An open pilot study of zonisamide augmentation in major depressive patients not responding to a low dose trial with duloxetine: preliminary results on tolerability and clinical effects

Abstract

BackgroundDespite multiple antidepressant options, major depressive disorder (MDD) still faces high non-response rates, eventually requiring anticonvulsant augmentation strategies too. The aim of this study was to explore such a potential role for zonisamide.MethodsA total of 40 MDD outpatients diagnosed using the Diagnostic and Statistical Manual for Mental Disorders, fourth edition criteria entered a 24 week open trial receiving duloxetine 60 mg/day for the first 12 weeks and subsequently (weeks 12 to 24) augmentation with zonisamide 75 mg/day if they did not respond to the initial monotherapy. Efficacy and tolerability were assessed using the Hamilton Scales for Anxiety and Depression (a 12 week score ≥50% vs baseline defined 'non-response'), the Arizona Sexual Experience Scale, the Patient Rated Inventory of Side Effects and the Young Mania Rating Scale.ResultsAt week 12, 15 patients out of 39 (38.5%) were responders, and 1 had dropped out; remarkably, 14 patients out of 24 (58.3%) had achieved response by week 24. Poor concentration and general malaise were associated with non-response both at week 12 and 24 (P = 0.001), while loss of libido and reduced energy were prominent among final timepoint non-responders. Patients receiving zonisamide also experienced weight reduction (2.09 ± 12.14 kg; P = 0.001) independently of the outcome.ConclusionsAlthough only a preliminary study due to strong methodological limitations, and thus requiring confirmation by further controlled investigations, the current results indicate zonisamide may be a potential augmentation option for some depressed patients receiving low doses of duloxetine.

The safety and long-term efficacy of zonisamide as adjunctive therapy for focal epilepsy

“…Long-term treatment has, however, only rarely reported depression as a relevant factor for drug withdrawal [40], and concordantly only one case of depression was reported in the long-term studies discussed here [29]. Interestingly, ZNS has also been reported to exert positive effects on mood in certain therapeutic settings [41].…”

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review

“…Finally, zonisamide was evaluated as a possible augmentation strategy in the treatment of TRD subjects, in consideration of partial pharmacodynamic overlap with lamotrigine, as well as the possible effect on the serotonergic system; the authors concluded that zonisamide might be a potential augmentation option for MDD patients not responding to duloxetine [ 90 ].…”

Investigating psychotropic properties of antiepileptic drugs

“…Most of them have demonstrated good efficacy in the treatment of acute mania, in particular CBZ [62], PHT [63], OXC [64] and possibly ZNS [65], although results for the latter are still controversial [66]. It will be, thus, of interest to have data on new compounds such as ESL and LCM.…”