Antidepressant therapy for unexplained symptoms & symptom syndromes – fibromyalgia and Chronic Fatigue Syndrome related research

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

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