Schizophrenia Bulletin Advance Access published online on April 15, 2008
Schizophrenia Bulletin, doi:10.1093/schbul/sbn018
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Antipsychotic Combinations vs Monotherapy in Schizophrenia: A Meta-analysis of Randomized Controlled Trials
2 The Zucker Hillside Hospital, Psychiatry Research, North Shore—Long Island Jewish Health System, Glen Oaks, New York, NY
3 Albert Einstein College of Medicine, Bronx, New York, NY
4 The Feinstein Institute for Medical Research, Manhasset, New York, NY
5 Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Ismaningerstr. 22, 81675 München, Germany
1 To whom correspondence should be addressed; The Zucker Hillside Hospital, Psychiatry Research, Glen Oaks, New York, NY 11004; tel: 718-470-4812, fax: 718-343-1659, e-mail: ccorrell{at}lij.edu.
Context: Despite lacking evidence for its safety and efficacy, antipsychotic cotreatment is common in schizophrenia.
Objective: To evaluate therapeutic and adverse effects of antipsychotic cotreatment vs monotherapy in schizophrenia.
Data Sources: Cochrane Schizophrenia Group register and hand searches of relevant journals/conference proceedings.
Study Selection: Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic.
Data Extraction and Analysis: Two authors independently extracted data. For homogenous dichotomous data, we calculated random effects, relative risk (RR), 95% confidence intervals (CIs), and numbers needed to treat (NNT). For continuous data, weighted mean differences were calculated.
Results: In 19 studies (1216 patients) with 28 monotherapy and 19 cotreatment arms, antipsychotic cotreatment was superior to monotherapy regarding 2 a priori defined coprimary outcomes: less study-specific defined inefficacy (N = 22, n = 1202, RR = 0.76, CI = 0.63–0.90, P = .002, NNT = 7, CI = 4–17, P = .0008, I2 = 78.9%) and all-cause discontinuation (N = 20, n = 1052, RR = 0.65, CI = 0.54–0.78, P < .00001). Results were consistent using Clinical Global Impressions thresholds of less than much (P = .006) and less than minimally (P = .01) improved. Specific psychopathology and adverse event data were insufficient to yield meaningful results. In sensitivity analyses, 5 efficacy moderators emerged: concurrent polypharmacy initiation, clozapine combinations, trial duration >10 weeks, Chinese trials, and second-generation + first-generation antipsychotics. In a meta-regression, similar dose combinations, second-generation + first-generation antipsychotics and concurrent polypharmacy initiation remained significant.
Conclusions: In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy. However, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research.
Keywords: antipsychotics / polypharmacy / combination / monotherapy / schizophrenia / efficacy / all-cause discontinuation / side effects / trial methodology
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Attard and F. Gaughran Review: limited evidence that adding a second antipsychotic improves clozapine treatment in schizophrenia Evid. Based Ment. Health, November 1, 2009; 12(4): 112 - 112. [Full Text] [PDF]
|
|
|
|
 |
|
 M. X. Patel, M. Taylor, and A. S. David Antipsychotic long-acting injections: mind the gap The British Journal of Psychiatry, November 1, 2009; 195(52): S1 - S4. [Abstract] [Full Text] [PDF]
|
|