olanzapine and Hypesthesia

Asenapine is a new second-generation antipsychotic that is understudied in borderline personality disorder (BPD). Only one study investigating the use of the drug in this indication (an open-label pilot study) has been conducted to date.. The present open-label, randomized, controlled trial aimed to evaluate the efficacy and tolerability of asenapine in comparison with olanzapine, the most broadly studied antipsychotic in BPD.. A total of 51 outpatients aged between 18 and 50 years with a diagnosis of BPD based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria were assigned for 12 weeks to asenapine (5-10 mg/day) or olanzapine (5-10 mg/day). Participants were assessed at baseline and after 12 weeks with the following instruments: the Clinical Global Impression Scale, Severity item (CGI-S), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Social Occupational Functioning Assessment Scale (SOFAS), Borderline Personality Disorder Severity Index (BPDSI), Barratt Impulsiveness Scale, version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self-Harm Inventory (SHI), and Dosage Record and Treatment Emergent Symptom Scale (DOTES). Analysis of variance repeated measures was performed. Intention-to-treat analysis with last observation carried forward was conducted.. There were 11 drop-outs (21.57%): six patients taking asenapine and five patients receiving olanzapine. Two patients who received asenapine stopped the drug, one due to oral hypoesthesia and the other due to moderate anxiety. Two patients receiving olanzapine discontinued the treatment because of significant weight gain (≥3 kg). The remaining seven drop-outs resulted from the lack of compliance with the trial prescription. Forty out of the 51 patients (78%) completed the trial: 19 patients received asenapine, while 21 patients received olanzapine. We found a significant within-subject effect (trial duration) for all rating scales, except from the HAM-D, the MOAS, and two items of the BPDSI, namely, "identity disturbance" and "parasuicidal behaviors." A significant effect between subjects was found for the two items of the BPDSI "affective instability" and "dissociation/paranoid ideation." Asenapine was found superior to olanzapine in reducing the affective instability score (P = 0.001), whereas olanzapine was found superior to asenapine in reducing dissociation/paranoid ideation (P = 0.012). However, the study was found to be underpowered to detect a difference between the drugs on the dissociation/paranoid ideation item of the BPDSI. Two patients receiving asenapine experienced akathisia and another two restlessness/anxiety, while three patients receiving olanzapine reported somnolence and two fatigue.. Asenapine and olanzapine were demonstrated to have a similar efficacy. While asenapine was found to be more efficacious than olanzapine in treating affective instability, olanzapine was superior to asenapine in treating paranoid ideation and dissociation. However, the study was underpowered to detect a difference between groups on the dissociation/paranoid ideation item. Both medications were well tolerated, with asenapine being related to a higher frequency of oral hypoesthesia and akathisia, and olanzapine being prone to induce weight gain. The open-label study design, lack of a placebo group, and small sample size constitute major limitations of this trial. Our findings need to be replicated in further studies. Clinical Trials Registry code: ACTRN12614000551695.

Topics: Adolescent; Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Borderline Personality Disorder; Dibenzocycloheptenes; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Hypesthesia; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome; Weight Gain; Young Adult

Evaluate the efficacy and safety of asenapine 2.5 mg twice daily (bid; n=97) or 5 mg bid (n=113) versus placebo (n=101) in adults with acute exacerbation of schizophrenia.. Adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) schizophrenia diagnosis were randomized to asenapine 2.5 mg bid, 5 mg bid, placebo, or olanzapine 15 mg once daily. The primary objective was to test superiority of asenapine versus placebo as measured by the change from baseline to day 42 in the Positive and Negative Syndrome Scale (PANSS) total score. The key safety objective was to evaluate weight change in asenapine versus olanzapine at day 42.. The primary efficacy endpoint was met; the difference in least squares mean change from baseline to day 42 in PANSS total score between asenapine 5 mg bid and placebo was -5.5 points (unadjusted 95% CI: -10.1, -1.0; multiplicity adjusted P=0.0356). Neither asenapine 2.5 mg bid nor olanzapine 15mg were superior to placebo. Both asenapine groups demonstrated significantly less weight gain than olanzapine at day 42. Significantly higher incidences of oral hypoesthesia and dysgeusia (combined) for asenapine 2.5 mg bid (5.2% vs 0.0%; P=0.0217) and 5 mg bid (7.1% vs 0.0%; P=0.0033) were observed versus placebo. There were no significant differences between asenapine and placebo for insomnia, extrapyramidal symptoms, akathisia, dizziness, or combination of somnolence/sedation/hypersomnia.. This study supports previous efficacy and safety findings of asenapine; asenapine 5 mg bid is the lowest effective dose in adults with schizophrenia. Asenapine was associated with significantly less weight gain than olanzapine at day 42.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzocycloheptenes; Disease Progression; Disorders of Excessive Somnolence; Dizziness; Double-Blind Method; Dysgeusia; Europe; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Hypesthesia; Least-Squares Analysis; Male; Mouth Diseases; Olanzapine; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Weight Gain