Bipolar Disorder and Comorbid Use of Illicit Substances

Medicina (Kaunas). 2021 Nov 17;57(11):1256. doi: 10.3390/medicina57111256.


Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.

Keywords: bipolar disorders; cannabis; cocaine; illicit drugs; mania; mood disorders; substance use disorders.

Publication types

  • Review

MeSH terms

  • Alcoholism*
  • Bipolar Disorder* / drug therapy
  • Bipolar Disorder* / epidemiology
  • Comorbidity
  • Humans
  • Psychotropic Drugs / therapeutic use
  • Substance-Related Disorders* / complications
  • Substance-Related Disorders* / epidemiology


  • Psychotropic Drugs