Basic mechanisms of augmentation of antidepressant effects with thyroid hormone.
The thyroid hormone triiodothyronine (T3) has been used both to augment and accelerate the clinical effects of antidepressants, particularly the tricyclics. More recent work indicates that it may have similar actions with regard to the SSRIs. Two main mechanisms have been put forward to explain its antidepressant actions, (a) an action at the nuclear level involving stimulation of gene transcription, (b) an action at the cell membrane level involving potentiation of neurotransmission. In particular, there is considerable evidence for potentiation by T3 of the actions of the neurotransmitter 5-HT or serotonin. This evidence, which is mainly based on in vivo microdialysis studies, is reviewed, and evidence based on human and animal neuroendocrine studies considered. The effects of T3, alone and together with the SSRI fluoxetine, on mRNA levels for the 5-HT1A and 5-HT1B autoreceptors, which mediate serotonergic neurotransmission by feedback actions at the levels of cell firing(somatodendritic 5-HT1A autoreceptors) and neurotransmitter release (nerve terminal 5-HT1B autoreceptors) were also determined. Administration of a combination of fluoxetine and T3 induced reductions in the transcription of these autoreceptors, which may explain the clinical potentiating effects of this combination, and thus link the nuclear and neurotransmitter hypotheses of T3 action.
Lifschytz
Tsuri
T
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Segman
Ronen
R
Shalom
Galit
G
Lerer
Bernard
B
Gur
Eitan
E
Golzer
Tanya
T
Newman
Michael E
ME
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D017551:Microdialysis; D011985:Receptors, Serotonin / Q000096:biosynthesis* / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014284:Triiodothyronine