Provigil (Modafinil) and Seroquel (Quetiapine) Combination Safety
Modafinil and quetiapine can be used together, but this combination requires caution because modafinil reduces quetiapine blood levels, potentially decreasing its effectiveness for psychiatric conditions. 1
Key Drug Interaction Mechanism
- Modafinil reduces quetiapine exposure through enzyme induction, specifically acting as a weak inducer of CYP2B6 and potentially affecting other metabolic pathways. 1
- The FDA drug label explicitly states: "Concomitant administration of armodafinil with quetiapine reduced the systemic exposure of quetiapine." 1
- This interaction means quetiapine may not achieve therapeutic blood levels when combined with modafinil, compromising treatment of schizophrenia, bipolar disorder, or other psychiatric conditions. 1
Clinical Management Strategy
If this combination is necessary, monitor closely for reduced quetiapine efficacy:
- Watch for return of psychiatric symptoms including psychosis, mood instability, or behavioral changes that suggest inadequate quetiapine levels. 1, 2
- Consider increasing quetiapine dose under psychiatric supervision if therapeutic response diminishes after starting modafinil. 1
- Evaluate whether the combination is truly necessary or if alternative wake-promoting strategies could be employed. 3
Additional Safety Considerations
- Modafinil is FDA Schedule IV with potential for abuse or dependency, and commonly causes insomnia, nausea, diarrhea, headache, and dry mouth. 3
- Quetiapine carries risks of weight gain, metabolic effects, and requires appropriate monitoring when used off-label for conditions like insomnia. 4
- Both medications can affect multiple neurotransmitter systems, though no direct pharmacodynamic interaction (like serotonin syndrome) is documented between them. 1, 2
Common Clinical Scenario
- This combination may arise when treating patients with psychiatric disorders who develop excessive daytime sleepiness, either from the underlying condition or as a side effect of quetiapine. 5
- Modafinil has been studied as augmentation therapy in depression with residual fatigue and sleepiness, though not specifically in combination with quetiapine. 5
Critical Pitfall to Avoid
Do not assume standard quetiapine dosing will remain effective after adding modafinil—the reduced drug exposure may lead to psychiatric decompensation if doses are not adjusted and monitoring intensified. 1