Iloperidone, asenapine, and lurasidone: a brief overview of 3 new second-generation antipsychotics.
ABSTRACT Three new second-generation antipsychotics were approved by the US Food and Drug Administration in 2009 and 2010: iloperidone, asenapine, and lurasidone. All 3 agents are approved for the treatment of acute schizophrenia in adults, and asenapine is also approved for the maintenance treatment of schizophrenia and as a monotherapy or as an adjunct to lithium or valproate for the treatment of bipolar manic or mixed episodes. The expectation is that these new agents will be less problematic regarding treatment-emergent weight gain and metabolic disturbances, which unfortunately can occur with several other second-generation antipsychotics. Asenapine is a sublingual preparation, in contrast to iloperidone and lurasidone, which are swallowed. Iloperidone and asenapine are dosed twice daily, in contrast to lurasidone, which is dosed once daily with food. Both asenapine and lurasidone can be initiated at a dose that is possibly therapeutic, but iloperidone requires 4 days of titration to reach its recommended target dose range. Although both asenapine and lurasidone can be associated with dose-related treatment-emergent akathisia, iloperidone is essentially free of extrapyramidal adverse effects or akathisia throughout its recommended dose range. Sedation and/or somnolence have been reported with each medication. They are the most common adverse events associated with asenapine treatment, and are clearly dose-related for lurasidone. In contrast, no therapeutic dose response for iloperidone, asenapine, or lurasidone is clearly evident from short-term clinical trials. Longer-term and naturalistic studies will be helpful in evaluating these agents and their role in the psychiatric armamentarium.
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ABSTRACT: Evidence-based medicine (EBM) is a broad concept, but the key elements include the incorporation of clinical judgment (which requires clinical experience) together with relevant scientific evidence while remaining mindful of the individual patient's values and preferences. Using the framework and philosophy of EBM, this systematic review summarizes the pharmacology, efficacy, and tolerability of newly approved oral antipsychotics, including iloperidone, asenapine, and lurasidone, and outlines what is known about agents that are in late-stage clinical development, such as cariprazine, brexpiprazole, zicronapine, bitopertin, and EVP-6124. Potential advantages and disadvantages of these agents over existing antipsychotics are outlined, centered on clinically relevant issues such as the potential for weight gain and metabolic abnormalities, potential association with somnolence/sedation, extra-pyramidal side effects, akathisia, and prolongation of the electrocardiogram (ECG) QT interval, as well as practical issues regarding dosing instructions, titration requirements, and drug-drug interactions. Lurasidone appears to be best in class in terms of minimizing untoward alterations in body weight and metabolic variables. However, iloperidone, asenapine, lurasidone, and cariprazine differ among themselves in terms of on-label dosing frequency (once daily for lurasidone and, presumably, cariprazine versus twice daily for iloperidone and asenapine), the need for initial titration to a therapeutic dose for iloperidone and possibly cariprazine, requirement to be taken sublingually for asenapine, requirement for administration with food for lurasidone, lengthening of the ECG QT interval (greater for iloperidone than for asenapine and no effect observed with lurasidone), and adverse effects such as akathisia (seen with cariprazine, lurasidone, and asenapine but not with iloperidone) and sedation (most notable with asenapine).CNS Drugs 09/2013; · 4.38 Impact Factor
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ABSTRACT: Lurasidone is a benzisothiazol derivative and an atypical antipsychotic approved by the US Food and Drug Administration for the acute treatment of adults with schizophrenia (October 2010) and bipolar 1 depression (June 2013). Lurasidone has a strong antagonistic property at the D2, serotonin (5-HT)2A, and 5-HT7 receptors, and partial agonistic property at the 5-HT1A receptor. Lurasidone also has lower binding affinity for the α2C and 5-HT2C receptor. Lurasidone is rapidly absorbed (time to maximum plasma concentration: 1-3 hours), metabolized mainly by CYP3A4 and eliminated by hepatic metabolism. In two large, well-designed, 6-week trials in adult patients with bipolar 1 depression, lurasidone monotherapy and adjunctive therapy with mood stabilizers were significantly more effective than placebo at improving depressive symptoms assessed using the Montgomery-Åsberg Depression Rating Scale total score. In both trials, lurasidone also reduced the Clinical Global Impression-Bipolar Severity depression score to a greater extent than placebo. In these two trials, discontinuation rates due to adverse events in the lurasidone group were small (<7%) and were not different from those of the placebo group. The most common adverse events in the lurasidone group were headache, nausea, somnolence, and akathisia. The changes in lipid profiles, weight, and parameters of glycemic control were minimal, and these findings were in line with those observed in schizophrenia trials. Further active comparator trials and long-term tolerability and safety data in bipolar patients are required. Lurasidone may be an option for the management of depressive symptoms in patients with bipolar 1 disorder, and it may be considered as a treatment alternative for patients who are at high risk for metabolic abnormalities.Neuropsychiatric Disease and Treatment 01/2013; 9:1521-1529. · 2.15 Impact Factor
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ABSTRACT: Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity.The Journal of clinical investigation 08/2013; · 15.39 Impact Factor