Long-term treatment of bipolar disorder: The controversial role of antidepressants

To the Editor

Although antidepressants are the most commonly used initial treatment for bipolar depression in the USA, no antidepressant is approved by the Food and Drug Administration for use in bipolar disorder (BD). Therefore, it has been repeatedly demonstrated that they can worsen BD, promoting mood instability (Ghaemi, 2012).

We present the case of a young BD patient who was treated with different classes of antidepressants maintained for a long period of time.

The patient is a 29-year-old Caucasian unmarried man with a family history positive for bipolar disorder. At the age of 22 he experienced a decreased need for sleep, distractibility, elevated mood and increasing goal-directed activities. These symptoms met the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for a manic episode and the patient was treated with lithium 900 mg/day (serum level 0.7–0.9 mEq/L) and olanzapine 20 mg/day. Olanzapine was gradually discontinued with mood stabilization.

One year later he presented depressed mood, ruminative pessimistic thoughts about the future, feelings of inadequacy, anhedonia, and decreased appetite. Sertraline 150 mg/day was added to his lithium treatment and symptomatology improved.

In the following 12 months, sertraline and lithium were maintained and he experienced two depressive episodes lasting 4 months each.

After a suicide attempt at age 25, sertraline was discontinued and treatment was modified to clomipramine 225 mg/day and lithium 900 mg/day. In the following year he had four depressive episodes lasting 2 months each without full inter-episode recovery.

Treatment was again modified to valproate 1000 mg/day (serum level 75 µg/ml) and lithium 900 mg/day. Depressive symptoms were well controlled and there were no mood recurrences for the following 3 years.

The International Society for Bipolar Disorders has recently admitted that all antidepressants can worsen BD by inducing mania or mood instability (Pacchiarotti et al., 2013).

In the case we described, all the antidepressants used were mood destabilizers in BD: tricyclics sped up the recurrence of short depressive episodes and serotonin reuptake inhibitors promoted a smaller number of mood episodes that lasted longer.

As reported in the literature, most large randomized clinical trials have proven the inefficacy of antidepressants in bipolar depression treatment, both in acute and in maintenance phases (Ghaemi, 2012).

Because complete response to a single mood stabilizer only occurs in about one-third of BD patients, polypharmacy with mood stabilizers, including second-generation antipsychotics and novel anticonvulsant agents, appears to be the most promising approach for long-term prevention of mood episodes in BD, including depressive episodes (Ghaemi et al., 1999).