Cochrane Briefs

Am Fam Physician. 2004 Oct 1;70(7):1269-1270.

Drug Treatments for Patients with Dysthymia

Clinical Question

Which drug treatments for dysthymia are most effective?

Evidence-Based Answer

All antidepressants studied have similar efficacy in the treatment of patients with dysthymia. Side effect profiles vary. The largest comparisons support the use of tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs).

Practice Pointers

Patients with dysthymia have less severe but more chronic symptoms than patients with depression. De Lima and colleagues published two systematic reviews1,2 on the treatment of dysthymia. The first review, by De Lima and Moncrieff,1 found that antidepressants are highly effective in treating dysthymia compared with placebo. Approximately four patients must be treated to achieve one response. However, it is not clear which antidepressant produces the best results.

To determine the most effective antidepressant, De Lima and Hotopf2 searched for randomized and quasi-randomized controlled trials comparing at least two active drug treatments. Patients in these studies had dysthymia for at least two years and were studied for four to 12 weeks in psychiatric, primary care, and community settings.

Tricyclic antidepressants, SSRIs and monoamine oxidase inhibitors had similar efficacy. Imipramine was the most commonly studied tricyclic antidepressant, and fluoxetine was the most commonly studied SSRI. Only one study compared SSRIs with tricyclic antidepressants. Both drug classes had a similar effect on mood, but the SSRIs had a lower dropout rate. Therefore, medication choice should be based on the side effect profile. No data are available on optimal dosage or length of treatment.


1. De Lima MS, Moncrieff J. Drugs versus placebo for dysthymia. Cochrane Database Syst Rev. 2000;4:CD001130.

2. De Lima MS, Hotopf M. A comparison of active drugs for the treatment of dysthymia. Cochrane Database Syst Rev. 2003;3:CD00404.

Optimal Dosage of Tricyclic Antidepressants

Clinical Question

What is the optimal dosage of tricyclic antidepressants in the acute phase of treatment of major depression in adults?

Evidence-Based Answer

Although the quality of the data limits the strength of the recommendation, current evidence shows that 75 to 100 mg per day of a tricyclic antidepressant is more effective than placebo. Higher dosages are not more effective and are associated with more dropouts because of side effects.

Practice Pointers

Although tricyclic antidepressants have been proved effective in the treatment of depression, there is little evidence for the optimal dosage. Despite the lack of evidence, the American Psychiatric Association recommends dosages of 100 to 300 mg per day.1

Furukawa and colleagues examined 41 trials of tricyclic antidepressants; 35 studies with 2,013 patients compared low dosages of tricyclics (75 to 100 mg per day) with placebo, and six studies with 551 participants compared low dosages of tricyclics with standard dosages (more than 100 mg per day). Most studies used amitriptyline and imipramine.

At four weeks, six to eight weeks, and three to 12 months, patients were more likely to respond to dosages of 75 to 100 mg per day than to placebo. These findings were similar for primary care patients. Standard dosages of tricyclics had a higher dropout rate because of side effects and were not more effective than low dosages.

The quality of the studies was limited by poor reporting and nonstandard diagnostic criteria, and there was significant heterogeneity between studies. Therefore, a definitive answer on the optimal dosage remains unknown. However, current evidence supports the use of low-dosage tricyclic antidepressants.

Furukawa T, et al. Low dosage tricyclic antidepressants for depression. Cochrane Database Syst Rev 2003; 3: CD003197.


1. Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association. Am J Psychiatry. 2000;157(4 suppl)1–45.

Copyright © 2004 by the American Academy of Family Physicians.
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