Asenapine: a less effective, yet, more dangerous neuroleptic!

The preferred treatment for manic episodes in patients with bipolar disorder is lithium, a "mood stabiliser". A well-documented neuroleptic such as haloperidol may be added when severe psychotic symptoms are also present. Asenapine, an "atypical" neuroleptic, is authorised in the European Union solely for the treatment of manic episodes in patients with bipolar disorder. It is administered sublingually, because oral absorption is virtually zero. Clinical evaluation of asenapine includes no trials versus lithium or versus another neuroleptic in patients also receiving lithium. Two double-blind randomised trials versus both placebo and olanzapine included a total of 976 patients. Another double-blind randomised placebo-controlled trial included 323 patients who were also receiving a mood stabiliser. In two of these three trials, the clinical relevance of the differences found between the asenapine and placebo groups was questionable. A comparison between asenapine and olanzapine, not planned in the protocol, favoured olanzapine. Serious adverse events were more common in the asenapine groups than in the groups receiving other neuroleptics. The adverse effect profile of asenapine largely overlaps that of other atypical neuroleptics. However, asenapine can also cause oral hypoaesthesia and severe hypersensitivity reactions (angioedema, hypotension, skin reactions, etc).Tardive dyskinesia has also been reported with asenapine. Sublingual administration may be impractical during a manic episode. Other neuroleptics are available for patients who have difficulty swallowing, such as oral solutions and orodispersible tablets. In practice, clinical trials of asenapine were not designed to answer questions posed by healthcare professionals and patients. Asenapine is no more effective or convenient to use than other neuroleptics, while it carries a risk of additional, sometimes severe, adverse effects. Patients with manic episodes should continue to receive lithium first, combined with a well-documented neuroleptic such as haloperidol if they have severe psychotic symptoms.