Treatment and Prevention of Bipolar Depression – Part 1

In February, an international group of psychiatric experts met to discuss the evidence base for treating and preventing depression in bipolar disorder. I am particularly interested in this subject because, as I mentioned last time, people with bipolar disorder, especially bipolar II, spend far more time in depression than they do in any other mood.

Food and Drug Administration Approved Bipolar Maintenance Medications

There are seven drugs approved by the Food and Drug Administration (FDA) in the maintenance phase of bipolar disorder treatment. These drugs have been shown to keep a person well and increase the time to the next bipolar episode. However, some tend to prevent mania while others prevent depression more effectively.

Lithium

In an 18-month study it was found that lithium monotherapy (treatment with lithium alone) increased the time to next mania, hypomania and mixed episodes in people with bipolar I. However, it did not increase the time to next depression. In another study with a more real-world population, lithium monotherapy was found to be more effective in increasing time to next depressive episode than valproate monotherapy. Lithium plus valproate in combination was more effective in increasing time to next manic episode.

Lamotrigine

In the above 18-month study, lamotrigine was found to increase the time to mania, hypomania, mixed and depressive episodes. Lamotrigine plus lithium may be even more effective at increasing time to next depressive episode according to another study.

Olanzapine

In one study, olanzapine was found to increase the time to next episode of any mood.

Aripiprazole

In one study it was found that those on maintenance aripiprazole had a longer time to relapse of mania episodes and had fewer mania episodes overall. Aripiprazole did not increase the time to next depressive episode.

Quetiapine

In a 2-year, open-label (patients knew what they were taking) trial, it was found that those taking quetiapine plus lithium or lithium plus divalproex had a significantly longer time to next manic and depressive episodes when compared to taking either lithium or divalproex alone.

Ziprasidone

In a study, ziprasidone plus either lithium or valproate found an increased time to manic or mixed episodes, but no benefit was found with depressive episodes.

Risperidone

Again, this medication showed a benefit in time to next manic episode but not in time to next depressive episode.

Psychosocial Interventions

It is worth noting that psychosocial interventions also increase the time to next depressive episode when combined with pharmacotherapy. Specifically, in one study, patients receiving intensive psychotherapy (up to 30 sessions in nine months) had a 58 percent greater likelihood of being clinically well during any month of follow-up than those who received brief psychoeducation (three sessions in six weeks). Other studies have also shown the benefit of intensive psychotherapy.

Treatments with the Strongest Evidence

Looking at the above information, the group ascertained the following have the strongest data for the prevention of depression:

• lamotrigine
• olanzapine
• adjunctive quetiapine
• adjunctive intense psychotherapy

In part two, I’ll discuss antidepressant use in bipolar treatment as well as the 10 overall recommendations from the International Consensus Group.

For all the details on the studies and references, please see the International Consensus Group on Depression Prevention in Bipolar Disorder.