REVIEW OF: Srisurapanont M et al, Drug Alcohol Depend 2021;219:108467

STUDY TYPE: Systematic review and network meta-analysis

Methamphetamine psychosis (MAP) is difficult to treat, and there are only so many antipsychotics in our repertoire. Randomized clinical trials (RCTs) to manage MAP are few and far between, and the literature thus far has indicated that no antipsychotic is superior to any other. What is a clinician to do?

In this study, the authors conducted a network meta-analysis of six RCTs with a total of 395 participants. Effectively, they created a head-to-head comparison of six antipsychotics for MAP [risperidone (four trials, n = 129); haloperidol (three trials, n = 93); aripiprazole (two trials, n = 48); paliperidone extended release (ER), quetiapine, and olanzapine (one trial each for a total n = 125)] and examined each medication for their ability to reduce psychotic symptoms.

The evidence in each trial was judged to be of low or very low quality, and none of the trials individually found significant differences between medications. However, when data from all the trials were pooled, the authors were able to establish somewhat of a hierarchy. Comparisons between medications were reported as standardized mean difference, which is a way of standardizing outcomes across studies that measure similar outcomes in various ways. Of all the possible head-to-head medication comparisons, a few significant differences were found. Quetiapine (300 mg/day) and olanzapine (20 mg/day) were the major winners and were superior to risperidone (4–8 mg/day) and aripiprazole (15 mg/day) for psychotic symptoms. Aripiprazole was the big loser—it was inferior to haloperidol (6–20 mg/day) and paliperidone ER (9 mg/day), as well as quetiapine and olanzapine.

The authors acknowledge that only six RCTs met inclusion criteria, and that the total n did not allow for robust conclusions to be drawn in all drug comparisons. Other shortcomings included lack of placebo control and overall study heterogeneity. The authors also point out that the D2 receptor blockade caused by these medications in the setting of methamphetamine withdrawal could heighten anhedonia and theoretically increase risk of return to drug use. Hyperphagia and hypersomnia resulting from methamphetamine withdrawal might compound the side effects from olanzapine and quetiapine. Given that MAP is often self-limiting, the recommendation is to taper off the antipsychotic after resolution of psychotic symptoms, typically a maximum of four weeks after methamphetamine use.

CATR’S Take
We recommend considering quetiapine and olanzapine first when treating patients for MAP, and reserving aripiprazole as a third-line treatment only. Be aware of side effect burden and taper these medications off as soon as possible.