1. Antidepressants for Bipolar Depression: Answering Clinical Questions
Flavio Guzmán, MD

2. Introduction Efficacy and safety of AD in BD: controversial
Antidepressants are not FDA-approved for bipolar depression:
Commonly prescribed
Monotherapy: common initial treatment
Baldessarini RJ, Leahy L, Arcona S, et al. Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders. Psychiatr Serv. 2007;58(1):85–91

3. Introduction Lack of conclusive evidence
International Society for Bipolar Disorders
Task force to seek consensus recommendations
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

4. Overview Acute treatment Maintenance treatment Monotherapy
Risk of manic switch
Drug classes associated with manic switch

5. Acute treatment

6. Acute treatment Acute treatment
When can antidepressants be used as adjunctive treatment?
When should we avoid them?
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

7. Acute treatment May be used: History of previous response
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

8. Acute treatment May be used: History of previous response
Should be avoided:
Two or more core manic symptoms
Rapid cycling
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

9. Maintenance treatment

10. Maintenance treatment
If the patient is already on an antidepressant:
Should we continue it? ?
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

11. Maintenance treatment
Maintenance treatment may be considered if patient relapses after stopping antidepressant ?
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

12. Monotherapy

13. Antidepressant monotherapy
Avoid monotherapy:
Weak evidence of efficacy
Potential risk for switches
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

14. Antidepressant monotherapy
EMBOLDEN II trial:
Paroxetine included as active comparator to:
Quetiapine
Placebo
No significant improvement in MADRS score
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

15. Antidepressant monotherapy
Antidepressants
Manic episodes
Depression
Long-term worsening
One-quarter of patients:
Rapid-cycling course
Goldberg, J. F., & Truman, C. J. (2003). Antidepressant‐induced mania: an overview of current controversies. Bipolar Disorders, 5(6),
Ghaemi, N. Bipolar disorder treatment. The Psychiatry Letter , September 2015

16. Antidepressant monotherapy
Vieta, E. (2014). Antidepressants in Bipolar I Disorder: Never as Monotherapy. American Journal of Psychiatry.

17. Risk of manic switch

18. Risk of manic switch Avoid in patients with: High mood instability
History of rapid cycling
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

19. Antidepressant use should be discouraged if history of:
Risk of manic switch
Antidepressant use should be discouraged if history of:
Mania
Hypomania
Mixed episodes
During antidepressant treatment
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

20. Discontinue antidepressant
Risk of manic switch
Monitor
Signs of:
- Mania
Hypomania
Psychomotor agitation
Discontinue antidepressant

21. Use in mixed states

22. Mixed states Avoid antidepressants if the patient has mixed features
Discontinue antidepressant if the patient is in mixed state
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

23. Antidepressant class

24. Antidepressant class TCA SNRI SNRIs, tryciclics and tetracyclics:
- Only after other antidepressants have been tried
Monitor closely:
- Increased risk of manic switch
TCA
SNRI
Pacchiarotti, I.et al  (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders.American Journal of Psychiatry.

25. Key points Do not prescribe antidepressants as monotherapy
Consider prescribing adjunctive antidepressants when there is a history of positive response
Avoid adjunctive antidepressants in patients with a history of rapid cycling or mixed features
McElroy, S. L. (2014). Prescribing antidepressants for bipolar depression: what does the evidence say?. The Journal of clinical psychiatry, 75(9), e24-e24.

26. End of presentation