Asenapine is an atypical
antipsychotic agent available in sublingual formulations (5 or 10 mg) and indicated in the US (
Saphris) for the acute treatment, as monotherapy or adjunctive
therapy, of manic and mixed episodes and in the EU (Sycrest) for the treatment of moderate to severe
manic episodes, in adult patients with bipolar I disorder. In two large (both n = 480), well designed, 3-week trials in adult patients with bipolar I disorder,
asenapine monotherapy was significantly more effective than placebo at improving
mania symptoms, as assessed using the Young
Mania Rating Scale total score (YMRS; primary endpoint), with significant differences between the
asenapine and placebo groups occurring after 2 days of treatment. In both trials, Clinical Global Impression for
Bipolar Disorder (CGI-BP) scale
mania severity scores exceeded those of placebo. In one trial, response and remission rates exceeded those of placebo. In a 9-week extension study that recruited completers from the monotherapy trials, there were no significant differences between
asenapine and
olanzapine groups in terms in Montgomery-Åsberg Depression Rating Scale (MADRS) scores, CGI-BP
mania severity scores, YMRS response rates or YMRS remission rates during the extension phase. In the extension study, the efficacy of
asenapine monotherapy appeared to be maintained over 40 weeks (total
treatment duration of 52 weeks). In a 12-week trial of
asenapine as adjunctive
therapy to
lithium or
valproate,
asenapine was more effective than placebo in improving manic symptoms, based on the difference between groups in the YMRS total score at week 3 (primary endpoint). Most adverse events associated with
asenapine were of mild to moderate severity, with <7% of
asenapine recipients experiencing serious adverse events (vs 7% with placebo). In a pooled analysis of the monotherapy trials, the most common adverse events (occurring in ≥ 5% of patients and at twice the incidence of placebo) reported during acute phase
asenapine monotherapy for bipolar
mania were
somnolence,
dizziness, extrapyramidal symptoms (EPS, other than
akathisia) and increased bodyweight, which were similar in nature to those occurring during longer-term monotherapy with
asenapine. EPS did not worsen in severity during longer-term
asenapine monotherapy.
Asenapine had minimal effects on plasma
glucose,
lipid and
prolactin levels over both short- and longer-term treatment periods, and had little pro-arrhythmogenic potential. Further active comparator trials and longer-term tolerability and safety data are required. In the meantime,
asenapine is a further option for the management of manic and/or mixed symptoms in patients with bipolar I disorder and may be of particular value for patients who are at high risk for metabolic abnormalities.