Psychiatric Pharmacy Essentials: Major Clinical Trials in Substance Use Disorders

Numerous pharmacologic regimens have been trialed for management of substance use disorders, often with concomitant behavioral interventions.

Essential Questions and References

What is the evidence for combination of pharmacotherapy and behavioral interventions for managing symptoms of alcohol use disorder?

COMBINE

• Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence. The COMBINE study: a randomized controlled trial. JAMA. 2006;295(17):2003-17. [PubMed]

What treatment options are available for treatment of opioid use disorder?

SUMMIT

• Pinto H, Maskrey V, Swift L, et al. The SUMMIT trial: a field comparison of buprenorphine versus methadone maintenance treatment. J Subst Abuse Treat. 2010;39(4)340-52. [PubMed]

X:BOT

• Lee JD, Nunes Jr EV, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309-18. [PubMed]
• Opheim A, Gaulen Z, Solli KK, et al. Risk of Relapse Among Opioid-Dependent Patients Treated With Extended-Release Naltrexone or Buprenorphine-Naloxone: A Randomized Clinical Trial. Am J Addict. 2021;30(5):453-460. doi:10.1111/ajad.13151

What treatment options are there for pregnant people with opioid use disorder?

• Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010;363(24):2320-31. [PubMed]

What is the evidence for use of varenicline in patients with psychiatric disorders?

EAGLES

• Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016;10037(387):2507-20. [PubMed]

How do e-cigarettes compare to traditional nicotine replacement therapy for smoking cessation?

• Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019;380(7):629-37. [PubMed]
• CDC. Electronic Cigarettes. [Weblink]

How does combination treatment for tobacco use disorder and alcohol use disorder impact smoking and alcohol cessation?

• Ray LA, Green R, Enders C, et al. Efficacy of combining varenicline and naltrexone for smoking cessation and drinking reduction: a randomized clinical trial. Am J Psychiatry. 2021;178(9):818-28. [PubMed]
• King A, Vena A, de Wit H, et al. Effect of combination treatment with varenicline and nicotine patch on smoking cessation among smokers who drink heavily: a randomized clinical trial. JAMA Netw Open. 2022;5(3):e220951. [PubMed]

What evidence is there for psychedelics for alcohol use disorder?

• Bogenschutz MP, Forcehimes AA, pommy JA et al. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015; 29(3): 289-99. [PubMed]
• Bogenschutz BP, Ross S, Bhatt S et al. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs. Placebo in the Treatment of Adult Patients With Alcohol Use Disorder. JAMA Psychiatry. 2022; 79(10):953-62. [PubMed]