Olanzapine Long-Acting Injection: A 24-Week, Randomized, Double-Blind Trial of Maintenance Treatment in Patients With Schizophrenia

Kane, John M.; Detke, Holland C.; Naber, Dieter; Sethuraman, Gopalan; Lin, Daniel; Bergstrom, Richard F.; McDonnell, David

doi:10.1176/appi.ajp.2009.07081221

Cited by 179 publications

(179 citation statements)

References 15 publications

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…Hospitalization rates for both treatment arms were adjusted linearly to a common follow-up period of 11 months. Kane et al 26 reported risk ratios based on exacerbation rates that include both rehospitalization and relapse. Risk ratios for the long-acting treatment arm were computed as a weighted average of the number of patients in the "very low" (n = 144), "low" (n = 140), "medium" (n = 318), and "high" (n = 141) dosage treatment arms.…”

Section: Discussionmentioning

confidence: 99%

“…Conclusive answers about treatment effectiveness require both methodological rigor in comparing treatment outcomes and 26 were recalculated omitting the patients receiving very low dose long-acting olanzapine. b Depot-oral comparisons in which all-cause discontinuation was the primary endpoint (see Table 2) were excluded from the analysis.…”

Section: Discussionmentioning

confidence: 99%

“…For RCTs, the adjusted RRs range from 0.50 (Gaebel et al, 25 oral quetiapine vs long-acting risperidone) to 2.03 (Kane et al, 26 oral olanzapine vs long-acting olanzapine). Among prospective observational studies, adjusted RRs range from 0.30 (Kim et al, 28 oral risperidone vs longacting risperidone) to 0.89 (Olivares et al, 5 oral atypical vs long-acting risperidone).…”

Section: Adjusting For Baseline Differences In Gender and Agementioning

confidence: 99%

“…Meta-analysis of adjusted endpoints resulted in an RR of 0.89 (95% CI, 0.64-1.22; P = .416) for RCTs, meaning that the null hypothesis that depot and oral formulations have similar efficacy cannot be rejected. Note that this analysis includes an adjusted RR of 2.03 from Kane et al, 26 which appears to be an outlier among RCTs, possibly due to the inclusion of depot patients with a very low treatment dose (see Sensitivity Analyses). To assess the degree of inconsistency within each study design grouping, we calculated the percentage of total variation across studies that is due to heterogeneity (rather than chance), I 2 .…”

Section: Adjusting For Baseline Differences In Gender and Agementioning

confidence: 99%

“…The study by Kane et al 26 included multiple long-acting olanzapine treatment arms with very low, low, medium, and high dosages, with the very low dose serving as a "reference Another potential issue may arise from the inclusion of the study by Rosenheck et al, 7 which permitted a limited degree of crossover between treatment arms. Removal of the study has no substantive effect on the estimated RR, although the 95% CI increases due to smaller sample size The findings from the duration adjustment are also reported in Table 3 …”

Section: Sensitivity Analysesmentioning

confidence: 99%

See 4 more Smart Citations

Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Kirson¹,

Weiden²,

Yermakov³

et al. 2013

J. Clin. Psychiatry

165

128

View full text Add to dashboard Cite

Objective: Nonadherence is a major challenge in schizophrenia treatment. While long-acting (depot) antipsychotic medications are often recommended to address adherence problems, evidence on the comparative effectiveness of depot versus oral antipsychotics is inconsistent. We hypothesize that this inconsistency could be due to systematic differences in study design. This review evaluates the effect of study design on the comparative effectiveness of antipsychotic formulations. The optimal use of different antipsychotic formulations in a general clinical setting depends on better understanding of the underlying reasons for differences in effectiveness across research designs.Data Sources: A PubMed literature review targeted English-language studies (2000-2011) with information on relapse, hospitalization, or allcause discontinuation for depot and oral antipsychotic treatment arms in schizophrenia. The time frame was chosen to reflect research focused on the newer generation of antipsychotic agents. The search required at least 1 term from each of the following categories: (1) schizophrenia; (2) inject, injection, injectable, injectables, injected, depot, long-acting; and (3) iloperidone, fluphenazine, haloperidol, paliperidone, risperidone, olanzapine, asenapine, flupentixol, flupenthixol, lurasidone, clopenthixol, fluspirilene, zuclopentixol, zuclopenthixol. Study Selection: Thirteen relevant studies were identified by 2 independent reviewers; these studies included information on 19 depot-oral comparisons.Data Extraction: Age-and gender-adjusted risk ratios (RRs) (depot/ oral) were calculated for the identified endpoints and pooled by study design (randomized controlled trial [RCT], prospective observational, and retrospective observational). Meta-analysis with random effects was used to estimate the pooled RRs, by study design. Average conversion factors between study designs were calculated as the ratios of pooled RRs.Results: Meta-analysis of adjusted endpoints showed no apparent benefit of depot over oral formulations in RCTs, with an RR of 0.89 (P = .416). In contrast, there was a significant advantage for depot formulations in other study designs (prospective RR = 0.62 [P < .001]; retrospective RR = 0.56 [P < .001]). These imply conversion factors of 1.43 and 1.59 between RCTs and prospective and retrospective designs, respectively. Conclusions:The comparative effectiveness of antipsychotic formulations is sensitive to research design. Depot formulations displayed significant advantages in nonrandomized observational studies, whereas in RCTs no difference was observed. The estimated conversion factors may facilitate comparison across studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Adjusting For Baseline Differences In Gender and Agementioning

confidence: 99%

Section: Adjusting For Baseline Differences In Gender and Agementioning

confidence: 99%

Section: Sensitivity Analysesmentioning

confidence: 99%

See 3 more Smart Citations

Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Kirson¹,

Weiden²,

Yermakov³

et al. 2013

J. Clin. Psychiatry

165

128

View full text Add to dashboard Cite

show abstract

Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia

et al. 2015

View full text Add to dashboard Cite

Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia

et al. 2021

View full text Add to dashboard Cite

IMPORTANCEThe doses of antipsychotic drugs needed for relapse prevention in schizophrenia is a debated issue.OBJECTIVE To examine dose-response findings in a meta-analysis of randomized clinical trials.DATA SOURCES Studies were identified through the Cochrane Schizophrenia Group's Study-Based Register of Trials (March 9, 2020), PubMed (January 1, 2021), and previous reviews. First authors and/or pharmaceutical companies were contacted for additional information.STUDY SELECTION Two reviewers independently selected randomized clinical trials that compared fixed doses of a second-generation antipsychotic, haloperidol, or fluphenazine for relapse prevention in patients with stable schizophrenia. DATA EXTRACTION AND SYNTHESIS Using the Preferred Reporting Items for SystematicReviews and Meta-analyses guideline, all parameters in duplicate were extracted and frequentist dose-response random-effects meta-analyses were conducted.MAIN OUTCOMES AND MEASURES Study-defined relapse (primary outcome), rehospitalization, Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale total score reduction from baseline, all-cause discontinuation, and dropouts due to adverse events. RESULTSEvidence from 72 dose arms from 26 studies with 4776 participants was analyzed. The efficacy-related dose-response curves had a hyperbolic shape meaning that the probability to relapse decreased rapidly with doses of up to 5-mg/d risperidone equivalent (relative relapse risk, 0.43; 95% CI, 0.31-0.57; standardized mean difference for Positive and Negative Syndrome Scale total score reduction, −0.55; 95% CI, −0.68 to −0.41), but flattened thereafter. In contrast, dropouts due to adverse events continued to increase beyond this dose (relative risk at 5 mg/d, 1.38; 95% CI, 0.87-2.55; relative risk at 15 mg/d, 2.68; 95% CI, 1.49-4.62). In a subgroup analysis of patients in remission, a plateau was reached earlier, at approximately 2.5-mg/d risperidone equivalent. CONCLUSIONS AND RELEVANCEThe findings of this meta-analysis suggest that doses higher than approximately 5-mg/d risperidone equivalent may provide limited additional benefit for relapse prevention but more adverse events. For patients in remission or who are receiving high-potency first-generation antipsychotics, doses as low as 2.5-mg/d risperidone equivalent may be sufficient. However, caution is needed at this low dose end when further decreases of dose may be accompanied by a disproportionally higher relapse risk. Moreover, the observations are averages, and factors such as slow or rapid metabolism, age, illness stage, comorbidities, and drug-drug interactions suggest that individual patients will often need higher or lower doses.

show abstract

Olanzapine Long-Acting Injection: A 24-Week, Randomized, Double-Blind Trial of Maintenance Treatment in Patients With Schizophrenia

Abstract: Olanzapine long-acting injection was efficacious in maintenance treatment of schizophrenia for up to 24 weeks, with a safety profile similar to oral olanzapine except for injection-related adverse events.

Cited by 179 publications

References 15 publications

Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia

Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia

Contact Info

Product

Resources

About