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Modafinil Improves Anti-depressant Response

Below is an abstract from a study by the University of Medicine and Dentistry of New Jersey.  The study focused on 7 depressed individuals who were either partially or completely non-responsive to Selective Serotonin Reuptake Inhibitors (SSRI’s).  These individuals were given Modafinil alongside their SSRI treatment and the effects were monitored.  The study had two key findings; firstly that the addition of Modafinil to SSRI treatment was highly effective, and secondly that symptoms of fatigue and tiredness were significantly reduced.


What this means for the bigger picture

First off, the discovery that Modafinil may improve responsiveness to SSRI treatment opens up the possibility of improving the treatment of depression.  The findings of the study also point towards the validity of future research into psychostimulants such as Modafinil as augmentations to traditional SSRI treatments.

The study also reinforces the suggestion that Modafinil is effective against tiredness and fatigue.



The study was extremely limited in scale; 7 Individuals is simply too small a cohort to truly prove or disprove any findings.  Moreover, due to the small nature of the trial it wasn’t conducted with any placebos, blinds or randomization, which again reduces the strength of its findings.


So what does this mean for Modafinil?

The study adds to existing body of knowledge suggesting that Modafinil is an effective treatment for fatigue, tiredness and sleep disorders.

Most importantly, this study suggests that Modafinil can work alongside traditional SSRI’s to improve their effectiveness.  With the SSRI industry valued at an estimated $100 billion it has the potential to fund further research into Modafinil and bring it into much broader mainstream usage than at present. 


Further Reading

This study was conducted in 2005 and continued the research into Modafinil augmention of SSRI’s.  The study is placebo controlled and includes around 300 participants, countering the two main drawbacks of the abstract discussed here.

For more information on how Modafinil may reduce tiredness and fatigue, check out this study on the wakefulness benefits of hypocretin.


See below for the complete abstract with key findings in bold.


Modafinil augmentation of antidepressant
treatment in depression
Menza MA, Kaufman KR, Castellanos A
Department of Psychiatry,
University of Medicine and Dentistry of New Jersey,
Robert Wood Johnson Medical School,
Piscataway 08854, USA.
[email protected]
J Clin Psychiatry 2000 May; 61(5):378-81


BACKGROUND: Despite a relative lack of controlled data, stimulants are often used to augment antidepressant treatment in patients who have had only a partial response to first-line therapy. Modafinil is a novel psychostimulant that has shown efficacy in, and was recently marketed for, treating excessive daytime sleepiness associated with narcolepsy. The mechanism of action of modafinil is unknown, but, unlike other stimulants, the drug is highly selective for the central nervous system, has little effect on dopaminergic activity in the striatum, and appears to have a lower abuse potential. METHOD: In this retrospective case series, we describe 7 patients with DSM-IV depression (4 with major depression and 3 with bipolar depression) for whom we used modafinil to augment a partial or nonresponse to an antidepressant. The Hamilton Rating Scale for Depression was administered as part of routine clinical practice prior to treatment and at each subsequent visit. RESULTS: At doses of 100 to 200 mg/day, all 7 patients achieved full or partial remission, generally within 1 to 2 weeks. All patients had some residual tiredness or fatigue prior to starting modafinil, and this symptom was particularly responsive to augmentation. Side effects were minimal and did not lead to discontinuation of the drug in any of the patients. CONCLUSION: Modafinil appears to be a drug with promise as an augmenter of antidepressants, especially in patients with residual tiredness or fatigue. It is a particularly attractive alternative to other stimulants because of its low abuse potential and Schedule IV status.