Osmotic-release oral system methylphenidate augmentation of antidepressant monotherapy in major depressive disorder: results of a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of adjunctive osmotic-release oral system (OROS) methylphenidate in outpatients with major depressive disorder (MDD) receiving a stable oral antidepressant regimen. METHOD: This multicenter, double-blind, randomized, placebo-controlled, parallel-group, 5-week trial enrolled 145 subjects who met DSM-IV-TR criteria for MDD and who had failed 1 to 3 previous antidepressant monotherapies (including current antidepressant) of adequate dose and duration. Augmentation therapy was initiated with 18 mg of OROS methylphenidate and increased to a maximum dose of 54 mg of OROS methylphenidate until an optimal dose was achieved. Efficacy scales included the Montgomery-Asberg Depression Rating Scale (MADRS), 7 atypical items from the 31-item Hamilton Rating Scale for Depression, the Clinical Global Impressions-Severity of Illness (CGI-S) scale, the CGI-Improvement scale (CGI-I), the Sex Effects scale, the Multidimensional Assessment of Fatigue (MAF) scale, and the Apathy Evaluation Scale (AES). Subjects were recruited at 17 community and academic centers across Canada. The study was conducted from June 8, 2005, to April 18, 2006. RESULTS: There was no statistically significant difference between the groups at endpoint on the MADRS. OROS methylphenidate was superior to placebo in improving apathy and fatigue as measured by the AES and the MAF. Statistically significant differences using mixed-model analysis were observed on the AES at all visits and at endpoint (p = .01) and on the MAF (p < .01). No differences were observed on other secondary measures, including the CGI-I and CGI-S. There were no clinically significant findings on electrocardiogram. CONCLUSIONS: OROS methylphenidate did not demonstrate statistical significance on the MADRS at endpoint. Apathy and fatigue were significantly improved with OROS methylphenidate treatment, which was well tolerated with minimal side effects. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00246233.

Do formulation switches exacerbate existing medical illness? Results of an open-label transition to orally disintegrating risperidone tablets.

BACKGROUND: Orally disintegrating risperidone tablets (Risperdal* M-TABs*) present an alternative method of drug delivery that may benefit physicians struggling to treat non-compliant patients, since it begins to dissolve within 5 s, preventing tablet cheeking or spitting. OBJECTIVES: To evaluate safety and maintenance of effect in symptomatically stable patients transitioned from compressed risperidone tablets to orally disintegrating risperidone tablets. METHODS: This open-label, multi-centre study enrolled 82 adults from four diagnostic groups (major depressive disorder (MDD), n = 25; bipolar disorder (BP), n = 21; dementia (DE), n = 20; schizophrenia (SZ), n = 16). Patients were switched from their previous dosage of compressed tablets (0.5, 1.0, 2.0, 3.0, or 4.0 mg/day) to an equivalent dosage of orally disintegrating risperidone and followed for 4 weeks. The primary effectiveness parameter evaluated was the Clinical Global Impression-Severity (CGI-S) scale. RESULTS: Most patients (24/25 MDD; 20/21 BP; 17/18 DE; 14/15 SZ) improved by 1 point on CGI-S from baseline or experienced no change at endpoint. Adverse events (AEs) occurring in any group at a > or =10% incidence included headache (19%) and pharyngolaryngeal pain (10%), reported in the BP group only. CONCLUSIONS: Patients stabilized on compressed risperidone tablets transitioned to the equivalent dose of orally disintegrating risperidone tablets with continued maintenance of effect, no decompensation and with minimal side effects.

A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder.

BACKGROUND: The thrice daily dosing regimen of immediate release methylphenidate (IR-MPH) for Attention Deficit/Hyperactivity Disorder (ADHD) requires in-school dosing, leading to issues surrounding dispensing and storage of controlled substances by school personnel and concerns over children?s privacy and the embarrassment associated with taking medication in public at school. OROS-methylphenidate (OROS-MPH) is a once-daily controlled-release formulation of methylphenidate (MPH) developed to overcome some of the limitations associated with IR-MPH and first-generation sustained-release formulations. Randomized, controlled trials (RCTs) that focus on treatment efficacy provide the best evidence for demonstrating whether an intervention works, but under ideal conditions one cannot discount the importance of efficacy study results. However, the most useful information to clinicians comes from an effectiveness study design. OBJECTIVES: To evaluate the effectiveness and tolerability of OROS-MPH versus usual care with IR-MPH in children aged 6 to 12 years with ADHD. METHODS: This 8 week, multicentre, open-label study randomized 147 subjects to either once-daily OROS-MPH or usual care with IR-MPH. Subjects were titrated to a clinically effective dose of either study medication over 4 weeks and maintained on that dose for an additional 4 weeks. The SNAP-IV parent-rating scale was used to assess effectiveness. RESULTS: OROS-MPH showed statistically significant superiority to IR-MPH in remission rate based on the 18 ADHD symptoms (p=0.0002, X2=13.8, df=1) and severity of ADHD and ODD symptoms (p=0.004, F=8.4, df=1,127), as well as on the following secondary assessments: IOWA Conners, Conners Parent Rating Scale (short version), Parent Stress Index, (short version); Visual Analogue Scale for social play; Clinical Global Impression-Severity, Clinical Global Impression-Improvement and Parent Satisfaction with treatment. OROS-MPH and IR-MPH were both well tolerated with a similar side effect profile. CONCLUSIONS: Once-daily OROS-MPH is significantly more effective than usual care with IR-MPH based on multiple outcome measures including remission rate.

Risperidone reduces aggression in boys with a disruptive behaviour disorder and below average intelligence quotient: analysis of two placebo-controlled randomized trials.

The present study aimed to analyse the effect of risperidone on a priori defined core aggression items. Data were pooled from 163 boys (aged 5-12 years, with or without comorbid attention-deficit/hyperactivity disorder) with a DSM-IV diagnosis of either conduct disorder or oppositional defiant disorder who had participated in either of two identical, 6-week, randomized, double-blind, placebo-controlled trials. All received treatment with either placebo or oral risperidone solution (0.01-0.06 mg/kg/day). Subjects had below average intelligence [intelligence quotient (IQ) 36-84] and a score of > or =24 on the Conduct Problem subscale of the Nisonger Child Behaviour Rating Form (N-CBRF). An expert advisory panel selected six core aggression items from the N-CBRF, from which a total Aggression Score (AS, range 0-18) was constructed. Compared to those treated with placebo, risperidone-treated subjects experienced significantly greater mean decreases from baseline in the AS at each of weeks 1-6 (P<0.001). By study endpoint, aggression among risperidone-treated subjects had declined by 56.4% (mean baseline AS 10.1; mean endpoint AS 4.4), which was more than twice that of placebo-treated subjects (mean baseline AS 10.6; mean endpoint AS 8.3; 21.7% reduction). Risperidone was efficacious in reducing symptoms of aggression in boys of below average IQ with disruptive behaviour disorders.