Universität zu Köln

Rink, Lena, Adams, Anne ORCID: 0000-0003-3286-1131, Braun, Cora, Bschor, Tom, Kuhr, Kathrin and Baethge, Christopher . Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials. Psychother. Psychosom.. BASEL: KARGER. ISSN 1423-0348

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Abstract

Introduction: Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose. Objective: This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder. Methods: A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers' product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031). Results: From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of -0.06 (-0.16 to 0.04) and -0.06 (-0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis. Conclusion: Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rink, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Adams, Anne UNSPECIFIED orcid.org/0000-0003-3286-1131 UNSPECIFIED Braun, Cora UNSPECIFIED UNSPECIFIED UNSPECIFIED Bschor, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhr, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Baethge, Christopher UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-577206
DOI:	10.1159/000520554
Journal or Publication Title:	Psychother. Psychosom.
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1423-0348
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DULOXETINE DOSING STRATEGIES; DOUBLE-BLIND; DESVENLAFAXINE 50; LITHIUM AUGMENTATION; 100 MG/DAY; PHASE-III; 120 MG; PLACEBO; EFFICACY; SAFETY Multiple languages Psychiatry; Psychology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57720