Universität zu Köln

Braun, C., Adams, A., Rink, L., Bschor, T., Kuhr, K. and Baethge, C. (2020). In search of a dose-response relationship in SSRIs-a systematic review, meta-analysis, and network meta-analysis. Acta Psychiatr. Scand., 142 (6). S. 430 - 443. HOBOKEN: WILEY. ISSN 1600-0447

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Abstract

Objective Recent meta-analyses on dose-response relationships of SSRIs are largely based on indirect evidence. We analyzed RCTs directly comparing different SSRI doses. Method Systematic literature search for RCTs. Two raters independently screened articles and extracted data. Across SSRIs, doses defined as low, medium, and high doses, based on drug manufacturers' product monographs, were analyzed in pairwise random-effects meta-analyses and in a sensitivity network meta-analysis with regard to differences in antidepressive efficacy (primary outcome). We also analyzed all direct comparisons of different dosages of specific SSRIs. (Prospero CRD42018081031). Results Out of 5333 articles screened, we included 33. Comparisons of dosage groups (low, medium, and high) resulted in only small and clinically non-significant differences for SSRIs as a group, the strongest relating to medium vs low doses (SMD: -0.15 [95%-CI: -0.28; -0.01) and not sustained in a sensitivity analysis. Among different doses of specific SSRIs, no statistically significant trend emerged for efficacy at higher doses, but 60 mg/day fluoxetine are statistically significantly inferior to 20 mg/day. Paroxetine results are inconclusive: 10 mg/day are inferior to higher doses, but 30 and 40 mg/day are inferior to 20 mg/day. Meaningful effects cannot be ruled out for certain drugs and dosages, often investigated in only one trial. Dropout rates increase with dose-particularly due to side effects. Network meta-analyses supported our findings. Conclusions There is no conclusive level I or level II evidence of a clinically meaningful dose-response relationship of SSRIs as a group or of single substances. High SSRI doses are not recommended as routine treatment.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Braun, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Adams, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rink, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bschor, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhr, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Baethge, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-315138
DOI:	10.1111/acps.13235
Journal or Publication Title:	Acta Psychiatr. Scand.
Volume:	142
Number:	6
Page Range:	S. 430 - 443
Date:	2020
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1600-0447
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RANDOMIZED CONTROLLED-TRIALS; MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND; FLUOXETINE THERAPY; CONTROLLED-RELEASE; 40 MG; CITALOPRAM; PLACEBO; EFFICACY; ANTIDEPRESSANT Multiple languages Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31513