• Improvement on quick inventory of depressive symptoms, 16 question self-report. [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
  

• Improvement on Snaith-Hamilton anhedonia scale [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
  
• Improvement on patient and clinician clinical global impression rating scale (CGI) [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
  
• Tolerability of varenicline measured by adverse symptoms checklist (SAFTEE-SI LCN modified) [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
  

Drug: varenicline
varenicline 0.5 mg po daily for days 1-3, 0.5 twice daily for days 4-7, 1 mg twice daily thereafter for study duration.

Outpatient smokers who are depressed despite current stable psychiatric medication regimens will be invited to participate.

They will receive varenicline dosed according to FDA-approved smoking cessation regime; patients will be assessed using QIDS-SR16, snaith-hamilton anhedonia rating scale, SAFTEE and clinical global improvement self-report scales and clinician global improvement scales at the above time intervals.

Concurrent medication, psychiatric and non-psychiatric, will be recorded, as will vital signs (BP, HR, weight) and tobacco use.

Inclusion Criteria:

1. Meets DSM-IV symptoms criteria for a mood disorder including major depression [unipolar or bipolar], depressive disorder NOS, dysthymia, adjustment disorder with depressed mood, or substance-induced mood disorder.
2. Failed to achieve full symptom remission with previous pharmacotherapy.
3. Current tobacco users.
4. Able to give written, informed consent.

Exclusion Criteria:

1. Past adverse reaction to varenicline.
2. Renal failure or dialysis.
3. Current pregnancy or breastfeeding.