Developing an individualized treatment plan for patients with schizoaffective disorder: from pharmacotherapy to psychoeducation

To develop an individualized treatment plan that addresses both psychotic and affective symptoms in patients with schizoaffective disorder, clinicians can take several steps. First, clinicians can confirm the diagnosis. In the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and in the International Classification of Diseases, Tenth Revision (ICD-10), schizoaffective disorder is defined differently, but, diagnostically, the disorder falls on a spectrum between bipolar disorder and schizophrenia and can be divided into bipolar and depressive types. Next, clinicians can evaluate predictors of outcome. Outcomes can be predicted by previous functioning, number of previous episodes, persistence of psychotic symptoms, and level of cognitive impairment. Then, clinicians can use evidence from clinical trials to guide selection of acute and maintenance phase treatment. Although data are limited, direct and indirect evidence from clinical trials support pharmacologic and psychoeducational interventions. In bipolar type schizoaffective disorder, evidence supports the use of an atypical antipsychotic and a mood stabilizer or atypical antipsychotic monotherapy. In the depressive type of the disorder, the combination of an atypical antipsychotic and an antidepressant is probably the best choice, but an atypical antipsychotic and a mood stabilizer could also be used. In both types of the disorder, patient psychoeducation can be beneficial in the maintenance phase of treatment. Adherence to treatment is essential for optimal outcome, and, besides patient psychoeducation, long-acting injectable antipsychotics and psychoeducation for caregivers may also improve adherence. In refractory cases, electroconvulsive therapy is an option.     

Adjunctive use of reboxetine in schizophrenia.

BACKGROUND: Schizophrenia is frequently complicated by depressive or negative symptoms that respond only moderately to treatment with antipsychotic drugs. Reboxetine is a novel antidepressant, which inhibits the reuptake of norepinephrine. We sought to study the efficacy and tolerability of the adjunctive use of reboxetine in a cohort of schizophrenic patients with prominent depressive or negative symptoms. METHODS: Sixteen schizophrenic inpatients were recruited for this study. All subjects received 4-8 mg of reboxetine/day while the antipsychotic medication (typical antipsychotics = 4; atypical antipsychotics = 12) was continued. All subjects underwent a standardized assessment including PANSS, CGI, HAMD, and CDSS before and after treatment with reboxetine (mean 26 +/- 17 d). RESULTS: All subjects tolerated treatment with reboxetine. Adverse effects were mild and did not require discontinuation of reboxetine. All clinical scores (PANSS 93.1 vs. 63.1; CGI 5.4 vs. 4.1; HAMD 20.4 vs. 8.1; CDSS 12.5 vs. 4.6) improved significantly under adjunctive treatment with reboxetine (all P < 0.01). CONCLUSION: The adjunctive use of reboxetine in schizophrenic patients was safe and well-tolerated. Our results suggest that the adjunctive use of reboxetine may be an effective treatment for depressive and negative symptoms in schizophrenia.     

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.     

Clinical predictors of acute response with quetiapine in psychotic mood disorders

BACKGROUND: In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response. METHOD: In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria. RESULTS: Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding. CONCLUSION: Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.     

Role of aripiprazole in treating mood disorders

Atypical antipsychotics have been used to treat patients with schizophrenia for many years, but now there is increasing evidence of their utility in the treatment of mood disorders. In the past few years, several atypical agents have received regulatory approval for use in mania. The evidence shows that atypical antipsychotics are effective in the treatment of manic symptoms, either alone or in combination with traditional mood stabilizers, such as lithium and divalproex. Although emerging data indicate that atypical antipsychotics will be a promising addition to those therapies that are currently available for managing patients during the maintenance phase of bipolar illness, their potential in the long-term management of bipolar disorder remains to be fully explored. Aripiprazole is a recently released antipsychotic medication that differs from other atypical antipsychotic agents by its mode of action as a dopamine D2 partial agonist. It is administered orally and has a long half-life. Randomized studies have demonstrated the efficacy of aripiprazole compared with placebo in the treatment of acute relapse of schizophrenia and schizoaffective disorder, maintenance treatment of schizophrenia, treatment of acute mania, and prevention of manic relapse in patients who responded to the drug during a manic episode. Further studies are ongoing in bipolar and unipolar depression. Aripiprazole is generally well tolerated compared with other antipsychotic medications, although commonly reported side effects include extrapyramidal symptoms and motoric activation similar to akathisia. Further studies and postmarketing data will be helpful in providing additional information regarding the comparative safety, efficacy and tolerability of aripiprazole in the treatment of affective disorders.     

Elderly patients with schizophrenia and depression: diagnosis and treatment

Background: The treatment of older patients with schizophrenia and depressive symptoms poses many challenges for clinicians. Current classifications of depressive symptoms in patients with schizophrenia include: Major Depressive Episodes that occur in patients with schizophrenia and are not classified as schizoaffective disorder, Schizoaffective Disorder, and Schizophrenia with subsyndromal depression in which depressive symptoms do not meet criteria for Major Depression. Research indicates that the presence of any of these depressive symptoms negatively impacts the lives of patients suffering from schizophrenia-spectrum disorders. Purpose: The purpose of this paper is to review the literature related to older patients with schizophrenia-spectrum disorders and co-occurring depressive symptoms, and to guide mental health professionals to better understand the diagnosis and treatment of depressive symptoms in patients with schizophrenia. Conclusions: The treatment of elderly patients with schizophrenia and depressive symptoms includes first reassessing the diagnosis to make sure symptoms are not due to a comorbid condition, metabolic problems or medications. If these are ruled out, pharmacological agents in combination with psychosocial interventions are important treatments for older patients with schizophrenia and depressive symptoms. A careful assessment of each patient is needed in order to determine which antipsychotic would be optimal for their care; second-generation antipsychotics are the most commonly used antipsychotics. Augmentation with an antidepressant medication can be helpful for the elderly patient with schizophrenia and depressive symptoms. More research with pharmacologic and psychosocial interventions is needed, however, to better understand how to treat this population of elderly patients.     

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.     

Schizoaffective disorder: a form of schizophrenia or affective disorder?

BACKGROUND: The diagnostic status of schizoaffective disorder continues to be controversial. Researchers have proposed that schizoaffective disorder represents a variant of schizophrenia or affective disorder, a combination of the 2, or an intermediate condition along a continuum between schizophrenia and affective disorder. METHOD: We compared outpatients aged 45 to 77 years with DSM-III-R diagnosis of schizoaffective disorder (N = 29), schizophrenia (N = 154), or nonpsychotic mood disorder (N = 27) on standardized rating scales of psychopathology and a comprehensive neuropsychological test battery. A discriminant function analysis was used to classify the schizoaffective patients based on their neuropsychological profiles as being similar either to schizophrenia patients or to those with nonpsychotic mood disorder. RESULTS: The schizoaffective and schizophrenia patients had more severe dyskinesia, had a weaker family history of mood disorder, had been hospitalized for psychiatric reasons more frequently, were more likely to be prescribed neuroleptic and anticholinergic medication, and had somewhat less severe depressive symptoms than the mood disorder patients. The schizophrenia patients had more severe positive symptoms than the schizoaffective and mood disorder patients. The neuropsychological performances of the 2 psychosis groups were more impaired than those of the nonpsychotic mood disorder patients. Finally, on the basis of a discriminant function analysis, the schizoaffective patients were more likely to be classified as having schizophrenia than a mood disorder. CONCLUSION: These findings suggest that schizoaffective disorder may represent a variant of schizophrenia in clinical symptom profiles and cognitive impairment.     

Obsessive-compulsive disorder and schizophrenia. A critical review

Co-occurrence of psychotic and obsessive-compulsive symptoms has been recognized for decades. This paper reviews published reports from five perspectives: schizophrenia with obsessive-compulsive symptoms, obsessive-compulsive disorder (OCD) with psychotic symptoms, schizophrenia-spectrum-personality disorder with obsessive-compulsive symptoms, obsessive-compulsive symptoms induced by atypical antipsychotics and similarities of functional neural circuits theory in OCD and schizophrenia. A MEDLINE search was conducted to identify relevant articles from 1960 until 2004. Only a few systematic data that explore the nature and significance of such occurrence have been published. More recent studies using systematic diagnostic criteria suggest that the rate of occurrence may not be rare at all. In schizophrenia, a similar dorsolateral prefrontal cortex circuit shares anatomic substrates similar to those of the OCD orbitofrontal circuit. Exploring the interface of schizophrenic and obsessive-compulsive symptoms is important for diagnostic clarity and could have important implications for treatment and long-term prognosis. The review emphasizes the different origins and natural course of co-occurrence of schizophrenic and obsessive-compulsive symptoms and their various outcome under atypical antipsychotics and selective serotonin reuptake inhibitors (SSRI). Further double-blind, randomized, placebo-controlled investigations in larger cohorts of schizophrenic and OCD patients are needed in order to identify a schizo-obsessive schizophrenia and a schizotypal subtype of obsessive compulsive disorder and to substantiate the algorithm for treatment.     

Atypical Antipsychotic Use in the Treatment of Psychosis in Primary Care

Atypical antipsychotics are a class of novel agents increasingly employed for the treatment of psychotic disorders. The pharmacodynamic properties of the atypicals appear to impact a broader spectrum of psychotic symptoms than had been appreciated with older generation antipsychotics. In addition, the atypical agents appear to have a reduced risk of neurologic side effects compared with conventional antipsychotic use. Both of these features enhance the appeal of the atypical antipsychotics and may be associated with enhanced patient compliance. The atypical antipsychotics appear to be effective for schizophrenia as well as other psychotic disorders, including schizoaffective disorder and mood disorders with psychotic features. Consequently, atypical antipsychotics are now considered to be the first-line treatment for schizophrenia, with the exception of clozapine, which is considered a second-line agent because of risks associated with its use. This review will discuss the literature on atypical antipsychotic efficacy in psychotic disorders. Issues related to antipsychotic use, dosing, adverse effects, and drug interactions are also discussed.     

Double-blind antiglucocorticoid treatment in schizophrenia and schizoaffective disorder: a pilot study.

BACKGROUND: Antiglucocorticoids, such as ketoconazole, have been investigated as antidepressant agents in major depression and other conditions. Despite evidence that a significant number of patients with schizophrenia and schizoaffective disorder are both hypercortisolemic and depressed, the antidepressant effects of antiglucocorticoids have never been assessed in these populations. METHODS: Fifteen symptomatic patients with diagnoses of schizophrenia or schizoaffective disorder, who were at least partially treatment-resistant, were treated with ketoconazole, up to 800 mg/day, (n = 8) or placebo (n = 7) for four weeks in a double-blind manner. The study medication was added to a pre-stabilized antipsychotic and/or antidepressant medication regimen. RESULTS: Ketoconazole treatment, compared to placebo, was associated with significant improvements in observer-rated depression, but not in subjectively rated depression, positive or negative psychotic symptom ratings, or cognitive performance scores. CONCLUSIONS: These pilot data partially support the hypothesis that antiglucocorticoids reduce depressive symptoms in patients with schizophrenia and schizoaffective disorder, although objective and subjective ratings may not be similarly affected during a four-week course of treatment. Further studies with larger sample sizes, more extensive endocrine assessments and longer duration of drug administration seem warranted.     

Double-Blind Antiglucocorticoid Treatment in Schizophrenia and Schizoaffective Disorder: A Pilot Study

Summary: Background: Antiglucocorticoids, such as ketoconazole, have been investigated as antidepressant agents in major depression and other conditions. Despite evidence that a significant number of patients with schizophrenia and schizoaffective disorder are both hypercortisolemic and depressed, the antidepressant effects of antiglucocorticoids have never been assessed in these populations.

Methods: Fifteen symptomatic patients with diagnoses of schizophrenia or schizoaffective disorder, who were at least partially treatment-resistant, were treated with ketoconazole, up to 800 mg/day, (n = 8) or placebo (n = 7) for four weeks in a double-blind manner. The study medication was added to a pre-stabilized antipsychotic and/or antidepressant medication regimen.

Results: Ketoconazole treatment, compared to placebo, was associated with significant improvements in observer-rated depression, but not in subjectively rated depression, positive or negative psychotic symptom ratings, or cognitive performance scores.

Conclusions: These pilot data partially support the hypothesis that antiglucocorticoids reduce depressive symptoms in patients with schizophrenia and schizoaffective disorder, although objective and subjective ratings may not be similarly affected during a four-week course of treatment. Further studies with larger sample sizes, more extensive endocrine assessments and longer duration of drug administration seem warranted.     

Atypical antipsychotics in the treatment of bipolar affective disorders

Antipsychotics are commonly used in the treatment of bipolar affective disorder. The use of conventional antipsychotic agents, though effective as antimanic agents, is associated with a number of limitations such as their acute side effect profile and their unsufficient mood stabilizing activity. In addition, exposure to conventional neuroleptics poses a risk for the development of tardive dyskinesia, especially in mood disorder patients. Growing evidence suggests that the novel, so-called atypical neuroleptics may offer a number of advantages in the treatment of bipolar disorder, including their thymoleptic activity and minimal risk for acute and long-term extraypyramidal symptoms. Clinical experience with clozapine and olanzapine as mood stabilizers suggests greater antimanic than antidepressant properties, while risperidone may have greater antidepressant properties with some liability for triggering or exacerbating mania. The mood stabilizing properties of further atypical drugs are currently under investigation. This review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder. We also present an overview concerning potential pharmakokinetic interactions based on the cytochrome P450 enzyme system when antipsychotics are combined with other mood stabilizing compounds. In conclusion, atypical antipsychotics should come to play an increasingly important role in the acute and long-term management of bipolar disorder, but there is a clear need for further controlled trials in this indication.     

Treatment of depressive mood in schizophrenia with the atypical antipsychotic quetiapine

Two patients with schizophrenia and depressive mood experienced remission in both their psychotic and depressive symptoms during treatment with the atypical antipsychotic quetiapine. These case reports illustrate the antipsychotic clinical efficacy of quetiapine and its antidepressant effects in the treatment of patients with schizophrenia and depressive mood.     

Risperidone augmentation of clozapine

OBJECTIVE: Atypical antipsychotics are frequently used as augmentation agents in clozapine-resistant schizophrenic patients. Risperidone (RIS) is the one most studied as a clozapine (CLZ) adjunct. The aim of this study is to critically review all published studies regarding the efficacy and safety of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients. METHODS: A MEDLINE search from January 1988 to June 2005 was conducted. Identified papers were examined against several clinical, pharmacological and methodological parameters. RESULTS: A total of 15 studies were found (2 randomized controlled trials, 3 open-label trials (OTs) and 8 case-studies (CSs)) comprising 86 schizophrenic or schizoaffective patients (mean age 38.4 years). Mean CLZ dosage during the combined treatment was 474.2 mg/day. Plasma CLZ levels were assessed in 62 patients (72.1%). RIS was added at a mean dosage of 4.6 mg/day for a mean of 7.9 weeks. Significant improvement in psychopathology was reported for 37 patients (43%). A lower RIS dosage and a longer duration of the trial seemed to be associated with a better outcome. Main side effects reported were: extrapyramidal symptoms or akathisia (9.3%), sedation (7%) and hypersalivation (5.8%). CONCLUSIONS: Existing evidence encourages the use of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.     

Comparative efficacy of typical and atypical antipsychotics as add-on therapy to mood stabilizers in the treatment of acute mania.

BACKGROUND: Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting. METHOD: This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. RESULTS: Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). CONCLUSION: Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.