Posted by SalArmy4me on August 29, 2001, at 18:15:45
Comparable to Paroxetine:
Dose Escalation vs. Continued Doses of Paroxetine and Maprotiline: A Prospective Study in Depressed Out-patients With Inadequate Treatment Response
Dose Escalation vs. Continued Doses of Paroxetine and Maprotiline: A Prospective Study in Depressed Out-patients With Inadequate Treatment ResponseBenkert O, Szegedi A, Wetzel H, et al (Univ of Mainz, Germany; Smith Kline Beecham Pharma GmbH, Munich); Acta Psychiatr Scand 95:288-296, 1997
Abstract 8-14
Introduction.-The therapeutic response to some antidepressant agents improves as the dosage is increased within certain limits, whereas dosage escalation offers no advantage with other antidepressants. A study of 544 outpatients with various degrees of depression compared the possible benefits of dosage escalation of paroxetine and maprotiline.
Methods.-The multicenter study was conducted in a randomized, double-blind manner. Eligible patients were aged 18 to 71 and had major or minor depression and a total score of 13 or greater on the 17-item Hamilton Depression Rating Scale. Paroxetine was started at 20 mg daily, given in a single oral dose in the morning; the other patients received maprotiline (100 mg) divided into 3 doses per day. Patients who failed to have sufficient clinical improvement after 3 weeks had the dosage increased or continued with the previous dosage for an additional 3 weeks.
Results.-Response rates were 40% mg at week 3 in the paroxetine 20 mg and maprotiline 100 mg group. At 6 weeks, approximately 75% to 80% of all groups (those increased and those maintained at the initial dose) had responded. Thirty-six nonresponders to paroxetine were randomized to continue the previous dosage and 50 to receive an increase to 40 mg daily; 48 nonresponders continued to receive 100 mg of maprotiline and 40 were given the increased dosage (150 mg). Dose escalation did not significantly increase therapeutic response with either antidepressant. Response was defined as a reduction of 50% or greater in the Hamilton Depression Rating Scale. Results were unchanged after patients were stratified according to baseline severity of depression. The incidence of adverse events was not increased by the larger dosage.
Conclusion.-This prospective study using explicit criteria for dosage escalation found no significant benefit when the dosages of paroxetine and maprotiline were increased for nonresponders (from 20 mg to 40 mg and from 100 mg to 150 mg daily, respectively). For most patients with acute depression, a dosage of 20 mg of paroxetine a day is optimal.
[r tri, filled] This article provides an example of a good idea that was limited by an inadequate experimental design. The authors are clearly aware of the limitations of this study of dosage escalation vs. continuation of the same dosage of either paroxetine or maprotiline in nonresponsive patients with major or minor depression. This is a particularly important problem which clinicians often face, and this study had a chance to provide some useful information. Unfortunately, the authors included a broad spectrum of patients and used only a 3-week observation period for assessing initial response, followed by a second 3-week period for assessing the effects of the second manipulation (dosage escalation vs. no change). Although it could be argued that the robust endpoint response rates in this group of patients should address my concern about the short initial treatment period, there was not adequate observation time for the patients who are randomized to an increased dosage vs. no dosage change. There may have been more resistant patients, and these patients may have required a longer period to become responders.
Of course, the lack of a placebo control, which the authors note, is another limitation of this study. The diagnostic categorization of these patients was not clear. They were assessed through "modified research diagnostic criteria," and for many patients all procedures were apparently carried out by experienced research assistants. This leaves open the question of both diagnostic and assessment capabilities, and since these individuals were not more thoroughly characterized in the article, the reader is left wondering whether this was another problematic aspect in the methodology. I selected this article because if 1 were to read quickly through it, one could easily walk away with the impression that in clinical practice it is not worthwhile to increase the dosage of an antidepressant if patients haven't responded after 3 weeks; this does not correlate with my clinical experience. This was clearly a study which involved a great deal of effort, and one which could have been made much better with closer attention to methodology.
R.B. Lydiard, Ph.D., M.D.
poster:SalArmy4me
thread:76863
URL: http://www.dr-bob.org/babble/20010828/msgs/76863.html