Meta-Analyses of the Efficacy and Tolerability of the Tricyclic Antidepressant Lofepramine

Abstract

Lofepramine is a tricyclic antidepressant related to imipramine. Meta-analyses were carried out with respect to efficacy and tolerability by combining outcome and adverse reaction from over 20 controlled trials comparing lofepramine with other tricyclic antidepressants. Lofepramine was at least as effective as the comparators with fewer adverse effects. In particular, the risk/benefit ratio seemed superior to the comparators amitriptyline, imipramine, clomipramine, maprotiline and desipramine.

The effect of low dose lofepramine in depressed elderly patients in general medical wards.

“…Although there have been case reports of abnormal liver function tests following treatment with lofepramine [13], in our study using low dose lofepramine the elevation of liver enzymes compared with patients on placebo was not significant. There were also no significant changes in heart rates nor electrocardiograms, supporting previous work done on the cardiac safety of lofepramine [3].…”

“…The safety of low dose lofepramine was reinforced in this study [3,5]. Although there have been case reports of abnormal liver function tests following treatment with lofepramine [13], in our study using low dose lofepramine the elevation of liver enzymes compared with patients on placebo was not significant.…”

“…For these reasons we decided to test the efficacy of low dose lofepramine (70 mg daily, which is a third to half the recommended dose) over 4 weeks. Lofepramine was chosen in preference to other tricyclic drugs because it may be as efficacious as the older tricyclics [3] and has less severe side-effects [4,5]. …”

Lessons to be learnt from meta-analyses of newer versus older antidepressants

“…However, a further meta-analysis of the use of moclobemide in 12 studies (730 patients) Tolerability has been assessed by counting dropouts in comparative studies (which may under estimate side-effect burden), apart from one metaanalysis which considered the percentage of patients experiencing side-effects (which may overestimate significant side-effects). Kerihuel & Dreyfus (1991) found significantly fewer patients on lofepramine compared with firstgeneration TCAs experienced at least one sideeffect (53 v. 64%). The OR was 0.6 (CI 0.5-0.7) and a recalculated RR gives 0.83 (0.77-0.89) indicating a 17% reduction with a range of 11-23%.…”

“…In a good-quality study Kerihuel & Dreyfus (1991)found patients responded better to lofepra mine than to older TCAs and maprotiline (mostly imipramine or amitriptyline; OR 1.4, CI 1.2-1.8). They were able to use 24out of 29 studies identified and verified the data of 602 of the total of 2040 patients using original case report forms.…”