Paroxetine and amitriptyline augmentation of lithium in the treatment of major depression: a double-blind study

To study the efficacy and safety of antidepressant augmentation of ongoing lithium therapy, lithium-maintained patients suffering from an breakthrough episode of major depression were randomly assigned under double-blind cond itions to receive paroxetine 20 mg/day (N = 19) or amitriptyline 75 mg/day (N = 23), The initial dosages could be increased after 2 weeks to 40 mg/day and 150 mg/day, respectively, and the patients were treated for a total of 6 weeks. Efficacy was assessed weekly with the 21-item Hamilton Rating Sca le for Depression (HAM-D) and the Clinical Global Impression Scale (CGI), a nd safety was assessed with the Dosage Record and Treatment Emergent Sympto m Scale. After 4 weeks, a significantly greater proportion of patients in t he paroxetine group had achieved a 50% reduction in baseline HAM-D scores, and the mean improvement in CGI severity of illness was significantly great er in the paroxetine group at weeks 3 and 5. The type and number of emergen t events occurring during study treatment corresponded to the known side ef fect profiles of paroxetine and amitriptyline. Serum lithium levels were no t affected by either antidepressant. The authors proposed that the more rap id improvement demonstrated by the group receiving the combination of Lithi um and paroxetine may be due to the synergistic serotonergic effects of the se two medications.