Switching Antidepressants After a First Selective Serotonin Reuptake Inhibitor in Major Depressive Disorder: A Systematic Review
J Clin Psychiatry 2006;67(12):1836-1855
© Copyright 2015 Physicians Postgraduate Press, Inc.
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Objective: Selective serotonin reuptake
inhibitors (SSRIs) are frequently used as a first
antidepressant for major depressive disorder but
have response rates of 50% to 60% in daily
practice. For patients with insufficient response to
SSRIs, switching is often applied. This article aims
to systematically review the evidence for
switching pharmacotherapy after a first SSRI.
Data Sources: A systematic literature
search (updated until Feb. 10, 2005) in MEDLINE, EMBASE, CINAHL, and PsychINFO (all
indexed years) identified randomized, controlled trials (RCTs) and open studies
investigating switching strategies. In the absence of
specific keywords for switching, we performed
"sensitive" searches using free text words
with wildcards ($): "switch$" or ("alternat$"
adj5 "treat$") or ("alternat$" adj5 "therap$") in
combination with the Cochrane Collaboration search filter for RCTs, the Cochrane Collaboration
Depression Anxiety and Neurosis Group search
filter for major depressive disorder, and MeSH
terms for antidepressants (in combination with
additional text words for all antidepressive
agents). Additionally, we included 4 recent
Sequenced Treatment Alternatives to Relieve
Depression publications. We limited searches to adults
and humans but did not apply language restrictions.
Study Selection: Relevant articles were
retrieved and critically appraised. The
methodology of the studies, the results on efficacy and
dropouts due to side effects, and remarks were
summarized in an evidence table. Three studies comparing
a switch to venlafaxine or SSRIs were pooled.
Data Synthesis: Eight RCTs and 23 open
studies were identified, studying populations with different levels of treatment resistance.
Definitions of response and remission rates varied
between studies. Observed response rates after switching to any of the classes of
antidepressants varied between 12% and 86%. Remission
rates varied between 7% and 82%. The number of previous treatments with antidepressants was
negatively correlated with treatment outcome. Rates
of dropout due to side effects varied considerably across agents (5%-39%). Switching to
venlafaxine showed a modest and clinically
equivocal benefit over SSRIs (number needed to treat =
13 [95% CI = 9.1 to 25.0]).
Conclusions: After a first SSRI, any
switch within or between classes of antidepressants
appears legitimate (second SSRI, novel dual-acting antidepressants, selective norepinephrine or
noradrenergic/dopaminergic agents, or tricyclic
antidepressant or mianserin). No unequivocal evidence is available to prove an advantage of
a between-class switch. More guidance by randomized empirical studies is needed. Clinical
implications and methodological considerations for
future studies are discussed.