In children and adolescents. Wigal et al29 reviewed pooled data from 3 randomized, double-blind, placebo-controlled studies of modafinil in pediatric ADHD (Table 4). Modafinil was well tolerated and improved ADHD symptoms and behaviors regardless of patients’ stimulant use history.
In a recent open-label study, 220 children and young adolescents with ADHD who had completed 4 weeks of a double-blind, placebo-controlled trial were evaluated for an additional 8 weeks. Modafinil improved ADHD symptoms and overall clinical condition as determined by the parent- or clinician-completed ADHD Rating Scale-IV Home Version, the parent-completed Conners’ ADHD/DSM-IV Scale Parent Version, and the clinician-rated CGI scale.30 Insomnia, headache, and decreased appetite were the most commonly reported adverse events.
In adults. The results of 2 double-blind, placebo-controlled trials of modafinil in adults with ADHD have been positive:
- In 1 study, modafinil (mean 206.8 mg/d) was more effective than placebo and comparable to dextroamphetamine in improving ADHD symptoms.31
- In another, modafinil (a single 200-mg dose) increased cognitive performance during treatment.32
Schizophrenia. Double-blind, randomized placebo-controlled studies have evaluated modafinil for improving cognitive function and reducing negative symptoms in patients with schizophrenia. Results have been inconsistent.
One double-blind, randomized, placebo-controlled crossover study of 20 patients with chronic schizophrenia found that modafinil, 200 mg/d, significantly improved short-term verbal memory span and attentional set shifting—the ability to discriminate and selectively attend to various stimulus dimensions (Table 5).33 Two other controlled studies showed no differences between the effects of modafinil and placebo on schizophrenia’s fatigue, cognition, or positive or negative symptoms.34,35
Summary. Although open-label studies have shown modafinil has beneficial effects on cognitive symptoms, controlled data are scarce. Reports of modafinil-induced psychosis or mania11 may limit the drug’s usefulness in schizophrenia patients.
Cocaine dependence. No medications are FDA-approved for treating cocaine dependence. A placebo-controlled, double-blind trial found that modafinil blunts cocaine euphoria under controlled conditions.36 This effect is hypothesized to be secondary to modafinil’s glutamate-enhancing and gamma-aminobutyric acid inhibitory effects.37
Summary. A single study supports using modafinil to improve outcomes in cocaine-dependent patients receiving standardized psychosocial treatment. More research is needed.
Table 4
Modafinil and ADHD: What the evidence says
Author | Study design | Modafinil dosage | Conclusion |
---|---|---|---|
Wigal et al, 200629 | Analysis of data from 3 double-blind, placebo-controlled trials; total 638 children/adolescents, some of whom had received prior stimulant therapy | 170 to 425 mg/d | Whether or not patients received prior stimulant treatment, modafinil significantly improved ADHD symptoms and was well tolerated |
Boellner et al, 200630 | 8-week, open-label extension of a 4-week double-blind, placebo-controlled trial; 220 subjects ages 6-14 | 100 to 400 mg/d | Modafinil improved ADHD symptoms and overall clinical condition |
Taylor et al, 200031 | 2-week, double-blind, placebo-controlled crossover comparing modafinil with dextroamphetamine; 22 adults | Mean 206.8 mg/d | Both modafinil and dextroamphetamine significantly improved ADHD symptoms compared with placebo |
Turner et al, 200432 | Double-blind, placebo-controlled crossover; 20 adults | Single 200-mg dose | Modafinil improved results on cognitive tests, including short-term memory span, visual memory, spatial planning, and sustained attention |
ADHD: attention-deficit/hyperactivity disorder |
Table 5
Modafinil for schizophrenia or cocaine dependence:
More research is needed
Author | Study design | Modafinil dosage | Conclusion |
---|---|---|---|
Schizophrenia | |||
Turner et al, 200433 | Double-blind, placebo-controlled crossover; 20 adults | 200 mg/d | Modafinil significantly improved attentional set shifting and short-term verbal memory span |
Sevy et al, 200534 | 8-week, double-blind, placebo-controlled; 24 subjects | Up to 200 mg/d | No significant difference between modafinil and placebo in reducing fatigue or positive or negative symptoms or in improving cognition |
Pierre et al, 200735 | 8-week, double-blind, placebo-controlled; 20 subjects | 100 to 200 mg/d | Modafinil did not significantly improve neurocognitive or negative symptoms |
Cocaine dependence | |||
Dackis et al, 200538 | 8-week, double-blind, placebo-controlled; 62 cocaine-dependent subjects | 400 mg/d | Patients receiving modafinil provided significantly more cocaine-negative urine samples and were significantly more likely to achieve =3 weeks cocaine abstinence than those receiving placebo |