Seizures associated with therapeutic doses of venlafaxine and trimipramine.

OBJECTIVE

To report a patient having a first-time seizure after receiving venlafaxine and trimipramine for depression.

METHODS

A 25-year-old white woman with chronic depression was treated with venlafaxine 150 mg/d and trimipramine 50 mg/d. Eleven days after increase of the trimipramine dosage to 100 mg/d, she was hospitalized because of seizures suggesting a secondary generalized grand-mal episode. The electroencephalogram showed a pathologic pattern with several generalized epileptiform discharges. Because of suspected drug-induced seizures, both antidepressants were stopped. After antidepressant drug cessation, the patient was symptom free and had no further seizure episodes within the following 12 months of follow-up. No other potential cause for the seizure episode could be identified.

CONCLUSIONS

Both venlafaxine and trimipramine have been associated with seizures, mainly after overdose. Venlafaxine-associated seizures at therapeutic doses have not been reported in the literature. We hypothesize that a pharmacodynamic or pharmacokinetic drug interaction between venlafaxine and trimipramine involving the CYP2D6 isoenzyme may have played a role in inducing the seizures.

CONCLUSIONS

Clinicians should be aware of the proepileptogenic effect of venlafaxine and trimipramine at therapeutic doses and that this combination may eventually increase the risk of seizures.