Olanzapine/Fluoxetine Deemed Optimal Bipolar Depression Treatment

Based on patient response rates and efficacy, olanzapine/fluoxetine (Symbyax) is the ideal first-line treatment for depression caused by bipolar disorder, according to a literature review published in Acta Psychiatrica Scandinavica.

Researchers from King’s College London examined 29 studies with a total of 8331 participants to identify the most effective and best-accepted drugs or drug combinations for the treatment of bipolar depression. The studies were divided into groups based on medication type: monoamine oxidase inhibitors (MAOIs), such as tranylcypromine, iproniazid, phenelzine, and moclobemide; selective serotonin reuptake inhibitors (SSRIs), including citalopram, escitalopram, sertaline, fluoxetine, flucoxamine, and paroxetine; tricylic antidepressants (TCAs), such as amitriptyline, desipramine, imipramine, and nortriptyline; and atypical antipsychotics, such as olanzapine monotheray, olanzapine/fluoxetine, quetiapine, and lurasidone.

Compared with placebo, lamotrigine, lurasidone, olanzapine monotherapy, olanzapine/fluoxetine, quetiapine, TCAs, and valproate were more effective in terms of depression scale outcomes. Of those drugs, quetiapine, valproate, lurasidone, olanzapine monotherapy, and olanzapine/fluoxetine were associated with increased response compared with placebo, and withdrawal symptoms were less likely to occur with olanzapine monotherapy and olanzapine/ fluoxetine than placebo.

Quetiapine was more effective than SSRIs, and TCAs were more effective than MAOIs. Olanzapine/fluoxetine treatment exhibited more efficacy than lamotrigine and olanzapine monotherapy in terms of response, and it was also superior to olanzapine monotherapy in terms of withdrawal.

Olanzapine/fluoxetine treatment had the highest probability of being ranked first for efficacy, while MAOIs were commonly ranked last, with the exception of placebo. While all active treatments were deemed more effective than placebo, only olanzapine monotherapy and olanzapine/fluoxetine showed significant advantage. With respect to bipolar patient response, olanzapine/fluoxetine treatment was most commonly ranked first for efficacy, with lurasidone ranked second and MAOIs most likely to be ranked last.

“Considering together, the estimates of the 2 primary outcomes suggested that olanzapine + fluoxetine and quetiapine can be said to have the most optimal balance of efficacy and safety with respect to switching,” the authors wrote. “Based on our analysis, olanzapine + fluoxetine should be recommended as the first-line treatment for bipolar depression.”

The authors noted that implementing their findings in clinical practice may prove difficult, given concerns regarding olanzapine’s long-term metabolic effects. However, they indicated that “a move towards greater use of olanzapine/fluoxetine is likely to be of benefit to patients if metabolic effects can be controlled.”