Bipolar Depression: Which Drug Works Best?

Clinicians would like to have better information about treatment options for bipolar depression, but clinical trials of any length are scarce.

Many researchers shy away from conducting trials on depression in bipolar disorder, with observers suspecting that realistic or inflated concerns about inducing mania may be the cause. As a result, bipolar depression remains very difficult to address.

A multinational team of researchers looked for answers in a meta-analysis published in the September 2015 issue of the Journal of Affective Disorder. Their focus was on disability and excess mortality in patients with bipolar depression.

Their analysis of randomized, placebo-controlled trials on the efficacy and adverse effects of treatments for acute bipolar depression included studies that tested antiepileptic drugs, antidepressants, lithium, and modern antipsychotics.

Although the researchers’ literature search was comprehensive, they were only able to find 22 studies involving 33 drug-placebo pairs.

They found that antidepressants—particularly the newer drugs in this class—possessed the best risk-benefit ratio. Regardless, the research findings were not strong enough to resolve most questions about the drugs’ optimal use in bipolar depression.

However, the researchers were able to prove that antiepileptic drugs are effective agents. Patients tended to have more difficulty tolerating carbamazepine and valproate—2 agents that have been used in bipolar depression for decades—than lamotrigine. The former treatments also had less favorable risk-benefit ratios.

Results varied for antipsychotics. Lurasidone, olanzapine plus fluoxetine, and quetiapine were effective, while aripiprazole and ziprasidone were not effective, and olanzapine alone was weakly effective. All of these antipsychotics were poorly tolerated with 1 exception: lurasidone.

A sole trial examined lithium’s effectiveness in bipolar depression, and it was rated least effective of all agents studied. Nevertheless, patients tolerated lithium well.

The researchers said their findings show that more study is clearly needed, especially for carbamazepine, lithium, and lurasidone. In the absence of evidence, they noted, clinicians continue to use empiric off-label experimentation with various drugs, which raises safety and efficacy questions.