Other studies have also suggested that lamotrigine has a favorable psychotropic profile and may improve mood in some patients (123–125). This observation is potentially confounded by decreased sedations and improved concentration after converting from less well-tolerated antiepileptic medications (126), but available evidence supports that lamotrigine can improve mood or even protect against adverse mood effects of other medications. For example, Mula et al. reported that concomitant treatment with lamotrigine was associated with reduced rates of adverse psychiatric reactions to levetiracetam (127) or topiramate (128).

Recently, an association between lamotrigine use and aseptic meningitis has been reported. While the mechanism underlying this relatively rare adverse effect is unclear, clinicians should consider this is cases of culture-negative meningitis (129).

Teratogenicity is another consideration in an assessment of safety. Data derived from rodents as well as human ex vivo placental perfusion studies suggest that lamotrigine easily and rapidly crosses the placenta (40). Comparison of lamotrigine serum concentration in maternal and umbilical cord blood has identified a median infant-to-mother concentration ratio of 0.9 (SD 0.2) (130). A direct comparison of the effect of lamotrigine on the fetus has been found to be lower than valproate and similar to carbamazepine with an odds ratio of 1.48 (95% CI 0.47, 4.69) (131). Data from the Australian Pregnancy Registry suggest a malformation rate of 5.2% in women receiving lamotrigine monotherapy and, further, failed to find dose-dependent increase in risk (132). A large population-based registry identified a 2.2% major congenital malformation rate from a first-trimester exposure group that included 1558 women (133). This registry lacked an internal control group, which precludes an odds ratio calculation, but the rate is similar to the general population. This registry also failed to detect an increased frequency of major malformations with increased lamotrigine dose. However, a higher rate of 3.2% also has been observed, and lamotrigine has not been found to be without teratogenic potential (134,135). Lamotrigine is present in maternal milk at potentially clinically significant concentrations (136).

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