Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial (original) (raw)
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BMC Psychiatry, 2012
Background: With many atypical antipsychotics now available in the market, it has become a common clinical practice to switch between atypical agents as a means of achieving the best clinical outcomes. This study aimed to examine the impact of switching from olanzapine to risperidone and vice versa on clinical status and tolerability outcomes in outpatients with schizophrenia in a naturalistic setting. Methods: W-SOHO was a 3-year observational study that involved over 17,000 outpatients with schizophrenia from 37 countries worldwide. The present post hoc study focused on the subgroup of patients who started taking olanzapine at baseline and subsequently made the first switch to risperidone (n=162) and vice versa (n=136). Clinical status was assessed at the visit when the first switch was made (i.e. before switching) and after switching. Logistic regression models examined the impact of medication switch on tolerability outcomes, and linear regression models assessed the association between medication switch and change in the Clinical Global Impression-Schizophrenia (CGI-SCH) overall score or change in weight. In addition, Kaplan-Meier survival curves and Cox-proportional hazards models were used to analyze the time to medication switch as well as time to relapse (symptom worsening as assessed by the CGI-SCH scale or hospitalization). Results: 48% and 39% of patients switching to olanzapine and risperidone, respectively, remained on the medication without further switches (p=0.019). Patients switching to olanzapine were significantly less likely to experience relapse (hazard ratio: 3.43, 95% CI: 1.43, 8.26), extrapyramidal symptoms (odds ratio [OR]: 4.02, 95% CI: 1.49, 10.89) and amenorrhea/galactorrhea (OR: 8.99, 95% CI: 2.30, 35.13). No significant difference in weight change was, however, found between the two groups. While the CGI-SCH overall score improved in both groups after switching, there was a significantly greater change in those who switched to olanzapine (difference of 0.29 points, p=0.013). Conclusion: Our study showed that patients who switched from risperidone to olanzapine were likely to experience a more favorable treatment course than those who switched from olanzapine to risperidone. Given the nature of observational study design and small sample size, additional studies are warranted.
Objective: The safety and efficacy profile of risperidone and olanzapine were compared in a double‑blind trial that used doses widely accepted in clinical practice. Methods: Subjects (n = 71) who met Diagnostic and Statistical Manual of Mental Disorders‑IV criteria for schizophrenia were randomly assigned to receive 2–8 mg/day of risperidone (mean modal dose = 5.5 mg/day) or 5–20 mg/day of olanzapine (mean modal dose = 14.4 mg/day) for 1 year. Results: The two study groups were similar at baseline in all aspects. Seventy‑four percent of the participants completed the trial, with no between‑differences in the proportion of dropouts. Olanzapine group showed significantly greater improvement in negative symptoms in assessments at 3rd, 6th, 9th, and 12th months (P = 0.05, 0.00, 0.00, and 0.00, respectively). Clinical global impression of severity (CGI‑S) scores were consistently lower in the olanzapine group at 3rd, 6th, and 9th months (P = 0.01, 0.03, and 0.05, respectively) as measured by positive and negative symptom scale (PANSS). Total scores on PANSS, positive symptoms, general psychopathology, and CGI improvement showed comparable improvement at 3rd, 6th, 9th, and 12th months of follow‑up (all subjects, including dropouts). Severity of extrapyramidal symptoms was low in both groups, with no between‑group differences. Mean change in body weight, fasting blood sugar, and fasting cholesterol was comparable in both groups. Risperidone group had significant hyperprolactinemia after one year (P = 0.03). Conclusions: Both treatments were well‑tolerated and efficacious. Greater reductions in severity of the illness and negative symptoms were seen with olanzapine consistently through 1 year. The frequency and severity of extrapyramidal symptoms were negligible and similar in the two treatment groups. Weight gain, hyperlipidemia, and hyperglycemia were comparable in both groups. Risperidone produced significant hyperprolactinemia.
American Journal of Psychiatry, 2005
The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/ recurrence. Method: Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score ≥20 entered the study and received open-label cotreatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score ≤12; 21-item Hamilton depression scale score ≤8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/ day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214). Results: Symptomatic relapse/recurrence (score ≥15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapinetreated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/ recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during openlabel cotreatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg). Conclusions: These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium cotreatment. Both agents were comparable in preventing depression relapse/recurrence.
BMC Medicine, 2008
In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone.
Review of olanzapine in the management of bipolar disorders
Neuropsychiatric Disease and Treatment, 2007
Olanzapine is an atypical antipsychotic currently with indications for the treatment of schizophrenia, acute mania and the prevention of relapse in bipolar disorder. A growing body of clinical evidence supports these indications. Acute mania trials have demonstrated superior efficacy of olanzapine to placebo, equal or superior efficacy to valproate and superior efficacy in combination therapy with lithium or valproate compared to mood stabilizer monotherapy. Olanzapine demonstrated a modest effect in the treatment of bipolar depression with a substantially enhanced effect in combination with fluoxetine. Maintenance trials showed olanzapine to be more efficacious than placebo in the prevention of manic and depressive relapses and non-inferior to lithium or valproate. Combination of olanzapine with lithium or valproate was also found to be more efficacious than lithium or valproate monotherapy in the prevention of manic relapse in patients with a partial response to monotherapy with lithium or valproate. These trials suggest that olanzapine is a viable option and an invaluable addition to the pharmacological armamentarium in the treatment of bipolar I disorder. However, this can often be mitigated by safety and tolerability concerns with this agent including weight gain and metabolic syndrome that warrants clinician vigilance and discernment that is imperative in today’s clinical practice.
Biological Psychiatry, 1999
Background: Depressive symptoms are common during the course of schizophrenia and may carry prognostic relevance. Methods: From a 28-week prospective, double-blind, randomized study of olanzapine and risperidone, a post hoc evaluation of changes on the Positive and Negative Syndrome Scale (PANSS) depression cluster (PDC) and the subsequent risk of relapse were analyzed by logistic regression. Results: Olanzapine was associated with a significantly higher categorical rate of improvement on the PANSS depression cluster (Ն7 points) (p Ͻ .05). Although the baseline severity of depressive symptoms was not a significant predictor of relapse, the degree of acute (8-week) mood improvement on the PANSS depression cluster (but neither negative or positive symptom changes) was related to the probability of a subsequent psychotic relapse. Acute mood improvement with olanzapine was inversely related to a nonsignificantly lower risk of relapse. However, an opposite and significant relationship was observed among risperidone-treated subjects. Risperidone-treated subjects with a greater degree of acute mood change were both 3.58 times more likely to relapse than their risperidone counterparts who had experienced less mood improvement (p ϭ .008) and 8.55 times more likely than olanzapinetreated subjects who had had similar mood improvements (p ϭ .001). Conclusions: These data suggest the underlying pharmacologic differences between the two drugs may bestow different rates of longer-term mood stabilization and relapse prevention. In a second series of analyses, worsening on the PANSS depression cluster in the 4 weeks or less preceding a clinical relapse was a significant prodromal predictor of relapse among all subjects. As a whole, subjects with a worsening on the PDC demonstrated a 1.77 times higher risk of a relapse during the subsequent 4 weeks (p ϭ .001). Among this mood-worsening stratum, risperidone-treated patients were 3.51 times more likely to relapse in those next 4 weeks (p ϭ .005) than their olanzapine counterparts. Future comparative drug studies in this area will further contribute to our understanding of the pathophysiology of mood change and its relationship to psychosis, including clinical relapse and how newer agents may differ in their respective delivery of long-term treatment outcomes.