Meta-analysis of the effects of adjuvant drugs in co-occurring bipolar and substance use disorder

Joaquim Radua; Lydia Fortea; José Manuel Goikolea; Iñaki Zorrilla; Miquel Bernardo; Manuel Arrojo; Ruth Cunill; Xavi Castells; Elisardo Becoña; Ana López-Durán; Marta Torrens; Judit Tirado-Muñoz; Francina Fonseca; Belén Arranz; Marina Garriga; Pilar A Sáiz; Gerardo Flórez; Luis San; Ana González-Pinto

doi:10.1016/j.rpsm.2023.01.005

Meta-analysis of the effects of adjuvant drugs in co-occurring bipolar and substance use disorder

Rev Psiquiatr Salud Ment. 2023 Feb 7:S1888-9891(23)00006-X. doi: 10.1016/j.rpsm.2023.01.005. Online ahead of print.

[Article in English, Spanish]

Authors

Joaquim Radua¹, Lydia Fortea², José Manuel Goikolea³, Iñaki Zorrilla⁴, Miquel Bernardo³, Manuel Arrojo⁵, Ruth Cunill⁶, Xavi Castells⁷, Elisardo Becoña⁸, Ana López-Durán⁸, Marta Torrens⁹, Judit Tirado-Muñoz¹⁰, Francina Fonseca⁹, Belén Arranz⁶, Marina Garriga³, Pilar A Sáiz¹¹, Gerardo Flórez¹², Luis San⁶, Ana González-Pinto⁴

Affiliations

¹ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, CIBERSAM, Spain; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
² Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, CIBERSAM, Spain. Electronic address: lfortea@recerca.clinic.cat.
³ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, CIBERSAM, Spain.
⁴ Instituto de Investigación Sanitaria BIOARABA, OSI Araba, Hospital Universitario, CIBERSAM, UPV/EHU, Vitoria, Spain.
⁵ Servicio de Psiquiatría, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago, Servicio Gallego de Salud (SERGAS) de Santiago de Compostela, Spain.
⁶ Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, CIBERSAM, Barcelona, Spain.
⁷ Grupo de Investigación TransLab, Departamento de Ciencias Médicas, Universitat de Girona, Spain.
⁸ Unidad de Tabaquismo y Trastornos Adictivos, Facultad de Psicología, Universidad de Santiago de Compostela, Spain.
⁹ Institut de Neuropsiquiatria Addiccions - Hospìtal del Mar, Universitat Autònoma de Barcelona, Universitat de Vic-Central de Catalunya, Red de Investigación en Atención Primaria de Adicciones-RIAPAD, Barcelona, Spain.
¹⁰ Departamento de Psicología, Facultad de Ciencias Biomédicas y de la Salud, Grupo de Investigación en Conducta, Emociones y Salud, Universidad Europea de Madrid, Madrid, Spain.
¹¹ Universidad de Oviedo, CIBERSAM, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto de Neurociencias del Principado de Asturias (INEUROPA), Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain.
¹² Unidad de Conductas Adictivas, Complejo Hospitalario de Ourense, CIBERSAM, Ourense, Spain.

PMID: 37689524
DOI: 10.1016/j.rpsm.2023.01.005

Abstract

Background: Individuals with bipolar disorder (BD) often have co-occurring substance use disorders (SUDs), which substantially impoverish the course of illness. Despite the importance of this dual diagnosis, the evidence of the efficacy and safety of adjuvant treatments is mostly unknown.

Objective: To perform a meta-analysis to evaluate the efficacy and safety of adjuvant drugs in patients with co-occurring BD and SUD.

Methods: We searched PubMed, Scopus, and Web of Knowledge until 30th April 2022 for randomized clinical trials (RCT) evaluating the efficacy and safety of adjuvant drugs compared to placebo in patients with a dual diagnosis of BD and SUD. We meta-analyzed the effect of adjuvant drugs on general outcomes (illness severity, mania, depression, anxiety, abstinence, substance craving, substance use, gamma-GT, adherence, and adverse events) and used the results to objectively assess the quality of the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. For completeness, we also report the specific effects of specific adjuvant drugs in patients with specific substance disorders.

Results: We included 15 RCT studies (9 alcohol, 3 cocaine, 2 nicotine, and 1 cannabis) comprising 628 patients allocated to treatment and 622 to placebo. There was low-quality evidence that adjuvant drugs may reduce illness severity (g=-0.25, 95% CI: -0.44, -0.06), and very-low quality evidence that they may decrease substance use (g=-0.23, 95% CI: -0.44, -0.02) and increase substance abstinence (g=0.21, 95% CI: 0.04, 0.38).

Discussion: There is low-quality evidence that adjuvant drugs may help reduce illness severity, probably via facilitating abstinence and lower substance use. However, the evidence is weak; thus, these results should be considered cautiously until better evidence exists.

Keywords: Abstinence; Adjuvant drugs; Adverse events; Alcohol; Bipolar disorder.

Publication types

Review