Efficacy Of Modafinil Research Articles

Role of modafinil in the treatment of patients with methamphetamine dependence; An update on randomized, controlled clinical trial

Purpose: Methamphetamine is a powerful, highly addictive stimulant which affects the central nervous system. Here we evaluated the efficacy of modafinil for the treatment of patients with MA dependence.Methods: A randomized parallel controlled trial study was designed to compare the effectiveness of take-home, self-administered modafinil treatment in the intervention and the controlled group in three months. The primary outcome measurements were severity and duration of craving, and self-reported methamphetamine consumption, which was confirmed by urine drug test.Results: The relapse rate in the intervention group was 40%, and the controlled group was 75%, indicating a decrease in relapse rate of MA in the intervention group. During the three months, the severity and the duration of the drug abuse craving in the intervention group were less than thecontrolled group. Patients in the intervention group experienced an increase in the retention rate and a decrease in the slip rate.Conclusion: The use of modafinil is not only effective on craving and relapse reduction, but also changes urine drug screens of patients with MA dependence to negative. The modafinil is safely indicated as an absolutely effective medication to reduce withdrawal symptoms and the craving ofpatients with MA dependence.
 Keywords: Modafinil, Methamphetamine dependence, Effectiveness, Clinical trial

The Efficacy of Modafinil as a Cognitive Enhancer: A Systematic Review and Meta-Analysis.

Animal models and human studies have identified the potential of modafinil as a cognitive enhancing agent, independent of its effects on promoting wakefulness in sleep-deprived samples. Given that single-dose applications of other putative memory enhancers (eg, D-cycloserine, yohimbine, and methylene blue) have shown success in enhancing clinical outcomes for anxiety-related disorders, we conducted a meta-analytic review examining the potential for single-dose effects for modafinil on cognitive functioning in non-sleep-deprived adults. A total of 19 placebo-controlled trials that examined the effects of single-dose modafinil versus placebo on the cognitive domains of attention, executive functioning, memory, or processing speed were identified, allowing for the calculation of 67 cognitive domain-specific effect sizes. The overall positive effect of modafinil over placebo across all cognitive domains was small and significant (g = 0.10; 95% confidence interval, 0.05-0.15; P < 0.001). No significant differences between cognitive domains were found. Likewise, no significant moderation was found for modafinil dose (100 mg vs 200 mg) or for the populations studied (psychiatric vs nonpsychiatric). In conclusion, the available evidence indicates only limited potential for modafinil to act as a cognitive enhancer outside sleep-deprived populations.

Intractability of Deficit Syndrome of Schizophrenia Against Adjunctive Modafinil.

Negative symptoms are a significant barrier to successful functional outcome and recovery in individuals with schizophrenia, and their management is not easy. Prior tryouts with antidepressants and some cognitive enhancers were not really encouraging, and experiments with modafinil had mixed and indecisive results. The objective of the present study was to assess modafinil's efficacy on subjective and objective aspects of negative symptoms of schizophrenia. This study was an 8-week randomized, placebo-controlled trial of modafinil, as an adjective to haloperidol, in treatment of 50 schizophrenic patients. Scale for the Assessment of Negative Symptoms (SANS) was used as the primary outcome measure, and Scale for Assessment of Positive Symptoms, Clinical Global Impressions-Severity Scale, Schedule for Assessment of Insight, Simpson Angus Scale, Psychological General Well-Being Schedule, and Nurses Observation Scale for Inpatient Evaluation were used as secondary measures. According to the findings, while more cases in the modafinil group (n = 14) showed a positive response in some of the subscales of SANS, in comparison with the placebo group (n = 6; P < 0.04), the intractability of the deficit syndrome of schizophrenia against augmentative modafinil was obvious because there was no significant decrease in the mean total score of SANS in the target group in comparison with the placebo group at the end of the assessment (P < 0.08). In addition, while no significant alteration in most of the secondary measures was evident, a significant improvement in Psychological General Well-Being Schedule (P < 0. 04) and Nurses Observation Scale for Inpatient Evaluation (P < 0. 05) was obvious at the end of the trial. According to the results, despite the fact that a remarkable influence by adjunctive modafinil was visible as regards the subjective measures, no significant improvement was evident with respect to deficit syndrome per se.

Meta-analysis of the Effect of Modafinil in Children and Adolescents with Attention Deficit and Hyperactive Disorder

Introduction Attention-deficit/hyperactivity disorder (ADHD) affects 5%-10% of school-aged children. Treatment includes medical use of stimulants. However, treatment of non-stimulant drugs should be considered as an alternative. The efficacy of Modafinil, a centrally acting agent that is structurally and pharmacologically different from stimulants in the treatment of ADHD was studied and abrupt discontinuation was not associated with symptoms of withdrawal or with rebound of symptoms of ADHD. Objectives To assess the evidence from randomized controlled trials the effect of Modafinil compared with placebo in the treatment of patients with Attention-deficit/hyperactivity disorder (ADHD) . Methods Meta-analysis of 3 randomized trials identified through Medline/Pubmed and Cochrane Library (as of September 2012). Summary of the outcome variables was computed using difference of two means of the ADHD-R Scale-IV and their corresponding standard error of the means under random effects models. Statistical analysis was done using Revman version 5. Results A total number of 932 participants with ADHD were represented. All studies included were randomized and placebo controlled. The main outcome measure is Change in Home and School Version of ADHD-R Scale – IV scores from baseline. Results showed mean difference between Modafinil and placebo using the Home Version is -10.13 (95% CI -14.11, -6.14). The overall effect was statistically significant (z=4.98; p Conclusions Modafinil is effective in improving symptoms in ADHD.

Efficacy of Modafinil on Fatigue and Excessive Daytime Sleepiness Associated with Neurological Disorders: A Systematic Review and Meta-Analysis

BackgroundModafinil is a novel wake-promoting agent approved by the FDA ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy, shift work sleep disorder and obstructive sleep apnea. Existing trials of modafinil for fatigue and EDS associated with neurological disorders provided inconsistent results. This meta-analysis was aimed to assess drug safety and effects of modafinil on fatigue and EDS associated with neurological disorders.MethodsA comprehensive literature review was conducted in order to identify published studies assessing the effects of modafinil on fatigue and EDS associated with neurological disorders. Primary outcomes included fatigue and EDS. Secondary outcomes included depression and adverse effects.FindingsTen randomized controlled trials were identified including 4 studies of Parkinson’s disease (PD), 3 of multiple sclerosis (MS), 2 of traumatic brain injury (TBI) and 1 of post-polio syndrome (PPS). A total of 535 patients were enrolled. Our results suggested a therapeutic effect of modafinil on fatigue in TBI (MD -0.82 95% CI -1.54 - -0.11 p=0.02, I2=0%), while a beneficial effect of modafinil on fatigue was not confirmed in the pooled studies of PD or MS. Treatment results demonstrated a clear beneficial effect of modafinil on EDS in patients with PD (MD -2.45 95% CI -4.00 - -0.91 p=0.002 I2=14%), but not with MS and TBI. No difference was seen between modafinil and placebo treatments in patients with PPS. Modafinil seemed to have no therapeutic effect on depression. Adverse events were similar between modafinil and placebo groups except that more patients were found with insomnia and nausea in modafinil group.ConclusionsExisting trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.

Using the Test of Variables of Attention to Determine the Effectiveness of Modafinil in Children With Attention-Deficit Hyperactivity Disorder (ADHD): A Prospective Methylphenidate-Controlled Trial

The efficacy of modafinil in comparison with methylphenidate in treatment of pediatric attention-deficit hyperactivity disorder (ADHD) has not been thoroughly investigated. This study compared the effect of modafinil versus methylphenidate on continuous attention task in children with ADHD, using the Test of Variables of Attention. Twenty-eight participants completed a baseline test followed by administration of a single dose of either methylphenidate or modafinil, after which the test was repeated. The test was performed a third time, after each subject received a dose of the medication not previously administered. Comparison of scores showed mean baseline, postmethylphenidate, and postmodafinil scores of -2.04, 0.017, and 0.09, respectively. No difference was found between improvements observed with either medication (P < .05). Adverse events for both agents were mild and self-limited, including abdominal pain, diarrhea, and hyposomnia. The authors conclude that modafinil is as effective as methylphenidate; however, a larger scale long-term study is required to confirm these results.

A double‐blind, placebo‐controlled trial of modafinil (200 mg/day) for methamphetamine dependence

To examine the safety and efficacy of modafinil (200 mg/day) compared to placebo in the treatment of methamphetamine dependence and to examine predictors of post-treatment outcome. Eighty methamphetamine-dependent subjects in Sydney, Australia were allocated randomly to modafinil (200 mg/day) (n = 38) or placebo (n = 42) under double-blind conditions for 10 weeks with a further 12 weeks post-treatment follow-up. Comprehensive drug use data (urine specimens and self-report) and other health and psychosocial data were collected weekly during treatment and research interviews at baseline, week 10 and week 22. Treatment retention and medication adherence were equivalent between groups. There were no differences in methamphetamine abstinence, craving or severity of dependence. Medication-compliant subjects tended to provide more methamphetamine-negative urine samples over the 10-week treatment period (P = 0.07). Outcomes were better for methamphetamine-dependent subjects with no other substance dependence and those who accessed counselling. There were statistically significant reductions in systolic blood pressure (P = 0.03) and weight gain (P = 0.05) in modafinil-compliant subjects compared to placebo. There were no medication-related serious adverse events. Adverse events were generally mild and consistent with known pharmacological effects. Modafinil demonstrated promise in reducing methamphetamine use in selected methamphetamine-dependent patients. The study findings support definitive trials of modafinil in larger multi-site trials.

Modafinil as an Adjunctive Treatment of Sedation, Negative Symptoms, and Cognition in Schizophrenia

Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability. PubMed was searched for trials published in English up to January 2008 evaluating modafinil's effects on fatigue, negative symptoms, and cognition in schizophrenia with combinations of the following terms: schizophrenia, modafinil, cognition, negative symptoms, and fatigue. Six trials were identified: 2 randomized, prospective, double-blind placebo-controlled trials; 3 randomized, prospective, double-blind placebo-controlled crossover trials; and 1 open-label pilot study. Case series and case reports were excluded in the data analysis, except to identify potential adverse reactions to modafinil. Studies were examined for number of subjects, trial duration, design, dosing, and outcomes with respect to sedation, negative symptoms, cognitive function, and tolerability. One of 4 reviewed studies found a significant effect of modafinil as an alerting agent for antipsychotic-induced fatigue and sedation. Neither of 2 reviewed studies found modafinil to improve negative symptoms of schizophrenia. Three of 6 reviewed studies showed that modafinil may improve short-term memory, attention, and the ability to shift mental sets. Two neuroimaging studies identified functional correlates in areas associated with working memory functions. The main adverse effect was found to be a small risk of psychosis exacerbation, which was seen in 5 of 83 patients (6.0%) in the active treatment groups as compared to 2 of 70 patients (2.9%) in the placebo groups. While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia. Well-powered, prospective, randomized placebo-controlled trials using the MATRICS battery concomitantly with functional outcome measures are necessary to elucidate modafinil's efficacy and effectiveness as an adjunctive treatment for sedation, negative symptoms, and cognitive deficits in schizophrenia. Hence, before prescribing modafinil to a schizophrenia patient, the possible risks and benefits of each particular case should be evaluated.

Modafinil in children and adolescents with attention-deficit/hyperactivity disorder:a preliminary 8-week, open-label study

ABSTRACTObjective: In a 4-week, double-blind, placebo-controlled study, the attention-promoting agent modafinil improved symptoms of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents and was well tolerated. To assess the continued efficacy of modafinil and obtain additional safety data, an 8-week, open-label study was conducted as an extension to the double-blind study.Method: Two hundred and twenty children and young adolescents (age range, 6–14 years) with ADHD who had completed 4 weeks of the double-blind period or had withdrawn for reasons other than an adverse event were enrolled. Patients received individually titrated doses of modafinil (100–400 mg), administered once daily or as a divided dose. Patients visited the clinic at open-label weeks 2, 4, and 8 for assessments of efficacy. Efficacy was assessed using the parent-or clinician-completed ADHD Rating Scale-IV (ADHD-RS-IV) Home Version, the parent-completed Conners' ADHD/DSM-IV Scale Parent Version (CADS-P), and the clinician-rated Clinical Global Impression of Improvement (CGI-I) scale. Adverse events were monitored.Results: Modafinil improved symptoms on all ADHD rating scales and subscales during the open-label extension. Mean change (baseline to final visit) in Total score on the ADHD-RS-IV was −14.6 (95% CI: −16.40 to −12.70); and −7.6 (95% CI: −8.65 to −6.62) and −6.9 (95% CI: −7.90 to −5.94) in the Inattention and Hyperactivity–impulsivity scores, respectively. The mean Total score [SD] on the CADS-P decreased from baseline (74.4 [10.3]) to the final visit (63.2 [13.1]) (change: −11.2, 95% CI: −13.08 to −9.65). Fiftythree percent of patients were rated as much or very much improved on the CGI-I. Insomnia (13%) and headache (10%) were the most common adverse events. No clinically meaningful changes were observed in physical examination findings, electrocardiography, blood pressure, pulse, or body temperature. Clinically significant changes (increase or decrease) in body weight of 7% or more were observed for 30 patients (14%), with decreases (mean, 3.2 kg) reported for 22 patients (10%) and increases (mean, 3.7 kg) reported for eight patients (4%).Conclusion: Modafinil remained efficacious and well tolerated in children with ADHD, improving ADHD symptoms and overall clinical condition during the open-label study. Limitations of the study include open-label dosing and lack of a placebo control.

Open-label study of adjunct modafinil for the treatment of patients with fatigue, sleepiness, and major depression treated with selective serotonin reuptake inhibitors

Despite the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depression, a significant number of patients show partial or no remission of symptoms. Some evidence suggests that psychostimulant augmentation may be helpful in treating patients with residual symptoms of depression. The efficacy of modafinil in augmenting SSRIs in depressed patients with residual fatigue or excessive daytime sleepiness has yet to be systematically investigated. In a series of 25 patients with major depressive disorder, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, who showed significant residual symptoms after an adequate SSRI trial (12 wk) and who were evaluated according to the Fatigue Severity Scale (FSS), subjects with scores > or = 4 were given open-label modafinil augmentation for a minimum of an additional 6 wk. Treatment response was assessed prospectively with the FSS, the Epworth Sleepiness Scale (ESS), and the Hamilton Rating Scale for Depression (HAM-D) during the first visit and at the second and sixth weeks. Twenty-one of 25 patients in this series who were treated with modafinil and SSRIs completed the 6-wk augmentation trial. At end-point assessment, all patients showed significant improvement in fatigue and sleepiness in FSS and ESS scores, as well as in HAM-D scores (P<.01). In the second week, 29.4% of patients had a HAM-D score <7, which was defined as remission; this rate was 64.7% in the sixth week. The rate of patients whose HAM-D score dropped by more than 50%, defined as responders to treatment, was 41.1% and 76.4% in the second and sixth weeks, respectively. Results of this preliminary, open-label trial suggest that modafinil may be effective in augmenting ongoing SSRI treatment for a portion of patients with major depression who have residual fatigue and sleepiness. Larger, placebo-controlled trials appear warranted to investigate the clinical efficacy and tolerability of modafinil augmentation of SSRI treatment in these patients.

Modafinil: new indications for wake promotion

In January 2004, the wake-promoting agent, modafinil, was approved in the US for the treatment of excessive sleepiness (ES) associated with obstructive sleep apnoea/hypopnoea syndrome (OSAHS) and shift-work sleep disorder (SWSD), representing an expansion of its labelling from the initial indication for ES associated with narcolepsy. A total of five randomised, placebo-controlled studies in these three disorders showed statistically significant benefits on various objective measures and subjective estimates of ES, including the Multiple Sleep Latency Test, Maintenance of Wakefulness Test, Epworth Sleepiness Scale and Karolinska Sleepiness Scale. Significant improvement was also seen in overall clinical condition (on the Clinical Global Impression of Change) and measures of sustained attention and reaction time (on the Psychomotor Vigilance Task). The clinical efficacy of modafinil, combined with improved safety over CNS stimulants, has made it the most prescribed medication for the treatment of ES associated with narcolepsy. Modafinil is the only medication approved for ES associated with OSAHS and SWSD (for OSAHS, it is indicated as an adjunct to standard treatments for the under-lying obstruction). Unlike many other medications used for ES, modafinil is not known to be abused. The most common adverse event reported in clinical studies was headaches; most were transient and mild-to-moderate in severity. Modafinil also has the potential for interactions with other drugs metabolised via cytochrome P450 enzyme pathways. Potential obstacles to the use of modafinil include an under-recognition of ES and its consequences. Increased education, both of the public and the medical community, should improve the recognition and therapy of ES.

The Month-of-Birth Pattern in Narcolepsy is Moderated by Cataplexy Severity and May Be Independent of HLA-DQB1*0602

A March peak and a September trough in the birth pattern of narcolepsy patients with clear-cut cataplexy was recently reported. The objectives of the present study were to determine whether the month-of-birth pattern would (a) vary with the presence and severity of cataplexy and (b) differ for patients positive and negative for HLA-DQB1*0602. Cross-sectional survey with data obtained from the clinical trials assessing the safety and efficacy of modafinil in the treatment of narcolepsy. Sleep clinics throughout the United States. A group of 530 narcolepsy patients diagnosed based on the International Classification of Sleep Disorders using clinical histories, nocturnal polysomnography, and Multiple Sleep Latency Tests. NA. A surplus of March births and a fall-off in September births was found in narcolepsy relative to the general population. This finding was only observed when cataplexy was moderate or severe. The month-of-birth pattern was similar for HLA-DQB1*0602 positive and negative patients. A March birth and HLA-DQB1*0602 positivity were independent risk factors in a logistic regression analysis. Environmental events during development may influence narcolepsy severity or the likelihood of developing the disease.

Modafinil in Fibromyalgia Treatment

Modafinil in Fibromyalgia Treatment

Modafinil in Diurnal Sleepiness. A Study of 123 Patients

The efficacy of modafinil, a psychostimulant drug acting on postsynaptic alpha-1 adrenergic receptors, as a treatment for excessive daytime sleepiness was studied in 123 patients. Subjects included 94 narcoleptic patients (76 with cataplexy), 23 hypersomnia patients and 6 patients with disrupted nocturnal sleep (DNS) and excessive daytime sleepiness (EDS). Clinical efficacy of the treatment on each symptom (EDS, cataplexy and DNS) was evaluated on a four-point scale from excellent to absent. The effectiveness of modafinil as a treatment for EDS was excellent in 17% of all patients, good in 63%, fair in 17% and absent in 3%. The incidence of side effects was rather low (14 of 123 patients) and most of them disappeared (11 patients) when doses were reduced.