The goal in the treatment of bipolar depression is to give an effective antidepressant without triggering hypomania or rapid cycling. Therefore, one treatment strategy is to use a foundational mood stabilizer, like lamotrigine, before starting therapy with an antidepressant such as an SSRI.

Therefore, the investigators retrospectively evaluated the clinical response and tolerability of concomitant lamotrigine and an SSRI in patients with bipolar I disorder.

The patients had participated in the preliminary phase of one of two open-label studies. One study had an 8-week open-label phase, and the other had a 16-week open-label phase.

During the open-label phase, patients received patients lamotrigine either as adjunctive or monotherapy. The patients discontinued the adjunctive SSRI at least one week before randomization. During this phase, the investigators examined patients weekly and documented the patients' scores on the Hamilton Depression Rating Scale version 17 (HAMD-D17), the Clinical Global Impression-Subjective Scale (CGI-S), and the Global Assessment Scale (GAS). The investigators also recorded any adverse events that patients experienced during the study period.

Among 1,305 patients in the trials, 21% received an SSRI along with lamotrigine. The SSRIs used in the studies consisted of paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), fluoxetine (Prozac), and fluvoxamine (Luvox). The patients were on this combination for a median of 7.3 weeks. The typical target dose for lamotrigine for the treatment of bipolar disorder is approximately 200 mg daily.

From baseline to the end of the open-label phase, investigators recorded approximately a 50% reduction on the HAM-D17 score for patients on the lamotrigine-SSRI combination. Similarly, they recorded a mean reduction of 1.6 points on the CGI-S scores and a mean increase, and therefore a benefit, of 16.6 on the GAS scores for such patients.

Patients on the lamotrigine-SSRI combinations had similar rates of adverse events to those on lamotrigine monotherapy. The most common of these were headache, in 18% of the combination-treated patients and 25% of the monotherapy patients; infection 4% of those on combination therapy and 12% of those on monotherapy; nausea, in 8% of those on combination therapy and in 12% of those on monotherapy; and an insignificant rash, in 7% of those on combination therapy and in 10% of those on monotherapy.

Because the United States Food and Drug Administration requires a black-box warning about serious rashes associated with lamotrigine therapy, these findings were reassuring, the investigators reported. No rapid cycling or manic events were reported, either. Therefore, the investigators concluded that the combination of lamotrigine and concomitant use of an SSRI could be beneficial in accomplishing the goals of mood stabilization and prevention of depression in patients with bipolar I disorder.

The study was funded by GlaxoSmithKline, the manufacturers of Lamictal.

[Presentation title: Abstract #NR795: Concomitant Lamotrigine and SSRIs in Bipolar I Disorder. Presented May 26, 2005.]

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