To the Editor: Lamotrigine, which at present has been indicated only for the treatment of epilepsy, has been reported to be possibly useful as an adjunctive treatment for bipolar disorder (1, 2). This letter presents two cases of its successful use as an adjunctive treatment for refractory major depression.
Ms. A was a 45-year-old woman who had been diagnosed with recurrent major depressive disorder; her therapeutic trials of bupropion, phenelzine, venlafaxine, imipramine, and nortriptyline had failed, and she had only been partially responsive to ECT. To her regimen of tranylcypromine, 70 mg/day, lithium carbonate, 1200 mg/day, and clonazepam (0.5 mg/day b.i.d. as needed, used sparingly for anxiety) treatment was added lamotrigine, 25 mg/day, and titrated to 75 mg/day within 3 weeks. Within 8 weeks, Ms. A reported a dramatic improvement in her mood and shortly thereafter returned to work. She continued to do well on this treatment regimen when assessed 6 months later.
Ms. B was a 43-year-old woman with recurrent major depressive disorder whose therapeutic trials of venlafaxine, fluoxetine, and paroxetine had failed. In addition, she could not tolerate a trial of nefazodone treatment. To her regimen of fluoxetine, 50 mg/day, and bupropion, 150 mg/day (sustained-release preparation), was added lamotrigine, 25 mg/day. Within 4 weeks, she, too, reported a dramatic improvement. "I can’t remember the last time I felt this good," she commented. She continued to do well when assessed 2 months later.
In both cases, the addition of lamotrigine to the current psychotropic regimen resulted in a significant improvement in mood. The agent was well tolerated, with no additional side effects reported by either patient. In addition, neither had developed a rash of any kind, possibly because of the low doses used. Caution apparently must be taken when adding to a regimen in which selective serotonin reuptake inhibitors are used, because these may increase lamotrigine levels, possibly resulting in toxicity (3). Whereas findings from a study with an N of two are resoundingly underwhelming, it appears that lamotrigine may be effective as an augmentation strategy in treating major depressive disorder, although future studies will be required to bear this out.