Effects of lamotrigine on the 5-HT1A receptor function in healthy human males

Lamotrigine, a new anticonvulsant, has recently been reported to be effective in treating patients with bipolar mania, depression, and schizoaffective disorder, suggesting that it is perhaps a mood stabilizer with antimanic and antidepressant properties. However, the mechanism of action underlying its efficacy in mood disorders is still unknown.

To explore the role of 5-HT1A receptors in the mechanism of action of lamotrigine, we measured the body temperature and plasma cortisol responses to a challenge with a selective 5-HT1A receptor agonist ipsapirone in ten healthy human males. Each subject received 0.3 mg/kg of ipsapirone hydrochloride tablets at time "0". Body temperature readings and blood samples for cortisol levels were obtained at 0, 30, 60, 90, 120, 150, 180 min. The ipsapirone challenge tests were repeated after 1 week treatment with lamotrigine (100 mg/day).

Treatment with lamotrigine for 1 week did not significantly alter the hypothermic or cortisol responses to ipsapirone.

The limitations of this study included small sample size, low treatment dose, short treatment interval, and lack of placebo control.

Our findings might suggest that 5-HT1A receptor function is not involved in the mechanism of action of lamotrigine in humans. Further placebo-controlled studies with a higher lamotrigine dose and a longer treatment interval in a larger number of subjects are needed to verify this.