The role of antidepressants in bipolar disorder treatment remains somewhat controversial and challenging. These medications may carry much more risk for people with bipolar disorder than is generally recognized. Generally antidepressant medication alone is not recommended because the drugs may flip a person into a manic or hypomanic episode.

In addition to “switching” and “rapid cycling” more subtle destabilizing effects are possible as antidepressants may make it more difficult to get a good outcome from an otherwise effective mood stabilizer treatment. There is even a concern that antidepressants may permanently alter the course of a person's bipolar illness, through a phenomenon called "kindling." Data strongly suggests that the use of standard antidepressant medication in combination with mood stabilizers in bipolar patients is no more effective than the use of mood stabilizers alone. Therefore, considerable caution should be used before starting an antidepressant in a patient with bipolar disorder.

Although depression is very much part of bipolar disorder, the conservative approach for the treatment of bipolar disorder is to first establish a mood stabilizing medication prior to beginning the antidepressant. The mood stabilizer has the effect of moderating or opposing the mania-inducing effects of the antidepressant. Having said that there are situations where unopposed antidepressants may be acceptable, as when suicide is an imminent threat. In those cases, alternative agents, such as quetiapine or lamotrigine, should be considered. When using an antidepressant, your doctor may prescribe an SSRI or buproprion (Wellbutrin) rather than a TCA or venlafaxine (Effexor) as a first-line treatment.