A Review of Asenapine in the Treatment of Bipolar Disorder

Abstract

Bipolar disorder places a significant burden on the affected individuals, their family, healthcare systems and the overall economy. More treatment options are needed, especially those with better efficacy and tolerability. Asenapine is a second-generation antipsychotic approved in Europe (brand name Sycrest®) for the treatment of moderate-to-severe manic episodes associated with bipolar I disorder in adults, and in the US (brand name Saphris®) for the treatment of manic or mixed episodes of bipolar I disorder in adults and children aged 10–17 years. It is the antagonistic activity at the D2 receptor that is likely responsible for the antimanic properties of asenapine. Clinical trials have demonstrated that asenapine mono- and add-on therapy is effective in the short- and long-term treatment of mania associated with bipolar I disorder in adult and paediatric patients. In addition, post hoc and pooled data analyses have shown that asenapine is effective in reducing clinically significant depressive symptoms in patients with bipolar I disorder. The most common adverse events associated with asenapine are somnolence, dizziness, extrapyramidal symptoms, increased bodyweight and oral hypoesthesia. However, the incidence of these events, particularly weight gain, is generally lower than with olanzapine. In one study, asenapine has been shown to improve health-related quality of life. Economic analyses indicate that the use of asenapine can, over time, lead to a reduction in the costs of treatment.

Asenapine: an atypical antipsychotic with atypical formulations

“…A black-cherry formulation is available to possibly lessen the unpleasant taste. 65 The etiology of the oral hypoesthesia is likely attributable to local anesthetic activity; however, the effects are typically transient and resolve within 1 h. 66 , 67 …”

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

“…The FDA approved asenapine for the treatment of schizophrenia (331) and bipolar disorders (332) in 2019. This drug is a new AAP with unique features that was introduced in Japan in 2016, and it is the only AP used sublingually; its chemical structure of (±)-Asenapine can be described as a tetracyclic framework wherein N-methylpyrrolidine ring fuses at third and fourth positions with chlorophenyl phenyl ether in a trans geometry (333) (see Figure 1).…”

“…Asenapine displays more potent antagonist activity toward 5-HT 2A receptor than D2 receptor (337,338), that is why it has a low propensity to cause PRL elevation (331,339,340); Therefore, this drug is one of the AP treatments of choice for breast cancer patients (341). Nevertheless, research groups reported that 2.3% of patients with bipolar disorder who received asenapine monotherapy had PRL levels ≥ 4 times the upper limit of the normal range, compared with those who received a placebo (332,342), In contrast, 9% of patients with schizophrenia who received asenapine (5 and 10 mg twice daily) had PRL levels over 2-fold the upper limit of the normal range compared with those who received a placebo (343).…”

The Influence of Long-Term Treatment with Asenapine on Liver Cytochrome P450 Expression and Activity in the Rat. The Involvement of Different Mechanisms

“…Asenapine is a novel atypical antipsychotic drug approved for the treatment of schizophrenia, ameliorating both positive and negative symptoms [ 24 , 25 , 26 , 27 ]. Asenapine has been also recommended for the treatment of manic/mixed episodes with or without psychotic features associated with bipolar I disorder, such as manic-depressive bipolar disorder [ 28 , 29 , 30 ]. As asenapine is a tetracyclic member of the dibenzooxepinopyrroles, derived from the tetracyclic antidepressant mianserin, it would be expected to have also an antidepressant effect [ 31 , 32 ].…”