Adjunct Modafinil for Fatigue and Wakefulness in MDD

Karl Doghramji, MD
Thomas Jefferson Medical College
Philadelphia, PA, USA


Investigators reported results from a small, randomized, double-blind trial of Modafinil as adjunct therapy for fatigue and sleepiness accompanying major depression. The two study groups were similar in age (average 45 years), antidepressants in use (fluoxetine most common), and baseline fatigue and sleepiness scores. After a 6-week trial, patients on Modafinil showed a nonsignificant improvement in both symptoms compared with those on placebo. Side effects in the Modafinil group such as headache and nervousness were relatively uncommon.

Fatigue and sleepiness are common among patients with depression: Dr. Doghrami cited prevalence statistics of 94% for fatigue and up to 16% for hypersomnia and noted that both fatigue and sleepiness are common even in complete responders to antidepressant medication.

A few small, uncontrolled trials have examined adjunct therapy with central nervous system stimulants with somewhat promising results. Dr. Doghramji's group hypothesized that Modafinil, a novel wake-promoting agent that has been used as therapy for sleepiness in patients with narcolepsy and obstructive sleep apnea and as therapy for fatigue in patients with multiple sclerosis, might prove useful for patients with major depression

Activity of Modafinil compared with methylphenidate and amphetamine

 


Study design and subject characteristics


TRIAL
Multicenter (11), 6-week, double-blind, randomized, placebo-controlled, parallel-group trial
Treatment arms: Antidepressant plus Modafinil or Antidepressant plus Placebo
Modafanil titrated individually during first week and once per week afterward as needed to dose of 100, 200, 300, or maximum of 400 mg daily
SUBJECTS
Average age 45 years for both arms (Note: Number of subjects in each arm was not given)
Baseline Hamilton Depression score =19 for both arms (that is, subjects are partial responders to antidepressant therapy)
Fluoxetine most common antidepressant in both arms (14 subjects in Modafinil arm, 19 subjects in placebo arm)
Number of patients who withdrew due to side effects was similar in both arms (4 subjects in Modafinil arm, 6 subjects in placebo arm)

Investigators found that there was statistically significant improvement in fatigue and sleepiness for the Modafinil arm compared with the placebo arm by 2 weeks. However, by the end of the study (week 6), the differences were no longer significant.

They concluded that Modafinil decreases fatigue and enhances wakefulness among patients who are partial responders to antidepressant therapy and that the drug is well tolerated.

 


Reporter: Elizabeth Coolidge-Stolz, MD