Modafinil Enhances Two-Year Outcome from Monoamine Oxidase Inhibitor Therapy in 3 Patients with Treatment-Resistant Depression

Background: Modafinil has complex, and as yet unclear, pharmacodynamics mechanisms. The prescribing of modafinil to augment monoamine oxidase inhibitor (MAOI) therapy was investigated for 3 patients with major depressive disorder determined to be treatment-resistant depression. Methods: As a retrospective report from a private psychiatry practice, 2 men and 1 woman with major depressive disorder, aged from 55 to 60 years, were evaluated and treated. All patients met criteria for treatment-resistant depression, with failure of 3 or more trials of medication with augmentation; one patient failed electroconvulsive therapy and vagal nerve stimulation. All patients had reported feeling some improvement before the addition of modafinil to existing MAOI therapy. However, immobilizing exhaustion in the 2 male patients and fatigue in the female patient impaired daily function. All patients suffered multiple serious medical comorbidities. Mitigating the influence of cycling or placebo, a 2-year period of response approximated treatment outcome. Results: With the addition of modafinil to MAOI therapy, modafinil all 3 patients improved in mood and alertness modafinil without adverse events (e.g., blood pressure, cardiac rate, extrapyramidal symptoms). Limitations: Although treatment was effective, the sample size was 3 patients. Conclusion: The mechanism by which modafinil improved the function of the 3 patients is unclear. Although many medications are contraindicated with MAOIs, most contraindications are unsubstantiated. In the present series of patients, there were no adverse events with either higher-than-recommended doses of MAOI or the combination of modafinil or tianeptine modafinil with MAOI.