olanzapine and Cocaine-Related-Disorders

Cocaine dependence is a public health problem characterised by recidivism and a host of medical and psychosocial complications. Cocaine dependence remains a disorder for which no pharmacological treatment of proven efficacy exists.. To evaluate the efficacy and the acceptability of antipsychotic medications for cocaine dependence.. This review is an update of a previous Cochrane review published in 2007. We searched up to 15 July 2015 in Cochrane Drugs and Alcohol Group Specialised Register (searched in CRSLive); the Cochrane Library (including the Cochrane Central Register of Controlled Trials (CENTRAL); the Database of Abstracts of Reviews of Effects (DARE)); PubMed; EMBASE; CINAHL and Web of Science. All searches included non-English language literature.. All randomised controlled trials and controlled clinical trials with focus on the use of any antipsychotic medication for the treatment of cocaine dependence.. We used standard methodological procedures expected by Cochrane.. We included 14 studies (719 participants). The antipsychotic drugs studied were risperidone, olanzapine, quetiapine, lamotrigine, aripiprazol, haloperidol and reserpine. Comparing any antipsychotic drugs versus placebo, we found that antipsychotics reduced dropout: eight studies, 397 participants, risk ratio (RR) 0.75 (95% confidence interval (CI) 0.57 to 0.97), moderate quality of evidence. We found no significant differences for any of the other primary outcomes considered: number of participants using cocaine during the treatment, two studies, 91 participants: RR 1.02 (95% CI 0.65 to 1.62); continuous abstinence, three studies, 139 participants: RR 1.30 (95% CI 0.73 to 2.32); side effects, six studies, 291 participants: RR 1.01 (95% CI 0.93 to 1.10); and craving, four studies, 240 participants: RR 0.13 (-1.08 to 1.35). For all of these comparisons we rated the quality of evidence as low.Comparisons of single drug versus placebo or versus another drug are conducted in few trials with small sample sizes, limiting the reliability of the results. Among these comparisons, only quetiapine seemed to outperform placebo in reducing cocaine use, measured by grams per week: mean difference (MD) -0.54 (95% CI -0.92 to -0.16), by US dollars spent per week: MD -53.80 (95% CI -97.85 to -9.75), and by craving: MD -1.23 (95% CI -2.19 to -0.27), but results came from one study with 60 participants.The major limitations of the studies were the high risk of attrition bias (40% of the included studies) and low quality of reporting, mainly for the risk of selection bias, performance and detection bias, that we rated as being at unclear risk for 75% to 80% of the studies. Furthermore, most of the included studies did not report results on important outcomes such as side effects, or use of cocaine during treatment and craving, which prevented the possibility of including them in statistical synthesis.. At present, there is no evidence supporting the clinical use of antipsychotic medications in the treatment of cocaine dependence, although results come from only 14 trials, with small sample sizes and moderate to low quality of evidence.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cocaine-Related Disorders; Haloperidol; Humans; Lamotrigine; Olanzapine; Patient Dropouts; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Reserpine; Risperidone; Triazines

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.. 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).. 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.. 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.. 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).. Antipsychotics had no advantages over placebo in regard to cocaine use and cocaine or psychostimulant abstinence or craving, while causing more intolerability-related discontinuations.

Topics: Amphetamine-Related Disorders; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Central Nervous System Stimulants; Cocaine; Cocaine-Related Disorders; Dopamine; Dopamine Uptake Inhibitors; Humans; Methamphetamine; Olanzapine; Outcome Assessment, Health Care; Piperazines; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Substance Withdrawal Syndrome; Synaptic Transmission; Treatment Outcome

Cocaine dependence is a public health problem characterized by recidivism and a host of medical and psychosocial complications. Cocaine dependence remains a disorder for which no pharmacological treatment of proven efficacy exists, although considerable advances in the neurobiology of this addiction could guide future medication development. To evaluate the efficacy and the acceptability of antipsychotic medications for cocaine dependence. We searched the following sources: MEDLINE (1966 to October 2006), EMBASE (1980 to October 2006), CINAHL (1982 to October 2006), Cochrane Drug and Alcohol Group Specialised Register (October 2006). We also searched the reference lists of trials, the main electronic sources of ongoing trials (National Research Register, meta-Register of Controlled Trials; Clinical Trials.gov) and conference proceedings likely to contain trials relevant to the review. All searches included also non-English language literature.. All randomised controlled trials and controlled clinical trials with focus on the use of any antipsychotic medication for cocaine dependence. Two authors independently evaluated the papers, extracted data, rated methodological quality. Seven small studies were included (293 participants): the antipsychotic drugs studied were risperidone, olanzapine and haloperidol. No significant differences were found for any of the efficacy measures comparing any antipsychotic with placebo. Risperidone was found to be superior to placebo in diminishing the number of dropouts, four studies, 178 participants, Relative Risk (RR) 0.77 (95% CI 0.77 to 0.98). Most of the included studies did not report useful results on important outcomes such as side effects, use of cocaine during treatment and craving. The results on olanzapine and haloperidol come from studies too small to give conclusive results.. Although caution is needed when assessing results from a limited number of small clinical trials there is no current evidence, at the present , supporting the clinical use of antipsychotic medications in the treatment of cocaine dependence. Furthermore, most of the included studies did not report useful results on important outcomes such as side effects, use of cocaine during the treatment and craving. Aiming to answer the urgent demand of clinicians, patients, families, and the community as a whole for an adequate treatment for cocaine dependence, larger randomised investigations should be designed investigating relevant outcomes and reporting data to allow comparison of results between studies. Moreover some efforts should be done also to investigate the efficacy of other type medications, like anticonvulsant, currently used in clinical practice.

Topics: Antipsychotic Agents; Benzodiazepines; Cocaine-Related Disorders; Haloperidol; Humans; Olanzapine; Randomized Controlled Trials as Topic; Risperidone

Although a growing body of research suggests that atypical neuroleptic medications are efficacious in the treatment of cocaine addiction among individuals with schizophrenia, more rigorously controlled trials are needed. To extend this research, we performed a 6-week double-blind study comparing olanzapine to haloperidol with the primary objective of reducing cue-elicited cocaine craving and the secondary aims of decreasing substance use, improving psychiatric symptoms, and determining an effect size for future studies.. Thirty-one subjects with cocaine dependence and schizophrenia were randomized to olanzapine or haloperidol, underwent a cue-exposure procedure, and completed psychiatric and substance abuse ratings.. Individuals in the olanzapine group who completed the study had a significant reduction on the energy subscale of the Voris Cocaine Craving Scale at study completion compared with individuals in the haloperidol group. The olanzapine-treated group also had lower, but not statistically significant, PANSS General Psychopathology Subscale scores and fewer positive urine toxicology screens compared with those in the haloperidol group.. This small, but rigorously controlled, pilot trial provides additional evidence for the use of atypical antipsychotics for the treatment of individuals with co-occurring schizophrenia and cocaine dependence. Reductions in craving were associated with medium to large effect sizes.

Topics: Adult; Antipsychotic Agents; Behavior, Addictive; Benzodiazepines; Cocaine-Related Disorders; Cues; Double-Blind Method; Haloperidol; Humans; Olanzapine; Pilot Projects; Psychiatric Status Rating Scales; Schizophrenia

To conduct a medication screening trial on the efficacy of olanzapine, valproate or coenzyme Q10/L-carnitine combination versus placebo for the treatment of cocaine dependence.. A four-arm, modified blinded, parallel group study in an out-patient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design.. The study was performed at the New York Medications Development Research Unit (MDRU).. All participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2-week screening period. Sixty-eight participants were enrolled with 39 completing the study.. After a 2-week screening period, 68 subjects were assigned randomly to receive either olanzapine (10 mg/day), valproate (1500 mg/day), coenzyme Q10 (200 mg/day) and L-carnitine (500 mg/day) combination or placebo for an 8-week treatment period. All subjects also received individual cognitive behavioral counseling during treatment.. Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self-report of drug use, and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs, and extrapyramidal side-effects tests.. Study retention was similar across all treatment groups, and all groups showed improvement across most measures of treatment efficacy over the duration of the study. None of the study medications, however, were superior to placebo on any of the primary or secondary outcome measures. Cocaine use, as measured by urine BE levels and self-report, was not significantly lower than placebo in any of the drug treatment groups. All study medications were equally well tolerated, and few medication side effects were observed.. This pilot study does not support the effectiveness of olanzapine, valproate or coenzyme Q10/L-carnitine combination for the treatment of cocaine dependence.

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Carnitine; Cocaine-Related Disorders; Coenzymes; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Selective Serotonin Reuptake Inhibitors; Ubiquinone; Valproic Acid

Comorbid cocaine abuse adversely affects clinical outcomes in schizophrenia. Using a prospective, randomized, parallel group design (N = 24), we tested the hypothesis that patients with schizophrenia treated with olanzapine have reduced cocaine craving and abuse compared with those treated with haloperidol. In addition, we examined whether this differential effect correlated with reductions in extrapyramidal symptoms, positive and negative symptoms, and/or depression. There were no significant differences overall in proportions of positive drug screens between treatment groups; no differences in positive, negative, or depressive symptoms; and few differences between treatment conditions in extrapyramidal symptoms. However, craving for cocaine was rated significantly lower by patients treated with haloperidol compared with patients treated with olanzapine. Important study limitations include a small sample size and high attrition rates. Larger controlled studies are necessary to determine optimal antipsychotic therapy for patients with schizophrenia and comorbid cocaine abuse.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Behavior, Addictive; Benzodiazepines; Cocaine-Related Disorders; Comorbidity; Depressive Disorder; Female; Haloperidol; Hospitals, Veterans; Humans; Male; Middle Aged; Olanzapine; Philadelphia; Research Design; Schizophrenia; Schizophrenic Psychology; Substance Abuse Detection

Multiple lines of evidence suggest both dopaminergic and serotonergic involvement in the reinforcing effects of cocaine. Medications such as olanzapine, which block dopamine D2 receptors, as well as serotonin receptors 5HT2A and 5HT2C may be able to reduce cocaine use in cocaine dependent patients by reducing the euphoric effects of cocaine and attenuating cocaine craving.. This was a 12-week, double blind, placebo controlled, pilot trial involving 30 cocaine dependent subjects. Subjects received either olanzapine (10 mg/day) or identical placebo. Outcome measures included treatment retention, qualitative urine benzoylecgonine tests, cocaine craving, clinical global impression scores, and results from the addiction severity index.. Treatment retention was slightly, but significantly, better in the placebo-treated subjects. Placebo-treated subjects were more likely to be abstinent from cocaine during the trial compared to olanzapine-treated subjects, based on urine benzoylecgonine results. Olanzapine was not superior to placebo in any outcome measure.. The results of this trial do not support the usefulness of olanzapine for the treatment of cocaine dependence. In fact, olanzapine may worsen cocaine treatment outcome.

Topics: Adolescent; Adult; Benzodiazepines; Cocaine; Cocaine-Related Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Pirenzepine; Retention, Psychology; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Alcoholism; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cocaine-Related Disorders; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Substance-Related Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Cocaine-Related Disorders; Double-Blind Method; Humans; Male; Olanzapine; Pilot Projects; Pirenzepine; Schizophrenia

Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model.. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine.. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine.. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

Topics: Animals; Benzodiazepines; Cocaine; Cocaine-Related Disorders; Disease Models, Animal; Drug Antagonism; Injections, Intraperitoneal; Longevity; Male; Mice; Mice, Inbred Strains; Olanzapine; Poisoning; Seizures; Selective Serotonin Reuptake Inhibitors; Vasoconstrictor Agents

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cocaine-Related Disorders; Female; Humans; Olanzapine

Topics: Acute Disease; Acute Kidney Injury; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cocaine-Related Disorders; Diabetic Ketoacidosis; Humans; Male; Olanzapine; Pancreatitis; Piperazines; Quinolones; Schizophrenia

The neuropharmacological profile of the atypical antipsychotic, olanzapine, is consistent with a potentially useful medication for cocaine abuse. The present study utilized an i.v. drug self-administration paradigm in nonhuman primates to obtain definitive evidence regarding the effectiveness of olanzapine to modulate the reinforcing effects of cocaine. The effects of olanzapine were compared directly to those of the neuroleptic, haloperidol. Rhesus monkeys (n=7) were trained to self-administer cocaine (0.03-0.3 mg/kg/injection) under a second-order, fixed-interval 600-s schedule with fixed ratio 20 components. Experimental sessions comprised five consecutive fixed intervals, each followed by a 1-min timeout. In drug-interaction experiments, a single dose of olanzapine (0.03-0.3 mg/kg) or haloperidol (0.01-0.03 mg/kg) was administered i.v. 15 min presession for at least three consecutive sessions. In drug-substitution experiments, different doses of olanzapine (0.01-0.1 mg/kg/injection) were substituted for cocaine until responding stabilized. Olanzapine caused dose-related decreases in cocaine self-administration at pretreatment doses that had no overt behavioral effects indicative of sedation. A dose of 0.1 mg/kg eliminated cocaine self-administration in all subjects. In contrast, doses of haloperidol that suppressed cocaine self-administration induced marked sedation and catalepsy. Olanzapine failed to maintain self-administration behavior above saline extinction levels over a range of unit doses. In vivo microdialysis experiments in a second group of awake rhesus monkeys (n=3) confirmed previous reports in rodents that olanzapine effectively increases extracellular dopamine in ventral striatum. The dose of olanzapine that markedly suppressed cocaine self-administration behavior increased dopamine to approximately 190% of control values. Lastly, pretreatment with fluoxetine had no systematic effect on olanzapine-induced increases in striatal dopamine. The results indicate that olanzapine can effectively suppress cocaine self-administration behavior in nonhuman primates at doses that enhance dopamine release but do not maintain drug self-administration.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Cocaine-Related Disorders; Data Interpretation, Statistical; Dopamine; Dose-Response Relationship, Drug; Female; Fluoxetine; Haloperidol; Macaca mulatta; Male; Microdialysis; Olanzapine; Selective Serotonin Reuptake Inhibitors; Self Administration

Topics: Antipsychotic Agents; Behavior, Addictive; Benzodiazepines; Cocaine-Related Disorders; Comorbidity; Diagnosis, Dual (Psychiatry); Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Secondary Prevention; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Behavior, Addictive; Benzodiazepines; Cocaine-Related Disorders; Crack Cocaine; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Pirenzepine; Secondary Prevention