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Liothyronine Plus Sertraline May Be Helpful for Major Depression
In patients with major depressive disorder, liothyronine added to sertraline may be helpful in those most likely to benefit from combined therapy, according to the results of a randomized controlled trial published in the June issue of the Archives of General Psychiatry.
"It is possible to achieve a 20% increase in response and remission rates in major depression by the addition of liothyronine (T3) to treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline," senior author Bernard Lerer, MD, a professor of psychiatry and director of the Biological Psychiatry Laboratory at Hadassah–Hebrew University Medical Center in Jerusalem, Israel, told Medscape. "This is a substantial clinical effect. Furthermore, liothyronine was not associated with increased adverse effects."
With SSRI treatment alone, fewer than 50% of patients achieve full remission, so there is a crucial need for antidepressant treatments that can achieve a higher remission rate than do currently available treatments. Previous studies suggest that the thyroid hormone triiodothyronine may potentiate antidepressant effects. The objective of the current study was therefore to determine the antidepressant efficacy and safety of liothyronine sodium (triiodothyronine [T3]) when given together with the SSRI sertraline hydrochloride to patients with major depressive disorder.
"Subject to regulations regarding off-label treatment, many clinicians already use liothyronine augmentation for treatment-resistant depressed patients, [and] our study suggests that liothyronine enhances response in patients who are not definitively resistant," Dr. Lerer said. "This is a relatively novel clinical concept — use of liothyronine as an enhancer to strengthen therapeutic outcome and not only as an augmenter in resistant patients. How to strengthen response and bring the maximum number of patients to remission is an important current concern in clinical psychopharmacology."
In this double-blind trial at outpatient referral centers, 124 adult outpatients meeting unmodified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depressive disorder without psychotic features were randomized to receive sertraline hydrochloride (50 mg/day for 1 week, 100 mg/day thereafter) plus liothyronine sodium (20 or 25 µg/day for 1 week, 40 or 50 µg/day thereafter) or sertraline plus placebo for 8 weeks.
The main end point was categorical response to treatment, defined as a 50% or greater decrease in scores on the 21-item Hamilton Rating Scale for Depression (HRSD) from baseline to study end point. Secondary outcomes were remission rate, defined as a final HRSD score of 6 or less, and visual analog scale improvement (50% of greater improvement) or remission (75% improvement).
In the intent-to-treat population, HRSD response rates were 70% in the sertraline-liothyronine group and 50% in the sertraline-placebo group (P = .02; odds ratio [OR], 2.93; 95% confidence interval [CI], 1.23 - 7.35). Remission rates were 58% with sertraline-liothyronine and 38% with sertraline-placebo (P = .02; OR, 2.69; 95% CI, 1.16 - 6.49).
"The main take-home point is that concurrent treatment with T3 in addition to an SSRI antidepressant is associated with higher response and remission rates compared to treatment with the antidepressant alone," Michael Gitlin, MD, a professor of psychiatry at Geffen School of Medicine of University of California, Los Angeles, told Medscape. Dr. Gitlin was not involved with the study but was asked to provide independent commentary. "If this finding is replicated, we might consider starting patients on an antidepressant plus T3 in some cases."