Lamotrigine added to valproate successfully treated a case of ultra-rapid cycling bipolar disorder
Version of Record online: 12 JAN 2007
Psychiatry and Clinical Neurosciences
Volume 61, Issue 1, pages 130–131, February 2007
How to Cite
WOO, Y. S., CHAE, J.-H., JUN, T.-Y. and BAHK, W.-M. (2007), Lamotrigine added to valproate successfully treated a case of ultra-rapid cycling bipolar disorder. Psychiatry and Clinical Neurosciences, 61: 130–131. doi: 10.1111/j.1440-1819.2007.01624.x
- Issue online: 12 JAN 2007
- Version of Record online: 12 JAN 2007
- Received 26 June 2006; revised 22 September 2006; accepted 1 October 2006.
Ultra-rapid cycling is defined as the occurrence of more than four mood episodes per month,1 and the treatment is difficult. Lamotrigine has been shown to have positive effects for patients with bipolar disorder, including some with rapid cycling.2 We report the case of a 25-year-old man with ultra-rapid cycling bipolar disorder, resistant to two mood stabilizers and antidepressants, who recovered with the inclusion of lamotrigine to valproate treatment.
Mr A is a 25-year-old man who has had a history of ultra-rapid cycling bipolar II disorder for 6 years. His illness started with a depressive episode in late adolescence. The patient also had hypomanic symptoms since the age of 22. Mood elevation had yielded only mild to moderate social dysfunction. Two years before visiting St Mary’s Hospital, Seoul (SMH), he began to experience recurrent ultra-rapid cycling mood episodes. He was diagnosed as having major depressive disorder and given paroxetine (20–40 mg/day) for 14 months and fluoxetine (40 mg/day) for 4 months with analytic psychotherapy. However, his illness did not improve. Five months before his visit to our clinic, his diagnosis was changed to bipolar disorder and he was treated with lithium (900 mg/day) for 5 months, but it was not effective. When he visited SMH, he was in the routine of 4–5 days of depression and 2–3 days of hypomania. It should be noted that in recent years there was no sustained euthymia for longer than a 2-week period. The patient was diagnosed as having ultra-rapid cycling bipolar disorder. His initial score on the 17-item Hamilton Rating Scale for Depression (HRSD) was 27 and the Young Mania Rating Scale (YMRS) was 18. Valproate was given for 9 weeks with sufficient plasma levels. However, valproate treatment had no sufficient success. We initiated lamotrigine gradually to attenuate the risk of rash at a dose of 12.5 mg/day, and valproate was maintained at the prior dose. Lamotrigine was titrated up to 100 mg/day over a 6-week period. Five weeks after initiation of lamotrigine, the patent’s depressive symptoms, including leaden paralysis, neck and shoulder pain, anhedonia and psychomotor retardation, significantly improved. Eight weeks after initiation of lamotrigine, the HRSD score was 6 and the YMRS score was 5. With this combination treatment, the patient achieved complete remission for more than 8 months.
The mechanisms of action of lamotrigine are not yet fully understood. Recent investigations have focused on signal transduction mechanisms, gene regulation and modulation of ion channel activities. The common mechanism of both lithium and lamotrigine is inhibition of the Ca2+ channel. It has been shown that lithium treatment alters cytoplasmic intracellular Ca2+ in the blood cells of bipolar patients.3 Recent evidence suggests that lamotrigine also alters intracellular Ca2+ homeostasis by inhibiting Ca2+ channels in certain regions of the brain.4 Moreover, there was a case report of a successful open trial of nimodipine, a dihydropyridine-type calcium antagonist, in the treatment of refractory ultra-rapid cycling bipolar disorder.5 Pazzaglia et al. suggested that nimodipine’s mechanisms of action, as a mood stabilizer, are related to the increased intracellular calcium in mania. In summary, lamotrigine may have mood stabilizing effects via its effect on presynaptic and/or postsynaptic Ca2+ channels. These findings are preliminary and need to be considered in the context of a single-case, open-label clinical trial. Nevertheless, this case highlights the potential use of lamotrigine in ultra-rapid cycling bipolar disorder and suggests a direction for further study and systematic assessment.