Association between venlafaxine use and the risk of withdrawal from nonopioid substances: a nationwide,...

Appropriate treatments for nonopioid substance use are currently unavailable. Venlafaxine may reduce withdrawal from nonopioid substances, but the effects have not been evaluated. We aimed to investigate the association between venlafaxine use and the risk of withdrawal from nonopioid substances.

We linked Taiwan's National Health Insurance Research Database and the Taiwan Illicit Drug Issue Database from January 2012 to December 2019. We used a case-case-time-control study involving a case-crossover analysis and a control-crossover analysis consisting of future cases. The outcomes were withdrawal from substances and all-cause mortality. For each individual, venlafaxine use during the hazard period (day - 8 to - 67 before the outcome) was compared with that during the 60-day reference period (between days - 248 and - 307). Conditional logistic regression was used to determine odds ratios with 95% confidence intervals to evaluate the associations between outcome events and the use of venlafaxine.

The participants' average age on the index date was 39.5 years (standard deviation 8.7), with 84.1% men and 88.3% having low income. Venlafaxine was significantly associated with a lower risk of withdrawal from substances (odds ratio 0.35, 95% confidence interval 0.13 to 0.96). However, we found no association between the recent use of venlafaxine and all-cause mortality (1.08, 0.55 to 2.14). The point estimates were similar in a series of sensitivity analyses, though not all analyses statistical significance.

This study provides strong ground for clinicians to consider the use of venlafaxine to reduce patient experiencing withdrawal symptoms from substances.