Adjunctive antidepressants for bipolar depression linked to reduced rehospitalization

Although there is weak evidence supporting the use of antidepressants in bipolar disorder, bipolar I disorder (BD-I) patients given adjunctive antidepressant (AD) therapy after hospital discharge experienced lower rates of, and a longer time period to, rehospitalization during 1-year follow-up, according to researchers in a recent article in European Neuropsychopharmacology.

“The results of this study suggest that adjunctive AD therapy to adequate mood stabilization at discharge from BD-I depressive episode hospitalization is associated with an additional protection from depressive relapse in the short- and long-term management of bipolar depression, without increasing the risk of affective switch,” wrote researchers led by Eldar Hochman, MD, PhD, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Depression is the most overpowering component of bipolar disorder, but few evidence-based treatments for BD depression exist. Moreover, many patients are refractory to evidence-based treatments and cannot tolerate their adverse effects, which creates an unmet need for alternative treatment for this illness.

In this study, Dr. Hochman and colleagues examined adjunctive use of antidepressants as maintenance therapy, which is even more controversial than antidepressant use for acute bipolar depression.

The study involved 98 BD-I patients who were hospitalized with a depressive episode between 2005 and 2013, and were followed up at 6 months and 1 year. These patients were initially discharged with a prescription of mood stabilizers and/or atypical antipsychotics with or without adjunctive AD.

Mood stabilizers prescribed at discharge included:

• lithium
• valproate
• carbamazepine
• lamotrigine

Atypical antipsychotics prescribed at discharge included:

• risperidone
• olanzapine
• quetiapine
• ziprasidone

Adjunctive antidepressants prescribed at discharge included:

• selective serotonin reuptake inhibitors (citalopram, escitalopram, sertraline, paroxetine, fluoxetine, fluvoxamine)
• serotonin norepinephrine reuptake inhibitors (venlafaxine, duloxetine)
• tricyclic antidepressants (nortriptyline, imipramine, doxepine, clomipramine)
• norepinephrine dopamine reuptake inhibitors (bupropion)
• atypical antidepressants (mirtazapine)

Of the total 98 patients, 18 (18.4%) were rehospitalized at 6 months for mood disorder and 22 (22.4%) were rehospitalized at one year. Rehospitalization rates in patients discharged with mood stabilizers/atypical antipsychotics and antidepressants was 9.2% compared with 36.4% of patients discharged with mood stabilizers/atypical antipsychotics only.

Average times to rehospitalization for any mood episode were longer in those initially discharged with antidepressants at 6 months (169.9 days vs 141 days) and at 1 year (335.6 days vs 252.3 days).

Similarly, average times to rehospitalization secondary to manic episodes were longer in patients initially discharged with antidepressants at 6 months (177.4 days vs 168.2 days) and 1 year (358.2 days vs 317.2 days).

Importantly, adjunctive use of antidepressants not only reduced rehospitalization rates overall but also decreased rehospitalizations due to manic episodes, which is of particular concern to psychiatrists.

Strengths of this study include its naturalistic chart review design and exclusion of antidepressant monotherapy. One limitation of this study is that treatment initially prescribed at discharge is not necessarily the same as long-term maintenance therapy. 

"Our results are immediately relevant to clinical practice,” Dr. Hochman said, “and should encourage clinicians to prescribe antidepressant therapy to bipolar disorder depression in patients with adequate mood stabilization."