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A review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: an evidence-based medicine approach.
CNS Drugs. 2013 Nov; 27(11):879-911.CD

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).

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Authors+Show Affiliations

Citrome L
New York Medical College, Valhalla, NY, USA, citrome@cnsconsultant.com.

MeSH

Administration, OralAntipsychotic AgentsBipolar DisorderDrug ApprovalEvidence-Based MedicineHumansRandomized Controlled Trials as TopicSchizophreniaTreatment Outcome

Pub Type(s)

Journal Article
Review
Systematic Review

Language

eng

PubMed ID

24062193

Citation

Citrome, Leslie. "A Review of the Pharmacology, Efficacy and Tolerability of Recently Approved and Upcoming Oral Antipsychotics: an Evidence-based Medicine Approach." CNS Drugs, vol. 27, no. 11, 2013, pp. 879-911.
Citrome L. A review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: an evidence-based medicine approach. CNS Drugs. 2013;27(11):879-911.
Citrome, L. (2013). A review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: an evidence-based medicine approach. CNS Drugs, 27(11), 879-911. https://doi.org/10.1007/s40263-013-0105-7
Citrome L. A Review of the Pharmacology, Efficacy and Tolerability of Recently Approved and Upcoming Oral Antipsychotics: an Evidence-based Medicine Approach. CNS Drugs. 2013;27(11):879-911. PubMed PMID: 24062193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: an evidence-based medicine approach. A1 - Citrome,Leslie, PY - 2013/9/25/entrez PY - 2013/9/26/pubmed PY - 2014/6/3/medline SP - 879 EP - 911 JF - CNS drugs JO - CNS Drugs VL - 27 IS - 11 N2 - 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). SN - 1179-1934 UR - https://www.unboundmedicine.com/medline/citation/24062193/A_review_of_the_pharmacology_efficacy_and_tolerability_of_recently_approved_and_upcoming_oral_antipsychotics:_an_evidence_based_medicine_approach_ L2 - https://dx.doi.org/10.1007/s40263-013-0105-7 DB - PRIME DP - Unbound Medicine ER -