From the FDA Drug Label
Results of in vitro experiments suggest that clearance of lamotrigine is unlikely to be reduced by concomitant administration of ... fluoxetine The potential interaction between lamotrigine and Prozac (fluoxetine) is that fluoxetine is unlikely to reduce the clearance of lamotrigine 1.
- No significant effect on lamotrigine clearance is expected when coadministered with fluoxetine.
From the Research
Lamotrigine and fluoxetine (Prozac) can interact significantly, potentially increasing lamotrigine blood levels, and patients taking both medications may experience increased side effects of lamotrigine. This interaction occurs because fluoxetine inhibits the liver enzymes that metabolize lamotrigine, leading to slower elimination and higher concentrations in the body, as suggested by a study on drug interactions between lamotrigine and psychoactive drugs, including fluoxetine 2. When starting this combination, healthcare providers typically reduce the initial lamotrigine dose and slow the titration schedule, often using about half the usual lamotrigine dose. Close monitoring for side effects is essential, particularly during the first few weeks of combined therapy or when changing doses of either medication. Blood level monitoring of lamotrigine may be recommended in some cases, as seen in a study on lamotrigine toxicity secondary to sertraline, where blood level monitoring helped determine the therapeutic and toxic ranges for anticonvulsants and antidepressants 3. Patients should never adjust these medications on their own and should immediately report any skin rashes, which could indicate a serious reaction requiring immediate medical attention. Despite these concerns, this combination is sometimes intentionally prescribed for treatment-resistant depression or bipolar disorder when benefits outweigh risks, as noted in various studies, including one on the lack of interaction between sertraline and lamotrigine in psychiatric patients 4. However, it's crucial to consider the potential for serotonin syndrome, a potentially life-threatening condition associated with increased serotonergic activity, as described in a case report involving lamotrigine, aripiprazole, and cocaine use 5. Key considerations for managing this interaction include:
- Reducing the initial lamotrigine dose
- Slowing the titration schedule
- Close monitoring for side effects
- Blood level monitoring of lamotrigine
- Immediate reporting of any skin rashes or signs of serotonin syndrome.