Dose Reduction/Discontinuation of Antipsychotic Drugs in Psychosis; Effect on Cognition and Functional Outcomes

Abstract

Backgrounds: There is a debate regarding the optimal timing of discontinuation of antipsychotic drugs in patients with first episode psychosis (FEP) or schizophrenia. We aimed to provide a review of the literature on which strategy (medication maintenance vs. dose reduction/discontinuation) is more likely to maximize outcomes, such as cognition and social function.Methods: Using PubMed, the Cochrane Library and systematic reviews, articles published between 2007 and 2018 were reviewed, which investigated the effect of dose reduction/discontinuation vs. maintenance treatment on measures of cognition and/or social function in FEP and schizophrenia.Results: Six studies were identified; 2 studies reported on cognition while 4 studies concern social function. All studies except one reported that improvement of functional outcomes in remitted patients with FEP or schizophrenia allocated to a dose reduction/discontinuation arm was equal to or better than that in patients for whom medication doses were maintained. One trial of social function with a 1-year follow-up period found a greater improvement in the medication maintenance group, while no group difference was observed with 3-year and 10-year follow-up periods. On the other hand, a 7-year follow-up study found a superiority for the dose reduction/discontinuation regimen in terms of social outcome. Two studies on cognition with a short follow-up period reported a greater improvement for the dose reduction/discontinuation group.Conclusions: Information on cognition and social function has been relatively sparse. These measures of functional outcome should be considered in deciding which strategy of antipsychotic treatments is beneficial in individual cases with FEP or schizophrenia.

Peripheral inflammatory and neurotrophic biomarkers of cognitive impairment in schizophrenia: a meta-analysis

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Three‐year longitudinal cognitive functioning in patients recently diagnosed with bipolar disorder

“…The present data also converge with emerging findings of drug effects on cognition in first‐episode bipolar disorder and first‐episode psychosis more broadly. Based on a recent review investigating the effects of either tapering/withdrawing or maintaining antipsychotic treatments in remitted first‐episode psychosis patients, Omachi & Sumiyoshi reported that patients who discontinued such treatments showed better cognitive outcomes than those who were maintained on antipsychotic treatments. In our initial 1‐year longitudinal study, we also reported better one‐year cognitive outcomes in executive functioning in patients who discontinued antipsychotic treatment .…”

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

“…The possibility has been raised that a proportion of patients whose first-episode has remitted may be candidates for discontinuation of antipsychotic medication in the medium to long term, at least within the context of a specialist first-episode service providing effective psychosocial interventions (Alvarez-Jimenez et al, 2016). According to such a view, the possible advantages for such patients might be the avoidance of adverse effects, improvement of the therapeutic relationship and better cognitive and social function (Omachi and Sumiyoshi, 2018; Wunderink et al, 2013). Relevant to such a view are the results of the MESIFOS study (Wunderink et al, 2007), which looked at outcomes for people with remitted first-episode, non-affective psychosis, who had been assigned to either continuing antipsychotic medication or a guided reduction in dosage, with withdrawal if achievable.…”