Tiagabine and the Treatment of Refractory Bipolar Disorder

Ms. A was a 46-year-old woman with a 23-year history of bipolar disorder type I with rapid cycling. Her illness had been difficult to manage. She had used the following medications in varying combinations and doses: lithium carbonate, imipramine, fluoxetine, divalproex, sertraline, gabapentin, clonazepam, alprazolam, thioridazine, risperidone, olanzapine, thiothixene, lamotrigine, and quetiapine.

Ms. A was taking a combination of quetiapine, lamotrigine, and alprazolam. This combination was initially effective; however, about 6 months later, she began to experience an increasing recurrence of mixed and manic symptoms. We elected to begin a trial of tiagabine. Her quetiapine therapy was discontinued and replaced with tiagabine, beginning at 1 mg/day (one-fourth of a 4-mg tablet) because she had a history of marked sensitivity to psychiatric medications. Lamotrigine and alprazolam treatment was continued. In response to the tiagabine, Ms. A commented that her mood was better than it had been in years. Her sleep was consistent, she was cognitively sharp, her energy and motivation were markedly improved, her dysphoria and anhedonia were resolved, and she could experience happiness. After 2 months of taking an average of 3 mg/day of tiagabine, she began to experience a manic episode. Restabilization was finally accomplished by increasing the tiagabine to 4 mg/day. She continued to experience benefit from tiagabine after 5 months. Her other psychiatric medications were lamotrigine (6.25 mg/day) and alprazolam (0.75 mg at bedtime) for insomnia.

Ms. B was a 42-year-old woman with a 6-year history of bipolar disorder type I. Her treatment course was initially turbulent. She was treated with the following medications in varying combinations and doses: lithium, temazepam, trazodone, amitriptyline, diazepam, sertraline, bupropion, paroxetine, fluoxetine, nortriptyline, divalproex, carbamazepine, flurazepam, and gabapentin. She was stabilized with a combination of lithium, venlafaxine, and flurazepam. Although she continued this combination therapy for several years, repeated occurrences of manic symptoms required adjunctive treatment. The following adjunctive medications were used without success: clonazepam, risperidone, haloperidol, lamotrigine, thioridazine, olanzapine, primidone, and quetiapine.

When Ms. B continued to experience marked recurrences of manic symptoms, we began a trial of tiagabine. Like Ms. A, Ms. B was sensitive to psychotropic drugs and was therefore started on the same low initial dose of 1 mg at bedtime. She gradually increased the dose to 4 mg at bedtime. She experienced no side effects and was able to lower her dose of flurazepam. Mood response was quite good; there was a marked reduction of manic symptoms. She took tiagabine for at least 3 months and was satisfied with the improved control of her manic symptoms. In addition to tiagabine, her other psychiatric medicines were venlafaxine (25 mg/day), lithium (300 mg/day), and flurazepam (7.5 mg at bedtime) for treatment of insomnia.