Though antidepressant drugs are effective in most persons with depression, the delayed onset of action results in significant complications, including: (1) reduced compliance, (2) slowing of the return to normal social/ occupational functioning, (3) increasing the risk of suicide, (4) contributing to cumulative hospital costs, and (5) prolonging the duration of suffering. There is thus a need for a maneuver that would speed the clinical response to antidepressants. One night's whole sleep deprivation (SD) is known to produce a significant, albeit transient, antidepressant effect. This project will study the potential for the prolongation of the response to SD by combination with imipramine (IMI). In addition, the hypothalamic-pituitary-thyroid axis is significantly involved in the regulation of the mood, and changes in this system are known to be related to response to SD.
The specific aims of the project include: (1) comparing the antidepressant effects of three treatment groups in patients with major depression: (a) IMI + SD, (b) SD alone, and (c) IMI alone (to test whether IMI will extend the antidepressant response to SD); (2) evaluating thyroid hormone function (i.e., TSH, delta max TSH after TRH, T3, T4, FT4-index, antithyroid antibodies [ATA], and thyroid binding globulin [TBG] before and after SD to assess whether thyroid function values are associated with response to SD; (3) investigating the relationship of both SD response and thyroid activity with antidepressant treatment outcome at day 28. 195 depressed persons aged 18-65 with a DSM- III-R diagnosis of major depression will be studied over a five year period. The patients will be randomly assigned to one of the three treatment groups. After initial assessment, patients will receive baseline thyroid testing (including T3, T4, TSH, ATA, TBG, and TSH response to TRH). After a minimum of five days, the subjects will undergo a one night's observed SD, with replication of the thyroid testing the next morning. They will then be randomized into the three treatment groups, and treated for a total of 28 days, while being rated on the Hamilton Rating Scale for Depression, the Beck Depression Inventory, and a rating specifically designed for this project the Sleep Deprivation Depression Rating Scale, at baseline and on SD + 1 - 10, 14, 21, and 28 days. Appropriate statistical comparisons will be made to evaluate the specific aims.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH045173-05
Application #
2246440
Study Section
Treatment Development and Assessment Research Review Committee (TDA)
Project Start
1990-08-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1996-07-31
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Orth, D N; Shelton, R C; Nicholson, W E et al. (2001) Serum thyrotropin concentrations and bioactivity during sleep deprivation in depression. Arch Gen Psychiatry 58:77-83
Shelton, R C; Mainer, D H; Sulser, F (1996) cAMP-dependent protein kinase activity in major depression. Am J Psychiatry 153:1037-42
Manier, D H; Eiring, A; Shelton, R C et al. (1996) Beta-adrenoceptor-linked protein kinase A (PKA) activity in human fibroblasts from normal subjects and from patients with major depression. Neuropsychopharmacology 15:555-61
Shelton, R C; Winn, S; Ekhatore, N et al. (1993) The effects of antidepressants on the thyroid axis in depression. Biol Psychiatry 33:120-6
Shelton, R C; Harvey, D S; Stewart, P M et al. (1993) Alprazolam in panic disorder: a retrospective analysis. Prog Neuropsychopharmacol Biol Psychiatry 17:423-34
Loosen, P T; Chambliss, B; Ekhator, N et al. (1993) Thyroid and adrenal dysfunction in abstinent alcoholic men: locus of disturbance. Neuropsychopharmacology 9:255-66
Shelton, R C; Loosen, P T (1993) Sleep deprivation accelerates the response to nortriptyline. Prog Neuropsychopharmacol Biol Psychiatry 17:113-23
Loosen, P T; Chambliss, B; DeBold, C R et al. (1992) Psychiatric phenomenology in Cushing's disease. Pharmacopsychiatry 25:192-8
Loosen, P T; Chambliss, B; Pavlou, S S et al. (1991) Adrenal function in abstinent alcoholic men. Prog Neuropsychopharmacol Biol Psychiatry 15:771-80