***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Comorbid cocaine abuse adversely affects clinical outcomes in schizophrenia . Using a prospect i ve , r and omized , 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 A partial blockade of the multiple actions of cocaine is one strategy by which cocaine dependence may be treated . Risperidone , a 5-hydroxytryptamine and dopamine D2 antagonist , is an atypical antipsychotic and was a c and i date medication for the treatment of cocaine dependence . One hundred ninety-three cocaine-dependent subjects were enrolled in a 12-week , r and omized , double-blind , placebo-controlled trial . Subjects initially received either placebo or 4 or 8 mg of risperidone , with a subsequent change to active doses of 2 mg and 4 mg . Subjects attended the clinic twice each week , provided urine sample s , obtained medication , and underwent one behavioral therapy session per week . The study was terminated at the interim analysis . Retention was worse for the 4- and 8-mg active medication groups . Side effects were primarily associated with the 8-mg dose , although neither 2 mg nor 4 mg was well accepted by subjects . There was no reduction in cocaine use associated with risperidone . The results suggest that although antagonists might be a useful treatment approach , such as in the treatment of opiate dependence , risperidone is unlikely to find broad acceptance with the treatment-seeking population OBJECTIVE There is no approved pharmaco-therapy for cocaine dependence .  Risperidone is an atypical antipsychotic drug with combined dopamine-2/serotonin-2 ( D(2)/5-HT(2 ) ) antagonist activity that has been effective in reducing cocaine use in some animal studies . We tested the efficacy of a long-acting , injectable preparation of risperidone on cocaine use in active cocaine users . METHOD Thirty-one cocaine-dependent men who met DSM-IV diagnostic criteria for current cocaine dependence entered a 12-week , r and omized , double-blind , placebo-controlled trial of intramuscular risperidone , 25 mg every other week . The primary outcome measure was cocaine use as measured by urinary concentration of cocaine metabolites . Secondary outcomes were self-report of cocaine use and craving , depressive symptoms as measured by the Hamilton Rating Scale for Depression ( HAM-D ) , and adverse events .  Participants were recruited during a 12-month period from October 2005 to September 2006 . RESULTS Both groups reduced their cocaine use during the study . There were no between-group differences in the primary measure of cocaine use ( urinary metabolites [ F = 0.7 , p = .41 ] ) or on craving measures . Those assigned to risperi-done reported significantly worsened depressive symptoms ( mean + /- SD HAM-D change scores : + 7.4 + /- 8.8 vs. -2.3 + /- 5.8 , respectively , F = 7.5 , p = .018 ) and gained significantly more weight ( mean weight change : + 6.3 + /- 9.4 lb vs. -4.0 + /- 8.9 lb , respectively , F = 4.65 , p = .044 ) than those assigned to placebo . CONCLUSION Treatment with long-acting injectable risperidone in active cocaine users was not associated with reduction in cocaine use or craving and was associated with worsening of depressive symptoms and weight gain . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00385801 Eighty cocaine-dependent individuals enrolled in outpatient treatment took part in a r and omized , double-blind , placebo-controlled trial of ritanserin , a 5-HT(2 ) antagonist , as an adjunct therapy . Participants attended an outpatient day hospital therapy program each day and received tablets containing placebo or 10 mg ritanserin for a 4-week period . Primary outcome measures included retention in treatment , urine drug tests , and self-reports of craving . Secondary outcome measures were depression scores on the Beck and Hamilton inventories , negative mood as measured by the Profile of Mood States , and life functioning as measured by the Addiction Severity Index . Although participants showed improvement over the 4 weeks , there were no group differences on any of the measures . These results fail to support the use of ritanserin as a complement to outpatient psychosocial therapy for cocaine dependence Concurrent abuse of cocaine and heroin is a common problem . Methadone is effective for opioid dependence . The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious . Two parallel studies were conducted . One examined sustained release d-amphetamine and the other risperidone for cocaine dependence , each in combination with methadone . In total , 240 subjects ( 120/ study ) were recruited , who were both cocaine and heroin dependent and not currently receiving medication . All provided consent . Both studies were carried out for 26 weeks , r and omized , double-blind and placebo controlled . Study I compared sustained release d-amphetamine ( escalating 15–30 or 30–60 mg ) and placebo . Study II examined risperidone ( 2 or 4 mg ) and placebo . All subjects underwent methadone induction and were stabilized at 1.1 mg/kg . Subjects attended clinic twice/week , provided urine sample s , obtained medication take-home doses for intervening days , and completed self-report measures . Each had one behavioral therapy session/week . In Study I , reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo . Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group . In Study II , methadone  reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups . There were no adverse medication interactions in either study . The results provide support for the agonist-like ( d-amphetamine ) model in cocaine dependence treatment but not for antagonist-like ( risperidone ) treatment . They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals It was reported that ritanserin , a 5HT2A/2C antagonist , improves negative symptoms when added to neuroleptics in in patients with predominantly negative symptoms . Nevertheless , the results of published studies are contradictory so far . This study was design ed to investigate the effect of ritanserin added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double blind and r and omized clinical trial . Eligible participants in this study were 40 patients with chronic schizophrenia . All patients were in patients and were in the active phase of the illness , and met DSM-IV-TR criteria for schizophrenia . Patients were allocated in a r and om fashion , 20 to risperidone 6 mg/day plus ritanserin 12 mg/day ( 6 mg bid ) and 20 to risperidone 6 mg/day plus placebo . The principal measure of the outcome was Positive and Negative Syndrome Scale ( PANSS ) . Although both protocol s significantly decreased the score of the positive , negative and general psychopathological symptoms over the trial period , the combination of risperidone and ritanserin showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores . The present study indicates ritanserin as a potential adjunctive treatment strategy for the negative symptoms of schizophrenia . Nevertheless , results of larger controlled trials are needed , before recommendation for a broad clinical application can be made Objective : 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 . Methods : Thirty-one subjects with cocaine dependence and schizophrenia were r and omized to olanzapine or haloperidol , underwent a cue-exposure procedure , and completed psychiatric and substance abuse ratings . Results : 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 . Conclusion : 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 AIMS To conduct a preliminary evaluation of the safety and efficacy of reserpine , gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence . DESIGN A 10-week out-patient study using the Cocaine Rapid Efficacy and Safety Trial ( CREST ) study design . SETTING The study was conducted at the Cincinnati Medication Development Research Unit ( MDRU ) . PARTICIPANTS Participants met Diagnostic and Statistical Manual version IV ( DSM-IV ) criteria for cocaine dependence . Sixty participants were enrolled , with 50 participants completing the final study measures . INTERVENTION The targeted daily doses of medication were reserpine 0.5 mg , gabapentin 1800 mg and lamotrigine 150 mg . All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis . MEASUREMENTS Primary outcome measures of efficacy included urine benzoylecgonine ( BE ) level , Cocaine Clinical Global Impression scale -- observer and self-report of cocaine use . Safety measures included adverse events , electrocardiograms ( ECGs ) , vital signs and laboratory tests . FINDINGS Subjective measures of cocaine dependence indicated significant improvement for all study groups . Urine BE results indicated a significant improvement for the reserpine group ( P < 0.05 ) and non-significant changes for the other study groups . No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified . There were three serious adverse events reported , none of which were related to study procedures . The medications appeared to be tolerated well . CONCLUSIONS The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment BACKGROUND Studies of cocaine-dependent subjects have shown that re-exposure to environmental cues previously associated with cocaine use produces a strong conditioned response characterised by autonomic hyperarousal and increases in subjective measures of cocaine craving . METHODS To evaluate the role of dopamine release by such cues , 20 cocaine-dependent in patients were r and omised in a single-dose , crossover , placebo-controlled design , to haloperidol ( 4 mg by mouth ) and placebo .  Plasma homovanillic acid ( HVA , a dopamine metabolite ) , adrenocorticotropic hormone ( ACTH ) , and cortisol were assayed before and after cue exposure . Craving and anxiety were measured before and after cues with visual analogue scales for desire to use cocaine now and for mood changes . FINDINGS Cocaine cues significantly increased anxiety , ACTH , cortisol , and HVA . Increases in anxiety and craving result ing from cue exposure were significantly antagonised by pretreatment with haloperidol . INTERPRETATION It has long been hypothesised that increases in extracellular concentrations of dopamine mediate the acute reinforcing effects of cocaine . Our data suggest that dopamine release may also mediate some of the conditioned responses to cocaine cues Sixty-five cocaine-dependent subjects were enrolled into a 10-week r and omized , double-blind study to determine the safety and efficacy of the serotonin-2 receptor antagonist , ritanserin ( 10 mg/day ) , in reducing cocaine consumption and craving . All subjects also participated in a structured intensive outpatient psychosocial program . Seventy-three percent of the participants completed the treatment program and follow-up . Subjects experienced a significant reduction in craving : 66.4 % and 32.5 % for the placebo and ritanserin groups , respectively . These reductions in craving were not paralleled by substantial decreases in cocaine use . Self-reported cocaine use was less frequent in 
    Output:
    
To date there is insufficient evidence to justify the use of antipsychotic drugs for cocaine dependence