Bipolar Depression: Mood Stabilizers Alone, or Antidepressant Augmentation?

S. Nassir Ghaemi, MD
Harvard Medical School
Cambridge, MA, USA


Antidepressants often induce mania and rapid cycling in bipolar patients. Guidelines for the treatment of bipolar patients include the preferred use of multiple mood stabilizers. Suicidal patients are always treated with antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are the drugs of choice. After 2 months of euthymia, patients are tapered off the antidepressant. Patients who fail two tapering regimens are maintained on antidepressants. Algorithms to guide the long-term treatment of bipolar disorder are provided.

Bipolar depression is often treated with standard mood stabilizers and antidepressant medications. Antidepressants are known to worsen the course of bipolar illness by inducing mania or rapid cycling. It is estimated that 25 to 50% of bipolar patients with rapid cycling started cycling as a result of antidepressant medications. For this reason, the clinical value of adding antidepressants to monotherapy with lithium, divalproex, or lamotrigine is unclear.

Dr. Ghaemi compared data from a recent study that treated bipolar patients with mood stabilizers alone and mood stabilizers combined with antidepressants. In a 6-week double-blind study, patients were divided into two groups.One group received valproate plus lithium. The other group was treated with mood stabilizer and paroxetine.Both groups were evaluated for bipolar symptoms using the Young Mania Rating Scale and the Hamilton Rating Scale for Depression.

The results indicate that both groups responded in a similar manner. From this data, Dr. Ghaemi concluded patients do not respond better to antidepressants. Dr. Ghaemi prefers to treat bipolar patients with multiple mood stabilizers. However, suicidal patients are always treated with antidepressants. Antidepressants are chosen based on lowest likelihood of inducing mood switching to mania. Dr. Ghaemi prefers to treat patients with selective serotonin reuptake inhibitors (SSRIs) rather than tricyclic antidepressants (TCAs). In particular, paroxetine, bupropion and citalopram are used before other antidepressants. After 2 months of euthymia, patients are slowly tapered off the antidepressant. Patients who fail two tapering regimens are maintained on antidepressants. Dr. Ghaemi estimates his use of antidepressants in bipolar patients is 20 to 50%.

Dr. Ghaemi presented this information in two algorithms.One algorithm was designed to aid clinicians in the long-term treatment of bipolar I patients.

The second algorithm provides guidelines for the long-term treatment of patients with bipolar II disorder.




Reporter: Andrea R. Gwosdow, PhD