From the Research
Combining fluoxetine, lurasidone, and modafinil requires caution due to potentially serious drug interactions, and these medications should not be taken together without close medical supervision. Fluoxetine (an SSRI antidepressant) can increase blood levels of both lurasidone (an antipsychotic) and modafinil (a wakefulness promoter) by inhibiting the CYP450 liver enzymes that metabolize these drugs, as noted in studies on drug interactions 1. This interaction may lead to increased side effects or toxicity. The combination of fluoxetine and lurasidone particularly increases the risk of QT interval prolongation, which can cause dangerous heart rhythm problems, although lurasidone is associated with a lower risk of QT prolongation compared to other antipsychotics 2. Additionally, combining fluoxetine with modafinil raises the risk of serotonin syndrome, a potentially life-threatening condition characterized by agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and hyperthermia.
Some key points to consider when combining these medications include:
- The risk of QT interval prolongation, which is a concern with many antipsychotics, but lurasidone has been found to have a lower risk compared to others 2.
- The potential for increased side effects due to the inhibition of CYP450 enzymes by fluoxetine, which can affect the metabolism of both lurasidone and modafinil.
- The risk of serotonin syndrome, which is a potentially life-threatening condition that requires immediate medical attention.
If these medications are deemed necessary together, dosage adjustments are typically required, with lurasidone doses often needing to be reduced by 50% when combined with fluoxetine, as suggested by studies on pharmacokinetic interactions 1. Patients should report any unusual symptoms immediately, including irregular heartbeat, severe headache, confusion, muscle stiffness, or fever. Never adjust these medications without medical guidance, considering the potential risks and benefits as outlined in reviews of SSRI adverse effects 3 and the comparison of QT prolongation risk among SSRIs 4.