A multi-centre,randomised, double-blind,placebo-controlled clinical trial of methylphenidate in the initial treatment of acute mania (MEMAP study)

Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).     

Sustained-release methylphenidate in methamphetamine dependence treatment: a double-blind and placebo-controlled trial

Background

The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of sustained-release methylphenidate (MPH-SR) in treatment of methamphetamine dependence.

Methods

Fifty-six individuals who met DSM-IV-TR criteria for methamphetamine dependence participated in this 10-week trial. The participants were randomly allocated into two groups and received 18 to 54 mg/day sustained-released methylphenidate or placebo for 10 weeks. Craving was evaluated by a visual analogue craving scale every week. Urinary screening test for methamphetamine was carried out each week. The Beck Depression Inventory-II (BDI-II) was used to monitor participant depressive symptoms at baseline and bi-weekly during the treatment period.

Results

At the end of the trial, the MPH-SR group was less methamphetamine positive compared to the placebo group and the difference was significant (p = 0.03). By the end of the study, MPH-SR group showed significantly less craving scores compared to the placebo group [MD (95% CI) = -10.28(0.88-19.18), t(54) = 2.19, p = 0.03]. There was greater improvement in the depressive symptoms scores in the intervention group compared to the placebo group [MD (95% CI) =2.03(0.31-3.75), t (54) =2.37, p = 0.02].

Conclusion

Sustained-released methylphenidate was safe and well tolerated among active methamphetamine users and significantly reduced methamphetamine use, craving and depressive symptoms.

Trial registration

IRCT201202281556N38     

小儿智力糖浆联合盐酸哌甲酯片治疗儿童注意缺陷多动障碍的疗效观察

目的探讨小儿智力糖浆联合盐酸哌甲酯片治疗儿童注意缺陷多动障碍的临床疗效。方法选择2012年1月—2014年12月重庆市开县人民医院儿科收治儿童注意缺陷多动障碍患者90例,随机分为对照组和治疗组,每组45例。对照组患者口服盐酸哌甲酯片,2片/次,1次/d。治疗组患者在对照组的治疗基础上口服小儿智力糖浆,10 m L/次,2次/d。3周为1个疗程,全部患者均治疗3个疗程。观察两组的临床疗效,同时比较两组治疗前后Conner行为评定量表各因子评分及不良反应情况。结果治疗后,对照组和治疗组总有效率分别为77.78%、88.89%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者冲动多动、多动指数、学习问题、品行问题、焦虑、身心问题评分均较较治疗前显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组治疗后各评分均显著低于对照组,两组比较差异有统计学意义(P0.05)。两组不良反应发生率比较差异无统计学意义。结论小儿智力糖浆联合盐酸哌甲酯片治疗儿童注意缺陷多动障碍,能够显著提高临床疗效,且无严重不良反应,具有一定的临床推广价值。     

Psychosis in a cocaine-dependent patient with ADHD during treatment with methylphenidate

Objective

The objective was to report a case of experienced psychosis during the treatment with methylphenidate (MPH) in a cocaine-dependent adult treated for attention-deficit/hyperactivity disorder (ADHD) with comorbid cocaine dependence.

Conclusion

ADHD is a frequent comorbidity in substance use disorder (SUD) patients. MPH may be effective in treating ADHD symptoms in SUD patients, thus preventing possible adverse outcomes. Cocaine-induced psychosis may be a risk factor for development of psychosis in the presence of a concurrent treatment with MPH.     

A Postmarketing Clinical Experience Study of Metadate® CD

Summary

Objective:The objective of the study was to investigate the effectiveness and safety of Metadate® CD (methylphenidate HCl, USP) Extended Release Capsules in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), in actual clinical practice.

Method:This was a multicenter, open-label, postmarketing study. Eligible patients were aged 6-17 with a diagnosis of ADHD and receiving either no treatment or maintenance treatment with another approved methylphenidate (MPH) product. Metadate® CD was administered once daily for 3 weeks, titrated against reported and observed symptoms. Clinical Global Impression (CGI) scores at Week 3 were used for the primary efficacy evaluation. Patient treatment satisfaction was determined by questionnaire at the final evaluation visit. Safety was assessed through adverse event reporting, laboratory tests and vital sign measurements.

Results: Overall, of the 308 patients in the Intent-To-Treat population, the majority (65%) demonstrated a positive response to Metadate® CD (defined as CGI Global Improvement rating of very much or much improved). In addition, patients previously treated with immediate-release or extended-release tablet formulations of MPH were successfully converted to Metadate® CD at a comparable dose. Most patients (87%) were very satisfied or moderately satisfied with study treatment, and among previously treated patients, 71% rated Metadate® CD as much better or better than their previous MPH treatment. Adverse events were consistent with current FDA-approved product labeling for Metadate® CD.

Conclusions: Metadate® CD is effective and well-tolerated in actual clinical use for ADHD.     

Neuroimaging markers for the prediction of treatment response to Methylphenidate in ADHD

BackgroundAttention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent mental disorders of childhood, which often continues into adulthood. Methylphenidate is one the most commonly used medication to treat ADHD, however up to 30% of patients do not respond to it.AimsThis paper aims to review studies, which employed neuroimaging to predict treatment response to Methylphenidate in ADHD.MethodsSystematic literature searches were performed using several databases. Selected articles had to describe an original study that identified neuroimaging markers for the prediction of treatment response to Methylphenidate in ADHD.ResultsEighty-three articles were found, of which twelve were selected for the present review. Several neuroimaging markers to predict response to MPH were suggested including DAT status, size of medial prefrontal cortex and corpus callosum.ConclusionSome promising findings have been identified and they should motivate additional work to establish more reliable neuroimaging markers of treatment response to MPH in ADHD.