‘Supercharge’ antidepressants by adding thyroid hormones
Why hormones help, and new data on SSRI augmentation.
Abraham et al33 added T3, 50 mcg/d, to the regimens of 12 patients with MDD who did not respond to SSRIs alone. One patient dropped out with side effects. After 4 weeks of T3 augmentation, 5 patients (42%) showed 50% or greater improvement in HAM-D scores from baseline.
Figure T3 augmentation of SSRIs in 20 patients with resistant major depressive disorder
Open T3 augmentation, 50 mcg/d, given to 20 nonresponders to 8 weeks of selective serotonin reuptake inhibitors (SSRIs) improved baseline CGI-S scores significantly (P=0.006) at 4 weeks in those with atypical depression and modestly (P>0.05) in those with melancholic depression.
Source: Reference 32Antidepressant accelerators. Five of seven early double-blind, controlled studies indicated that adding small doses of thyroid hormones at the beginning of antidepressant treatment accelerated treatment response. All were limited by small sample sizes and other methodologic problems. A more-recent meta-analysis of six studies totalling 125 patients by Altshuler et al34 found:
- T3 was significantly more effective than placebo in accelerating clinical response to tricyclics
- the acceleration effect was more pronounced for women than for men.
Clinical recommendations
Thyroid hormones can be useful to augment and accelerate treatment of MDD. Evidence strongly supports their use with tricyclic antidepressants and suggests they also can be effective adjuvants for patients who do not respond to SSRIs.
Either T3 (up to 50 mcg/d) or T4 (up to 150 mcg/d) can be used as augmentation. T3’s antidepressant properties are considered more effective than those of T4, but the only head-to-head study supporting this conclusion was small (38 patients).14 Some T4 augmentation studies used very high dosages (300 to 600 mcg/d),12 which increase the risk of acute overdose.
Start T3 augmentation at 25 mcg/d and increase, if tolerated, to 50 mcg/d after 1 week. Measure baseline serum thyroid-stimulating hormone (TSH), and do not treat patients with TSH <0.5 mIU/L). Baseline TSH, T4, or T3 levels do not predict response to T3 augmentation in euthyroid MDD patients.32
Common side effects. Adjuvant T3, 25 to 50 mcg/d, was well-tolerated in our study of 20 patients also taking SSRIs:
- 2 (10%) experienced fatigue and diaphoresis
- 1 each (5%) had tremor, dry mouth, headaches, muscle aches, and vivid dreams.32
We saw no significant changes in blood pressure, but heart rates increased significantly in our 4-week study—from 76±12 bpm (range 60 to 96) to 82±9 bpm (range 66 to 96). Thus, T3 augmentation may not be indicated for patients with coronary artery disease or chronic heart failure. Patients’ weight decreased an average 2.5±6.6 lbs (range –20 to +7).
Thyroid hormones may cause hypoglycemia and change insulin requirements in patients with diabetes. High doses of T3 or T4 may be associated with hyperthyroidism, weight loss, nervousness, sweating, tachycardia, insomnia, heat intolerance, menstrual irregularities, palpitations, psychosis, or fever. Discontinue treatment if these symptoms develop.
Onset of antidepressant effect. Assess patient response in 4 to 6 weeks, whether using augmentation to address antidepressant nonresponse14,25 or to accelerate response.33 If you detect only partial improvement, studies support continuing treatment up to 8 weeks.
Treatment duration. No guidelines exist on how long to continue thyroid hormones after the initial antidepressant response. TSH levels become suppressed (TSH <0.1 mIU/L) after 4 weeks of T3, 50 mcg/d, in patients with normal baseline thyroid function.32 This suggests thyroid hormone’s booster effect is self limited, and augmentation may not need to continue after 2 to 3 months—even in responders.
T3 augmentation at 25 mcg/d can be discontinued immediately. For 50 to 75 mcg/d, taper across 1 to 2 weeks. The hypothalamic-pituitary-thyroid axis returns to normal function 6 to 8 weeks after T3 augmentation is stopped.
In this model, thyroid hormone augmentation can be used to boost antidepressant efficacy several months at a time. If effective, the same strategy could be tried again for subsequent MDD episodes.
Related resources
- DeBattista C. Augmentation and combination strategies for depression. J Psychopharmacol 2006;20(3):11-18.
- Massachusetts General Hospital Psychiatric Academy (including web-casts on treatment-resistant depression. www.mghcme.com
Drug brand names
- Desipramine • Norpramin
- Imipramine • Tofranil
- Levothyroxine (T4) • Levoxyl, Levothroid, Synthroid, others
- Liothyronine (synthetic T3) • Cytomel
Disclosures
The author receives research support from Aspect Medical Systems, Forest Laboratories, and Janssen Pharmaceutica; is a consultant to Pfizer, Inc., and Forest Laboratories; and a speaker for Eli Lilly and Co., Pfizer, Inc., and Cephalon.
