Triiodothyronine
augmentation of selective serotonin reuptake
inhibitors (SSRIs) in SSRI-resistant subjects
with major depressive disorder
Several
studies have shown the efficacy of
triiodothyronine (T3) for augmenting the
efficacy of tricyclic antidepressants (TCAs) in
treatment-resistant subjects with major
depressive disorder (MDD). Few studies,
generally with a small number of patients,
however, have focused on whether T3 was
efficacious in combination
withselective
serotonin reuptake inhibitors (SSRIs). The
efficacy of T3 augmentation of SSRIs in subjects
with MDD resistant to SSRI treatment was thus
investigated. Efficacy was also assessed
in patients with melancholic and atypical
MDD.
Twenty subjects aged between 18 and 65 years met
DSM-IV criteria for MDD, had a score of at
least16 on the 17-item Hamilton Rating Scale for
Depression (HAM-D-17), and shown minimal or no
response to a standard course of antidepressant
treatment with a SSRI taken for at least 8
weeks. Melancholic and atypical subtypes of MDD
were diagnosed using Structured Clinical
Interview for DSM-IV Axis I Disorders criteria.
All subjects started a 4-week open treatment
with T3 50 µg daily, and the
SSRIs were continued at preenrollment doses.
Treatment response was defined as HAM-D-17
reduction of at least 50% during the study and
remission was defined as a final HAM-D-17 score
less than 8.
After 4 weeks of treatment, the mean severity of
depression decreased from HAM-D-17 score of 20.5
± 3.6 to 14.0 ± 7.1 (p < 0.001).
Seven subjects (35%) were treatment responders
and 6 of these achieved remission. The 5
subjects with atypical depression showed greater
improvement (final HAM-D-17 scores 6.6 ±
1.8 vs. 16.4 ± 4.5), higher rates of
treatment response (100% [5/5] vs. 13.3%
[2/15]) and remission (80.0%
[4/5] vs. 13.3% [2/15]) (p <
0.01 for all analyses), compared to subjects
with non-atypical MDD. The 8 subjects with
melancholic MDD responded the least with a
greater severity of depression at the end of the
study (final HAM-D-17 scores of 18.3 ± 6.6
vs. 11.1 ± 6.1) (p < 0.03) compared to
subjects with non-melancholic MDD.No
differential efficacy of T3 augmentation was
noted in men compared with women. The thyroid
augmentation was relatively well tolerated.
T3 augmentation of SSRIs may therefore be a
promising treatment strategy for some patients
with SSRI-resistant MDD. It appears that it is
more effective in patients with atypical MDD and
less effective in melancholic MDD. These results
are worthy of replication in a controlled design
study with a larger population and longer
duration. Iosifescu
DV, Nierenberg AA, Mischoulon D, Perlis RH,
Papakostas GI, Ryan JL, Alpert JE, Fava M. An
open study of triiodothyronine augmentation of
selective serotonin reuptake inhibitors in
treatment-resistant major depressive disorder. J
Clin Psychiatry 2005, 66:1038-1042.