Asenapine monotherapy in the acute treatment of both schizophrenia and bipolar I disorder

Pharmacy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, UK.
Neuropsychiatric Disease and Treatment (Impact Factor: 2.15). 10/2009; 5:483-90. DOI: 10.2147/NDT.S5742
Source: PubMed

ABSTRACT Asenapine is a new atypical antipsychotic agent currently under development for the treatment of schizophrenia and bipolar disorder. It has high affinity for various receptors including antagonism at 5HT(2A), 5HT(2B), 5HT(2C), 5HT(6) and 5HT(7) serotonergic receptor subtypes, alpha(1A), alpha(2A), alpha(2B) and alpha(2C) adrenergic and D(3) and D(4) dopaminergic receptors. As with other atypicals, asenapine exhibits a high 5HT(2A):D(2) affinity ratio. Although similar to clozapine in its multi-target profile, it shows no appreciable affinity for muscarinic receptors. Asenapine has shown efficacy in alleviating both positive and negative symptoms of schizophrenia compared with placebo. Although promising, further studies are required in order to determine whether it has advantages over placebo and other antipsychotics in alleviating cognitive impairment associated with schizophrenia. It has also shown long-term efficacy comparable with olanzapine in bipolar I disorder. Asenapine is generally well tolerated and appears to be metabolically neutral. It has low propensity to cause weight gain and prolactin elevation. There were no concerns in the studies about its effects on the cardiovascular system and QTc prolongation. The incidence of extrapyramidal symptoms with asenapine however has been found to be higher than that with olanzapine. It may be a useful alternative to aripiprazole in schizophrenia and bipolar disorder in patients who are at high risk of metabolic abnormalities.

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    ABSTRACT: Abstract Objective: Asenapine is the first tetracyclic antipsychotic approved in Canada for the treatment of schizophrenia (SCZ). Asenapine has shown a comparable efficacy profile to other atypical antipsychotics and it is associated with a favourable metabolic profile and less weight gain. This study aimed to assess the economic impact of asenapine compared to other atypical antipsychotics in the treatment of SCZ in Canada. Methods: A decision tree combined with a Markov model was constructed to assess the cost-utility of asenapine compared with other atypical antipsychotics. The decision tree takes into account the occurrence of extrapyramidal symptoms, the probability of switching to a different antipsychotic, and the probability of gaining weight. The Markov model takes into account long-term metabolic complications including diabetes, hypertension, coronary heart diseases, and stroke. In the base-case analysis, asenapine was compared to olanzapine. Asenapine was also compared with other atypical antipsychotics commonly used in Canada in alternative scenarios. Analyses were conducted from both Canadian Ministry of Health (MoH) and societal perspectives over a five-year time horizon. Results: In the treatment of SCZ, asenapine is a dominant strategy over olanzapine from both MoH and societal perspectives. Compared to quetiapine, asenapine is also a dominant strategy. Furthermore, asenapine has a favourable economic impact compared to ziprasidone and aripiprazole, as these antipsychotics are not cost effective compared to asenapine from both MoH and societal perspectives. Conclusion: Despite the short time horizon, the lack of compliance data and the assumptions made, this economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine and to most of the atypical antipsychotics frequently used in Canada.
    Journal of Medical Economics 02/2014; DOI:10.3111/13696998.2014.897627
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    ABSTRACT: Since the 1970s, clinicians have increasingly become more familiar with hyperprolactinemia (HPRL) as a common adverse effect of antipsychotic medication, which remains the cornerstone of pharmacological treatment for patients with schizophrenia. Although treatment with second-generation antipsychotics (SGAs) as a group is, compared with use of the first-generation antipsychotics, associated with lower prolactin (PRL) plasma levels, the detailed effects on plasma PRL levels for each of these compounds in reports often remain incomplete or inaccurate. Moreover, at this moment, no review has been published about the effect of the newly approved antipsychotics asenapine, iloperidone and lurasidone on PRL levels. The objective of this review is to describe PRL physiology; PRL measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in adolescent and adult patients; and revisit lingering questions regarding this hormone. A literature search, using the MEDLINE database (1966-December 2013), was conducted to identify relevant publications to report on the state of the art of HPRL and to summarize the available evidence with respect to the propensity of the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review shows that although HPRL usually is defined as a sustained level of PRL above the laboratory upper limit of normal, limit values show some degree of variability in clinical reports, making the interpretation and comparison of data across studies difficult. Moreover, many reports do not provide much or any data detailing the measurement of PRL. Although the highest rates of HPRL are consistently reported in association with amisulpride, risperidone and paliperidone, while aripiprazole and quetiapine have the most favorable profile with respect to this outcome, all SGAs can induce PRL elevations, especially at the beginning of treatment, and have the potential to cause new-onset HPRL. Considering the PRL-elevating propensity of the newly approved antipsychotics, evidence seems to indicate these agents have a PRL profile comparable to that of clozapine (asenapine and iloperidone), ziprasidone and olanzapine (lurasidone). PRL elevations with antipsychotic medication generally are dose dependant. However, antipsychotics having a high potential for PRL elevation (amisulpride, risperidone and paliperidone) can have a profound impact on PRL levels even at relatively low doses, while PRL levels with antipsychotics having a minimal effect on PRL, in most cases, can remain unchanged (quetiapine) or reduce (aripiprazole) over all dosages. Although tolerance and decreases in PRL values after long-term administration of PRL-elevating antipsychotics can occur, the elevations, in most cases, remain above the upper limit of normal. PRL profiles of antipsychotics in children and adolescents seem to be the same as in adults. The hyperprolactinemic effects of antipsychotic medication are mostly correlated with their affinity for dopamine D2 receptors at the level of the anterior pituitary lactotrophs (and probably other neurotransmitter mechanisms) and their blood-brain barrier penetrating capability. Even though antipsychotics are the most common cause of pharmacologically induced HPRL, recent research has shown that HPRL can be pre-existing in a substantial portion of antipsychotic-naïve patients with first-episode psychosis or at-risk mental state.
    CNS Drugs 03/2014; DOI:10.1007/s40263-014-0157-3 · 4.38 Impact Factor
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    ABSTRACT: Introduction: Asenapine is a second-generation (atypical) antipsychotic currently marketed for the treatment of schizophrenia and bipolar mania/mixed episodes. Areas covered: The purpose of this review is to describe the clinical profile of asenapine. Expert opinion: Asenapine's efficacy in the treatment of schizophrenia and in the acute management of bipolar manic or mixed episodes, within the recommended therapeutic dose range of 5 - 10 mg twice a day, is evidenced by a broad clinical development program. Asenapine's overall tolerability profile is notable for the potential for sedation (time-limited) and, to a lesser extent, extrapyramidal symptoms/akathisia, dizziness, and oral hypoesthesia. Asenapine's effects on weight and metabolic variables appear modest, as are its effects on the ECG QTc interval and on prolactin.
    Expert Opinion on Drug Safety 05/2014; DOI:10.1517/14740338.2014.908183 · 2.74 Impact Factor

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