• Hamilton Depression Scale (HAM-D) [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]
• Fuse Words Test [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]
• Nonsense Syllables Test [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]
• Complex Tones Test [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]

• Hamilton Depression Scale (HAM-D)
• Fuse Words Test
• Nonsense Syllables Test
• Complex Tones Test

• Clinical Global Impression Scale (CGI) [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]
• Atypical Depression Diagnostic Scale (ADDS) [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]
• Deragotis Sexual Performance Scale [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]
• Snaith-Hamilton Pleasure Scale [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]
• Spielberger State/Trait Anxiety Scale [ Time Frame: 6 mos. ] [ Designated as safety issue: No ]

• Clinical Global Impression Scale (CGI)
• Atypical Depression Diagnostic Scale (ADDS)
• Derogotis Sexual Performance Scale
• Snaith-Hamilton Pleasure Scale
• Spielberger State/Trait Anxiety Scale

Depressed patients will have hearing tests and then be treated with up to three treatments (i.e., Fluoxetine, Imipramine and Placebo) until remitted, to see whether test results predict specific outcomes.

Preliminary data suggest that depressed patients with increased left hemispheric laterality of perceptual processing are unlikely to improve during six weeks' treatment with placebo, while being very responsive to either imipramine or fluoxetine. Depressed patients who do not show evidence of poor right hemispheric functioning respond significantly more often to placebo than those with poor right hemispheric functioning, and do not show an advantage of drug over placebo. 100 depressed patients will be tested with verbal and nonverbal dichotic tests, and then treated sequentially with Placebo, Fluoxetine and Imipramine until remitted. Preferential hemisphere for auditory processing will be correlated with treatment outcome.

• Major Depression
• Dysthymia
• Depressive Disorder NOS

• Drug: Fluoxetine
• Drug: Imipramine

• Bruder GE, Otto MW, McGrath PJ, Stewart JW, Fava M, Rosenbaum JF, Quitkin FM. Dichotic listening before and after fluoxetine treatment for major depression: relations of laterality to therapeutic response. Neuropsychopharmacology. 1996 Aug;15(2):171-9.
• Bruder GE, Stewart JW, Tenke CE, McGrath PJ, Leite P, Bhattacharya N, Quitkin FM. Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant. Biol Psychiatry. 2001 Mar 1;49(5):416-25.
• Bruder GE, Stewart JW, McGrath PJ, Deliyannides D, Quitkin FM. Dichotic listening tests of functional brain asymmetry predict response to fluoxetine in depressed women and men. Neuropsychopharmacology. 2004 Sep;29(9):1752-61.
• Stewart JW, Quitkin FM, McGrath PJ, Bruder GE. Do tricyclic responders have different brain laterality? J Abnorm Psychol. 1999 Nov;108(4):707-10.
• Bruder GE, Stewart JW, Voglmaier MM, Harrison WM, McGrath P, Tricamo E, Quitkin FM. Cerebral laterality and depression: relations of perceptual asymmetry to outcome of treatment with tricyclic antidepressants. Neuropsychopharmacology. 1990 Feb;3(1):1-10.
• Bruder GE, Sedoruk JP, Stewart JW, McGrath PJ, Quitkin FM, Tenke CE. Electroencephalographic alpha measures predict therapeutic response to a selective serotonin reuptake inhibitor antidepressant: pre- and post-treatment findings. Biol Psychiatry. 2008 Jun 15;63(12):1171-7. Epub 2007 Dec 3.

Inclusion Criteria:

• Ages between 18-65
• Meets DSM-IV criteria for current Major Depression, Dysthymia or Depression NOS

Exclusion Criteria:

• Known hearing impairment
• Active suicidal ideation (history of suicide attempts will be evaluated on a case by case basis)
• HAMD > 20
• Current (past six months) alcohol and/or drug abuse or dependence
• Medical condition likely to require intervention contraindicated with study medication (e.g., known arrhythmia likely to be exacerbated by Imipramine)
• Bipolar I
• Psychosis
• If currently taking antidepressants or mood stabilizers, cannot be off psychotropic medication for 7 weeks (10 weeks for Prozac) or felt to require other psychiatric medication (other than occasional sleep or Anxiety medication)
• Premenopausal women not using known effective birth control
• Not currently depressed (whether considered due to current treatment or not)