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Antidepressants Less Effective, Have Greater Psychiatric Risks When Used to Treat Bipolar Depression

Antidepressant therapy is less effective in patients with bipolar depression than in those with unipolar depression, and can lead to manic switching, cycle acceleration, and loss of treatment response, according to a retrospective study of matched patients. Manic switching can be potentially prevented with the use of mood stabilisers, however.

Antidepressants are widely used in patients with unipolar and bipolar depression, although the effectiveness and safety of long-term antidepressant use in bipolar patients has had little investigation. Furthermore, few studies have looked at modern antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs), bupropion, mirtazapine, and nefazodone.

S. Nassir Ghaemi, MD, at the Cambridge Hospital, Massachusetts, United States, and colleagues evaluated antidepressant response in 41 patients with bipolar depression and 37 age- and sex-matched patients with unipolar depression.

Patients had DSM-IV major affective disorders and had been exposed to a total of 228 antidepressant trials. The primary medications used in these trials were SSRIs, mainly venlafaxine; bupropion; or tricyclics. A number of patients were also taking mood stabilisers, such as carbamazepine, divalproex, and lithium.

Manic switching occurred in almost half of the patients with bipolar depression. The authors note that this rate is "at about 10 times [the] typically reported spontaneous rates."

The use of mood stabilisers appeared to prevent manic switching, as bipolar patients who were not taking mood stabilisers were 4.3 times more likely to have antidepressant-induced mania than those taking stabilisers.

Cycle acceleration was noted in 25% of bipolar patients, but was not prevented by mood stabilisers. Furthermore, rapid cycling occurred in 32% of bipolar patients taking antidepressant for 1 year or longer.

Loss of response to therapy was also more common in patients with bipolar depression, affecting 53.8% as compared to 15.8% of patients with unipolar depression (P = .01). The risk of response loss was not affected by type of bipolar disorder or the use of mood stabilisers.

In addition, bipolar patients more frequently showed early nonresponse to therapy as compared to unipolar patients (P = .26).

Despite these unfavourable results, bipolar patients were less likely to relapse after discontinuing antidepressants. Relapse occurred 4.7 times more frequently in unipolar versus bipolar patients (P = .004).

Similar results were observed regardless of the type of antidepressant used.

The authors conclude that these results "support our impression that antidepressants have lesser benefits and greater psychiatric risks among bipolar than unipolar depressed patients." They also "suggest a need for randomised long-term trials of treatments for bipolar depression, currently the dominant morbidity in treated bipolar disorder patients."

Am J Psychiatry 2004 Jan;161:1:163-5. "Antidepressant Treatment in Bipolar Versus Unipolar Depression"

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