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Pharmacotherapy for Cocaine Use Disorder-a Systematic Review and Meta-analysis.

ABSTRACT: BACKGROUND:Currently, there are no accepted FDA-approved pharmacotherapies for cocaine use disorder, though numerous medications have been tested in clinical trials. We conducted a systematic review and meta-analysis to better understand the effectiveness of pharmacotherapy for cocaine use disorder. METHODS:We searched multiple data sources (MEDLINE, PsycINFO, and Cochrane Library) through November 2017 for systematic reviews and randomized controlled trials (RCTs) of pharmacological interventions in adults with cocaine use disorder. When possible, we combined the findings of trials with comparable interventions and outcome measures in random-effects meta-analyses. We assessed the risk of bias of individual trials and the strength of evidence for each outcome using standardized criteria. Outcomes included continuous abstinence (3+ consecutive weeks); cocaine use; harms; and study retention. For relapse prevention studies (participants abstinent at baseline), we examined lapse (first cocaine positive or missing UDS) and relapse (two consecutive cocaine positive or missed UDS'). RESULTS:Sixty-six different drugs or drug combinations were studied in seven systematic reviews and 48 RCTs that met inclusion criteria. Antidepressants were the most widely studied drug class (38 RCTs) but appear to have no effect on cocaine use or treatment retention. Increased abstinence was found with bupropion (2 RCTs: RR 1.63, 95% CI 1.02 to 2.59), topiramate (2 RCTs: RR 2.56, 95% CI 1.39 to 4.73), and psychostimulants (14 RCTs: RR 1.36, 95% CI 1.05 to 1.77), though the strength of evidence for these findings was low. We found moderate strength of evidence that antipsychotics improved treatment retention (8 RCTs: RR 1.33, 95% CI 1.03 to 1.75). DISCUSSION:Most of the pharmacotherapies studied were not effective for treating cocaine use disorder. Bupropion, psychostimulants, and topiramate may improve abstinence, and antipsychotics may improve retention. Contingency management and behavioral interventions along with pharmacotherapy should continue to be explored. SR REGISTRATION:Prospero CRD42018085667.

SUBMITTER: Chan B

PROVIDER: S-EPMC6854210 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Pharmacotherapy for Cocaine Use Disorder-a Systematic Review and Meta-analysis.

Chan Brian B Kondo Karli K Freeman Michele M Ayers Chelsea C Montgomery Jessica J Kansagara Devan D

Journal of general internal medicine 20190610 12

<h4>Background</h4>Currently, there are no accepted FDA-approved pharmacotherapies for cocaine use disorder, though numerous medications have been tested in clinical trials. We conducted a systematic review and meta-analysis to better understand the effectiveness of pharmacotherapy for cocaine use disorder.<h4>Methods</h4>We searched multiple data sources (MEDLINE, PsycINFO, and Cochrane Library) through November 2017 for systematic reviews and randomized controlled trials (RCTs) of pharmacologi ...[more]

PMID: 31183685

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Project description:ImportanceIn the US and the United Kingdom, cocaine use is the second leading cause of illicit drug overdose death. Psychosocial treatments for cocaine use disorder are limited, and no pharmacotherapy is approved for use in the US or Europe.ObjectiveTo compare treatments for active cocaine use among adults.Data sourcesPubMed and the Cochrane Database of Systematic Reviews were searched for clinical trials published between December 31, 1995, and December 31, 2017.Study selectionThis meta-analysis was registered on Covidence.org (study 8731) on December 31, 2015. Clinical trials were included if they (1) had the term cocaine in the article title; (2) were published between December 31, 1995, and December 31, 2017; (3) were written in English; (4) enrolled outpatients 18 years or older with active cocaine use at baseline; and (5) reported treatment group size, treatment duration, retention rates, and urinalysis results for the presence of cocaine metabolites. A study was excluded if (1) more than 25% of participants were not active cocaine users or more than 80% of participants had negative test results for the presence of cocaine metabolites at baseline and (2) it reported only pooled urinalysis results indicating the presence of multiple substances and did not report the specific proportion of positive test results for cocaine metabolites. Multiple reviewers reached criteria consensus. Of 831 records screened, 157 studies (18.9%) met selection criteria and were included in the analysis.Data extraction and synthesisThis study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Search results were imported from PubMed XML into Covidence.org then Microsoft Excel. Data extraction was completed in 2 iterations to ensure fidelity. Analyses included a multilevel random-effects model, a multilevel mixed-effects meta-regression model, and sensitivity analyses. Treatments were clustered into 11 categories (psychotherapy, contingency management programs, placebo, opioids, psychostimulants, anticonvulsants, dopamine agonists, antidepressants, antipsychotics, miscellaneous medications, and other therapies). Missing data were imputed using multiple imputation by chained equations. The significance threshold for all analyses was P = .05. Data were analyzed using the metafor and mice packages in R software, version 3.3.2 (R Foundation for Statistical Computing). Data were analyzed from January 1, 2018, to February 28, 2021.Main outcomes and measuresThe primary outcome was the intention-to-treat logarithm of the odds ratio (OR) of having a negative urinalysis result for the presence of cocaine metabolites at the end of each treatment period compared with baseline. The hypothesis, which was formulated after data collection, was that no treatment category would have a significant association with objective reductions in cocaine use.ResultsA total of 157 studies comprising 402 treatment groups and 15 842 participants were included. Excluding other therapies, the largest treatment groups across all studies were psychotherapy (mean [SD] number of participants, 40.04 [36.88]) and contingency management programs (mean [SD] number of participants, 37.51 [25.51]). Only contingency management programs were significantly associated with an increased likelihood of having a negative test result for the presence of cocaine (OR, 2.13; 95% CI, 1.62-2.80), and this association remained significant in all sensitivity analyses.Conclusions and relevanceIn this meta-analysis, contingency management programs were associated with reductions in cocaine use among adults. Research efforts and policies that align with this treatment modality may benefit those who actively use cocaine and attenuate societal burdens.

Project description:BACKGROUND:This paper is a systematic review and meta-analysis of the efficacy of available medications for the treatment of restricted/repetitive behavior (RRBs) in Autism Spectrum Disorder (ASD). METHOD:We searched MEDLINE, Embase, PsycINFO, The Cochrane Library (Cochrane Database of Systematic Reviews (CDRS), the Cochrane Central Register of Controlled Trials (CENTRAL), database of Abstracts of Reviews of Effects (DARE)), Scopus, Epistimonikos, Clinicaltrials.gov, and included all randomized controlled trials published after 1993 that were directed at RRBs in patients with ASD of all ages. We extracted the relevant data from the published studies with a predefined data extraction form and assessed the risk of bias. The primary outcomes were change in restricted/repetitive behavior. We performed a meta-analysis using the random effect model and included studies with given mean and standard deviation. This study is registered with PROSPERO number CRD42018092660). RESULTS:We identified 14 randomized controlled trials that met initial inclusion criteria. After closer inspection, nine trials - involving 552 patients in total - were included in the final analysis. The meta-analysis found no significant difference between medications (including fluvoxamine, risperidone, fluoxetine, citalopram, oxytocin, N-Acetylcysteine, buspirone) and placebo in the treatment of RRBs in ASD (P?=?0.20). Similarly, the sub-group meta-analysis also showed no significant difference between Selective Serotonin Reuptake Inhibitor (SSRIs) and placebo in the treatment of RRBs in ASD (P?=?0.68). There was no evidence of publication bias. CONCLUSION:This meta-analysis finds little support for the routine use of medications to treat restricted/repetitive behaviors in Autism Spectrum Disorder. Further research of large, balanced trials with precise assessment tools and long-term follow-up are needed. TRIAL REGISTRATION:The study protocol is registered in PROSPERO (Reference number: CRD42018092660).

Project description:BackgroundPrevious meta-analyses of treatments for pulmonary arterial hypertension (PAH) have not shown mortality benefit from any individual class of medication.MethodsMEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through November 2009 for randomized trials that evaluated any pharmacotherapy in the treatment of PAH. Reference lists from included articles and recent review articles were also searched. Analysis included randomized placebo controlled trials of at least eight weeks duration and studies comparing intravenous medication to an unblinded control group.Results1541 unique studies were identified and twenty-four articles with 3758 patients were included in the meta-analysis. Studies were reviewed and data extracted regarding study characteristics and outcomes. Data was pooled for three classes of medication: prostanoids, endothelin-receptor antagonists (ERAs), and phosphodiesterase type 5 (PDE5) inhibitors. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for mortality, 6-minute walk distance, dyspnea scores, hemodynamic parameters, and adverse effects. Mortality in the control arms was a combined 4.2% over the mean study length of 14.9 weeks. There was significant mortality benefit with prostanoid treatment (RR 0.49, CI 0.29 to 0.82), particularly comparing intravenous agents to control (RR 0.30, CI 0.14 to 0.63). Mortality benefit was not observed for ERAs (RR 0.58, CI 0.21 to 1.60) or PDE5 inhibitors (RR 0.30, CI 0.08 to 1.08). All three classes of medication improved other clinical and hemodynamic endpoints. Adverse effects that were increased in treatment arms include jaw pain, diarrhea, peripheral edema, headache, and nausea in prostanoids; and visual disturbance, dyspepsia, flushing, headache, and limb pain in PDE5 inhibitors. No adverse events were significantly associated with ERA treatment.ConclusionsTreatment of PAH with prostanoids reduces mortality and improves multiple other clinical and hemodynamic outcomes. ERAs and PDE5 inhibitors improve clinical and hemodynamic outcomes, but have no proven effect on mortality. The long-term effects of all PAH treatment requires further study.

Project description:Importance:Substance use disorders (SUDs) represent a pressing public health concern. Combined behavioral and pharmacological interventions are considered best practices for addiction. Cognitive behavioral therapy (CBT) is a first-line intervention, yet the superiority of CBT compared with other behavioral treatments when combined with pharmacotherapy remains unclear. An understanding of the effects of combined CBT and pharmacotherapy will inform best-practice guidelines for treatment of SUD. Objective:To conduct a meta-analysis of the published literature on combined CBT and pharmacotherapy for adult alcohol use disorder (AUD) or other SUDs. Data Sources:PubMed, Cochrane Register, MEDLINE, PsychINFO, and Embase databases from January 1, 1990, through July 31, 2019, were searched. Keywords were specified in 3 categories: treatment type, outcome type, and study design. Collected data were analyzed through September 30, 2019. Study Selection:Two independent raters reviewed abstracts and full-text articles. English language articles describing randomized clinical trials examining CBT in combination with pharmacotherapy for AUD and SUD were included. Data Extraction and Synthesis:Inverse-variance weighted, random-effects estimates of effect size were pooled into 3 clinically informative subgroups: (1) CBT plus pharmacotherapy compared with usual care plus pharmacotherapy, (2) CBT plus pharmacotherapy compared with another specific therapy plus pharmacotherapy, and (3) CBT added to usual care and pharmacotherapy compared with usual care and pharmacotherapy alone. Sensitivity analyses included assessment of study quality, pooled effect size heterogeneity, publication bias, and primary substance moderator effects. Main Outcomes and Measures:Substance use frequency and quantity outcomes after treatment and during follow-up were examined. Results:The sample included 62 effect sizes from 30 unique randomized clinical trials that examined CBT in combination with some form of pharmacotherapy for AUD and SUD. The primary substances targeted in the clinical trial sample were alcohol (15 [50%]), followed by cocaine (7 [23%]) and opioids (6 [20%]). The mean (SD) age of the patient sample was 39 (6) years, with a mean (SD) of 28% (12%) female participants per study. The following pharmacotherapies were used: naltrexone hydrochloride and/or acamprosate calcium (26 of 62 effect sizes [42%]), methadone hydrochloride or combined buprenorphine hydrochloride and naltrexone (11 of 62 [18%]), disulfiram (5 of 62 [8%]), and another pharmacotherapy or mixture of pharmacotherapies (20 of 62 [32%]). Random-effects pooled estimates showed a benefit associated with combined CBT and pharmacotherapy over usual care (g range,?0.18-0.28; k?=?9). However, CBT did not perform better than another specific therapy, and evidence for the addition of CBT as an add-on to combined usual care and pharmacotherapy was mixed. Moderator analysis showed variability in effect direction and magnitude by primary drug target. Conclusions and Relevance:The present study supports the efficacy of combined CBT and pharmacotherapy compared with usual care and pharmacotherapy. Cognitive behavioral therapy did not perform better than another evidence-based modality (eg, motivational enhancement therapy, contingency management) in this context or as an add-on to combined usual care and pharmacotherapy. These findings suggest that best practices in addiction treatment should include pharmacotherapy plus CBT or another evidence-based therapy, rather than usual clinical management or nonspecific counseling services.

Dataset Information

Pharmacotherapy for Cocaine Use Disorder-a Systematic Review and Meta-analysis.

Publications

Pharmacotherapy for Cocaine Use Disorder-a Systematic Review and Meta-analysis.

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