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.