Treament guidelines do not recommend the use of antidepressants as monotherapy in patients with bipolar depression because of the risk of switching to a manic episode. US and UK guidelines do suggest the use antidepressants as add-on therapy to antimanic drugs in acute depressive episodes (mainly as second-line therapy, except for UK guidelines). SSRIs are generally preferred over TCAs and MAOIs (guidelines).

Weaknesses:

Limited data on acute therapy and no data on controlled maintenance therapy in patients with bipolar depression

• Antidepressant monotherapy may induce mania or rapid cycling and should therefore be avoided. For breakthrough depression, the first step is to optimize the dose and/or serum levels of the mood stabilizer. If this is unsuccessful, consider the addition of (1) an antidepressant; or (2) a second mood stabilizer.  Upon remission or recovery, antidepressants should be tapered – to minimize the risk of switching while the mood stabilizer is continued. It is appropriate to withdraw antidepressant treatment after 2–3 months to avoid precipitating mania and/or rapid cycling. [Australian Guidelines]
• For treatment of an acute manic or mixed episode, antidepressants should be tapered and discontinued. [BAP Guidelines]
• Studies of antidepressants in unipolar depression systematically excluded patients with a Bipolar I course. Accordingly, it would be unwise to extrapolate specific findings from the unipolar literature to the treatment of bipolar disorder. [BAP Guidelines]
• The first-line pharmacological treatment for bipolar depression is the initiation of either lithium or lamotrigine. Antidepressant monotherapy is not recommended. [APA Guidelines]
• While standard antidepressants such as SSRIs have shown good efficacy in the treatment of unipolar depression, for bipolar disorder they have generally been studied as add-on therapy to medications such as lithium or valproate. [APA Guidelines]
• When confronted with patients taking 2 or 3 of the recommended drugs who still having depressive symptoms, clinicians should consider augmenting with an antidepressant (SSRI) as a last resort. [ICG Guidelines]

Weaknesses:

May cause switching and/or cycle acceleration

• For treatment of an acute depressive episode, combination therapy with an antidepressant and an antimanic drug is recommended. Antidepressant monotherapy is not recommended. Clinicians and patients should be aware of the risk of mania, hypomania, or rapid cycling in patients with bipolar II or bipolar spectrum disorder treated with antidepressants alone. Lamotrigine can be considered for bipolar depression, especially if an antidepressant has previously appeared to provoke mood instability. [BAP Guidelines]
• In 30–40% of cases, rapid cycling may be preceded by exposure to antidepressants, and worsened by treatment with antidepressants. [BAP Guidelines]
• Antidepressant monotherapy may induce mania or rapid cycling and should therefore be avoided. For breakthrough depression, the first step is to optimize the dose and/or serum levels of the mood stabilizer. If this is unsuccessful, consider the addition of (1) an antidepressant; or (2) a second mood stabilizer.  Upon remission or recovery, antidepressants should be tapered – to minimize the risk of switching while the mood stabilizer is continued. It is appropriate to withdraw antidepressant treatment after 2–3 months to avoid precipitating mania and/or rapid cycling. [Australian Guidelines]
• For treatment of an acute manic or mixed episode, antidepressants should be tapered and discontinued. [BAP Guidelines]
• For treatment of a manic or mixed episode, antidepressants may precipitate or exacerbate manic or mixed episodes and generally should be tapered and discontinued if possible. [APA Guidelines]