College of Psychiatric and Neurologic Pharmacists

The safety and efficacy of antidepressants for patients with bipolar disorder continues to remain a source of tremendous controversy.  Initial reports of antidepressant-induced mania or hypomania led to marked concern among practitioners that antidepressants were highly likely to destabilize mood and worsen the course of illness in most people with bipolar disorder.  More recent investigations indicate that the potential for antidepressants to cause mania or hypomania is a rarer phenomenon than originally thought, occurring in about 10-15% of bipolar disorder patients.  Moreover, studies from the past two decades identify patient-specific risk factors for the emergence of antidepressant-associated mania or hypomania, suggesting its potential significance as an illness endophenotype.  Clinical studies suggest that the risk for mood destabilization from antidepressants appears higher in individuals with bipolar I (rather than bipolar II) disorder, as well as those with concomitant manic/hypomanic symptoms during depressive illness phases, recent manic or hypomanic episodes, comorbid alcohol or drug abuse, and past histories of antidepressant-induced mood destabilization.  Furthermore, risk may be somewhat higher with noradrenergic antidepressants (such as tricyclics or serotonin/norepinephrine reuptake inhibitors) than with purely serotonergic or primarily dopaminergic agents.  Co-therapy with antimanic drugs such as lithium may not reliably mitigate the risk for antidepressant-induced mania or hypomania.

Contrary to most practice guidelines, randomized trials suggest that lack of efficacy poses a greater and more common risk than mood destabilization when using antidepressants for bipolar depression.  Only the combination of fluoxetine with olanzapine has demonstrated better antidepressant efficacy in bipolar depression trials than mood stabilizers alone.  Controlled trials point to the efficacy and utility of novel pharmacotherapies as offering greater value than traditional antidepressants for the treatment of bipolar depression, including certain second generation antipsychotics (e.g., quetiapine and olanzapine-fluoxetine combination), the stimulants modafinil and armodafinil, the dopamine agonist pramipexole, lamotrigine plus lithium, and intravenous ketamine.

1. Analyze evidence from controlled trials regarding efficacy of antidepressants in the treatment of acute bipolar depression.
2. Evaluate factors that increase the risk of antidepressant-induced mania.
3. Assess appropriateness of antidepressant use in bipolar depression based on patient-specific factors.
4. Formulate a treatment plan for a patient with bipolar depression.

Activity Dates: 05/01/2011 - 05/01/2014
ACPE Contact Hours: 1.0
ACPE Number: 0284-9999-11-002-H01-P (Application)
Nursing Credit Reminder: Note that ACPE and ACCME credit is accepted for certification renewal.

This course is provided online at cpnp.org and consists of the speaker audio and slides. A PDF file of the slides is also provided and access is available to participants indefinitely although ACPE credit is available only through the course expiration date.

Participants in this course must complete an examination and achieve a score of 60% or greater. Successful completion of the course also requires the completion of a course evaluation. ACPE statements of credit can be retrieved by participants online at cpnp.org immediately upon successful completion of the course.

If you are a pharmacist, nurse practitioner or other healthcare professional involved in the medication therapy management of psychiatric and/or neurological patients, we invite you to participate in this online course.

Supported by an educational grant from Janssen, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., administered by Ortho-McNeil Janssen Scientific Affairs, LLC and Lilly USA, LLC.

This programming was supported in part by grants from Bristol-Myers Squibb, Cyberonics, Merk and Sunovion.