title: Asenapine as adjunctive treatment for acute mania associated with bipolar disorder: results of a 12-week core study and 40-week extension.
abstract: In a 12-week randomized, placebo-controlled study evaluating the efficacy and safety of adjunctive asenapine, bipolar I disorder patients experiencing manic or mixed episodes despite pretreatment with lithium or valproate monotherapy were treated with flexible-dose, twice-daily asenapine 5 or 10 mg (n = 158) or placebo (n = 166). The primary efficacy end point was change from baseline Young Mania Rating Scale (YMRS) total score at week 3. Secondary outcomes included YMRS response and remission and Clinical Global Impression for Bipolar Disorder and Montgomery-Asberg Depression Rating Scale score changes. Patients completing the core study were eligible for a 40-week double-blind extension assessing safety and tolerability. Adjunctive asenapine significantly improved mania versus placebo at week 3 (primary end point) and weeks 2 to 12. The YMRS response rates were similar at week 3 but significantly better with asenapine at week 12. The YMRS remission rates and changes from baseline on Clinical Global Impression for Bipolar Disorder for mania and overall illness were significantly better with asenapine at weeks 3 and 12. No other statistically significant differences on secondary outcomes were observed. Only a small number of patients entered the extension, making firm statistical conclusions on efficacy difficult. Treatment-emergent adverse events reported by 5% or more of asenapine patients and at twice the incidence of placebo were sedation, somnolence, depression/depressive symptoms, oral hypoesthesia, and increased weight in the 12-week core study. Adjunctive asenapine to lithium or valproate was more effective than mood stabilizer monotherapy in the core study and was well tolerated for up to 52 weeks.
authors.affiliation: Merck, Rahway, NJ 07065, USA. armin.szegedi@merck.com
authors.forename: Armin
authors.initials: A
authors.lastname: Szegedi
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.forename: Let
authors.initials: L
authors.lastname: Stet
authors.forename: Mary
authors.initials: M
authors.lastname: Mackle
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: John
authors.initials: J
authors.lastname: Panagides
mesh_terms: D000208:Acute Disease; D000328:Adult; D000339:Affect / Q000187:drug effects; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D003986:Dibenzocycloheptenes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D016651:Lithium Carbonate; D014635:Valproic Acid; C522667:asenapine