May 29, 2019
In this masterclass, Charles L.
Raison, MD, returns to the MDedge Psychcast to discuss the
risks and benefits of antidepressants. He previously appeared on
the Psychcast in episodes
Dr. Raison is Mary Sue and Mike Shannon Chair for Healthy Minds,
Children & Families and professor, School of Human Ecology, and
professor, department of psychiatry, School of Medicine and Public
Health, University of Wisconsin-Madison.
Later, Renee Kohanski, MD,
discusses the need for psychiatrists to take care of and nourish
Show Notes by Jacqueline Posada, MD, consultation-liaison
psychiatry fellow with the Inova Fairfax Hospital/George Washington
University program in Falls Church, Va.
Treatment with antidepressants
STAR-D trial, a large effectiveness trial (n = 4,000), looked
at the effect of SSRIs and other medications for the treatment of
- As an effectiveness trial, STAR-D looked at “real” patients
with comorbidities (as opposed to efficacy trials, which use
“perfect patients” with no comorbidities to minimize confounding
- Only 30% of patients went into complete remission with first
step of treatment with an SSRI (citalopram) at the highest
- Almost 50% experienced a response (a 50% reduction in symptoms
of depression on standardized scale).
Cynicism and hope for antidepressants
- To obtain Food and Drug Administration approval, a medication
requires two positive studies (showing that the drug beats
placebo), and on average, an SSRI requires five to seven studies to
get the two positive studies.
- A meta-analysis of negative SSRI studies that were “filed away”
found only a 1.8-point difference on Hamilton Depression
Rating Scale score between SSRI vs placebo.
- The difference between SSRI and placebo in treatment
disappeared among patients who were less depressed.
- Geddes et al., presented a more balanced view in a published
meta-analysis of 522 trials that included more than 100,000
- Antidepressants had a modest benefit, compared with
- In head-to-head studies, some antidepressants were better than
others, such as amitriptyline, escitalopram, mirtazapine,
paroxetine, venlafaxine, and vortioxetine.
Predictors of response
- Poor response to antidepressants: Presence of comorbid anxiety
disorder, failure of first or subsequent antidepressant trials.
- Within STAR-D, among those who failed three treatment steps,
only 13% responded to the next treatment.
- Good response to antidepressants: An acute response to an
antidepressant predicts long-term response.
- A 20% or greater improvement within 2 weeks of treatment
resulted in a higher chance of remission, compared with those who
don’t initially respond, who then had a less than 5% chance of
Are antidepressants good for everyone?
- The difference between active antidepressants and placebo is
- A latent growth curve analysis of placebo vs. antidepressants
for depression showed that there are two separate trajectories with
antidepressants: 70% will respond and are vastly improved, while
30% actually do worse.
- A National Institute of Mental Health study from 1980s
randomized patients to two types of psychotherapy vs. tricyclic
antidepressants (TCAs) vs. waitlist control group. Treatment took
place for 16 weeks, and patients were followed for 18 months.
- People who went into remission on TCAs were more likely to
relapse than those who went into remission on psychotherapy.
- Epidemiological Catchment Area (ECA) trial: Prospective data of
92 people from the total 3,500 in the study.
- Of the 92 with a first major depressive episode, 50% had a
second major depressive episode.
- Of those who were treated into complete remission, even after 5
years, more than 50% had a relapse of their depression.
Conclusion: Relapse of depression is common when
patients come off antidepressants
- To stay well, a patient with depression should continue to
receive an antidepressant.
- Clinicians must ask: Do the antidepressants increase the risk
of relapse of depression?
- Depression is a disabling disease, so treatment is necessary.
But clinicians should question for whom and when antidepressants
should be used.
Turner EH et al. Selective publication of antidepressant trials
and its influence on apparent efficacy. N Engl J Med.
Cipriani A et al. Comparative efficacy and acceptability of 21
antidepressant drugs for the acute treatment of adults with major
depressive disorder: A systematic review and network meta-analysis.
Lancet. 2018 Apr 7:391(10128):1357-66.
Penninx BW et al. Two-year course of depressive and anxiety
disorders: Results from the Netherlands study of depression and
J Affect Disord. 2011 Sep;133(1-2):76-85.
Perlman K et al. A systematic meta-review of predictors of
antidepressant treatment outcome in major depressive disorder.
J Affect Disord. 2019 Jan 15;243:503-15.
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