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

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

Drug: Bupropion, Escitalopram, Imipramine

Bupropion:wk 1:150 mg/d; wks 2-3: 300 mg/d; wks 4-6: 450 mg/d Escitalopram: wk 1: 10 mg/d; wks 2-3: 20 mg/d; wk4: 30 mg/d; wks 5-6: 40 mg/d Imipramine: wk 1: 25 mg/d; wk 2:50 mg/d; wk 3: 100 mg/d, 150 mg/d after 3 days, wk 4: 200 mg/d, 250 mg/d after 3 days, wk 5: 300 mg/d; wk 6: 300 mg/d.

*all increases only if tolerated.

Preliminary data suggest that depressed patients with increased left hemispheric laterality of perceptual processing are unlikely to improve during 6 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 patients will be tested with verbal and nonverbal dichotic tests, and then treated sequentially with bupropion, escitalopram, and imipramine. Preferential hemisphere for auditory processing will be correlated with treatment outcome.

Inclusion Criteria:

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

Exclusion Criteria:

1. Known Hearing impairment
2. Active suicidal ideation (history of suicide attempts will be evaluated on a case by case basis).
3. HAMD>20
4. Current (past 6 months)alcohol and/or drug abuse or dependence
5. Medical condition likely to require intervention contraindicated with study medication (e.g., known arrhythmia likely to be exacerbated by Imipramine)
6. Bipolar I
7. Psychosis
8. Non-response to adequate trial of study medication (i.e., > or = 4 weeks on > or = bupropion 300mg/d, escitalopram 30mg/d, or imipramine 200mg/d)
9. Premenopausal women not using known effective birth control
10. Not currently depressed (whether considered due to current treatment or not)
11. History of seizure, seizure disorder, anorexia nervosa, or bulimia -