Antidepressants in Bipolar Disorder: No Benefit, Possible Harm

Caroline Cassels

May 30, 2013

SAN FRANCISCO — Antidepressant use in patients hospitalized with bipolar depression (BD) is ineffective at best, and at worst may be harmful to some patients, new research suggests.

Investigators at Brown University in Providence, Rhode Island, found there was no difference in hospital readmission rates among patients who received antidepressants and those who did not. Furthermore, they found that in patients with BD, when controlling for comorbid anxiety, one antidepressant — venlafaxine — was associated with a 3-fold higher rate of hospital readmission.

"The study is a good naturalistic look at the use of antidepressants in bipolar depression, and it really shows that in our sample, at our hospital, antidepressants weren't useful," principal investigator Jessica Lynn Warner, MD, told Medscape Medical News.

"We didn't see any benefit in terms of keeping patients out of the hospitals with the use of antidepressants, and this finding is consistent with the literature," she added.

The findings were presented here at the American Psychiatric Association's 2013 Annual Meeting.

Few Options

According to investigators, recent findings from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study indicate that adding an antidepressant to a mood stabilizer confers no additional benefit over use of a mood stabilizer alone.

However, the researchers observed that despite these data, antidepressants were frequently prescribed at their hospital in inpatients with BD, and they hypothesized that the ongoing use of these medications "might reflect a clinical advantage not observed in research trials."

To evaluate this potential effect, the investigators conducted retrospective chart review and used all-cause hospital readmission rates as a naturalistic metric of psychiatric outcomes in the first year post discharge.

The study was conducted in 377 patients aged 18 to 65 years with bipolar I disorder, most recent episode depressed, who were discharged from a single center from January 1, 2008, to July 12, 2011.

Participants were divided into those who were prescribed an antidepressant at discharge (n = 233) and those that were not (n = 144). Primary outcome measures were the impact of antidepressant exposure on readmission rates and time to readmission in the year post discharge. Secondary analysis examined the impact of individual antidepressants, anxiety, and affective switch rates.

A total of 211 patients (56%) were readmitted within 1 year of discharge, regardless of antidepressant status.

Further, the investigators found no difference in 1-year admission rates between the 2 study groups (P = .77) and no group differences in time to readmission (P = .88) between the 2 groups. The mean time to readmission was 205 ± 152 days.

The reason clinicians persist in prescribing antidepressants in this patient population when the evidence suggests they confer no benefit is unclear. However, Dr. Warner speculated that it may be due to the fact that there are so few effective treatment options for this severely ill population.

"These patients are often very ill, and other medications such as mood stabilizers haven't really worked, so clinicians are turning to antidepressants in the hope that they will have some benefit. Unfortunately, the evidence doesn't really bear this out. It would be helpful to find treatments that worked in these patients," said Dr. Warner.

Particularly Poor Treatment Choice

The study also revealed that patients with comorbid anxiety disorders had significantly higher readmission rates and shorter time to readmission regardless of antidepressant status.

After controlling for anxiety, they found that patients who were discharged while receiving venlafaxine were 3 times more likely to be readmitted compared with those who did not receive an antidepressant at discharge or those who received other antidepressants (hazard ratio = 2.99; 95% confidence interval, 1.26 - 7.07).

The investigators note that previous research has linked venlafaxine to higher rates of affective switch, in which patients "switch" from depression to mania.

According to investigators, the finding in the current study linking the drug to higher rates of readmission "adds to the evidence that venlafaxine may be a particularly poor choice for patients with bipolar disorder."

"Clinicians need to be cautious in their use of antidepressants for bipolar depression and continue to refer back to the literature and take note of what it shows in terms of their efficacy," said Dr. Warner.

Dr. Warner reports no relevant financial relationships.

The American Psychiatric Association's 2013 Annual Meeting. Abstract NR5-06. Presented May 19, 2013.

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