Effectiveness and Weight Effects of Open-Label Lamotrigine With and Without Concomitant Psychotropic Medications in Patients With Bipolar I Disorder

Michael N. ZarZar, MD; Jay Graham, PharmD; Jeremy Roberts; Thomas Thompson, MD; Kevin Nanry

In This Article


Bipolar disorder is a chronic and disabling condition that affects nearly 4% of American adults at some point during their lives.[1] Several classes of medications have demonstrated efficacy in treating symptoms of bipolar disorder, including lithium, anticonvulsants, antipsychotics, and antidepressants.[2] Patients with bipolar disorder usually require maintenance therapy to reduce the risk for relapse.[3] According to American Psychiatric Association (APA) treatment guidelines for bipolar disorder published in 2002,[3] empirical evidence most strongly supports the use of lithium and valproate for maintenance therapy, and possible alternatives include lamotrigine, carbamazepine, and oxcarbazepine. For patients treated with an antipsychotic agent during an acute manic episode, the APA guidelines recommend discontinuation of the antipsychotic agent after the resolution of the episode unless it is required to control persistent psychosis or to prevent recurrence. There is currently limited evidence demonstrating that antipsychotics are as effective as lithium or valproate for maintenance therapy.[4,5,6] However, patients who experience persistent subthreshold symptoms or breakthrough mood episodes may benefit from the addition to maintenance therapy of another mood-stabilizing agent, an atypical antipsychotic, or an antidepressant. The use of an antidepressant agent as monotherapy is not recommended for either acute or maintenance treatment because of the risk of precipitating a manic episode.

The anticonvulsant lamotrigine was approved by the US Food and Drug Administration in 2003 for the maintenance treatment of bipolar I disorder in adults and is currently the only medication approved to delay the time to occurrence of depressive as well as manic, hypomanic, and mixed episodes in patients with bipolar I disorder.[7,8,9,10] Lamotrigine was also associated with improved completion rates compared with placebo in a study of patients with rapid-cycling bipolar disorder, although most of the difference was seen in patients with bipolar II disorder.[11] The most common treatment-emergent adverse events among patients with bipolar I disorder receiving lamotrigine in 2 clinical trials of maintenance treatment included nausea, insomnia, and somnolence.[7] Unlike some other anticonvulsants and antipsychotics used to treat patients with bipolar disorder, such as valproate and olanzapine, lamotrigine is not associated with changes in body weight.[12,13,14]

Registration trials of treatments for bipolar disorder typically exclude patients who are taking other psychotropic medications or discontinue these medications before randomization. However, about half of all patients with bipolar disorder are prescribed 2 or more psychotropic medications.[15] Thus, it is important to examine the efficacy and safety of medications for bipolar disorder in patients taking various concomitant psychotropic drugs. A large 12-week, open-label, multicenter trial was conducted to assess the rate of rash among patients instructed to use specific dermatologic precautions compared with those receiving usual care; the primary results have been reported elsewhere.[16] The purpose of this post hoc analysis of data from that trial was to examine patients with bipolar disorder in a naturalistic setting receiving lamotrigine as monotherapy or adjunctive therapy with or without concomitant valproate, lithium, antipsychotics, or antidepressants.


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