To the Editor: The importance of glutamatergic projections can be seen superficially in neuroimaging studies where blood flow to the anterior cingulate cortex, ventral orbital cortex, and amygdala is increased during craving for a variety of addictive drugs.^1,2 Cocaine craving was found to be significantly associated with time-to-relapse.³ Furthermore, several lines of evidence suggest a link between cocaine-primed craving and depressive symptomatology.⁴ Lamotrigine reduces acute depressive symptoms (epilepsy, treatment-resistant depression)^5,6 and has been shown to be effective in reducing cocaine craving in bipolar disorder comorbid with cocaine dependence⁷ and alcohol use disorders.⁸ Lamotrigine affects glutamate by inhibiting high-voltage-activated calcium channels that are located presynaptically, and consequently inhibits its release.^2,9

I present three patients diagnosed with cocaine dependence according to the DSM-IV criteria. They had used cocaine for an average of 5.4 years, and they had made an average of 3.1 quit attempts in their lifetimes. Patients had used cocaine for an average of 12.10 days during the 30 days before completing the baseline assessment battery. Their average baseline Cocaine Craving Questionnaire—Brief¹⁰ score was 48 and corresponding Beck Depression Inventory (BDI) score was 17. After 12 weeks on lamotrigine monotherapy, 200 mg/day, the respective scores decreased to 7 on the BDI and 21 on the Cocaine Craving Questionnaire, with no reports of relapse.

My results suggest that lamotrigine might have bimodal action by reducing craving and depression symptoms and thus could be a useful drug in preventing relapse in cocaine dependence.