DOSE-ESCALATION VS CONTINUED DOSES OF PAROXETINE AND MAPROTILINE - A PROSPECTIVE-STUDY IN DEPRESSED OUT-PATIENTS WITH INADEQUATE TREATMENT RESPONSE

In view of the fact that controlled prospective studies on the benefit s of dose escalation of the selective serotonin re-uptake inhibitor (S SRI) paroxetine are lacking, we conducted a double-blind, randomized, parallel-group multicentre study designed to compare the possible bene fits of dose escalation of paroxetine and maprotiline in patients suff ering from major or minor depression according to modified Research Di agnostic Criteria (RDC) with inadequate treatment response. The study sample consisted of 544 out-patients with different degrees of severit y of depression. Patients received either 20 mg paroxetine (n=271) or 100 mg maprotiline (n=273) for the first 3 weeks in a double-blind man ner. Response after 3 weeks was defined using explicit operationalized criteria. Patients with inadequate treatment response (paroxetine gro up, n=86; maprotiline group, n=88) were again randomized to either con tinuation of the previous dosage (paroxetine, n=36; maprotiline, n=48) or increased doses, i.e. 40 mg paroxetine (n=50) or 150 mg maprotilin e (n=40), respectively. Intention-to-treat and completer analyses were performed. Defining response as a reduction in Hamilton Depression Ra ting Scale (17-item version) (HAMD-17) score of at least 50% from base line, no significant benefits of dose escalation were found for either paroxetine or maprotiline. Stratification according to baseline sever ity of depression also revealed no significant benefits of dose escala tion. After dose escalation, new adverse events that had not been pres ent during treatment with lower doses rarely occurred. Our results sup port the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients.