The International Journal of Neuropsychopharmacology

Algorithm-based treatment of major depression in an outpatient clinic: clinical correlates of response to a specific serotonin reuptake inhibitor and to triiodothyronine augmentation

Ofer Agid a1c1 and Bernard Lerer a1
a1 Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Jerusalem, Israel

Article author query
agid o   [PubMed][Google Scholar] 
lerer b   [PubMed][Google Scholar] 


Clinicians who treat major depression are faced with a bewildering choice of antidepressants. Given that all have a lag period before they are effective, choice of the right antidepressant can potentially minimize the duration of symptoms, reduce cost and enhance compliance. Unfortunately, there is very little evidence upon which to base such a decision. We developed a treatment algorithm for non-psychotic, unipolar major depression, and applied it in our clinic. It includes progression from a specific serotonin reuptake inhibitor (SSRI), usually fluoxetine, from a dose of 20 mg to a dose of 40 mg in patients who do not respond. Non-responders to this dose receive augmentation with triiodothyronine (T3, 25–50 μg). All interventions are for fixed time periods and guided by overall clinical improvement as defined by the Clinical Global Inventory. Ninety patients commenced open-label treatment with 20 mg SSRI (fluoxetine, n=81; paroxetine, n=9). Seventy-four patients completed 4 wk of treatment and 44 (48.9%) were responders (intent to treat analysis). Raising the SSRI dose to 40 mg for a further 2 wk was effective in only 5 patients (16.6%). Non-responders to SSRI were significantly more depressed at baseline as reflected by their rating scales scores. Addition of T3 was effective in 10 out of 16 women (62.5%) while none of the 9 males responded. Although values were within the normal range, patients who responded to T3 had higher serum thyroid-stimulating hormone levels than those who did not. Our experience with algorithm-based treatment of unipolar, non-psychotic major depression in outpatients suggests that more than 40% of patients will not respond to initial treatment with an SSRI even when the dose is increased to 40 mg/d; that severity of depression may be an important predictor of response and that T3 may be useful as an augmenter of response in SSRI non-responders but may be less effective in men than in women. The effect of T3 may be related to thyroid function even within the normal range.

(Received August 4 2002)
(Reviewed September 27 2002)
(Revised October 27 2002)
(Accepted October 30 2002)

Key Words: Algorithm; augmentation; fluoxetine; major depression; paroxetine; specific serotonin reuptake inhibitor; triiodothyronine.

c1 Dr O. Agid, CAMH, Clarke Division, 250 College St., PET Centre, Toronto, ON M5T 1R8, Canada. Tel.: 416-535-8501 (ext. 6412) Fax: 416-260-4164 E-mail: