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 antidepressants with serotonergic properties. It can be expected that combinations of lithium (which is itself serotonergic) with such antidepressants will enhance not only efficacy, but also the incidence of side effects, including tremor. To quantitatively monitor the effect of antidepressant augmentation of ongoing lithium therapy on tremor, lithium-maintained patients with a breakthrough episode of major depression were randomly assigned under double-blind conditions to receive paroxetine 20 mg/day (N = 14) or amitriptyline 75 mg/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 weeks. Tremor activity was assessed weekly, quantitatively by accelerometry and qualitatively with the Dosage Record and Treatment Emergent Symptom Scale. Statistical analysis detected no significant difference between the treatment groups with respect to changes in mean tremor activity relative to baseline. However, analysis of the pooled data showed that tremor increased significantly during the course of combined lithium and antidepressant therapy, with the greatest increments occurring independent of dosage approximately 3 weeks after initiation of combination treatment. Although the mean tremor 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. Increased tremor was not associated with decreased medication compliance, and no patient discontinued treatment because of increased tremor. Tremor frequency was not affected by the study treatments.
Clinical Development CNS/GI, SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA. Rocco_2_Zaninelli@sbphrd.com
R
R
Zaninelli
M
M
Bauer
M
M
Jobert
B
B
Müller-Oerlinghausen
D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000009:adverse effects*; D000928:Antidepressive Agents / Q000009:adverse effects*; D018692:Antimanic Agents / Q000009:adverse effects*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018021:Lithium Chloride / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects*; D018709:Statistics, Nonparametric; D014202:Tremor / Q000139:chemically induced*
D000928:Antidepressive Agents; D018692:Antimanic Agents; D000639:Amitriptyline; D017374:Paroxetine; D018021:Lithium Chloride