Depression SSRI vs Tricyclics 
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 Depression SSRI vs Tricyclics

Depression: SSRI vs tricyclics



Simon GE, VonKorff M, Heiligenstein JH, et al . Initial antidepressant
choice in primary care. JAMA 1996;275:1897-1902.

Reviewed by

Ian Bushell M.D., Warren Newton M.D.

Clinical question

Is the selective serotonin reuptake inhibitor fluoxetine more effective or
more costly than the tricyclic antidepressants desipramine and imipramine in
the treatment of depression in primary care?


Serotonin reuptake inhibitors (SSRIs) dominate antidepressant prescribing in
the United States. Recent meta-analyses have shown similar effectiveness and
safety profiles between SSRI agents and tricyclic antidepressants (TCAs).
The purpose of this study was to compare the overall effectiveness and cost
of fluoxetine to desipramine and imipramine in primary care patients with

Population studied

A total of 536 patients, identified by primary care practitioners in a
staff-model health-maintenance organization (HMO), participated in this
study. Most of these patients had a diagnosis of major depression, though
26% were diagnosed with mild depression and 7% with dysthmia. Most of the
patients (75%) reported previous episodes of depression.

Study design and validity

The study design is a randomized, unblinded trial of usual care with either
fluoxetine, desipramine, or imipramine. The patients' physicians controlled
all aspects of the therapy, including starting dose, follow-up visits,
medication adjustments or changes and referrals. Patient status was
evaluated after 1, 3 and 6 months of therapy. Statistical analysis was by
intention to treat. This study design closely mimics the clinical use of
antidepressants by family physicians. The major weakness in the design is
the inattention to the role of psychotherapy in these patients. The patients
received substantial amounts of therapy, but the report gives very little
attention to the type and intensity of therapy, and its effect was not
evaluated in the analysis.

Outcomes measured

The primary outcomes of this study were resolution of depression and the
effect of therapy on quality of life scores. The economic impact of the
depressive episode also was evaluated using HMO data, and included
outpatient office charges, cost of laboratory monitoring, pharmacy charges,
and inpatient costs.


At 1, 3 and 6 months, there was no clinically or statistically significant
difference in any of the clinical outcomes: about half of the patients on
each drug achieved clinical remission. Relatively few patients continued
medication at the minimum effective dose cited by the recent AHCPR
guidelines,1 although significantly more patients with fluoxetine (61%) met
this criterion than desipramine (49%) or imipramine (48%). The average dose
of either TCA was only about 100 mg. Significantly fewer patients taking
fluoxetine discontinued it because of adverse effects before one month-9% vs
27% (desipramine) or 28% (imipramine) (p = 0.001). Total cost between the
three {*filter*} were similar: the higher drug cost of fluoxetine therapy -
approximately $100 more for six months of therapy -was balanced by charges
for more frequent hospitalizations and office visits by patients receiving a

Recommendations for clinical practice

This report provides strong evidence that there is no difference in clinical
outcomes between among fluoxetine, desipramine, and imipramine when used for
mild to moderate depression in {*filter*}s diagnosed by family physicians. This
report also shows that the total cost of care for patients receiving
fluoxetine is comparable to those given the other medications. However, cost
calculations may be different in other settings. The findings about
side-effects confirm the usual clinical wisdom about SSRIs, but the
increased incidence of side effects in the TCA treated patients did not
affect quality of life scores. Why have SSRIs become so popular, both with
physicians and patients? The answer is not due to efficacy, but rather a
combination of side effect profile, pharmaceutical marketing, and the
popular culture. A major influence may be the current fashion of the SSRI
agents. Cued by countless glowing reports in the popular press, our patients
know about these medicines and come asking for them. This popularity will
improve their placebo power and minimize the discomfort of side-effects, at
least for a few years.


1. Depression Guideline Panel. Depression in Primary Care: Volume 2,
Clinical Practice Guideline. Rockville, Md: US Department of Health and
Human Services, Public Health Service, Agency for Health Care Policy and
Research; 1993.

Sun, 08 Feb 2004 23:35:54 GMT
 [ 1 post ] 

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