Evidence-Based Reviews

Modafinil: Not just for sleep disorders?

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Matt’s parents request that their son be treated with a different type of agent. A trial of atomoxetine is not as effective as the initial methylphenidate dosage and produces similar side effects. We then consider modafinil because of its side effect profile. We start Matt on 100 mg once daily and titrate up to 200 mg/d 4 weeks later. Matt and his parents notice an immediate improvement in his ADHD symptoms with no side effects.

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
Summary. Once-daily dosing and minimal abuse potential make modafinil an attractive option for ADHD. Comparative studies with stimulants and nonstimulants such as atomoxetine as well as longer-term independent studies are needed. Modafinil might increase the risk of Stevens-Johnson syndrome when used in children and adolescents.11

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

To test this hypothesis, a double-blind, placebo-controlled trial randomly assigned 62 cocaine-dependent subjects to a single morning dose of modafinil, 400 mg, or placebo for 8 weeks during manual-guided, twice-weekly cognitive-behavioral therapy. Modafinil-treated patients provided significantly more cocaine-negative urine samples (P=0.03) and were significantly more likely to achieve ≥3 weeks of cocaine abstinence (P=0.05) compared with those who received placebo (Table 5).38

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

AuthorStudy designModafinil dosageConclusion
Wigal et al, 200629Analysis of data from 3 double-blind, placebo-controlled trials; total 638 children/adolescents, some of whom had received prior stimulant therapy170 to 425 mg/dWhether or not patients received prior stimulant treatment, modafinil significantly improved ADHD symptoms and was well tolerated
Boellner et al, 2006308-week, open-label extension of a 4-week double-blind, placebo-controlled trial; 220 subjects ages 6-14100 to 400 mg/dModafinil improved ADHD symptoms and overall clinical condition
Taylor et al, 2000312-week, double-blind, placebo-controlled crossover comparing modafinil with dextroamphetamine; 22 adultsMean 206.8 mg/dBoth modafinil and dextroamphetamine significantly improved ADHD symptoms compared with placebo
Turner et al, 200432Double-blind, placebo-controlled crossover; 20 adultsSingle 200-mg doseModafinil 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

AuthorStudy designModafinil dosageConclusion
Schizophrenia
Turner et al, 200433Double-blind, placebo-controlled crossover; 20 adults200 mg/dModafinil significantly improved attentional set shifting and short-term verbal memory span
Sevy et al, 2005348-week, double-blind, placebo-controlled; 24 subjectsUp to 200 mg/dNo significant difference between modafinil and placebo in reducing fatigue or positive or negative symptoms or in improving cognition
Pierre et al, 2007358-week, double-blind, placebo-controlled; 20 subjects100 to 200 mg/dModafinil did not significantly improve neurocognitive or negative symptoms
Cocaine dependence
Dackis et al, 2005388-week, double-blind, placebo-controlled; 62 cocaine-dependent subjects400 mg/dPatients receiving modafinil provided significantly more cocaine-negative urine samples and were significantly more likely to achieve =3 weeks cocaine abstinence than those receiving placebo

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