Run-in periods and clinical outcomes of antipsychotics in dementia: A meta-epidemiological study of placebo-controlled trials

Tessa A Hulshof, Sytse U Zuidema, Christine C Gispen-de Wied, Hendrika J Luijendijk*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

7 Citations (Scopus)
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PURPOSE: Run-in periods are used to identify placebo-responders and washout. Our aim was to assess the association of run-in periods with clinical outcomes of antipsychotics in dementia.

METHODS: We searched randomized placebo-controlled trials of conventional and atypical antipsychotics for neuropsychiatric symptoms (NPS) in dementia in electronic sources and references of selected articles. We extracted (a) the presence of a run-in period, use of placebo/investigated drug during run-in (versus washout only), and run-in duration (1 week or more) and (b) the reduction in NPS, number of participants with somnolence, extrapyramidal symptoms (EPS), and deaths per treatment group. We pooled clinical outcomes comparing antipsychotic and placebo groups in trials with and without run-in.

RESULTS: We identified 35 trials. Twenty-nine trials used run-in. The pooled standardized mean difference in the reduction of NPS was -0.170 (95% CI, -0.227 to -0.112) in trials with run-in and -0.142 (95% CI, -0.331 to 0.047) in trials without run-in. The pooled odds ratio for somnolence was 2.8 (95% CI, 2.3-3.5) in trials with run-in and 3.5 (95% CI, 1.2-10.7) in trials without run-in; for EPS, these ORs were 1.8 (95% CI, 1.4-2.2) and 2.0 (95% CI, 1.3-3.1) respectively, and for mortality 1.4 (95% CI, 1.0-2.0) and 1.6 (95% CI, 0.7-3.4). The use of placebo/investigated drug during run-in and run-in duration did not affect the estimates in a consistent way.

CONCLUSIONS: The use of run-in in trials might have led to overestimated efficacy and especially underestimated risks of side effects of antipsychotics compared with placebo for NPS in dementia.

Original languageEnglish
Pages (from-to)125-133
Number of pages9
JournalPharmacoepidemiology and Drug Safety
Issue number2
Early online date15-Nov-2019
Publication statusPublished - 2020

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