Effects of changing from typical to atypical antipsychotic drugs on subjective sleep quality in patients with schizophrenia in a Japanese population

OBJECTIVE: To investigate the effects of the atypical antipsychotic drugs risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of sleep in patients with schizophrenia. METHOD: Subjects were 92 inpatients (mean age = 59.9 years) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects were randomly assigned to receive 1 of 4 atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality and psychopathology were assessed twice: at baseline and 8 weeks after switching. Data were collected from June 2001 to December 2001. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine, risperidone, or quetiapine, but not with perospirone, in comparison with conventional antipsychotic drugs. Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline. In addition, improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS. CONCLUSION: These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs, suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement. These improvements were correlated with improvement of negative symptoms.     

A model of anticholinergic activity of atypical antipsychotic medications

BACKGROUND: Atypical antipsychotics clozapine, olanzapine, and quetiapine have significant affinity for the muscarinic receptors in vitro, while aripiprazole, risperidone, and ziprasidone do not. Dissimilarity in binding profiles may contribute to the reported differences in the anticholinergic effects of these antipsychotics. However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic. METHODS: We developed a model to assess the potential anticholinergic activity (AA) of atypical antipsychotics at therapeutic doses. A radioreceptor assay was used to measure in vitro AA at 6 clinically relevant concentrations of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone. Using published pharmacokinetic data, in combination with the measured in vitro AA, dose-AA curves were generated. RESULTS: Clozapine, and to a lesser extent olanzapine and quetiapine showed dose-dependent increases in AA. At therapeutic doses, the AA (in pmol/mL of atropine equivalents) was estimated to range from 27-250, 1-15, and 0-5.4 pmol/mL for clozapine, olanzapine, and quetiapine, respectively. Aripiprazole, risperidone, and ziprasidone did not demonstrate AA at any of the concentrations studied. CONCLUSIONS: Therapeutic doses of clozapine, olanzapine, and, to a lesser extent, quetiapine are associated with clinically relevant AA.     

Cognitive effects of atypical antipsychotic drugs in first-episode drug-nave schizophrenic patients

Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-nave patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.     

Effects of anticholinergic drug withdrawal on memory, regional cerebral blood flow and extrapyramidal side effects in schizophrenic patients

It has been suggested that anticholinergic drugs impair immediate memory and working memory in patients with schizophrenia. Opinions remain divided as to the influence of anticholinergic drug withdrawal on the psychopathology and extrapyramidal side effects (EPS) in these patients. In our previous study, regional cerebral blood flow (rCBF) was reduced in all regions of patients taking anticholinergic drugs. Anticholinergic drugs were withdrawn in 21 schizophrenic inpatients. Immediate and verbal working memory, rCBF, psychopathology, and EPS were investigated before and after anticholinergic withdrawal. There was improvement in immediate memory, verbal working memory, and psychopathology, as well as an increase in rCBF after withdrawal from anticholinergic drugs. EPS showed no significant changes. Factors that may predict the improvement of immediate memory after withdrawal of anticholinergic drugs are more severe baseline psychopathology and use of a higher anticholinergic drug dose at baseline. Improvement of working memory may be predicted by a higher baseline rCBF in the left anterior cerebral artery region. Withdrawal from anticholinergics should be considered in schizophrenic patients, and it is important to taper these drugs over at least four weeks.     

Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic

BACKGROUND: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. METHOD: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.     

Quetiapine in the treatment of focal tardive dystonia induced by other atypical antipsychotics: a report of 2 cases

The authors report 2 patients with schizophrenia who developed focal tardive dystonia secondary to treatment with atypical antipsychotics (risperidone, olanzapine). When quetiapine was gradually introduced and other antipsychotics were discontinued, these patients experienced remarkable and sustained improvement of their dystonic symptoms, without loss of psychotic symptom control. The mechanism by which quetiapine may improve tardive dystonia caused by other atypical antipsychotics is unclear. Due to its receptor and pharmacologic profile, quetiapine is the atypical antipsychotic that is most similar to clozapine (without its hematologic side effects), which leads the authors to consider it for the treatment of tardive movement disorders.     

Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia

OBJECTIVE: To assess changes in cognitive function in stable outpatients with schizophrenia switched to ziprasidone from conventional antipsychotics (n = 108), olanzapine (n = 104), or risperidone (n = 58) because of suboptimal efficacy or poor tolerability. METHODS: In three separate 6-week trials, patients received ziprasidone 40 mg b.i.d. for 2 days, followed by 20-80 mg b.i.d. for the next 40 days. Before switching, and at endpoint, patients were evaluated with tests of working and secondary verbal memory, vigilance, visuomotor speed, verbal fluency, and executive functioning. Principal components factor analysis was performed to test for clustering of cognitive variables. RESULTS: Significant improvements were seen at endpoint in secondary verbal memory (in all three groups), vigilance (in patients switched from conventional antipsychotics or risperidone), executive function (in patients switched from conventional antipsychotics or risperidone), and verbal fluency. Factor analysis on baseline scores suggested reduction of the cognitive variables to three factors: verbal skills, attention and short-term memory, and executive functioning. Analysis of z-transformed mean change in factor scores showed significant improvement in verbal skills and global score following the switch from conventional antipsychotics, olanzapine, or risperidone. CONCLUSIONS: Patients requiring a change in antipsychotic therapy may exhibit cognitive improvement following a switch to ziprasidone.     

Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment

OBJECTIVE: When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation. METHOD: Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]). RESULTS: Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation. CONCLUSIONS: For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.     

Effects of olanzapine and other antipsychotics on cognitive function in chronic schizophrenia: a longitudinal study

This study aimed to determine the effect of olanzapine and other antipsychotic drugs on cognitive functions after 6months of treatment. Baseline, 3month and 6month psychopathological and cognitive evaluations were made. Thirty-eight partially responsive outpatients with DSM-IV chronic schizophrenia diagnosis were included in the study. On the indication of their attending psychiatrists, 21 patients initiated treatment with olanzapine, and 17 remained on their previous treatment with other antipsychotic drugs. Cognitive assessments were blind to medication and psychopathological status.The olanzapine group presented a significantly greater improvement in negative symptomatology and verbal memory than the comparison group in repeated-measures of MANOVAs between baseline, 3month and 6month assessments. These differences remained statistically significant after covarying out gender, treatment with other atypical antipsychotics, biperidene doses and changes in positive and negative symptoms. In order to match previous differences between groups, cognitive baseline scores for each test were introduced as covariates, resulting in a significant improvement for the olanzapine group in negative symptomatology and the interference task of the Stroop test.We then re-analyzed the data, dividing the comparison group into two groups: risperidone-treated patients (n=9) and patients receiving conventional antipsychotic drugs (n=8). Post-hoc analyses between groups were carried out with baseline cognitive assessment as covariate. The olanzapine group improved significantly more than the risperidone group in negative symptomatology and in the interference task of Stroop test. The improvement in the number of categories of the Wisconsin Card Sorting Test was higher in risperidone patients than in those receiving olanzapine or conventional antipsychotic treatment. Conventional antipsychotic drugs did not present a significant improvement over atypical antipsychotic drugs in any cognitive function.In summary, in patients suffering from chronic schizophrenia, atypical antipsychotic agents were associated with slight differential improvements over time in attentional, verbal memory and executive functions compared with conventional neuroleptic drugs. No differential improvements were found in social functioning, verbal fluency, non-verbal domains of memory or visuo-motor abilities.     

Effectiveness and safety of antipsychotics in early onset psychoses: a long-term comparison

The effectiveness and safety of various antipsychotics was evaluated in a long-term study on 47 patients, 29 with schizophrenia and 18 with schizoaffective disorder, aged 10 to 17 years (mean 15.5) at onset. Follow-up ranged from 3 years (all 47 patients) to 11 years (19 patients). Data were collected on the following antipsychotics: haloperidol, risperidone, olanzapine, quetiapine, aripiprazole and clozapine. Cases with positive response were significantly more frequent with clozapine as compared to haloperidol, risperidone and olanzapine. Risperidone was significantly better than haloperidol at the 3-year follow-up. A comparison of the degree of clinical improvement evaluated with PANSS and CGI in patients treated with drugs in subsequent periods showed clozapine led to significantly greater improvement as compared to haloperidol, risperidone and olanzapine, and risperidone as compared to haloperidol. Data on long-term functioning significantly favored clozapine as compared to all the other drugs. Discontinuation due to side effects involved 20% patients with clozapine, lower percentage with the other drugs. The results of this study on early-onset schizophrenic and schizoaffective disorders confirm that even in the long-term, clozapine is more effective than haloperidol, risperidone and olanzapine. Despite a relevant incidence of adverse effects, clozapine seems to have unique effectiveness in treating children and adolescents with early-onset schizophrenic disorders.     

Influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia: comparison of middle-aged and older adults.

OBJECTIVE: The authors investigated the influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia. METHODS: Subjects were 86 inpatients (mean age: 61.4 years) who had been receiving treatment with conventional antipsychotic drugs and who met DSM-IV criteria for schizophrenia. Their antipsychotic medication was changed from conventional antipsychotics to one of four atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, or risperidone). Patients were grouped by age (older or younger than 65 years). Subjective sleep quality and psychopathology were assessed twice: 1) at baseline, and 2) 8 weeks after switching to the atypical antipsychotic drugs. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the Positive and Negative Syndrome Scale (PANSS) was used to measure psychopathology. RESULTS: The proportion of the patients who experienced improved subjective sleep quality was significantly higher in the elderly than in the middle-aged group. Logistic-regression analysis revealed that the improvement in subjective sleep quality through administration of atypical antipsychotic drugs was predicted by increased age, daytime dysfunction, and longer sleep latency at baseline. CONCLUSION: These results demonstrate that atypical antipsychotic drugs are beneficial to the quality of sleep in elderly patients with schizophrenia.     

Olanzapine vs. other antipsychotics in actual out-patient settings: six months tolerability results from the European Schizophrenia Out-patient Health Outcomes study

OBJECTIVE: The European Schizophrenia Out-patient Health Outcomes study is an observational study investigating treatment in schizophrenia. We report treatment-emergent adverse events during the first 6 months of treatment. METHOD: The rate of extrapyramidal symptoms (EPS), anticholinergic use, weight gain and sexual related dysfunctions were assessed in 8,400 out-patients. RESULTS: Patients typical antipsychotics and risperidone experienced significantly more EPS and anticholinergic use than patients in the clozapine, olanzapine, and quetiapine cohorts. Patients treated with amisulpride, typical antipsychotics and risperidone were significantly more likely to have sexual related dysfunctions and/or amenorrhea. Increases in weight and body mass index occurred in all cohorts, but were significantly greater in the olanzapine and clozapine cohorts. CONCLUSION: Patients treated with olanzapine, quetiapine and clozapine had better tolerability outcomes regarding EPS and sexual related dysfunctions compared with patients receiving risperidone, amisulpride and typicals. Patients treated with olanzapine and clozapine had higher weight increases than patients treated with risperidone, quetiapine and typicals.     

Influence of chronic treatment with olanzapine, clozapine and scopolamine on performance of a learned 8-arm radial maze task in rats

Cognitive deficit is a significant symptom in schizophrenic patients. Use of atypical antipsychotics has been demonstrated to improve some cognitive functions in schizophrenics, as well as in patients with dementia. However, side effects like sedation and muscarinic antagonism induced by these drugs have detracted from this improvement. We are interested in determining the behavioural effect of acute and chronic treatments with olanzapine and clozapine, two atypical antipsychotics, in a paradigm of working memory, and the influence on behavioural response of possible motor effects during test performance. Unspecific muscarinic antagonist scopolamine has been used for comparison. Male Wistar rats were trained on the 8-arm radial maze up to an accuracy level in choice of 80%. Distance travelled in the maze was also measured during test performance. Acute olanzapine, clozapine and scopolamine caused significant impairment of correct performance. Rats treated with olanzapine and clozapine presented a decrease in motor activity level at the same time. After the test at acute dosage, rats were chronically treated for 14 days with olanzapine, clozapine or scopolamine and 24 h after the last dose were again tested in the 8-arm radial maze. Under this procedure, chronic treatment with olanzapine, clozapine and scopolamine did not impair correct task performance and did not modify distance travelled. We concluded that the sedative effect masked a possible effect on working memory after acute administration of olanzapine and clozapine, whereas chronic treatment with olanzapine, clozapine and scopolamine did not adversely affect working memory performance. In the case of scopolamine, it suggests that chronic muscarinic antagonism does not induce memory impairment and for atypical antipsychotics, it suggests that chronic treatment induced a tolerance to acute motor effects of these drugs.     

Effect of quetiapine in the treatment of panic attacks in patients with schizophrenia: 3 case reports

The authors describe three schizophrenic patients who suffered from panic attacks and experienced marked improvement of these episodes after switching to quetiapine from their previous antipsychotics (haloperidol, bromperidol, and risperidone), which have high dopamine antagonistic properties such as haloperidol, bromperidol, and risperidone.     

The effect of chronic treatment with typical and atypical antipsychotics on working memory and jaw movements in three- and eighteen-month-old rats

The effects of chronic treatment with typical and atypical antipsychotics on acquisition, working memory, motor activity, and rat tardive dyskinesia (TD) were studied in 3- and 18-month-old Sprague-Dawley rats. Acquisition and working memory were studied in eight-arm radial mazes. TD liability of antipsychotic drugs (APD) was evaluated in rat model of TD in which spontaneous repetitive jaw movements (RJM) occur during withdrawal from neuroleptic treatment. Motor behavior was assessed using the traverse beam test. D1 and D2 receptor occupancy was determined in the rat brain during treatment with typical and atypical antipsychotics. Chronic administration of clozapine, haloperidol, and risperidone impaired acquisition of the eight-arm radial maze in both young and aging rats while olanzapine had no effect. Retention tests showed that aging rats made more errors than the adults and that the antipsychotics haloperidol and risperidone significantly impaired retention in both age groups. Evaluation of motor behavior revealed that typical and atypical antipsychotics used in comparable doses in young rats had no effect on motor behavior, whereas in aging rats performance was impaired by clozapine, haloperidol, and risperidone but not by olanzapine. RJM responses were increased during washout from haloperidol treatment in young and aging rats whereas olanzapine, clozapine, and risperidone had no effect. D2 receptor occupancy in haloperidol- and risperidone-treated rats was above 70% while olanzapine and clozapine receptor occupancy was below 70%, which is the threshold for the appearance of extrapyramidal syndrome (EPS) and TD.     

Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics

OBJECTIVE: Clozapine, the prototype of atypical antipsychotics, remains unique in its efficacy in the treatment of refractory schizophrenia. Its affinity for dopamine D(4) receptors, serotonin 5-HT(2A) receptor antagonism, effects on the noradrenergic system, and its relatively moderate occupancy of D(2) receptors are unlikely to be the critical mechanism underlying its efficacy. In an attempt to elucidate the molecular/synaptic mechanism underlying clozapine's distinctiveness in refractory schizophrenia, the authors studied the in vivo D(1) and D(2) receptor profile of clozapine compared with other atypical antipsychotics. METHOD: Positron emission tomography with the radioligands [(11)C]SCH23390 and [(11)C]raclopride was used to investigate D(1) and D(2) receptor occupancy in vivo in 25 schizophrenia patients receiving atypical antipsychotic treatment with clozapine, olanzapine, quetiapine, or risperidone. RESULTS: Mean striatal D(1) occupancies ranged from 55% with clozapine to 12% with quetiapine (rank order: clozapine > olanzapine > risperidone > quetiapine). The striatal D(2) occupancy ranged from 81% with risperidone to 30% with quetiapine (rank order: risperidone > olanzapine > clozapine > quetiapine). The ratio of striatal D(1)/D(2) occupancy was significantly higher for clozapine (0.88) relative to olanzapine (0.54), quetiapine (0.41), or risperidone (0.31). CONCLUSIONS: Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors. Whether its effect on D(1) receptors represents agonism or antagonism is not yet clear, as this issue is still unresolved in the preclinical arena. This distinctive effect on D(1)/D(2) receptors may be responsible for clozapine's unique effectiveness in patients with schizophrenia refractory to other typical and atypical antipsychotics.     

Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics

BACKGROUND: Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain. METHOD: The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002. RESULTS: Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups. CONCLUSION: Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.     

Cognitive effects and antipsychotic treatment

Cognitive impairment has long been recognized as central to the abnormalities that occur in schizophrenia, since neurocognitive deficits are predictive of a number of outcome indices, and they pose a significant obstacle to any attempts at social rehabilitation. This raises the possibility that treatments producing improvements in cognitive function might, in turn, prove to have synergistic effects with psychosocial interventions. Rather than improving cognitive deficits, conventional antipsychotics may instead contribute to the impairment seen in many patients with schizophrenia. These damaging effects on cognition might be expected not only when antipsychotic drugs with intrinsic anticholinergic properties are used but also when anticholinergic drugs are prescribed for the relief of treatment-emergent extrapyramidal symptoms. The atypical antipsychotic drugs may be effective in this area, either in amelioration of the cognitive impairments that occur in schizophrenia or in arresting any continuing decline. New-generation atypical agents, such as quetiapine and risperidone, have minimal intrinsic anticholinergic effects, which suggest that some of the additional negative effects on cognition can be avoided. A number of large-scale, long-term follow-up studies of atypical antipsychotics are currently underway, in 'real world' settings, to assess not only control of symptoms of schizophrenia but also improvement in social, occupational, and inter-personal functioning.     

Adjunctive risperidone, olanzapine and quetiapine for the treatment of hospitalized patients with bipolar I disorder: a retrospective study

This study evaluated the overall effectiveness and tolerability of atypical antipsychotics (risperidone vs. olanzapine vs. quetiapine) used in the treatment of bipolar inpatients. After screening 463 patients, the medical records of 158 inpatients with bipolar I disorder, who were given olanzapine, risperidone or quetiapine as adjuncts to mood stabilizers for at least 1 month and not administered with any other antipsychotics, were examined. Details of the tolerability and effectiveness were reviewed according to the treatment records during their hospital stay. The results showed equivalent effectiveness based on the Clinical Global Impression (CGI) and Global Assessment Functioning (GAF) score between the three atypical antipsychotics. The frequency of the extrapyramidal symptom-related side effects were higher in the risperidone-treated group than in the olanzapine and quetiapine-treated group. This suggests that risperidone, olanzapine and quetiapine have a comparable effectiveness in inpatients with bipolar I disorder in a naturalistic setting. However, there were some differences in tolerability between these results as reported from previous Western studies.     

Hospitalization risks in the treatment of bipolar disorder: comparison of antipsychotic medications

OBJECTIVES: This study compared the relative risk for hospitalization of patients with bipolar and manic disorders receiving atypical and typical antipsychotics. METHODS: This retrospective study was based on administrative claims data extracted from the PharMetrics database during 1999 through 2003. Comparisons were made among atypical antipsychotics (risperidone, olanzapine, quetiapine or ziprasidone), as well as between each of these versus a combined group of the leading typical antipsychotics. Relative risk for hospitalization was estimated with Cox proportional regression, which adjusted for differences in patient characteristics. RESULTS: Risperidone and olanzapine demonstrated higher risks for hospitalization than quetiapine [hazard ratio (HR) 1.19, p < 0.05 for both], translating into higher annual mental health inpatient charges of $260 per patient. Risperidone and olanzapine also showed higher estimated risks than ziprasidone, which approached the p < 0.05 threshold. Differences between each of the atypicals and the combined typicals were not significant. Patients with putative rapid cycling had a threefold greater risk for hospitalization than other patients with bipolar disorder. In these patients, comparisons among atypical antipsychotics showed that risperidone had a significantly higher hospitalization risk than olanzapine (HR 3.31, p < 0.05), resulting in higher annual mental health inpatient charges of $4,930 per patient. CONCLUSIONS: In the treatment of bipolar and manic disorders, risperidone and olanzapine were associated with a higher risk for hospitalization than quetiapine, and possibly ziprasidone. In the treatment of putative rapid cyclers, olanzapine was associated with a lower risk for hospitalization than risperidone.