Long-term efficacy and safety of lamotrigine for all types of bipolar disorder

Abstract

Background: We investigated whether the long-term efficacy and safety of lamotrigine (LTG) for bipolar disorder (BP) differs between disease types (BP-I, BP-II, or BP not otherwise specified [BP-NOS]), and the efficacy of the concomitant use of antidepressants (ADs).

Methods: For >1 year, we observed 445 outpatients with BP (diagnosed by DSM-IV criteria) who initiated LTG treatment between July 1 and October 31, 2011, using the Himorogi Self-rating Depression (HSDS) and Anxiety Scales and the Clinical Global Impression-Improvement scale and also recorded adverse events.

Results: Treatment efficacy was observed at week 4, with the improved HSDS scores sustained until week 52 for all types of BP; 50% of the patients with any type of BP could be treated with LTG for 1 year, whereas ~40% could be treated for >1.5 years. However, 25% of the patients were withdrawn within the first 4 weeks. The overall incidence of adverse events was 22.9% (104/455): 34.1% (14/41) for BP-I, 22.7% (15/66) for BP-II, and 22.2% (75/338) for BP-NOS. The most common adverse event was skin rash: 22.0% for BP-I, 16.7% for BP-II, and 12.1% for BP-NOS.

Limitations: There was no control group. Data were collected retrospectively.

Conclusion: With careful and adequate titration, long-term treatment with LTG is possible for any type of BP, with BP-NOS patients, the largest population in clinical practice, responding particularly well. Symptoms can improve with or without ADs. Large-scale prospective studies of the efficacy of ADs in bipolar treatment are warranted.

Keywords: antidepressant; anxiety; bipolar disorder; lamotrigine; long-term efficacy; skin rash.

Figure 1

Time course changes in adherence to lamotrigine treatment. Notes: Kaplan–Meier curves showing adherence to lamotrigine treatment for all patients (n=455; A) and for each disease type (B). The rate for all patients was sustained at 39.6% from 637 days (1.74 years) onward with a median duration of 399 days (1.1 years). The first 25% of the patients withdrew within 28 days (4 weeks), with no withdrawals after 637 days. The bipolar I rate was sustained at 51.2% from 602 days (1.6 years) onward, and so the median duration could not be calculated; the longest duration was 1,359 days (3.7 years). The first 25% of the patients withdrew within 40 days (5.7 weeks). The bipolar II rate was sustained at 41.4% from 637 days (1.7 years) onward with a median duration of 340 days (0.93 years) and with the longest duration being 1,211 days (3.3 years). The first 25% of the patients withdrew within 21 days (3 weeks). The bipolar NOS rate was sustained at 36.6% from 586 days (1.60 years) onward with a median duration of 373 days (1.0 year) and the longest duration being 988 days (2.7 years). The first 25% of the patients withdrew within 28 days (4 weeks). Although the curves differ considerably in appearance, no statistically significant differences were observed between them (P=0.45, log-rank test). Abbreviation: NOS, not otherwise specified.