Safety and tolerability of anticonvulsant medication in bipolar disorder

Anticonvulsants (AC) are widely used and recommended as a treatment option in different phases of bipolar disorder (BD). In contrast to ample evidence for efficacy in acute mania, there is generally less unambiguous evidence for maintenance treatment or bipolar depression, and data on long-term tolerability in BD are sparse, although this varies greatly between different compounds. This review summarizes the clinically relevant tolerability and safety profile of ACs commonly used for the treatment of BD based on findings from randomized controlled trials (RCT).

Systematic search of the English literature between January 1991 and May 2015 revealed a total of nine RCTs investigating valproate, five RCTs with carbamazepine and 8 with lamotrigine For these ACs we found information on side effect profiles for both acute and maintenance RCTs, albeit of varying quality, whereas for topiramate (five RCTs), gabapentin and esclicarbazepine acetate (one RCT each) only acute treatment RCTs have been published. Descriptive side effect profiles from open-label studies exist for several other ACs rarely used in BD, and are included in this review as a brief narrative chapter.

Whereas both valproate and carbamazepine are associated with, in part, severe adverse events, lamotrigine emerges as a relatively safe and well tolerated treatment option, especially in maintenance treatment and prevention of depressive relapse in BD. Lack of proven efficacy and side effect profile of other, less rigorously studied ACs restricts their use only to very selected BD cases.