Long-Acting Risperidone and Oral Antipsychotics in Unstable Schizophrenia

Rosenheck, Robert A.; Krystal, John H.; Lew, Robert A.; Barnett, Paul G.; Fiore, Louis D.; Valley, Danielle; Thwin, Soe Soe; Vertrees, Julia E.; Liang, Matthew H.

doi:10.1056/nejmoa1005987

Cited by 200 publications

(174 citation statements)

References 33 publications

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“…While randomization is the best strategy to estimate treatment effects from a statistical perspective (in terms of eliminating bias due to selection into treatment), it is possible that the RCT setting does not fully reflect other aspects of how oral therapies are used in general clinical practice. As the RCT has to match services and prescription monitoring for the oral subjects to equal those of long-acting depot subjects-possibly eliminating differences that would manifest themselves in general clinical practice-the study design may have limitations with 7 reported rates of hospitalization at 10.8 months for the long-acting risperidone and 11.3 months for oral antipsychotics. Hospitalization rates for both treatment arms were adjusted linearly to a common follow-up period of 11 months.…”

Section: Discussionmentioning

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%

“…5,6 However, the findings in the clinical literature regarding the comparative effectiveness of depot versus oral antipsychotics in schizophrenia have been inconsistent. [7][8][9] These findings have challenged the field to consider the proper role of long-acting depot therapy. Some argue that the widely held notion of superiority of long-acting medication is overstated.…”

mentioning

confidence: 99%

“…Some argue that the widely held notion of superiority of long-acting medication is overstated. 7,10,11 If so, then efforts to increase long-acting depot utilization will not yield hoped-for improvements in relapse prevention. The lack of consistent findings in the literature raises important practical questions of therapy in managing schizophrenia.…”

mentioning

confidence: 99%

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Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Kirson¹,

Weiden²,

Yermakov³

et al. 2013

J. Clin. Psychiatry

159

128

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Sensitivity Analysesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Kirson¹,

Weiden²,

Yermakov³

et al. 2013

J. Clin. Psychiatry

159

128

View full text Add to dashboard Cite

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“…In a sample of 335 patients, depot risperidone and oral aripiprazole did not differ in loss of retention, time in remission, or time to relapse (29). LAI risperidone failed to be more effective than oral antipsychotics in prevention of hospitalization among 369 patients (30). Similarly, LAI olanzapine pamoate was as effective as oral olanzapine in time and number of treatment discontinuation and relapse prevention in a sample of 525 stabilized outpatients (31).…”

Section: Long-acting Injectable Antipsychotics (Depot Formulations)mentioning

confidence: 99%

Adherence and Long-Acting Injectable Antipsychotics in Schizophrenia: An Update

Mohr¹,

Volavka²

2012

Dusunen Adam

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Antipsychotic Medications for Schizophrenia

Suzuki

2014

JAMA

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considered as continuous and categorical variables. The association of tobacco use with oral HPV-16 was explored using logistic regression. All multivariable models included variables considered significant (2-sided P < .05) in bivariable analysis and important factors based on the literature. 2 Analyses were performed using SUDAAN software version 11.0.1 (RTI International).Results | Among 6887 participants, 2012 (28.6%; 95% CI, 26.5%-30.9%) were current tobacco users and 63 (1.0%; 95% CI, 0.8%-1.3%) had oral HPV-16 detected. Current tobacco users were more likely than nonusers to be male, younger, less educated, and to have a higher number of lifetime oral sexual partners ( Table 1). In bivariable analysis, selfreported and biological measures of tobacco exposure as well as oral sexual behavior were significantly associated with prevalent oral HPV-16 infection ( Table 2). Oral HPV-16 prevalence was greater in current tobacco users (2.0%; 95% CI, 1.3%-3.1%) compared with never or former tobacco users (0.6%; 95% CI, 0.4%-0.9%) (P = .004). Mean cotinine (157.7 ng/mL vs 57.2 ng/mL, P = .002) and NNAL levels (0.36 ng/mL vs 0.12 ng/mL, P = .02) were higher in individuals with vs without oral HPV-16 infection.All biomarkers of tobacco exposure remained associated with oral HPV-16 infection after adjustment for other factors (Table 2). Significant dose-response relationships were observed between cotinine (P = .02 for trend) or NNAL (P = .01 for trend) levels and odds of oral HPV-16 infection (Table 2). Each log increase in cotinine, approximating 3 cigarettes per day, was independently associated with oral HPV-16 prevalence (adjusted odds ratio, 1.31; 95% CI, 1.07-1.60). Each log increase in NNAL, approximating 4 cigarettes per day, was independently associated with oral HPV-16 prevalence (adjusted odds ratio, 1.68; 95% CI, 1.23-2.28).

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Long-Acting Risperidone and Oral Antipsychotics in Unstable Schizophrenia

Cited by 200 publications

References 33 publications

Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Adherence and Long-Acting Injectable Antipsychotics in Schizophrenia: An Update

Antipsychotic Medications for Schizophrenia

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