Universität zu Köln

Baethge, Christopher, Braun, Cora, Rink, Lena, Schwarzer, Guido ORCID: 0000-0001-6214-9087, Henssler, Jonathan ORCID: 0000-0001-8123-5853 and Bschor, Tom (2022). Dose effects of tricyclic antidepressants in the treatment of acute depression - A systematic review and meta-analysis of randomized trials. J. Affect. Disord., 307. S. 191 - 199. AMSTERDAM: ELSEVIER. ISSN 1573-2517

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Abstract

Background: Tricyclic antidepressants (TCA) continue to be an important group of drugs, but it is unclear whether a dose-response relationship is supported by high-level evidence. Methods: Systematic review in the Cochrane Collaboration's Central Register of Controlled Trials (CENTRAL) of studies randomizing patients to at least two doses of one TCA, complemented by searches in Medline, Embase, and PsycInfo. In multilevel regression, we calculated the standardized mean difference (SMD) in antidepressant efficacy per mg TCA dose increase, and we analyzed drop-outs due to adverse events. Finally, we computed random effects meta-analyses of all dose comparisons investigated in a minimum of two studies. Results: Out of 5365 studies screened, we included 15 randomized trials on 24 comparisons of 14 different dose contrasts. We found a statistically non-significant positive effect of increasing the dose: 0.34 SMD with 100 mg/d dose increase ([-0.03; 0.70] p = 0.073). While several comparisons showed no clear signal of a dose gradient, 300 mg of imipramine/desipramine is statistically significantly superior to 150 mg (SMD: 0.80 [0.28; 1.33], p = 0.003, I-2: 0%). Drop-outs increased with higher doses, albeit not statistically significantly: Odds ratio (OR) of 1.44 with 100 mg dose increase [0.54; 3.86]. Overall, risk of bias was high. Limitations: Limited number of studies with mainly high risk of bias. Conclusions: So far, data on a dose-response relationship in TCAs from direct dose comparisons are inconclusive. Clinically, escalation to high doses may be justified if side effects are bearable.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Baethge, Christopher UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Cora UNSPECIFIED UNSPECIFIED UNSPECIFIED Rink, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarzer, Guido UNSPECIFIED orcid.org/0000-0001-6214-9087 UNSPECIFIED Henssler, Jonathan UNSPECIFIED orcid.org/0000-0001-8123-5853 UNSPECIFIED Bschor, Tom UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-684677
DOI:	10.1016/j.jad.2022.03.075
Journal or Publication Title:	J. Affect. Disord.
Volume:	307
Page Range:	S. 191 - 199
Date:	2022
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1573-2517
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLINICAL-PRACTICE GUIDELINES; AMITRIPTYLINE; DISORDERS Multiple languages Clinical Neurology; Psychiatry Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68467