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Step‐wise loss of antidepressant effectiveness with repeated antidepressant trials in bipolar II depression
Author(s) -
Amsterdam Jay D,
LorenzoLuaces Lorenzo,
DeRubeis Robert J
Publication year - 2016
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12442
Subject(s) - venlafaxine , antidepressant , depression (economics) , medicine , bipolar ii disorder , pharmacodynamics , lithium (medication) , major depressive episode , randomized controlled trial , mood , bipolar disorder , psychology , psychiatry , pharmacokinetics , hippocampus , economics , macroeconomics
Objective This study examined the relationship between the number of prior antidepressant treatment trials and step‐wise increase in pharmacodynamic tolerance (or progressive loss of effectiveness) in subjects with bipolar II depression. Methods Subjects ≥18 years old with bipolar II depression (n=129) were randomized to double‐blind venlafaxine or lithium carbonate monotherapy for 12 weeks. Responders (n=59) received continuation monotherapy for six additional months. Results After controlling for baseline covariates of prior medications, there was a 25% reduction in the likelihood of response to treatment with each increase in the number of prior antidepressant trials (odds ratio [ OR ]=0.75, unstandardized coefficient [B]=−0.29, standard error ( SE) =0.12; χ 2 =5.70, P <.02], as well as a 32% reduction in the likelihood of remission with each prior antidepressant trial ( OR =0.68, B =−0.39, SE =0.13; χ 2 =9.71, P =.002). This step‐wise increase in pharmacodynamic tolerance occurred in both treatment conditions. Prior selective serotonin reuptake inhibitor ( SSRI ) therapy was specifically associated with a step‐wise increase in tolerance, whereas other prior antidepressants or mood stabilizers were not associated with pharmacodynamic tolerance. Neither the number of prior antidepressants, nor the number of prior SSRI s, or mood stabilizers, were associated with an increase in relapse during continuation therapy. Conclusions The odds of responding or remitting during venlafaxine or lithium monotherapy were reduced by 25% and 32%, respectively, with each increase in the number of prior antidepressant treatment trials. There was no relationship between prior antidepressant exposure and depressive relapse during continuation therapy of bipolar II disorder.