Unipolar depression in adults: Augmentation of antidepressants with thyroid hormone
- Michael Gitlin, MD
Michael Gitlin, MD
- Professor of Clinical Psychiatry
- Geffen School of Medicine at UCLA
Thyroid hormone can be used in two different ways to treat unipolar major depression. Most commonly, thyroid hormone is used as augmentation for patients who respond insufficiently to antidepressant monotherapy [1-3]. In addition, thyroid hormone can be started simultaneously with a tricyclic at the beginning of pharmacotherapy to accelerate response compared with tricyclic antidepressant monotherapy [4,5]. However, a faster response to treatment does not increase the number of patients who respond by the end of treatment . Thyroid hormone is generally administered as triiodothyronine (T3).
Interest in treating major depression with thyroid hormone initially arose in part because of overlap in the symptoms of major depression and hypothyroidism, including dysphoria, psychomotor retardation, cognitive impairment, fatigue, and weakness [7,8]. Although diminished thyroid function is present in some cases of major depression, adjunctive T3 may be effective for depressed patients who are euthyroid .
The use of thyroid hormone in treating major depression is reviewed here. Treatment resistant depression is discussed separately, as is the initial treatment of depression and treatment of hypothyroidism. (See "Unipolar major depression in adults: Choosing initial treatment" and "Treatment of primary hypothyroidism in adults" and "Unipolar depression in adults: Treatment of resistant depression".)
Indications for treating nonpsychotic, unipolar major depression with triiodothyronine (T3) include :
●Augmenting response – T3 is added to ongoing antidepressant monotherapy because the patient has not responded adequately; this is the most common indication.
- Practice Guideline for the Treatment of Patients With Major Depressive Disorder, Third Edition, 2010 http://www.psych.org/MainMenu/PsychiatricPractice/PracticeGuidelines_1.aspx (Accessed on January 27, 2011).
- Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord 2009; 117 Suppl 1:S26.
- Bauer M, Bschor T, Pfennig A, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders in Primary Care. World J Biol Psychiatry 2007; 8:67.
- Cooper-Kazaz R, Lerer B. Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors. Int J Neuropsychopharmacol 2008; 11:685.
- Altshuler LL, Bauer M, Frye MA, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry 2001; 158:1617.
- Papakostas GI, Cooper-Kazaz R, Appelhof BC, et al. Simultaneous initiation (coinitiation) of pharmacotherapy with triiodothyronine and a selective serotonin reuptake inhibitor for major depressive disorder: a quantitative synthesis of double-blind studies. Int Clin Psychopharmacol 2009; 24:19.
- Prange, AJ Jr, Wilson, et al. Hormonal alterations of imipramine response: A review. In: Hormones, Behavior, and Psychopathology, Sachar, EJ (Eds), Raven Press, New York 1976. p.41.
- Preskorn SH. Treatment options for the patient who does not respond well to initial antidepressant therapy. J Psychiatr Pract 2009; 15:202.
- DeBattista C. Augmentation and combination strategies for depression. J Psychopharmacol 2006; 20:11.
- Joffe RT. Refractory depression: treatment strategies, with particular reference to the thyroid axis. J Psychiatry Neurosci 1997; 22:327.
- Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16:606.
- Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006; 163:28.
- Thase ME, Haight BR, Richard N, et al. Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials. J Clin Psychiatry 2005; 66:974.
- Thase ME, Nierenberg AA, Vrijland P, et al. Remission with mirtazapine and selective serotonin reuptake inhibitors: a meta-analysis of individual patient data from 15 controlled trials of acute phase treatment of major depression. Int Clin Psychopharmacol 2010; 25:189.
- Hirschfeld RM, Montgomery SA, Aguglia E, et al. Partial response and nonresponse to antidepressant therapy: current approaches and treatment options. J Clin Psychiatry 2002; 63:826.
- Depression: The Treatment and Management of Depression in Adults (Updated Version). National Clinical Practice Guideline 90. National Institute for Health & Clinical Excellence http://guidance.nice.org.uk/CG90/Guidance/pdf/English (Accessed on January 27, 2011).
- Aronson R, Offman HJ, Joffe RT, Naylor CD. Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Arch Gen Psychiatry 1996; 53:842.
- Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry 2006; 163:1519.
- Zhou X, Ravindran AV, Qin B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry 2015; 76:e487.
- Joffe RT, Singer W, Levitt AJ, MacDonald C. A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression. Arch Gen Psychiatry 1993; 50:387.
- Joffe RT, Singer W. A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants. Psychiatry Res 1990; 32:241.
- Rosenthal LJ, Goldner WS, O'Reardon JP. T3 augmentation in major depressive disorder: safety considerations. Am J Psychiatry 2011; 168:1035.
- Appelhof BC, Brouwer JP, van Dyck R, et al. Triiodothyronine addition to paroxetine in the treatment of major depressive disorder. J Clin Endocrinol Metab 2004; 89:6271.
- Cooper-Kazaz R, Apter JT, Cohen R, et al. Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry 2007; 64:679.
- Shelton RC, Osuntokun O, Heinloth AN, Corya SA. Therapeutic options for treatment-resistant depression. CNS Drugs 2010; 24:131.
- Garlow SJ, Dunlop BW, Ninan PT, Nemeroff CB. The combination of triiodothyronine (T3) and sertraline is not superior to sertraline monotherapy in the treatment of major depressive disorder. J Psychiatr Res 2012; 46:1406.
- GOAL OF TREATMENT
- AUGMENTING RESPONSE TO ONGOING ANTIDEPRESSANT THERAPY
- Evidence of efficacy
- Compared with other adjunctive treatments
- Pretreatment evaluation
- Choice of thyroid hormone
- Dose and administration
- Length of an adequate trial
- Predictors of response
- Safety issues
- - Side effects
- - Laboratory monitoring
- - Drug-drug interactions
- Long-term treatment
- ACCELERATING RESPONSE TO AN ANTIDEPRESSANT
- ENHANCING RESPONSE TO AN ANTIDEPRESSANT