Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia

BACKGROUND: Although growing research indicates that the atypical antipsychotic agent clozapine is effective in patients with schizophrenia, little is known about the efficacy of clozapine in patients with schizoaffective disorder or psychotic mood disorders. The purpose of this study was to assess whether or not clozapine is effective in some patients with schizoaffective disorder or psychotic mood disorders. METHOD: By surveying treating clinicians and chart data, we assessed treatment response in 85 consecutive patients, including 39 with schizophrenia, 25 with schizoaffective disorder, and 14 with bipolar disorder with psychotic features, who received clozapine for at least 6 weeks at our center. RESULTS: All patients were either inadequately responsive to or unable to tolerate standard somatic therapies. Compared to patients with schizophrenia, patients with schizoaffective disorder and bipolar disorder with psychotic features displayed significantly higher response rates to clozapine. CONCLUSION: Clozapine may be a useful drug in the treatment of patients with schizoaffective disorder or psychotic mood disorders who are treatment resistant or intolerant of side effects.     

Cross-sectional similarities and differences between schizophrenia, schizoaffective disorder and mania or mixed mania with mood-incongruent psychotic features.

BACKGROUND: The cross-sectional clinical differentiation of schizophrenia or schizoaffective disorder from mood-incongruent psychotic mania or mixed mania is difficult, since pathognomonic symptoms are lacking in these conditions. AIMS OF THE STUDY: To compare a series of clinical variables related to mood and cognition in patient groups with DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, mood-incongruent psychotic mania and mood-incongruent psychotic mixed mania. METHODS: One hundred and fifty-one consecutive patients were evaluated in the week prior to discharge by using the structured clinical interview for DSM-III-R-patient edition (SCID-P). Severity of psychopathology was assessed by the 18-item version of the brief psychiatric rating scale (BPRS) and negative symptoms by the scale for assessment of negative symptoms (SANS). Level of insight was assessed with the scale to assess unawareness of mental disorders (SUMD). RESULTS: There were no differences in rates of specific types of delusions and hallucinations between subjects with schizophrenia, schizoaffective disorder, psychotic mania and psychotic mixed mania. SANS factors scores were significantly higher in patients with schizophrenia than in the bipolar groups. Patients with mixed state scored significantly higher on depression and excitement compared to schizophrenia group and, to a lesser extent, to schizoaffective group. Subjects with schizophrenia showed highest scores on the SUMD indicating that they were much more compromised on the insight dimension than subjects with psychotic mania or mixed mania. CONCLUSION: Negative rather than affective symptomatology may be a useful construct to differentiate between schizophrenia or schizoaffective disorders from mood-incongruent psychotic mania or mixed mania.     

Outcome of schizoaffective disorder at two long-term follow-ups: comparisons with outcome of schizophrenia and affective disorders

OBJECTIVE: This research assessed whether the outcome of schizoaffective disorder is more similar to that of schizophrenia or that of affective disorders. METHOD: The authors conducted a prospective follow-up study of 101 schizoaffective, schizophrenic, bipolar manic, and depressed patients assessed at three times: during hospitalization and 2 and 4-5 years later. The follow-up test battery involved detailed assessment of social functioning, work performance, symptoms, posthospital treatment, and rehospitalization. RESULTS: Outcome for schizoaffective patients 4-5 years after hospitalization differed significantly from that for patients with unipolar depression. However, the differences between schizoaffective and bipolar manic patients were more equivocal. Unlike the patients with bipolar disorder, only a limited number of patients with schizoaffective disorder showed complete recovery in all areas throughout the year preceding the 2-year follow-up and the year preceding the 4- to 5-year follow-up. The differences in outcome between schizoaffective and schizophrenic patients were also mixed. These two groups showed some similarities in outcome, but there were fewer schizoaffective than schizophrenic patients with uniformly poor outcome in all areas. CONCLUSIONS: Overall, schizoaffective patients showed some similarities to both schizophrenic and bipolar manic patients. Schizoaffective patients had somewhat better overall posthospital functioning than patients with schizophrenia, somewhat poorer functioning than bipolar manic patients, and significantly poorer functioning than patients with unipolar depression. The data suggest that when mood-incongruent, schizophrenic-like psychotic symptoms are present in the acute phase, they predict considerable difficulty in outcome, even when affective syndromes are also present, as in schizoaffective disorder. It is likely that schizoaffective disorder is not just a simple variety of affective disorder.     

Efficacy of quetiapine and risperidone against depressive symptoms in outpatients with psychosis

BACKGROUND: The treatment of psychotic symptoms in patients with mood disorders is a complex challenge. Antipsychotic medications in these individuals may be associated with extrapyramidal symptoms (EPS), worsening of depression, and functional impairment. Atypical antipsychotics such as quetiapine and risperidone are associated with a decreased incidence of adverse events such as EPS. The objective of this study was to compare the efficacy and tolerability of quetiapine and risperidone for the treatment of depressive symptoms in outpatients with psychosis. METHOD: In this 4-month, multicenter, open-label trial, patients were randomly assigned in a 3:1 ratio of quetiapine to risperidone, and both drugs were flexibly dosed. Eligible patients had psychoses and demonstrated 1 of several DSM-IV diagnoses, including schizoaffective disorder, bipolar I disorder, major depressive disorder, delusional disorder, Alzheimer's dementia, schizophreniform disorder, vascular dementia, and substance abuse dementia. Patients were classified as mood disordered if they had bipolar disorder, major depressive disorder, or schizoaffective disorder. Efficacy was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions scale. The Hamilton Rating Scale for Depression (HAM-D) was used to assess the level of depressive symptoms. The primary tolerability assessment was presence or absence of substantial EPS, defined as EPS severe enough to require an alteration in treatment. RESULTS: A total of 554 patients were randomly assigned to quetiapine and 175 to risperidone. Mean doses at 16 weeks were 318 mg for quetiapine and 4.4 mg for risperidone. Although both agents produced improvements in mean HAM-D scores, quetiapine produced a greater improvement than risperidone in all patients (p =.0015). Within the mood-diagnosed population, incidences of both substantial EPS (p =.001) and at least moderate EPS (p =.0373) occurred significantly less frequently among patients taking quetiapine. For patients with non-mood diagnoses, incidences of substantial EPS were fewer for patients taking quetiapine than for those taking risperidone (p =.062); however, this was not statistically significant. CONCLUSION: These results suggest that quetiapine may be a useful agent in the management of depressive symptoms in patients with psychosis.     

"Schizoaffective disorder": an invalid diagnosis? A comparison of schizoaffective disorder, schizophrenia, and affective disorder

The authors compared patients meeting widely accepted criteria for the diagnosis of schizoaffective disorder, manic type, with patients meeting rigorous criteria for manic disorder and schizophrenia, using three methods of validation: family history, short-term treatment response, and long-term outcome. No significant differences were found between patients with manic disorder and schizoaffective disorder. However, consistent and often highly significant differences separated patients with schizophrenia from those with manic disorder and schizoaffective disorder. The findings suggest that schizoaffective disorder, as currently defined, is not a valid and independent entity. The authors suggest that psychotic disorders not diagnosable as manic-depressive illness or schizophrenia and without apparent organic basis would best be called "undiagnosed" or "atypical" psychosis. Further, while proposals for new diagnoses or for subtyping of schizophrenia or manic-depressive illness should be encouraged, these should undergo rigorous screening for validity before being accepted into clinical use.     

Psychosis in a pediatric mood and anxiety disorders clinic: phenomenology and correlates

OBJECTIVES: To examine the demographics and phenomenology of psychosis in a sample of children and adolescents referred to a mood and anxiety disorders clinic. METHOD: Patients (N = 2,031) were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode version and classified as definite, probable, or nonpsychotic. Clinical and demographic characteristics of the groups were compared,and symptoms of psychosis were analyzed using factor analysis. RESULTS: Definite psychotic symptoms were seen in approximately 90 (4.5%) patients: 80% of these reported hallucinations (mainly auditory), 22% delusions, and 3.3% thought disorder. Of the patients with definite psychotic symptoms, 24% had bipolar disorder, 41% had major depression, 21% had subsyndromal depression, and 14% had schizophrenia spectrum disorders (schizophrenia and schizoaffective disorders). Factor analysis of the definite psychotic symptoms yielded 4 factors: hallucinations, thought disorder, delusions, and manic thought disorder. Psychotic patients had a higher frequency of comorbid disorders and suicidal ideation than nonpsychotic patients. CONCLUSIONS: Outpatient youngsters with mood disorders frequently present with psychotic symptoms, in particular auditory hallucinations. These patients commonly have comorbid psychiatric disorders and suicidal ideation.     

Treatment of schizoaffective disorder and schizophrenia with mood symptoms.

OBJECTIVE: Patients with concurrent schizophrenic and mood symptoms are often treated with antipsychotics plus antidepressant or thymoleptic drugs. The authors review the literature on treatment of two overlapping groups of patients: those with schizoaffective disorder and those with schizophrenia and concurrent mood symptoms. METHOD: MEDLINE searches (from 1976 onward) were undertaken to identify treatment studies of both groups, and references in these reports were checked. Selection of studies for review was based on the use of specified diagnostic criteria and of parallel-group, double-blind design (or, where few such studies addressed a particular issue, large open studies). A total of 18 treatment studies of schizoaffective disorder and 15 of schizophrenia with mood symptoms were selected for review. RESULTS: For acute exacerbations of schizoaffective disorder or of schizophrenia with mood symptoms, antipsychotics appeared to be as effective as combination treatments, and there was some evidence for superior efficacy of atypical antipsychotics. There was evidence supporting adjunctive antidepressant treatment for schizophrenic and schizoaffective patients who develop a major depressive syndrome after remission of acute psychosis, but there were mixed results for treatment of subsyndromal depression. There was little evidence to support adjunctive lithium for depressive symptoms and no evidence concerning its use for manic symptoms in patients with schizophrenia. CONCLUSIONS: Empirical data suggest that both groups of patients are best treated by optimizing antipsychotic treatment and that atypical antipsychotics may prove to be most effective. Adjunctive antidepressants may be useful for patients with major depression who are not acutely ill. Careful longitudinal assessment is required to ensure identification of primary mood disorders.     

Insight into illness in schizophrenia, schizoaffective disorder, and mood disorders with psychotic features

OBJECTIVE: Deficits in insight have been found in one study to be more common and severe in patients with schizophrenia than in patients with schizoaffective and major depression with and without psychosis but not more severe than they are in patients with bipolar disorder. The goals of this study were to replicate this finding independently and to clarify whether patients with schizophrenia differ from patients with bipolar disorder in a larger study group. METHOD: Using the Scale to Assess Unawareness of Mental Disorder, the authors evaluated 29 inpatients with schizophrenia, 24 with schizoaffective disorder, and 183 with mood disorders with psychotic features (153 with bipolar disorder and 30 with unipolar depression). RESULTS: Patients with schizophrenia had poorer insight than patients with schizoaffective disorder and patients with psychotic unipolar depression but did not differ from patients with bipolar disorder. CONCLUSIONS: The lack of significant differences between patients with schizophrenia and patients with bipolar disorder was not a result of low statistical power. This replication and more detailed examination of diagnostic group differences in insight have clinical, theoretical, and nosological implications.     

Case report on the management of depression in schizoaffective disorder, bipolar type focusing on lithium levels and measurement-based care

There is little evidence supporting the management of depression in schizoaffective disorder, bipolar type. Managing bipolar depression can be a daunting task for clinicians. Most bipolar patients spend 80% of their time in the depressive phase of illness. In contrast with full-blown mania, patients and family frequently fail to recognize bipolar depression, which may interfere with early diagnosis and treatment. With only a few medications approved for bipolar depression, treatment becomes very challenging. There is evidence to support that schizoaffective depression has a worse outcome than psychotic depression and nonpsychotic depression. We report a patient with schizoaffective disorder, bipolar type with severe depression who responded to an adequate level of lithium and subsequently, on a combination of lithium and quetiapine. Finally, we emphasize the importance of measurement-based care. To our knowledge, this is the first case report focusing on the management of depression in schizoaffective disorder, bipolar type.     

Quetiapine dosage in bipolar disorder episodes and mixed states

OBJECTIVE: Although the maximal quetiapine doses in the published studies were restricted to 800 mg/day, higher quetiapine doses are not unusual in clinical practice. The aim of the present study was to evaluate the effectiveness, tolerability and clinical reasons associated to the use of high dosage of quetiapine (>800 mg), when used under routine clinical conditions, in a sample of bipolar disorder and schizoaffective bipolar inpatients. METHODS: Charts of all bipolar and schizoaffective adult inpatients, who had received quetiapine for a mood episode between 1999 and 2005 were retrospectively reviewed. These charts also included the assessment of manic and depressive symptoms on admission and at discharge using the Beck-Rafaelsen Mania Scale (MAS) and the Montgomery Asberg depression rating scale (MADRS), respectively. RESULTS: Data of 50 patients were analyzed. The overall F in repeated measures ANOVA revealed a significant MAS scores reduction between admission and discharge. MAS scores reduction did not differ between the high and low quetiapine groups. Similarly, a significant MADRS reduction was found. Again, no differences between the high and the low dose group were found. Logistic regression analysis of the 50 patients revealed only mixed episodes predicted high quetiapine dosage. CONCLUSIONS: The present study confirms quetiapine efficiency and tolerability in the treatment of bipolar episodes, even in doses > to 800 mg and found a link between quetiapine doses and mixed episodes.     

Mood patterns and classification in bipolar disorder

PURPOSE OF REVIEW: The aim of this review is to highlight recent studies that have questioned the current split of mood disorders into the categories of bipolar and depressive disorders. RECENT FINDINGS: A continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder was supported by several lines of evidence: depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support the splitting between mania/hypomania and depression); family history, major depressive disorder is the most common mood disorder in relatives of bipolar probands; lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; bipolar features in major depressive disorder; major depressive disorder shifting to bipolar disorders; history of manic/hypomanic symptoms in major depressive disorder and correlation between lifetime manic/hypomanic symptoms and depressive symptoms in major depressive disorder; factors of hypomania inside major depressive disorder; recurrent course of major depressive disorder; depression more common than mania and hypomania in bipolar disorders; trait mood lability in major depressive disorder. SUMMARY: This review of the recent findings on the relationship between bipolar disorders (especially bipolar II disorder) and depressive disorders seems to support a continuity among mood disorders, and runs against the current classification of mood disorders dividing them into independent categories. Further research is needed in the area, in part because of its possible treatment impact.     

Atypical antipsychotics in the treatment of affective symptoms: a review.

Atypical antipsychotics have demonstrated beneficial effects on affective symptoms, in addition to antipsychotic activity. Consequently, their role in the treatment of bipolar disorder and treatment-resistant or psychotic depression has been explored. Adjunctive atypical antipsychotic therapy appears to benefit patients experiencing manic episodes of bipolar disorder, and some studies suggest that monotherapy may also be efficacious. Clinical studies of patients with schizoaffective disorder and major depression support the use of atypical antipsychotics to treat depression. This review focuses on risperidone, olanzapine, quetiapine, and ziprasidone and provides evidence that these drugs demonstrate activity against manic episodes of bipolar disorder when used as adjunctive therapy and possibly as monotherapy and that depression in patients with schizoaffective disorder also responds to these agents.     

Olanzapine therapy in treatment-resistant psychotic mood disorders: a long-term follow-up study

BACKGROUND: Recent studies suggest a role for the atypical antipsychotic olanzapine in the acute treatment of psychotic mood disorders, but long-term data are unavailable. The purpose of this naturalistic study was to determine the long-term effectiveness and tolerability of olanzapine as add-on therapy in psychotic mood disorders. METHOD: Hospital records were reviewed for 125 inpatients at the state psychiatric hospital in Buffalo, N.Y., who received at least 6 weeks of add-on olanzapine treatment for psychotic mood disorders (schizoaffective disorders [bipolar and depressive type], bipolar disorders [I, II, and NOS], and major depressive disorder). A group of schizophrenic patients served as a control group (N = 50). Baseline measures, including age, gender, number of hospitalizations in the 2 years prior to olanzapine treatment, concomitant medications, the Clinical Global Impressions scale (CGI), and the Global Assessment of Functioning-Equivalent (GAF-EQ) and Kennedy Axis V psychological impairment, violence, social skills, and activities of daily living subscale scores, were obtained. Follow-up information was obtained from the patients at least 6 months after initiation of olanzapine or by chart review and discussion with the treating psychiatrist. Patients with a diagnosis of psychotic mood disorders were compared with patients with the non-affective psychotic disorder (schizophrenia) on a variety of outcome measures. RESULTS: Follow-up information was available on 102 patients (82%). Mean follow-up was 15 months; 50 (49%) of the 102 patients remained on olanzapine treatment at follow-up (32 psychotic mood disorder, 18 schizophrenic). The primary reason for discontinuation in both groups was lack of response. Both the psychotic mood disorder and schizophrenic groups had comparable outcomes on the CGI and GAF-EQ. Improvement on the Kennedy Axis V psychological impairment and social skills subscales was seen only in the psychotic mood disorders group (p < .01); both groups showed significant (p < .02) improvement in the violence subscale. Sustained mood-stabilizing effect was evident in only 7/27 (26%) of the psychotic mood disorders patients continuing on add-on olanzapine treatment at follow-up. CONCLUSION: Lack of response was the primary reason for discontinuation of add-on olanzapine in both groups. Mood symptoms predicted a better response to add-on olanzapine in patients with psychotic mood disorders on selective outcome measures. However, only 26% of the patients with psychotic mood disorders sustained a clinically meaningful mood-stabilizing effect with add-on olanzapine treatment at follow-up.     

Efficacy and safety of risperidone in the treatment of schizoaffective disorder: initial results from a large, multicenter surveillance study. Group for the Study of Risperidone in Affective Disorders (GSRAD)

BACKGROUND: An adequate therapy for psychotic disorders needs to be effective against mood as well as psychotic symptoms. Analyses of data from clinical trials of risperidone in schizophrenia and small open-label studies in mania suggest that risperidone may have this broad efficacy profile. We present data on a 6-week trial of risperidone for the treatment of schizoaffective disorder that was part of a larger, 6-month surveillance study of patients with affective disorders. METHOD: One hundred two patients suffering from schizoaffective disorder (DSM-IV or ICD-10) entered the trial. Inclusion criteria consisted of a current DSM-IV diagnosis of schizoaffective disorder, bipolar type; DSM-IV manic or mixed psychotic episode; and a Young Mania Rating Scale (YMRS) score > 7 for a mixed episode (> 20 for a manic episode). Assessments included the YMRS, the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), the 4-item Clinical Global Impressions (CGI) scale, and the UKU Side Effect Rating Scale subscale for neurologic side effects. For patients entering the study, open-label risperidone therapy was added to their existing regimens of mood-stabilizing treatments. Other antipsychotic drugs were not allowed. RESULTS: Ninety-five patients completed the 6-week trial. At week 6, the mean +/- SD dose of risperidone was 4.7+/-2.5 mg/day. The mean scores on the assessment scales at baseline and week 6 (unless otherwise stated) were as follows: YMRS, 22.7 and 4.7, an improvement of 18.0 points (p < .0001); PANSS (at baseline and week 4), 74.1 and 54.2, an improvement of 19.9 points (p < .0001); HAM-D, 14.0 and 7.4, an improvement of 6.6 points (p < .0001); CGI (at baseline and week 4), 2.6 and 1.7, an improvement of 0.9 points (p < .0001). At week 4, most patients had shown improvement in symptom severity, and 9.3% were completely symptom-free. There were no statistically significant differences between baseline and week 4 in the severity of extrapyramidal symptoms as measured by the UKU. Risperidone was well tolerated; side effects were few and generally mild. CONCLUSION: The results to date with risperidone indicate that it may have both antipsychotic and mood-stabilizing properties. Despite the limitations of the open-label design, the results indicate that risperidone is a safe and effective therapy in combination with mood-stabilizers for the treatment of patients with manic, hypomanic, and depressive symptoms of mixed episodes in schizoaffective disorder, bipolar type.     

Psychotic symptoms and age of onset in affective disorders.

Prevalence of hallucinations and delusions was studied in 1,763 patients with unipolar major depression, bipolar affective disorder, and schizoaffective disorder. The authors found that the presence of psychotic features was negatively associated with age of onset for the group as a whole, and bipolar affective disorder (manic or mixed type) specifically. The clinical implications of the findings are discussed.     

Cholesterol levels in mood disorders: high or low?

Objectives: To assess cholesterol levels in patients with mood disorders.

Methods: All consecutively admitted patients meeting inclusion criteria (n=50) who were hospitalized in an affective disorders unit received assessments of cholesterol levels. Correlations were made with diagnosis using DSM-IV criteria, current mood states, and other clinical and demographic features of illness. Exclusion criteria included current alcohol abuse, medical illnesses that could influence cholesterol levels, eating disorders, and age greater than 70 years.

Results: Cholesterol levels did not differ based on diagnostic status of unipolar depression or bipolar disorder. In the total sample, cholesterol levels were lower in patients with current manic (170.2±38.9, p=0.05) and depressive (182.0±42.0) than in mixed (226.4±43.3) episodes (p=0.05). In subgroups of patients with bipolar disorder, manic episodes (169.9±38.8, n=9) were associated with lower cholesterol levels than depressive (201.0±49.4) or mixed (226.4±44.4) episodes (p=0.02 for comparison of manic and mixed episodes). Body mass index (BMI), age, alcohol use, and gender did not account for these findings.

Conclusions: Cholesterol levels were lower in manic and depressive than in mixed episodes. No differences were found between diagnoses of unipolar or bipolar mood disorders. Cholesterol may be a state rather than a trait function, and may be influenced by the acute mood state.     

Burden of illness in bipolar depression

Bipolar depression is the underrecognized and unappreciated phase of bipolar disorder. Nevertheless, bipolar depression is responsible for much of the morbidity and mortality associated with the disorder. Depressive symptoms are far more prevalent than hypomanic or manic symptoms in bipolar patients, and they are associated with a heavier burden of illness, including reduced functioning, increased risk of suicidal acts, and high economic costs. Because most patients with bipolar disorder present with depression, misdiagnoses of major depressive disorder are common, even typical. Comorbid psychiatric disorders are also prevalent and may obscure the diagnosis and complicate treatment strategies. Depressed patients should be carefully assessed for manic or hypomanic symptoms to help reveal possible bipolar disorder. In addition to evaluation of psychiatric symptoms, a close examination of family history, course of illness, and treatment response will aid the clinician in making an accurate diagnosis. Treatment of acute depression in bipolar patients may require therapy combining agents such as lithium, divalproex, lamotrigine, carbamazepine, and atypical antipsychotics or using such agents in combination with an anti-depressant. Olanzapine/fluoxetine combination is the only medication currently approved for the treatment of bipolar depression. Antidepressant monotherapy should not be used, because there is evidence that such treatment increases the risk of switching into mania/hypomania and could induce treatment-refractory conditions such as mixed or rapid-cycling states. Maintenance therapy will be required by most patients, since discontinuation of mood stabilizers or antidepressants frequently leads to relapses in depressive symptoms. Prompt diagnosis and the use of specific therapeutic agents with evidence of efficacy may help reduce the disease burden associated with bipolar depression.     

Psychotic and nonpsychotic bipolar mixed states: comparisons with manic and schizoaffective disorders

Summary We studied 259 female inpatients with bipolar spectrum disorders, of whom 26 (10%) were schizoaffective. Of the remaining 233, 61 (27%) met our conservatively set criteria for index mixed expisodes (simultaneous presence of depressive and manic syndromes). These patients with rigorously defined mixed states were, in turn, about equally divided between psychotic and non-psychotic subgroups. The psychotic mixed patients (n=32) were closer to the bipolar I pattern, and more often seem to come from a familial background of psychotic mood disorders; the nonpsychotic mixed patients (n=29) conformed more closely to the bipolar II pattern, and more often had a hyperthymic and cyclothymic temperament and a family background of non-psychotic disorders and substance abuse. A three-way comparison between psychotic manic (n=24), psychotic mixed (n=32), and schizoaffective (n=26) patients revealed few significant differences in temperamental, familial and course patterns. As expected, psychotic manic patients more often arose from a hyperthymic base and pursued a predominantly manic course; psychotic mixed patients were less likely to arise from such a base and more likely to pursue a mixed course. Finally, schizoaffective had earlier age at onset and longer duration of illness, suggesting that these patients had a more severe illness. Otherwise, interepisodic social adaptation was comparable in the three psychotic groups. The findings overall suggest that the presence of psychosis had relatively little impact on mixed states, which appear more based on temperamental characteristics.     

Clozapine for treatment-refractory schizophrenia, schizoaffective disorder, and psychotic bipolar disorder: a 24-month naturalistic study

BACKGROUND: The aim of this study was to evaluate the 24-month response to clozapine in patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder. METHOD: Ninety-one psychotic patients with a principal DSM-III-R diagnosis of schizophrenia (N = 31), schizoaffective disorder (N = 26), or bipolar disorder with psychotic features (N = 34) were treated naturalistically with clozapine at flexible dosages over a 24-month period. Improvement was assessed by the 18-item Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity of Illness scale. RESULTS: All patients showed significant improvement 24 months from intake (p < .001). Such an improvement was significantly greater among patients with schizoaffective disorder or bipolar disorder than in patients with schizophrenia (p < .05). The presence of suicidal ideation at intake predicted greater improvement at endpoint. CONCLUSION: Clozapine appears to be effective and relatively well tolerated in acute and long-term treatment of patients with psychotic bipolar disorder or schizoaffective disorder who have not responded to conventional pharmacotherapies.