OBJECTIVE: To determine the efficacy of antidepressant therapy for
unexplained symptoms or symptom syndromes.
We identified original studies through searching MEDLINE,
EMBASE, PsycLIT, the Federal Research in Progress database,
and The Cochrane Library. We also searched the bibliographies
of primary and review articles for additional studies.
SELECTION CRITERIA: We excluded trials of patients with
neuropathic, oncologic, or degenerative joint pain.
Independent duplicate review of 392 articles identified 94
relevant reports of randomized trials involving 6595 patients
across 6 symptom syndromes. Independent duplicate assessment
was made for inclusion and data abstraction. Meta-analysis was
performed on extractable placebo-controlled data. MAIN
RESULTS: Of 94 included trials, most studied either tricyclic
antidepressants, antiserotonin antidepressants, selective
serotonin reuptake inhibitors (SSRIs), or multiple agents for
the treatment of the following syndromes: headache (50),
fibromyalgia (18), functional gastrointestinal syndromes (13),
idiopathic pain (11), tinnitus (2), and chronic fatigue (2).
The quality of the studies was fair (mean score = 4.8 on a
scale of 0 to 8). A majority of the studies (69%) demonstrated
benefit for at least one outcome measure. Symptom improvement
typically did not correlate with depression response in the
few studies where it was assessed. Meta-analysis of all
extractable data showed a substantial benefit from
antidepressants: For the dichotomous outcome of improvement,
the odds ratio was 3.4 (95% confidence interval [CI], 2.6 –
4.5), and for continuous outcomes, the standardized mean
difference was 0.87 (95% CI, 0.59-1.14). The absolute
percentage difference in improvement between the
antidepressant and placebo arms was 32%, yielding a number
needed to treat of 3 to improve one person’s symptoms.
Meta-regression indicated no differential effect across the
classes of antidepressants; however, onbivariate tally
tricyclic studies were associated with a greater likelihood of
efficacy than SSRI studies (P = .02).
Antidepressants can be effective for various physical symptoms
and symptom syndromes. The relation of outcome to depression
and the efficacy of SSRIs needs further study.
O’Malley PG, Jackson JL, Santoro J, Tomkins G, Balden E, Kroenke K