Drug Therapy to Treat Minor Depression

Minor depression is highly prevalent, causes substantial morbidity and disability, presents a
serious risk factor for the development of major depressive disorder, yet is under recognized
and under treated. Researchers have determined that patients with minor depression frequently
seek treatment from general practitioners and are often treated with prescription
antidepressants. There is a need to evaluate the effectiveness of St. John's Wort in the
management of minor depression. If the proposed study demonstrates the efficacy of St. John's
Wort and/or citalopram, it will suggest treatment paradigms that can be tested and applied in
primary care settings.

Subjects participated in a 12-week double-blind randomized study comparing St. John's Wort,
citalopram, and placebo. Subjects were recruited through clinical referrals and community
advertising. Data were obtained at the baseline visit (just prior to randomization) and at
postrandomization visits conducted at 2-week intervals for the next 12 weeks, for a modified
intent-to-treat sample consisting of all 73 subjects with at least 1 post-randomization visit
(evaluable sample).

Inclusion Criteria:

- Minor Depression symptoms for at least 6 months

- Endorse one of the DSM-IV "A" criteria for MDD and at least one other symptom of MDD
or endorse both of the "A" criteria for MDD

- Global Assessment of Functioning (GAF) score < 70

- Short form health survey (SF-36) social functioning score <= 75% or an emotional role
functioning score <= 67%

- HAM-D-17 score 10-17, inclusive

- Minor depression symptoms for at least 6 months

Exclusion Criteria:

- Major depressive disorder (MDD) or dysthymia within the past year or in partial
remission of MDD

- At least a 12-week course of either citalopram at a minimum or 40 mg/day or St. John's
Wort at a minimum of 900 mg/day during the current episode of depression

- Previous intolerance to either citalopram or St. John's Wort or history of nonresponse
to either citalopram at a minimum of 40 mg/day or St. John's Wort at a minimum of 900
mg/day for at least 12 weeks

- Unstable medical illness, including cardiovascular, hepatic, renal, respiratory,
endocrine, neurologic, or hematologic disease

- Uncontrolled seizure disorder

- The following DSM-IV diagnoses: organic mental disorders; substance use disorders,
including alcohol, active within the last year or patients with a positive urine drug
screen; schizophrenia; delusional disorder; psychotic disorders not elsewhere
classified; bipolar disorder; bereavement; adjustment disorder; antisocial personality
disorder; panic disorder, social phobia, generalized anxiety disorder (GAD), or
obsessive compulsive disorder (OCD). Patients may have a lifetime diagnosis of an
anxiety disorder as long as it is not current.

- Mood-congruent or mood-incongruent psychotic features

- Psychotropic drugs

- Hypothyroidism

- Investigational psychotropic drugs within the last year

- Positive toxicology screen

- Medications metabolized by the CYP3A4 system, where induction of this system poses a
risk to the medical stability of the patient

- Pregnancy or refusal to use a medically accepted method of contraception

- Serious suicide or homicide risk

- Psychotherapy beginning less than 3 months ago