One of the main difficulties in assessing the utility of asenapine over other antipsychotics across negative, and cognitive symptoms, is the general lack of published data on these two domains. Asenapine certainly appears to confirm to the standards of antipsychotics as it reduces positive symptomology in patients with schizophrenia. The effects of asenapine on negative and cognitive symptoms are however less clear. While there is some evidence of beneficial effects on negative and cognitive symptoms [40
], these effects have primarily been reported in abstract format [40
] and require further long-term evidence. It must be made clear, that although similar equivocal data are found for other antipsychotics being used today, those antipsychotics have at least more extensively published studies to draw conclusions from. The advantages, if any, that asenapine will have over its competitors will be in terms of weight gain and route of administration.
Asenapine is administered using sublingual tablets, which could be an advantage in a patient population as it is less likely to be ‘cheeked’. As it only takes 10 s for asenapine to dissolve, the tablet is unlikely to be ingested in a manner that would reduce its bioavailability. The disadvantage of this route of administration is, however, that patients cannot eat or drink for 10 min after ingestion. Given that asenapine is reported to have a bitter taste, strict compliance with the administration instructions may prove challenging for patients, especially as the drug has to be taken twice daily in comparison to once-a-day dosing for most other antipsychotic agents (ziprasidone is also dosed twice daily). The twice daily dosing requirement confers its own disadvantage independent of the sublingual administration, as increases in dosing frequencies appear to have a significant negative effect on schizophrenia patients’ adherence to antipsychotic medication regimens [62
]. Thus compliance may prove to be one of the primary issues psychiatrists consider when choosing whether or not to prescribe asenapine.
Two major advantages asenapine may have are less EPS than typical antipsychotics and less weight gain than some other atypical antipsychotics, observed in both short- and long-term studies. Moreover, asenapine has no appreciable effect on glucose and lipids. Thus physicians may elect to switch patients who have gained substantial weight from other “tried and true” atypicals (e.g., olanzapine) to asenapine.
While extensive studies on pro-cognitive effects have yet to be published for asenapine, some data can be gleaned from animal studies. It is apparent that asenapine can improve executive functioning in rats, albeit in rats with medial prefrontal cortical lesions [63
]. Although no patient with schizophrenia equates to frontal lobe lesioned patients, there are some similarities in executive dysfunction [64
]. We are not suggesting here that prefrontal lesioned rats are a model for schizophrenia, nor did the authors [63
], but the cognitive profile of asenapine may be further elucidated by assessing the effects of the drug in frontal lobe lesioned patients. Moreover, the doses used in this study were lower than those used to counter amphetamine-induced hyperactivity or apomorphine-induced disruption in PPI [20
]. Given that the 5 mg tablet may produce D2
receptor occupancy at higher levels than is required for the demonstration of antipsychotic activity derived from other antipsychotics [28
], perhaps a lower dose formulation could be assessed. Further support for such a formulation comes from the suggestion that asenapine may not impair cognitive functioning as measured by attention and short term memory in normal rats until sedative doses are reached, unlike olanzapine and risperidone [20
The possibility of using lower doses is perhaps emphasized from clinical data in patients with bipolar disorder, as asenapine (albeit at the 10 mg BID dose) has been indicated to treat acute mania also [65
]. Given that the 10 mg twice daily dose may cause more adverse effects in the form of akathisia but hasn’t been shown to be substantially more effective in treating schizophrenia, lower doses of asenapine than 5 mg may also be worth testing. The research from asenapine effects on bipolar disorder also suggests that physicians who have patients with a prominent mood component (i.e., symptoms of mania) to their schizophrenia may find asenapine useful.
Ultimately, more long term studies are required for asenapine before definitive judgments on its utility in the treatment of schizophrenia can be made. Asenapine certainly proves efficacious in acute schizophrenia, but its putative less deleterious effects on cognition will only be disseminated following long-term studies. Given the data on cognition from animal work, which can inform research when assessed in the MATRICS test battery of cognition for schizophrenia [39
], lower doses and tests selective for cognitive domains should be employed in these longer term studies.