title: Antipsychotics for cocaine or psychostimulant dependence: systematic review and meta-analysis of randomized, placebo-controlled trials.
abstract: OBJECTIVE
  Since cocaine and psychostimulant dependence are related to increased dopamine release, antipsychotics have been tried to reduce their reinforcing properties. A meta-analysis was undertaken to assess the efficacy and tolerability of antipsychotics in cocaine- or stimulant-dependent patients.
  
  
  METHODS
  We searched PubMed, Cochrane Library databases, and PsycINFO from database inception until June 24, 2013, using the following keywords: (randomized OR random OR randomly) AND (placebo) AND (methylphenidate OR cocaine OR methamphetamine OR amphetamine OR 3,4-methylenedioxymethamphetamine) AND (dependence OR abuse) AND (antipsychotic OR neuroleptic OR 34 specific antipsychotic names).
  
  
  METHODS
  Included were randomized, placebo-controlled trials of antipsychotics lasting at least 2 weeks in patients with primary cocaine or psychostimulant dependence. Of 363 hits, we removed 316 duplicates, 20 references based on abstract/title, and 13 ineligible full-text articles, retaining 14 trials for this meta-analysis.
  
  
  METHODS
  Two authors independently extracted the data. Coprimary outcomes included degree of substance use and lack of abstinence. Risk ratio (RR), 95% CI, and standardized mean difference were calculated.
  
  
  RESULTS
  Ten studies in patients with primary cocaine dependence (risperidone = 5, olanzapine = 3, reserpine = 2; n = 562) and 4 in those with amphetamine/methamphetamine dependence (aripiprazole = 4; n = 179) were meta-analyzed (14 studies, total n = 741). When study results were pooled together, antipsychotics did not differ from placebo in regard to cocaine use days and lack of cocaine or amphetamine/methamphetamine abstinence, severity of addiction, cocaine or amphetamine/methamphetamine craving, Clinical Global Impressions-Severity of Illness (CGI-S) scores, depression, anxiety, compliance, all-cause discontinuation, and several side effects. However, antipsychotics caused more intolerability-related discontinuation than placebo (P = .0009). Individually, aripiprazole was superior to placebo in regard to CGI-S (P = .001), while olanzapine was inferior to placebo in regard to cocaine craving (P = .03) and risperidone was inferior to placebo in regard to depression (P = .002).
  
  
  CONCLUSIONS
  Antipsychotics had no advantages over placebo in regard to cocaine use and cocaine or psychostimulant abstinence or craving, while causing more intolerability-related discontinuations.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks.
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000493:pharmacokinetics; D003042:Cocaine / Q000009:adverse effects* / Q000493:pharmacokinetics; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008694:Methamphetamine / Q000009:adverse effects* / Q000493:pharmacokinetics; D000077152:Olanzapine; D017063:Outcome Assessment, Health Care; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D009435:Synaptic Transmission / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D015363:Quinolones; D001569:Benzodiazepines; D008694:Methamphetamine; D000068180:Aripiprazole; D003042:Cocaine; D018967:Risperidone; D000077152:Olanzapine; D004298:Dopamine