Combined Pharmacotherapy and Cognitive Behavioral Therapy for Adults With Alcohol or Substance Use Disorders: A Systematic Review and Meta-analysis.

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.