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Switching from Depressed to Manic with Antidepressants

switchingOftentimes, bipolar disorder initially presents with one or more episodes of major depression.[1] When treated with an antidepressant, an episode of mania or hypomania usually occurs.1 This switching of mood into mania, a mixed-state, or psychosis can be dangerous.1 Switching is prevalent among youth and young adults exposed to treatment with an antidepressant or stimulant for a depressive, anxiety, or attention disorder.1 This is due to a manifestation of undiagnosed bipolar disorder.1

The DSM-5 now considers that severe mood elevation with antidepressants justifies the diagnosis of bipolar disorder, while earlier editions considered it a drug-induced reaction.1 Before the development of today’s modern psychopharmacology, the distinctions between recurrent unipolar depression and bipolar disorder within a broad manic-depressive concept were not critical; however, today the diagnostic distinction has a considerable clinical significance for prognosis and treatment, especially when it comes to when and how long to use antidepressants and mood-stabilizing agents.1

The available research relevant to antidepressant-associated mood switches and the changes of diagnosis from unipolar depression to bipolar disorder were reviewed.1 Searches identified 100,000 patients with major depressive disorder who were treated with antidepressants and did not have a history of mania or hypomania.1 Mood-switching occurred in 8.2 percent of these patients, 4.3 times greater in youth than in adults.1

Twelve studies of patients who were initially thought to have unipolar major depressive disorder and required a new diagnosis of bipolar disorder were analyzed.1 It was found that the mood-elevating actions of antidepressants were involved in mood-switching, uncovering the underlying bipolar disorder and warranting a new diagnosis.1 Therefore, this information increases the value of long-term treatment with antimanic or mood-stabilizing agents.1

Overall, mood-switching is not uncommon, as it occurs in approximately six to eight percent of patients who present with unipolar major depression and receive antidepressant treatment.1 As switching is more common in youths than in adults, it is probably due to the fact that adults with bipolar disorder are more likely to have been correctly diagnosed and excluded from the studies.1

Depressed patients who become manic during antidepressant treatment are likely to have other characteristics of bipolar disorder, calling for them to be closely monitored during antidepressant treatment.1 Even a single mood-switch with an antidepressant can now warrant a diagnosis of bipolar disorder, but it may not be sufficient enough to support indefinite treatment with mood-stabilizers.1 It is not even proven that mood-stabilizer are protective against mood-switching, although there is a better record than with antidepressants.1

If a patient presents with unipolar depression and has a family history of bipolar disorder, multiple recurrences of depression, particular temperamental traits, a previous postpartum disorder, excessive activation with a mood-elevating drug, and agitated and dysphoric features, it may not be a good idea to treat with antidepressants, but to evaluate the less apparent symptoms during a thorough diagnosis.1



[1] Baldessarini, R., Faedda, G., Offidani, E., Vazquez, G., Marangoni, C., Serra, G., et al. (2013, November 8). “Switching” of Mood From Depression to Mania With Antidepressants. Psychiatric Times. Retrieved November 19, 2013, from http://www.psychiatrictimes.com/bipolar-disorder/switching-mood-depression-mania-antidepressants

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