Serotonin transporter occupancy of high-dose selective serotonin reuptake inhibitors during major depressive disorder measured with [11C]DASB positron emission tomography.

RATIONALE: Previous work has shown 80% serotonin transporter (5-HTT) occupancy to be a consistent finding at the minimum therapeutic dose during selective serotonin reuptake inhibitor (SSRI) treatment. [(11)C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine positron emission tomography ([(11)C]DASB PET) is currently the best method available to quantify 5-HTT occupancy in humans. OBJECTIVES: The purpose of the present study is to determine 5-HTT occupancy during high dose SSRI treatment using [(11)C]DASB PET. MATERIALS AND METHODS: Twelve healthy subjects and 12 subjects with major depressive disorder completed the protocol. Depressed subjects received one [(11)C]DASB PET scan after a minimum of 4 weeks treatment at high doses of venlafaxine, sertraline, or citalopram. Baseline 5-HTT binding potential (BP) was taken as the average 5-HTT BP of the 12 healthy subjects. RESULTS: Mean striatal 5-HTT occupancy for each antidepressant group was approximately 85% at high therapeutic dose. This was significantly greater than 80% (one-sample t test; p < 0.04, venlafaxine group; p < 0.02, sertraline group; p < 0.01, citalopram group) for each high dose antidepressant group. CONCLUSIONS: Significantly greater 5-HTT blockade at high dose provides a rationale for raising the dose from the minimum therapeutic dose in specific clinical circumstances. It is likely that 15% unoccupied 5-HTT remains, which should be addressed in future drug development.

Lithium and triiodothyronine augmentation of antidepressants.

OBJECTIVE: To evaluate the relative benefits of the combination of lithium and triiodothyronine (T3) in augmentation of antidepressants, compared with either lithium or T3 alone. METHODS: We performed a 2-week, randomized, double-blind, placebo-controlled pilot study of the addition of lithium compared with T3 compared with the combination of both in subjects with major depressive disorder who had not responded to an antidepressant. RESULTS: All groups improved significantly over the 2 weeks of treatment, but there were no significant between-group differences. CONCLUSION: There may be no advantage to a combination of these augmenting agents, although we failed to show separation between active treatments and placebo.

Reboxetine: a preliminary report on its use through the Special Access Program.

OBJECTIVE: To describe the effectiveness and tolerability of reboxetine under Special Access Program conditions in Canada in a group of patients with refractory depressive disorders. DESIGN: Retrospective open-label study. SETTING: Six clinical academic settings in Canada, primarily tertiary institutional settings. PATIENTS: Twenty-six female and 19 male outpatients with depressive disorders, primarily unipolar depression. Most of the patients were treatment resistant. INTERVENTION: Reboxetine through the Special Access Program. OUTCOME MEASURE: Severity of depression before treatment with reboxetine was retrospectively assessed with the Clinical Global Impression (CGI) Global Severity Scale; change with treatment was evaluated with the CGI Global Improvement Scale. RESULTS: Before reboxetine treatment, 20 (44%) patients scored in the moderate CGI severity category, 11 (24%) in the marked category and 12 (27%) in the severe category. The dose range for reboxetine was 2-16 mg, with 40 (89%) patients in the 4-10 mg range. With reboxetine treatment, 25 (56%) patients were considered "very much improved" or "much improved"; 8 (18%) patients were "minimally improved"; 7 (16%) received ratings that reflected "no change" or minimal worsening, and 5 (11%) were rated as "much worse" or "very much worse." CONCLUSIONS: Reboxetine was effective at a clinically meaningful level in decreasing severity of depression in 56% of patients. Given the high rate of prior resistance to other antidepressant therapies, there is a definite role for this agent in the treatment of depressive disorders.

Thyroid hormone treatment of primary unipolar depression: a review.

A substantial number of depressed patients will fail to respond to standard antidepressant therapy. Thyroid hormones, particularly T3, may be particularly useful in enhancing response to antidepressants. This review focuses on the use of T3 augmentation in unipolar major depression. The study clearly suggests that approximately half of patients will respond to T3 augmentation of antidepressants. There are several limitations to the literature including the fact that most studies have used T3 in tricyclic rather than SSRI failure and most are of relatively short duration, up to 3 wk. Further studies are required of T3 efficacy with newer classes of antidepressants, optimal dose of T3 to be used and the duration of T3 augmentation, particularly if the acute trial is successful.