A systematic review of manipulations to pharmaceutical dosage forms used in psychotropic tapering plans

To identify, evaluate and summarize all published literature that investigated manipulations to pharmaceutical dosage forms of psychotropic medications that could be used for the purposes of tapering.

A systematic literature review was carried out of the available published literature on manipulations performed to psychotropic medications to obtain a decreased dose of the active pharmaceutical ingredient. All studies that involved the manipulation of pharmaceutical dosage forms of antidepressants or benzodiazepine receptor agonists and subsequent pharmaceutical analysis of active pharmaceutical ingredient content were eligible for inclusion. The electronic databases searched were: MEDLINE, Web of Science, EMBASE, PsycINFO and CINAHL.

Sixteen studies met inclusion criteria. The manipulation methods carried out in the identified studies involved tablet splitting (4 studies), formulation of liquid suspensions (8 studies) and diluting existing marketed liquid formulations (4 studies). Ten of the included studies reported a mean target dose recovery within the 95-105% range after the manipulation was performed. All studies in which a dilution was performed to an oral liquid formulation (n = 4) reported results within this percentage recovery range. None of the included studies investigated the accuracy of manipulations across the full dose range of a tapering schedule.

This review identified a limited amount of published research on the accuracy of different methods of manipulating psychotropic medications. Diluting liquid formulations to achieve lower doses merits further investigation. Further research comparing different manipulation methods is also required to determine the best approach for tapering to lower doses.