Serotonergic Gene Variation in Substance Use Pharmacotherapy: A Systematic Review

Abstract

Drug addiction is a serious disease with damaging effects on the brain and physical health. Despite the increase in the number of affected individuals, there are few effective pharmacological treatment options for substance use disorders. The study of the influence of an individual's genetic features on the treatment response may help to identify more efficacious treatment options. This systematic review focuses on the serotonergic system because of its relevant role in mood and impulse control disorders, and its contribution to the development and maintenance of drug use disorders. In particular, we examine the role of serotonergic genes in the response to pharmacotherapy for alcohol, cocaine and nicotine addiction. Current evidence suggests that genetic variability of the serotonergic biosynthesis enzyme tryptophan hydroxylase 2 (TPH2) and the serotonin transporter (SLC6A4) genes mediates the efficacy of several addiction treatments, such as ondansetron and disulfiram, and the antidepressants bupropion, nortriptyline and sertraline.

Pharmakotherapie der Alkoholentwöhnung: Update und neue Entwicklungen

“…Eine Übersichtsarbeit über den Einfluss serotonerger Genvariationen auf das Ansprechen pharmakotherapeutischer Methoden der Rückfallprophylaxe bei Abhängigkeitserkrankungen weist auf die Bedeutung von Genen für das Enzym Tryptophanhydroxylase 2 ( TPH2 ) und den Serotonintransporter ( SLC6A4 ) hin, welche die Wirkung von Ondansetron und Disulfiram modulieren [ 10 ].…”

Medications for substance use disorders (SUD): emerging approaches

“…A polymorphism in the dopamine-beta-hydroxylase gene has also been associated with clinical response to disulfiram, in persons with cocaine use disorders [41]. Polymorphisms in the serotonin transporter gene have also been associated with differential clinical response to the 5HT3 antagonist ondansetron, in the treatment of alcohol use disorders [42,43]. Given the ongoing dissemination of genotyping technology outside research settings, pharmacogenetic approaches may eventually become established as clinical tools for personalized treatment of specific addictive diseases.…”

“…Also, ondansetron, a 5HT3-antagonist which is approved as an antiemetic, may be studied for its effects on smoking. Ondansetron has also been studied in alcohol use disorders, and potential pharmacogenetic associations to its effectiveness have been reported [42,129]. …”

Genes and Alcohol Consumption

“…The serotonergic system has important roles in mood and impulse control and is implicated in the development and maintenance of alcohol and other drug abuse disorders (Bauer, Graham, Soares, & Nielsen, 2015). Ethanol intake and preference increased in a knockin mouse line (Tph2KI) expressing a hypofunctional variant of the rate-limiting serotonin (5-HT) synthesis enzyme, tryptophan hydroxylase 2 (Sachs, Salahi, & Caron, 2014) (Table 4).…”