Abstract: Eight studies met the inclusion criteria involving 394 participants with AsPD. Data were available from four studies involving 274 participants with AsPD. No study set out to recruit participants solely on the basis of having AsPD, and in only one study was the sample entirely of AsPD participants. Eight different drugs were examined in eight studies. Study quality was relatively poor. Inadequate reporting meant the data available were generally insufficient to allow any independent statistical analysis. The findings are limited to descriptive summaries based on analyses carried out and reported by the trial investigators. All the available data were derived from unreplicated single reports. Only three drugs (nortriptyline, bromocriptine, phenytoin) were effective compared to placebo in terms of improvement in at least one outcome. Nortriptyline was reported in one study as superior for men with alcohol dependency on mean number of drinking days and on alcohol dependence, but not for severity of alcohol misuse or on the patient's or clinician's rating of drinking. In the same study, both nortriptyline and bromocriptine were reported as superior to placebo on anxiety on one scale but not on another. In one study, phenytoin was reported as superior to placebo on the frequency and intensity of aggressive acts in male prisoners with impulsive (but not premeditated) aggression. In the remaining two studies, both amantadine and desipramine were not superior to placebo for adults with opioid and cocaine dependence, and desipramine was not superior to placebo for men with cocaine dependence. The body of evidence summarised in this review is insufficient to allow any conclusion to be drawn about the use of pharmacological interventions in the treatment of antisocial personality disorder.

Plain-language summary: We considered eight studies, but none of them recruited participants solely on the basis of having antisocial personality disorder. While most studies included in this review looked at treatments to reduce drug or alcohol misuse in people with antisocial personality disorder, no study focused on treating the disorder itself. Studies varied in terms of choice of outcomes. While some studies reported outcome measures that were originally defined in the review protocol as being of particular importance in this disorder (for example, aggression, social functioning and adverse effects resulting from the use of medication), no study reported on reconviction. In summary, we were unable to draw any firm conclusions from the existing literature.  Nonetheless, there was some evidence that nortriptyline (a drug used to treat depression) could help people with antisocial personality disorder to reduce their misuse of alcohol. There was also some evidence that phenytoin (a drug used to treat epilepsy) could help to reduce the intensity of impulsive aggressive acts in people with antisocial personality disorder. Further research is required to clarify which medications are effective for treating the core features of this disorder. This research is best carried out using carefully designed clinical trials. Such trials should recruit sufficient numbers of people on the basis of having the disorder and use outcome measures that are of particular relevance to this disorder. They should also focus on recently marketed drugs where these have largely replaced older medications (for example, nortriptyline and phenytoin) which are no longer widely used.