Antipsychotic Withdrawal Symptoms: A Systematic Review and Meta-Analysis

Abstract

Objective Avoiding withdrawal symptoms following antipsychotic discontinuation is an important factor when planning a safe therapy. We performed a systematic review and meta-analysis concerning occurrence of withdrawal symptoms after discontinuation of antipsychotics. Data Sources We searched the databases CENTRAL, Pubmed, and EMBASE with no restriction to the beginning of the searched time period and until October 1, 2019 (PROSPERO registration no. CRD42019119148). Study Selection Of the 18,043 screened studies, controlled and cohort trials that assessed withdrawal symptoms after discontinuation of oral antipsychotics were included in the random-effects model. Studies that did not implement placebo substitution were excluded from analyses. The primary outcome was the proportion of individuals with withdrawal symptoms after antipsychotic discontinuation. We compared a control group with continued antipsychotic treatment in the assessment of odds ratio and number needed to harm (NNH). Data Extraction We followed guidelines by the Cochrane Collaboration, PRISMA, and MOOSE. Results Five studies with a total of 261 individuals were included. The primary outcome, proportion of individuals with withdrawal symptoms after antipsychotic discontinuation, was 0.53 (95% CI, 0.37–0.70; I 2 = 82.98%, P < 0.01). An odds ratio of 7.97 (95% CI, 2.39–26.58; I 2 = 82.7%, P = 0.003) and NNH of 3 was calculated for the occurrence of withdrawal symptoms after antipsychotic discontinuation. Conclusion Withdrawal symptoms appear to occur frequently after abrupt discontinuation of an oral antipsychotic. The lack of randomized controlled trials with low risk of bias on antipsychotic withdrawal symptoms highlights the need for further research.

Clozapine discontinuation withdrawal symptoms in schizophrenia

“… 31 , 34 , 35 , 37 – 41 These cases suggest that symptoms appear within a few days and continue for several weeks 34 , 42 – 45 ; however studies in other antipsychotics suggest that symptoms may continue for longer. 11 Furthermore, cholinergic rebound has been reported in patients on a range of doses of clozapine, including doses as low as 50 mg per day. 37 …”

“…A wide spectrum of somatic and psychiatric symptoms have been reported ( Figure 1 ), including psychotic, autonomic, gastrointestinal and psychomotor. 11 Some of these withdrawal symptoms, such as nausea and vomiting, have been described in other antipsychotics, whilst others, such as catatonia, appear to be specific to clozapine. 11 Whilst epidemiological evidence is limited, withdrawal symptoms have been reported most often in association with abrupt discontinuation.…”

“… 11 Some of these withdrawal symptoms, such as nausea and vomiting, have been described in other antipsychotics, whilst others, such as catatonia, appear to be specific to clozapine. 11 Whilst epidemiological evidence is limited, withdrawal symptoms have been reported most often in association with abrupt discontinuation. 11 Furthermore, symptoms often appear as a cluster, and elucidating these groups may yield insights into the underlying mechanisms responsible.…”

“… 11 Whilst epidemiological evidence is limited, withdrawal symptoms have been reported most often in association with abrupt discontinuation. 11 Furthermore, symptoms often appear as a cluster, and elucidating these groups may yield insights into the underlying mechanisms responsible. To date, there has not been an attempt to summarise the evidence on clozapine-induced withdrawal symptoms.…”

Entzugssyndrom nach dem Absetzen von Lithium – Eine systematische Literaturübersicht

“…Die Evidenzlage legt ein grundsätzliches Auftreten von Entzugssyndromen nach Absetzen von Lithium nahe, lässt in ihrer Eingeschränktheit jedoch keine Aussagen über Prädiktoren zu. Die Datenlage zum Nutzen einer schrittweisen Reduktion anstatt eines abrupten Absetzens ist auch für andere psychiatrische Pharmaka wie Antidepressiva und Antipsychotika noch unzureichend [5,21], ein langsames Ausschleichen ist jedoch grundsätzlich zu empfehlen. Unabhängig von Entzugssyndromen wird dies generell zur Reduktion von Rebound-Phänomenen und Rückfällen/Rezidiven empfohlen [22,23].…”