Changes in quantitatively assessed tremor during treatment of major depression with lithium augmented by paroxetine or amitriptyline

Tremor is a relatively frequent side effect of Lithium and of antidepressan ts with serotonergic properties. It can be expected that combinations of Li thium (which is itself serotonergic) with such antidepressants will enhance not only efficacy, but also the incidence of side effects, including tremo r. To quantitatively monitor the effect of antidepressant augmentation of o ngoing lithium therapy on tremor, Lithium-maintained patients with a breakt hrough episode of major depression were randomly assigned under double-blin d conditions to receive paroxetine 20 mg/day (N = 14) or amitriptyline 75 m g/day (N = 17). The initial dosages could be increased after 2 weeks to 40 mg/day and 150 mg/day, respectively, and the patients were treated for 6 we eks. Tremor activity was assessed weekly, quantitatively by accelerometry a nd qualitatively with the Dosage Record and Treatment Emergent Symptom Scal e. Statistical analysis detected no significant difference between the trea tment groups with respect to changes in mean tremor activity relative to ba seline. However, analysis of the pooled data showed that tremor increased s ignificantly during the course of combined Lithium and antidepressant thera py, with the greatest increments occurring independent of dosage approximat ely 3 weeks after initiation of combination treatment. Although the mean tr emor activity subsided toward the end of treatment, tremor activity on the whole was still significantly greater after 6 weeks of combined Lithium and antidepressant treatment than at the start of combination therapy. Increas ed tremor was not associated with decreased medication compliance, and no p atient discontinued treatment because of increased tremor. Tremor frequency was not affected by the study treatments.