Review of: Takeuchi H and Remington G, J Psychopharmacol 2020;34(8):914–919

Type of study: Meta-analysis of randomized controlled trials

Antipsychotic switching is a routine part of schizophrenia care, but what’s the best way to go from one medication to another? This article compared three strategies: 1) abruptly stopping the old antipsychotic and starting the new one, 2) gradually tapering the old antipsychotic as soon as the new one is added, and 3) performing “wait-and-gradual” discontinuation (ie, waiting more than 1 day after starting the new antipsychotic before tapering off the old one). Earlier meta-analyses found no differences when comparing options 1 vs 2 and 2 vs 3. This new study compared option 1 (abrupt) with option 3 (wait-and-gradual).

The analysis included 6 comparisons of these switch strategies from randomized controlled trials involving 351 patients with chronic schizophrenia. The primary outcomes were dropouts due to all causes, inefficacy, or intolerability. Secondary outcomes included a variety of measures of psychotic symptoms and antipsychotic side effects. Most of the wait-and-gradual studies tapered off the old antipsychotic over 1 week, though one study took 2 weeks to taper and another took 6 weeks. The average follow-up after the switch was 5 to 6 weeks. Sponsorship of the individual studies was not mentioned, but there was no evidence of publication bias. The meta-analysis received no financial sponsorship.

The main finding was that patients were 1.6 times more likely to drop out for any cause (including but not limited to withdrawal of consent and loss to follow-up) with abrupt vs wait-and-gradual discontinuation. For discontinuation due to inefficacy and intolerability, there was a trend favoring the wait-and-gradual method, but it did not reach statistical significance. There were no significant differences in the various measures of side effects and psychotic symptoms between the two strategies. The main weakness of this meta-analysis was the small number of studies included.

TCPR’s Take
When switching antipsychotics, first add the new one in, then taper the old one off over at least 1 to 2 weeks.