Abstract: We found five double-blind placebo-controlled trials that met our inclusion criteria. These trials assessed effectiveness and safety of drugs in a total of 50 people with intellectual disability demonstrating SIB. Four trials compared the effects of naltrexone versus placebo and one trial compared clomipramine versus placebo. One of the naltrexone versus placebo trials reported that naltrexone had clinically significant effects (≥ 33% reduction) on the daily rates of three of the four participants' most severe form of SIB and modest to substantial reductions in SIB for all participants; however, this study did not report on statistical significance. Another trial reported that naltrexone attenuated SIB in all four participants, with 25 mg and 50 mg doses producing a statistically significant decrease in SIB (P value < 0.05). Another trial (eight people) indicated that naltrexone administration was associated with significantly fewer days of high frequency self injury and significantly more days with low frequency self injury. Naltrexone had different effects depending on the form and location of self injury. Another trial with only 26 participants found that neither single-dose (100 mg) nor long-term (50 and 150 mg) naltrexone treatment had any therapeutic effect on SIB. Comparison of clomipramine versus placebo found no statistically significant benefit for any outcome measure, which included SIB rate and intensity, stereotypy and adverse events. However, it showed clinically significant improvement in the rate and intensity of SIB and stereotypy. There were very few noteworthy adverse events to report in any of the four trials in which these were reported. All trials were at high risk of bias, apart from one trial (Lewis 1996), which was probably at low risk of bias. The short period of follow-up was a significant drawback in the design of all five trials, as it did not allow long-term assessment of behaviour over time. We were unable to examine the efficacy of antidepressants other than clomipramine, antipsychotics, mood stabilisers or beta-blockers as we did not identify any relevant placebo-controlled trials. There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating SIB. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo.

Plain-language summary: In this review we aimed to assess if medications used in the management of SIB in adults with intellectual disability are safe and help reduce the behaviours. We looked for studies that compared antidepressants, antipsychotics or mood stabilisers with no active medication (placebo). We found only five studies: four examined the effects of naltrexone, an opioid antagonist (which works through modulating pain perception) and one examined the antidepressant clomipramine. There were only a total of 50 participants included in these studies, which was not enough to determine whether or not the intervention resulted in any improvement. Three of the naltrexone studies and the one clomipramine study indicated the drugs resulted in clinical improvement in SIB, but more evidence is needed. The data is too limited for us to be able to draw any firm conclusions about the benefits or safety of any medications for SIB in this population. We need more studies where many more participants are involved to know whether medications help in reducing SIB and if they are safe.