A randomized, double‐blind, placebo‐ and risperidone‐controlled study on valnoctamide for acute mania

Abstract

Valnoctamide was well tolerated at 1500 mg/d but lacked efficacy in the treatment of symptoms in patients with acute mania. Possible differences between the biological mechanisms of action of valproic acid and valnoctamide are discussed.

Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development

“…Samples for the determination of plasma valnoctamide concentrations were collected at the end-of-study visit. 98 Valnoctamide did not differ significantly from placebo on any of the study endpoints. However, in the per-protocol analysis, changes in total YMRS scores showed a trend of significance (P = 0.17) in favor of valnoctamide.…”

“…These results suggest that valnoctamide, at least in combination with risperidone, might be efficacious in more severely affected population, particularly because it is known that in general more severely ill patients show greater therapeutic response to antimanic drugs . The limitations of the latest study are further highlighted in that in the same study risperidone itself failed to do better than placebo in improving the primary outcome measure, although it should be acknowledged that the sample size for the risperidone group was smaller . Overall, further studies on the therapeutic potential of valnoctamide as an antimanic medication appear to be justified, particularly in the light of its good tolerability and its lack of teratogenic activity in animal models, which is an incentive to assess valnoctamide for its potential efficacy in epilepsy as a second generation to valproic acid …”

“…The Clinical Global Impression Scale for Bipolar Disorder was also utilized, as well as the Positive and Negative Syndrome Scale to evaluate psychosis. Samples for the determination of plasma valnoctamide concentrations were collected at the end‐of‐study visit …”

“…99 The limitations of the latest study are further highlighted in that in the same study risperidone itself failed to do better than placebo in improving the primary outcome measure, although it should be acknowledged that the sample size for the risperidone group was smaller. 98 Overall, further studies on the therapeutic potential of valnoctamide as an antimanic medication appear to be justified, particularly in the light of its good tolerability and its lack of teratogenic activity in animal models, which is an incentive to assess valnoctamide for its potential efficacy in epilepsy as a second generation to valproic acid. 96,97 10 | CONCLUSIONS Review of the data presented at the EILAT XIV Conference, summarized in this report and in an accompanying article, 1 indicates that major efforts in preclinical and clinical research are continuing in order to develop novel AEDs.…”

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Antimanic efficacy has not been demonstrated for allopurinol (level 1 negative),167 eslicarbazepine/licarbazepine (level 2 negative),168 gabapentin (Level 2 negative), lamotrigine (level 1 negative),143 omega‐3 fatty acids (level 1 negative),169 topiramate (level 1 negative),143 valnoctamide (level 2 negative),170, 171 or zonisamide (level 2 negative)172 (Table 13). …”