Paroxetine and imipramine treatment of depressed patients in a controlled, multicentre study with plasma amino acid measurements

A double-blind controlled, comparative study of paroxetine and the tricyclic antidepressant imipramine was carried out in Denmark. Patients aged between 18 and 70 years took part in the study, which lasted for at least 12 weeks and a maximum of one year. Thirty-one patients with DSM-III-R depression took part in the study. Patients were given gradually increasing doses of paroxetine and imipramine until week 2 of the study when dosages were fixed at 30 mg paroxetine and 150 mg imipramine daily. Clinical efficacy was assessed using the DUAG scale which included the 17-item HAMD rating scale, and the MES. Tolerability was assessed using the UKU side-effects scale and laboratory monitoring. In addition plasma levels of drugs and amino acids were determined. Paroxetine showed a faster onset of action than imipramine and after week 2 both drugs were equally effective. Paroxetine was significantly better tolerated than imipramine, 81% of the paroxetine-treated patients tolerated treatment very well or reasonably well compared with 83% of the imipramine group. No correlation was obtained between efficacy and amino acid levels in the imipramine group. However, in the paroxetine group there was a significant correlation between the ratio of tryptophan to large neutral amino acids and final HAMD score. Twelve patients (seven on paroxetine and five on imipramine) continued into long-term treatment. HAMD scores remained stable in six of the paroxetine patients and one improved. Two imipramine patients remained stable and three changed from complete to partial responders. In conclusion, paroxetine was shown to be as effective as and better tolerated than imipramine and was more effective in long-term treatment.