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Treatment and Prevention of Bipolar Depression – Part 2
While antidepressants are not indicated in the treatment of bipolar depression as monotherapy, they are still commonly prescribed. Part two of this article looks at how the International Consensus Group viewed the evidence for antidepressant use in bipolar disorder treatment and episode prevention.
Antidepressants appear to have a very different risk and reward profile depending on the specific antidepressant or antidepressant class but there aren’t enough studies for information on all possibilities. One thing we do know, based on a 10-year study though, is that those treated with antidepressant monotherapy had more switching to mania or hypomania and more suicide attempts than those who received an antidepressant with a mood stabilizer.
Antidepressant Therapy for Bipolar Depression
In one study, paroxetine (Paxil) monotherapy was compared with quetiapine (Seoquel) monotherapy in bipolar depression. Paroxetine was not much more effective than the placebo, while quetiapine was more effective than both.
One study showed no clear benefit when either paroxetine or venlafaxine (Effexor) was added to a mood stabilizer while another study did show improvement in a very similar scenario. However, the best evidence seems to be for adjunctive treatment with fluoxetine (Prozac). In one study, fluoxetine combined with olanzapine (Zyprexa) more successfully treated bipolar depression than either placebo or olanzapine alone.
(In the U.S., a fluoxetine / olanzapine combination is available in a single medication known as Symbyax.)
It’s important to note that serotonin-norepinephrine reuptake inhibitors like venlafaxine (Effexor) and tricyclic antidepressants appear to have a much greater risk of mood switching when compared to selective serotonin reuptake inhibitors (like paroxetine).
The biggest predictor of a positive response to adjunctive antidepressant treatment was a past history of positive response to antidepressants. Nonresponders:
- had a greater number of mood switches during prior antidepressant treatment
- had a greater number of total depressive and hypomanic episodes
The group noted that antidepressants should not be added when any manic symptoms are present due to the increased risk of mood switching. Patients with a history of rapid-cycling or mixed episodes are also not good candidates for antidepressant treatment.
Long-Term Use of Antidepressants in Bipolar Disorder
Varied evidence exists on the long-term use of antidepressants in bipolar depression treatment. In one meta-analysis, long-term adjunctive treatment with an antidepressant showed little value over mood stabilizer treatment alone and an (insignificant) trend towards mania was seen. However, it should be noted that these studies are mostly old and most often contained the use of tricyclic antidepressants, and not the newer agents.
In other studies, mood stabilizers with antidepressants were found to increase continued remission rates by up to 100 percent when compared to mood stabilizers alone.
One of the experts of the group noted that this more current data agreed with his clinical judgement and experience. According to this doctor, “in those patients for whom antidepressants are effective, continuing the antidepressant is reasonable.” Continued antidepressant use may also be considered when a patient has a comorbidity like obsessive-compulsive disorder or anxiety.
Overall Recommendations for the Prevention of Bipolar Depression
The International Consensus Group ends with 10 recommendations in the prevention of bipolar depression. They are:
- Quetiapine, lithium and lamotrigine are recommended for acute depressive episodes. It’s recommended that medications be continued from the acute stage into the maintenance stage.
- Taper antidepressants in the maintenance phase, if used, unless there is a history of relapse after discontinuing antidepressants.
- Lithium is recommended as the first line (and for those with suicidal ideation or previous suicide attempts), but should be administered at an adequate dosage for an adequate duration.
- Lamotrigine is preferred for patients with a predominance of depression, atypical depression, obesity or medication comorbidities. Lamotrigine is not recommended for those with mixed episodes. Lamotrigine is not recommended as monotherapy for those with depression with psychotic features, but can be combined with an antipsychotic. Lamotrigine is recommended for patients with a history of switching while on antidepressant treatment.
- Olanazpine and quetiapine is preferred for patients with a predominance of mania and without obesity or diabetes mellitus and who do not gain weight while taking the drug.
- Quetiapine plus lamotrigine, lamotrigine plus lithium, lithium plus quetiapine, or all three medications can be used in combination.
- Long-acting risperidone is appropriate for patients with adherence issues, but patients should be monitored for prolactin side effects.
- Valproate may be effective for maintenance treatment of bipolar disorder.
- Maintenance electroconvulsive therapy (ECT) may be recommended for patients who are treatment-resistent.
10. Patient and family psychoeducation is encouraged.
For all the details on the studies and references, please see the International Consensus Group on Depression Prevention in Bipolar Disorder.