An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder.

The study planned 16 participants but included only 5 for the primary outcome, so it was underpowered. Seven participants contributed tolerability data and six contributed sleep data. Each outcome had very little data. The treatment period was only one week, and the authors noted that short-term improvements may be due to factors other than the active drug. All participants were already taking medications commonly used for aggression, most often antipsychotics and/or mood stabilizers, so the separate effect of nicotine cannot be isolated. The main outcome was caregiver-rated and subjective, and the authors noted a placebo effect in most measures. One enrolled subject was excluded after completing trial procedures for being older than the approved range. One participant's caregiver did not provide week 1 ratings or sleep ratings. One participant's behavior ratings were excluded because they were not confined to the specified time frame. More participants contributed primary outcome data in the group receiving nicotine first and placebo second, so order effects cannot be ruled out. Most participants could not complete self-report anxiety or anger scales, so participant-reported effects were not available. The degree to which the 7 mg daily dose engages the putative mechanistic target is unknown.

The authors declared no conflicts of interest.

Do not read the 4 of 6 caregiver-reported improvements or the two open-label continuations as proof that nicotine treats aggression in autism. The primary irritability outcome was not statistically significant, the trial was underpowered, and all participants were already taking medications for aggression.