Clinical Study of Generic and Brand Bupropion in Depression

The protocol is a prospective, randomized, double-blinded, crossover study in 75 subjects
(target, 60 evaluable) with Major Depressive Disorder (MDD) receiving bupropion HCl 300mg XL
(branded or generic). Subjects will be studied for a total of approximately 28 weeks: an
approximately 4 week lead-in phase during which participants remain on their existing
bupropion product, and then four randomized cross-over phases of approximately 6 weeks on
each of the four bupropion study drugs (brand and 3 generics). For each of the four bupropion
products, subjects will have (a) formal pharmacokinetic evaluation (24 hr plasma and urine)
at steady-state, (b) every 3-week in-person standard structured clinical evaluations of
depressive symptoms and side effects, and (c) once daily smart phone-based assessments to
capture information on symptoms and side effects.

Inclusion Criteria

Each subject must meet all of the following criteria:

1. Adult outpatients age 18-75 years

2. Currently on once daily bupropion HCl 300mg XL (brand or any generic), for a minimum
of 4 months

3. Major depressive disorder (MDD), in partial or full remission for at least 4 months,
as confirmed by the SCID. Spontaneous relapse of depression unrelated to medication
changes is less likely - about 5% chance per year - after remission has been
maintained for at least 4 months.2

4. Ability to understand and willingness to comply with study procedures, and to provide
written informed consent

Exclusion Criteria

Subjects will not be enrolled if any of the following criteria exist:

1. Remission from depression not clearly attributed to bupropion treatment

2. Current severe side effects attributable to bupropion

3. Poor adherence to bupropion treatment per patient self- report and history of refill
persistence

4. History of active seizure disorder, or seizure treatment within past year

5. History of significant hepatic or renal disease, based on physician assessment

6. Currently taking drugs or natural products known to influence cytochrome P450B6
(CYP2B6) activity

7. Currently taking drugs for hepatitis C or multiple sclerosis, due to their ability to
cause depression

8. Dementia or other significant cognitive impairment, per diagnosis or investigative
team's assessment

9. Lifetime diagnosis of schizophrenia, schizoaffective or schizophreniform dis-order,
delusional disorder, or current psychotic symptoms diagnosed by SCID

10. Abuse of or dependence on alcohol or other substances within the past 6 months as
determined by SCID, and confirmed by study physician interview

11. Current suicidal ideation