder. Bipolar disorder meets this criterion; schizophrenia does not because the psychotic symptoms and chronic course used to diagnose it are not disease-specific. Psychotic symptoms are not diagnostic of bipolar disorder but define its severity.⁶

Evidence for validity? Bipolar disorder’s two extremes in mood and behavior are so different from those in persons without bipolar disorder or with any other condition that homogeneous bipolar populations can be identified and studied with confidence.^2,5,13,21 DSM-IV-TR diagnostic symptoms for bipolar disorder are unique (Table 2).

For a psychiatric disorder to be considered valid, patients must share other characteristics. Bipolar disorder has been validated as a specific disease by consistent genetic,^1,13,23,24 pharmacologic,^2,14,15 and epidemiologic¹ data accumulated across 30 years. The concordance for bipolar disorder in monozygotic twins is approximately 75%, and susceptibility loci for bipolar disorder are established.^23,24

Table 2

Characteristics indicating a mood disorder, not schizophrenia*

History	Past diagnosis or symptoms of a mood disorder; family history of mood disorder or alcoholism
Past medications	Lithium, valproic acid, or other mood stabilizers
Periods of uncharacteristic and excessive goal-directed activities	Political, religious, legal, sexual, business, criminal, medical, physical, spending, calling, writing, preaching, cleaning, planning, exercise
Presence of uncharacteristic emotions or conflict	Irritability, anger, violence, conflict with law enforcement, elation, grandiosity (paranoia), sadness, hopelessness, crying, suicidal ideation
Periods of appropriate affect	Smiles, laughs, cries, irritable, angry
Mood-congruent delusions and/or hallucinations	Consider grandiosity when there is paranoia and fear
Episodes of relatively normal function/remission; premorbid personality positive	Friends, dating, team sports, group activities, election to an office/title, club or gang memberships
Current social interactions	Enjoys a friendship, active interactions with spouse and own children, regular interactions with others
*Absence of any or all does not rule out mood disorder.

 

Does the diagnosis matter? Failing to make an accurate initial diagnosis can worsen the course of patients who present with psychosis (Table 3):

• Bipolar illness not treated with mood stabilizers progresses, with episodes becoming more frequent and severe.^2,14,15
  
• Antipsychotics are given longer and in higher dosages for schizophrenia than for psychotic bipolar disorder and tend to have more common, chronic, and disabling adverse effects than do antidepressants and mood stabilizers.^14,16
  
• Mr. C was given an antidepressant without mood stabilization, which is contraindicated in bipolar I disorder (especially mixed type) because the cycling rate increases.^2,14,15
  

Paranoia and fear often hide grandiosity that is diagnostic of bipolar disorder, but patients such as Mr. C focus on perceived threats to their lives, not their grandiose delusions. Admitting physicians listening to their paranoid complaints may overlook the grandiose source and the possibility of psychotic bipolar disorder. Mr. C’s manic grandiosity explains the motivation for each of his psychotic behaviors: paranoid delusions, catatonia, and coprophilia.

Several initial signs could have raised suspicion that Mr. C had psychotic bipolar disorder (Table 4). Standard-of-care treatment in psychotic patients is predicated on early and correct diagnosis. On the basis of the evidence and our experience, we recommend that you look for bipolar symptoms when a patient:

• presents for the first time with psychosis, and you rule out an organic cause
  
• is readmitted for treatment of psychotic symptoms after having been diagnosed with schizophrenia.
  

Table 3

Consequences of misdiagnosing psychotic mood disorder as schizophrenia

For patient Less likely to receive a mood stabilizer or antidepressant Without a mood stabilizer, cycles increase and occur more rapidly; symptoms worsen More likely to receive neuroleptics for life, increasing risk for severe and permanent side effects Greater stigma with schizophrenia Less likely to be employed More likely to receive disability for life More likely to “give up”
For clinician Increased risk of liability if patient given long-term neuroleptics instead of mood stabilizers develops tardive dyskinesia or commits suicide

Table 4

Mr. C’s symptoms that indicated bipolar disorder

Religiosity	Loud preaching and no past special interest in religion
Catatonia	Most frequently associated with bipolar disorder
Paranoia; fear	Usually hides grandiosity, which is diagnostic of mania
Distractibility	Could not stay focused in the diagnostic interview; showed ‘flight of ideas’
Pressured speech	Rapid, disorganized thoughts
Disorganization	Hallmark of mania; present in all patients with severe mania
Functional psychosis	If an organic cause is ruled out, a psychotic mood disorder is the most likely diagnosis
Trouble with the law	Police found patient disturbing neighborhood and escorted him to hospital
Patient history	Severe depression
Family history	Mother was treated for depression with ECT
ECT: electroconvulsive therapy

What is standard of care? Patients with psychotic mania warrant polypharmacy:

• an antipsychotic, with or without a benzodiazepine for sedation, to enhance ward safety and treat acute psychotic symptoms
  
• and a first-line mood stabilizer such as valproate, carbamazepine, lithium, or lamotrigine, followed by atypical antipsychotics.
  

Antidepressants appear to be contraindicated, even in psychotic bipolar depressed patients.^14,15 We suggest that you taper and discontinue the initial antipsychotic when psychotic symptoms resolve. Some data indicate that continuing antipsychotics in psychotic bipolar patients is detrimental after the psychosis has resolved.¹⁷ Medication-resistant cases may require two or three mood stabilizers and possibly an atypical antipsychotic.

The idea that “symptoms should be treated, not the diagnosis” is inaccurate and provides substandard care. When psychotic symptoms overwhelm and obscure bipolar symptoms, giving only antipsychotics is beyond standard of care.

Related resources

• Berrettini WH. Molecular linkage studies of bipolar disorders. Bipolar Disord 2001;3:276-83.
  
• Lake CR, Hurwitz N. Schizoaffective disorders are psychotic mood disorders; there are no schizoaffective disorders. Psychiatry Res 2006 (in press).
  
• Pope HG, Lipinski JF. Diagnosis in schizophrenia and manic-depressive illness, a reassessment of the specificity of “schizophrenic” symptoms in the light of current research. Arch Gen Psychiatry 1978;35:811-28.
  
• Post RM. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 1992;149:999-1010.
  

Drug brand names

• Haloperidol • Haldol
  
• Lamotrigine • Lamictal
  
• Lithium • Lithobid
  
• Lorazepam • Ativan
  
• Carbamazepine • Tegretol
  
• Valproate • Depakote
  

Disclosures

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

Acknowledgements

The patient described in this case report gave informed, written consent to interviews and to the anonymous publication of his treatment.

The authors thank Anita Swisher for technical assistance.

When a patient presents with psychotic symptoms, you might not recognize or pursue hints of bipolarity if you assume psychosis means schizophrenia. Yet psychotic bipolar disorder can explain every sign, symptom, course, and other characteristic traditionally assumed to indicate schizophrenia (Table 1). The literature, including recent genetic data,^1-6 marshals a persuasive argument that patients diagnosed with schizophrenia usually suffer from a psychotic bipolar disorder.

Consider here how a cascade of changing signs and symptoms, initially unrecognized, caused five sequential re-evaluations of one psychotic patient’s primary Axis I diagnosis. His case highlights why the correct initial diagnosis of the disease causing psychosis is essential to effective treatment.^4,7-9

Table 1

DSM-IV-TR criteria for schizophrenia vs. psychotic mood disorder

Schizophrenia diagnosis6	Seen in psychotic mood disorders
Criterion A
Hallucinations and delusions	50% to 80% explained by mood16,21
Paranoia	Hides grandiosity4
Catatonia	75% explained by mood7,8
Disorganized speech and behavior	All patients with moderate to severe mania1-5
Negative symptoms	All patients with moderate to severe depression4
Criterion B
Social and job dysfunction	All patients with moderate to severe bipolar disorder5,13
Criterion C
Chronic continuous symptoms	Patients can have psychotic symptoms continuously for 2 years to life5,6,13

Case: Carved in stone

Police officers carry Mr. C, age 30, into the emergency department. He is mentally disorganized and arrives in a rigid, catatonic posture. According to a neighbor, Mr. C was kneeling motionless on his mother’s front lawn, alternating between mutism and inappropriately loud, disorganized religious preaching. When his arm is lifted, it remains as placed. He is admitted to the acute care inpatient unit.

Mr. C’s most striking symptoms are catatonia and psychosis. Postural rigidity, waxy flexibility, and automatic obedience are characteristics of catatonia.^6-8 An organic cause is first considered, such as hyperthyroidism, cerebrovascular accident, cerebral neoplasm, head trauma, seizure disorder, dementia, neuroleptic malignant syndrome, pheochromocytoma, or—especially—intoxication from illegal drugs.⁷

While awaiting results from physical, mental status, and lab exams and imaging studies, staff assign him two admitting diagnoses: catatonic disorder due to a general medical condition and psychotic disorder not otherwise specified.⁶

Case: Inconclusive workup

Mr. C denies using illegal substances or alcohol, which his mother confirms. He has no history of seizures or other medical conditions. His distractibility prevents him from focusing on a formal mental status exam. Physical exam, urine drug screen, lab results, and imaging studies are unremarkable except for an admitting blood pressure of 145/95 mm Hg and pulse of 115 beats per minute. These readings normalize within 1 hour. IM haloperidol and lorazepam are given as needed for agitation, but physicians withhold scheduled medications to allow staff to observe his symptoms.

Organic causes of catatonia now seem less likely, though past use of drugs such as phencyclidine that can cause chronic psychosis cannot be ruled out. Schizophrenia is considered likely because catatonia is one of schizophrenia’s five core diagnostic symptoms.⁶ Catatonia can also be a symptom of bipolar disorder.^6-9 Staff make a preliminary diagnosis of schizophrenia, catatonic type.

Case: ‘Hit men are after me’

Staff observe Mr. C responding to threatening auditory hallucinations. His affect is “fearful to terrified.” He says he hears the voice of God warning him of danger and continuing a running commentary on his actions. He fears for his life because “hit men have been sent to kill me” and have “infiltrated” the inpatient ward. He does not eat, saying his food is poisoned. He says these beliefs have escalated over the past year.

Mr. C’s catatonic symptoms resolve overnight, but obtaining additional history is difficult because of his paranoia. He denies any history of bizarre behavior or past contact with mental health services. He claims not to be especially religious. He is unmarried and lives with his mother, is college-educated, but has held only menial jobs.

Inpatient staff shifts its diagnostic focus to functional disorders associated with auditory hallucinations, paranoid delusions, and gross disorganization. According to Schneider and the DSM-IV-TR,^6,10 hearing a voice “keeping up a running commentary on one’s behavior” is especially diagnostic of schizophrenia.

Because of the rapid resolution of his “catatonic” symptoms and prominence of paranoia, they change his diagnosis on day 2 to schizophrenia, paranoid type. Mr. C meets all diagnostic criteria for schizophrenia except one: the staff has overlooked and has not adequately excluded a psychotic mood disorder.

Case: A turn for the worse

That night, nursing staff find Mr. C naked and cowering in the fetal position in a corner of his room. He has smeared his feces on his face and in his hair and mouth. While being cleaned up, he suddenly begins quoting scripture in a loud, disorganized voice. His expressed thoughts are incomprehensible. He is given haloperidol and lorazepam immediately; oral haloperidol is continued at 10 mg bid.

 

Both Bleuler and Kraepelin concluded “coprophilia and coprophagia are unique to children and patients with schizophrenia.”^11,12 The DSM casebook cites Kraepelin’s description of a catatonic patient who “smeared feces about” as a “classic, textbook case” of schizophrenia.¹¹ The casebook goes on to say: “In the absence of any known general medical condition, the combination of coprophilia, disorganized speech, and catatonic behavior clearly indicates the diagnosis of schizophrenia.”

Mr. C shows each of these. Staff changes his diagnosis again—to schizophrenia, disorganized type, which carries a poor prognosis.^11,12

Case: Banking and ray guns

By day 5, Mr. C’s mental status is normalizing and his psychosis improving. He volunteers for a weekly student case conference. There, he reveals additional information that staff could have discovered at admission with more-focused questions.

He reports that 2 years earlier he suffered severe suicidal depression. Six months later, during a hypomanic episode, he began “toying with the idea” that he might become part owner of his local bank. He believes “the Secret Service decided to transfer ownership to me.”

His plans upon acquiring the bank include buying three houses and six cars valued at several million dollars and running for state governor. For weeks before admission, he did not need sleep, experienced an increase in energy and activities, and his mind was racing. His job seemed so “trivial” that he quit. Immediately before his hospital admission, his delusions intensified to include an “evil conspiracy” to murder him for ownership of the bank and he feared his execution was imminent.

He explains his catatonic behavior on the lawn by his belief that “hit men” hiding across the street aimed a “motion-detecting, heat-seeking ray gun” at him so that if he had “moved an inch,” he would die. He says the “feces incident” was an effort to get himself transferred to the state hospital, where he thought he would be safer because his present caretakers were “infiltrated.” He also says his mother received electroconvulsive therapy in her 20s.

These symptoms—especially the striking grandiosity, lack of need for sleep, racing thoughts, hallucinations and delusions—define a manic episode with psychotic features. Only one manic episode as described here is diagnostic of bipolar disorder, type I.^2,6,13 Staff changes his diagnosis to schizoaffective disorder, a compromise used to include patients with bipolar and psychotic (schizophrenic) features. Some authors contend schizoaffective disorder is psychotic bipolar disorder and not a separate disease.^3,4,9

Case: From SSRI to lithium

After 2 weeks, Mr. C is discharged on haloperidol, 5 mg bid, but no mood stabilizer. He receives follow-up care at a community mental health center. When he develops severe depressive symptoms 6 months after discharge, the attending psychiatrist starts him on a selective serotonin reuptake inhibitor (SSRI). Within 2 weeks, Mr. C switches from depression to a mixed, dysphoric mania. After the SSRI is discontinued and lithium is added to his haloperidol, his mood gradually stabilizes to moderate depression. He develops rigidity, masked faces, and a fine tremor in his hands.

About 10% of bipolar depressed patients given an antidepressant—especially without a mood stabilizer—switch to mania, and their cycle frequency increases.^2,13-15 A correct initial diagnosis and treatment with a mood stabilizer might have avoided Mr. C’s switch.

Mixed bipolar disorder with overlapping depressive and manic symptoms is often resistant to monotherapy, requiring two or more mood stabilizers such as lithium and an anticonvulsant.¹⁴ Without a mood-stabilizing combination, the mixed, rapid-cycling type of bipolar disorder is likely to progress, with more-rapid and more-severe episodes.^2,13-15 Adding lamotrigine, a mood stabilizer with antidepressant effects, can help.^2,14

Stopping the SSRI is correct, despite Mr. C’s severe depression, to avoid increasing the cycle frequency.^13-15 Some authors recommend tapering the antipsychotic, using it only as needed for psychotic features after psychosis has resolved.^14-17 Continuing antipsychotic drugs after psychosis has remitted increases rates of cycling to depression, depressive and extrapyramidal symptoms, and medication discontinuation.¹⁷ Lithium may have aggravated Mr. C’s antipsychotic-induced parkinsonism, but discontinuing haloperidol may have been the most therapeutic decision.

The community mental health staff changes his diagnosis again, this time to bipolar disorder, type I, mixed, severe with psychotic features. We concur that this is correct.

Case: A diagnostic step back

Two years later, Mr. C is working and continues to take lithium and haloperidol prescribed at the mental health center. His intermittent depressive episodes persist, but—apparently because he has not had another manic episode—the staff switches his diagnosis back to schizoaffective disorder.

We disagree with this change. A diagnosis of schizoaffective disorder precludes ideal pharmacotherapy for Mr. C’s rapid-cycling bipolar disorder and increases the risk of adverse drug effects and stigma. Persuasive evidence shows that schizoaffective disorder is psychotic bipolar disorder; there is no schizoaffective disorder (Box).^3,4,16-18

 

Box

Misdiagnosis of psychosis

Bipolar disorder can be missed when patients present with psychotic symptoms, but clinicians could have initially recognized Mr. C’s bipolar disorder. His diagnostic trail illustrates important points about psychotic presentations:

• Predominant psychotic symptoms can obscure mood disturbances.
  
• Mistakenly believing that psychosis means schizophrenia can jeopardize patient care.
  
• When paranoia and fear hide grandiosity, then mania—not schizophrenia—is likely.
  
• Psychotic mood disorders—not schizophrenia—cause functional psychosis; there is no schizophrenia (Box).
  
• Pursuing mood symptoms in psychotic presentations is critical in an initial diagnostic interview.
  

Questioning the concept that hallucinations, delusions, catatonia, and disorganization are specific to and diagnostic of schizophrenia is not new. In 1978, Pope and Lipinski compared symptoms, course, outcome, family history, and responses to lithium in bipolar disorder and schizophrenia.³ They and others find no symptom, group of symptoms, or course that differentiates schizophrenia from psychotic bipolar disorder.^{3-5,8,9,16,18,19} They conclude that most cases diagnosed as schizophrenia or schizoaffective disorder are misdiagnosed cases of bipolar illness, whereas others question the validity of schizophrenia.²⁰

Bipolar disorder has a broad spectrum of severity and course; it frequently reaches psychotic levels that can become chronic.^2,5,21 Psychotic symptoms of rigorously diagnosed bipolar patients can deteriorate until their overwhelming psychosis obscures bipolar symptoms.^5,6,13,21 Like most, if not all, acutely psychotic bipolar patients, Mr. C shows all diagnostic criteria for schizophrenia.^1-6,21

Patients with severe, psychotic bipolar disorder can stop responding to medication and suffer chronic deterioration without remission.^5,21 They can lose their jobs, families, friends, and health until they are homeless, hungry, sick, and psychotic. A deteriorating course such as this has typically defined the schizophrenic process, but this concept has been reassessed.^1-6,13,15

Most, but not all, bipolar type I patients experience psychosis. Mr. C’s bipolar symptoms were not initially obvious because of predominant psychosis and were revealed only with specific, focused questions. Without the student case conference, his diagnosis might have remained schizophrenia. His treatment would have remained substandard because of the conventional belief that schizophrenia requires lifelong antipsychotics, usually without mood stabilizers.

Our patient satisfied all DSM-IV-TR criteria for both schizophrenia and psychotic bipolar. Bleuler and Schneider would have diagnosed him as having schizophrenia because they thought all psychotic disorders were schizophrenic.^10,12 They were incorrect, as psychotic symptoms are common in patients with severe bipolar disorder.^1-6,13,22

Cinical implications

Our observations about this case suggest four important clinical questions:

• Do data justify diagnosing patients such as Mr. C with bipolar disorder and not schizophrenia?
  
• Do data substantiate either diagnosis as valid?
  
• Does the diagnosis matter?
  
• What is standard-of-care treatment for these patients?
  

Which diagnosis? No psychiatric disorder can be validated as rigorously as Koch’s postulates did for infectious diseases. To be considered scientifically grounded, a psychiatric illness must show one or more symptoms not found in any other disorder. Bipolar disorder meets this criterion; schizophrenia does not because the psychotic symptoms and chronic course used to diagnose it are not disease-specific. Psychotic symptoms are not diagnostic of bipolar disorder but define its severity.⁶

Evidence for validity? Bipolar disorder’s two extremes in mood and behavior are so different from those in persons without bipolar disorder or with any other condition that homogeneous bipolar populations can be identified and studied with confidence.^2,5,13,21 DSM-IV-TR diagnostic symptoms for bipolar disorder are unique (Table 2).

For a psychiatric disorder to be considered valid, patients must share other characteristics. Bipolar disorder has been validated as a specific disease by consistent genetic,^1,13,23,24 pharmacologic,^2,14,15 and epidemiologic¹ data accumulated across 30 years. The concordance for bipolar disorder in monozygotic twins is approximately 75%, and susceptibility loci for bipolar disorder are established.^23,24

Table 2

Characteristics indicating a mood disorder, not schizophrenia*

History	Past diagnosis or symptoms of a mood disorder; family history of mood disorder or alcoholism
Past medications	Lithium, valproic acid, or other mood stabilizers
Periods of uncharacteristic and excessive goal-directed activities	Political, religious, legal, sexual, business, criminal, medical, physical, spending, calling, writing, preaching, cleaning, planning, exercise
Presence of uncharacteristic emotions or conflict	Irritability, anger, violence, conflict with law enforcement, elation, grandiosity (paranoia), sadness, hopelessness, crying, suicidal ideation
Periods of appropriate affect	Smiles, laughs, cries, irritable, angry
Mood-congruent delusions and/or hallucinations	Consider grandiosity when there is paranoia and fear
Episodes of relatively normal function/remission; premorbid personality positive	Friends, dating, team sports, group activities, election to an office/title, club or gang memberships
Current social interactions	Enjoys a friendship, active interactions with spouse and own children, regular interactions with others
*Absence of any or all does not rule out mood disorder.

 

Does the diagnosis matter? Failing to make an accurate initial diagnosis can worsen the course of patients who present with psychosis (Table 3):

• Bipolar illness not treated with mood stabilizers progresses, with episodes becoming more frequent and severe.^2,14,15
  
• Antipsychotics are given longer and in higher dosages for schizophrenia than for psychotic bipolar disorder and tend to have more common, chronic, and disabling adverse effects than do antidepressants and mood stabilizers.^14,16
  
• Mr. C was given an antidepressant without mood stabilization, which is contraindicated in bipolar I disorder (especially mixed type) because the cycling rate increases.^2,14,15
  

Paranoia and fear often hide grandiosity that is diagnostic of bipolar disorder, but patients such as Mr. C focus on perceived threats to their lives, not their grandiose delusions. Admitting physicians listening to their paranoid complaints may overlook the grandiose source and the possibility of psychotic bipolar disorder. Mr. C’s manic grandiosity explains the motivation for each of his psychotic behaviors: paranoid delusions, catatonia, and coprophilia.

Several initial signs could have raised suspicion that Mr. C had psychotic bipolar disorder (Table 4). Standard-of-care treatment in psychotic patients is predicated on early and correct diagnosis. On the basis of the evidence and our experience, we recommend that you look for bipolar symptoms when a patient:

• presents for the first time with psychosis, and you rule out an organic cause
  
• is readmitted for treatment of psychotic symptoms after having been diagnosed with schizophrenia.
  

Table 3

Consequences of misdiagnosing psychotic mood disorder as schizophrenia

For patient Less likely to receive a mood stabilizer or antidepressant Without a mood stabilizer, cycles increase and occur more rapidly; symptoms worsen More likely to receive neuroleptics for life, increasing risk for severe and permanent side effects Greater stigma with schizophrenia Less likely to be employed More likely to receive disability for life More likely to “give up”
For clinician Increased risk of liability if patient given long-term neuroleptics instead of mood stabilizers develops tardive dyskinesia or commits suicide

Table 4

Mr. C’s symptoms that indicated bipolar disorder

Religiosity	Loud preaching and no past special interest in religion
Catatonia	Most frequently associated with bipolar disorder
Paranoia; fear	Usually hides grandiosity, which is diagnostic of mania
Distractibility	Could not stay focused in the diagnostic interview; showed ‘flight of ideas’
Pressured speech	Rapid, disorganized thoughts
Disorganization	Hallmark of mania; present in all patients with severe mania
Functional psychosis	If an organic cause is ruled out, a psychotic mood disorder is the most likely diagnosis
Trouble with the law	Police found patient disturbing neighborhood and escorted him to hospital
Patient history	Severe depression
Family history	Mother was treated for depression with ECT
ECT: electroconvulsive therapy

What is standard of care? Patients with psychotic mania warrant polypharmacy:

• an antipsychotic, with or without a benzodiazepine for sedation, to enhance ward safety and treat acute psychotic symptoms
  
• and a first-line mood stabilizer such as valproate, carbamazepine, lithium, or lamotrigine, followed by atypical antipsychotics.
  

Antidepressants appear to be contraindicated, even in psychotic bipolar depressed patients.^14,15 We suggest that you taper and discontinue the initial antipsychotic when psychotic symptoms resolve. Some data indicate that continuing antipsychotics in psychotic bipolar patients is detrimental after the psychosis has resolved.¹⁷ Medication-resistant cases may require two or three mood stabilizers and possibly an atypical antipsychotic.

The idea that “symptoms should be treated, not the diagnosis” is inaccurate and provides substandard care. When psychotic symptoms overwhelm and obscure bipolar symptoms, giving only antipsychotics is beyond standard of care.

Related resources

• Berrettini WH. Molecular linkage studies of bipolar disorders. Bipolar Disord 2001;3:276-83.
  
• Lake CR, Hurwitz N. Schizoaffective disorders are psychotic mood disorders; there are no schizoaffective disorders. Psychiatry Res 2006 (in press).
  
• Pope HG, Lipinski JF. Diagnosis in schizophrenia and manic-depressive illness, a reassessment of the specificity of “schizophrenic” symptoms in the light of current research. Arch Gen Psychiatry 1978;35:811-28.
  
• Post RM. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 1992;149:999-1010.
  

Drug brand names

• Haloperidol • Haldol
  
• Lamotrigine • Lamictal
  
• Lithium • Lithobid
  
• Lorazepam • Ativan
  
• Carbamazepine • Tegretol
  
• Valproate • Depakote
  

Disclosures

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

Acknowledgements

The patient described in this case report gave informed, written consent to interviews and to the anonymous publication of his treatment.

The authors thank Anita Swisher for technical assistance.