T3 augmentation of SSRI resistant depression
Abraham G, Milev R, Stuart Lawson J.
Department of Psychiatry,
University of Toronto, ON, Canada;
Mood and Anxiety Unit-Inpatient,
Centre for Addiction and Mental Health,
Toronto, ON, Canada.
J Affect Disord. 2006 Feb 14;


PURPOSE OF STUDY: To investigate whether the addition of triiodothyronine (T3) helps relieve depressive symptoms in non-hypothyroid major depressive disorder patients who failed to respond to an adequate course of standard SSRI antidepressant treatments. METHODS: Patients who fulfilled the DSM-IV criteria for non-psychotic major depression, able to give informed consent, and failed to show satisfactory antidepressant response after a minimum of six weeks adequate treatment were recruited. To enter the study their Hamilton Depression (17-item HAMD) score had to be 18 or more, thyroid-stimulating hormone (TSH) value within the normal range, and a normal thyrotropin releasing hormone-stimulation test (TRH-ST). All patients continued taking the same SSRI which they had been taking before they entered the study. At the completion of TRH-SH they were all started on 25 mug of T3 and the dose was increased to 50 mug within a week when tolerated; they continued the combination of T3 and the SSRI for a minimum of three weeks. RESULTS: Twelve patients, comprising eight females and four males, entered the study. One female patient withdrew during the first week of side effects, eleven patients completed the trial. The patients ranged from 26 to 77 years of age, with the mean age for males and females being 52.3 and 45.1 years, respectively. Five patients were taking sertraline (mean dose=130 mg/day) and 4 were taking citalopram (mean dose=50 mg/day), two were on fluvoxamine (150 mg/day) and one patient was on 40 mg of paroxetine. The women took a mean daily dose of 40.6 mug of T3 for a mean duration of 3.75 weeks, while the men were on a mean daily dose of 43.8 mug of T3 for 3.5 weeks. T3 augmentation was associated with a statistically significant drop (p<.003) in the mean HAMD at end of the three weeks compared to baseline scores. Five patients (42%) showed >/=50% improvement on HAMD scores, with three achieving full remission (HAMD scores< / =7) at the end of the study. There were no reliable differences between responders and non-responders in baseline HAMD scores, number of previous antidepressant trials, gender or Deltamax TSH. CONCLUSION: T3 augmentation resulted in improvement of mood scores. The responders' rate of 42% in our study is comparable to the response rates reported using T3 or lithium to augment tricyclic antidepressants or other combination strategies used to treat resistant depression. Even though one patient withdrew prematurely due to side effects, the remaining 11 patients tolerated the addition of T3 very well. With the availability of T3, a viable, safe, inexpensive and effective augmentation treatment, the recent trend of replacing T3 with other novel strategies appears unwarranted.
T3 v T4
Bipolar disorder
Thyroid hormones
Augmentation strategies
Triiodothyronine (T3): structure
Hypothyroidism and depression
High-dosage thyroxine as an antidepressant
Thyroid hormone, mood modulation and the brain
Mechanisms of thyroid augmentation of antidepressants

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