Depression
Conditions
Keywords
Minor Depression, St. John's Wart
Brief summary
This 6-month study will compare the effectiveness of citalopram (Celexa®), hypericum (St. John's Wort), and placebo for the treatment of minor depression.
Detailed description
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).
Interventions
DRUGCitalopram
Established Selective Serotonin Reuptake Inhibitor antidepressant
DRUGSt. John's Wort
Natural extract from the St. John's Wort plant.
DRUGPlacebos
Placebo pill
Sponsors
National Institute of Mental Health (NIMH)
National Center for Complementary and Integrative Health (NCCIH)
Office of Dietary Supplements (ODS)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Assessed Using the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C) | Change from Baseline to Week 12 | We expect that subjects with minor depression treated for 12 weeks with St. John's Wort or citalopram will have significantly greater reduction in depressive symptom severity than those treated with placebo. This will be measured by blind ratings on the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C) which has a total score range from 0 to 84 with 0 being not depressed at all and 84 being the most depressed. The change will be calculated by subtracting the Week 12 score from the Baseline score. |
| Number of Adverse Events (Physical Symptoms) Emerging or Worsening During 12 Weeks of Treatment | Change from Baseline to Week 12 | We expect that subjects treated for Minor Depression for 12 weeks with either St. John's Wort or citalopram will have similar safety profiles to subjects treated with placebo, and will not differ by more than 20% in rates of adverse side effects (e.g., nausea, headache, insomnia, hypersomnia, diarrhea) from subjects treated with placebo. This was measured by the number of adverse events (physical symptoms) emerging or worsening during 12 weeks of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Citalopram Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks. | 24 |
| St. John's Wort Subjects in this arm received 810 mg/day of St. John's Wort taken orally (in three tablets of 270mg each) for 12 weeks. | 26 |
| Placebo Subjects in this arm received double-dummy (look-alike) placebo for 12 weeks. | 23 |
| Total | 73 |
Baseline characteristics
| Characteristic | Citalopram | St. John's Wort | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 12.5 | 42.2 years STANDARD_DEVIATION 14.1 | 51.4 years STANDARD_DEVIATION 16.6 | 48.1 years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 26 Participants | 22 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 24 participants | 26 participants | 23 participants | 73 participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 11 Participants | 37 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 12 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 24 | 22 / 26 | 18 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 26 | 0 / 23 |
Outcome results
Primary
Efficacy Assessed Using the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C)
We expect that subjects with minor depression treated for 12 weeks with St. John's Wort or citalopram will have significantly greater reduction in depressive symptom severity than those treated with placebo. This will be measured by blind ratings on the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C) which has a total score range from 0 to 84 with 0 being not depressed at all and 84 being the most depressed. The change will be calculated by subtracting the Week 12 score from the Baseline score.
Time frame: Change from Baseline to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Citalopram | Efficacy Assessed Using the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C) | -11.47 units on a scale | Standard Error 1.36 |
| St. John's Wort | Efficacy Assessed Using the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C) | -9.35 units on a scale | Standard Error 1.23 |
| Placebo | Efficacy Assessed Using the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C) | -10.49 units on a scale | Standard Error 1.37 |
Primary
Number of Adverse Events (Physical Symptoms) Emerging or Worsening During 12 Weeks of Treatment
We expect that subjects treated for Minor Depression for 12 weeks with either St. John's Wort or citalopram will have similar safety profiles to subjects treated with placebo, and will not differ by more than 20% in rates of adverse side effects (e.g., nausea, headache, insomnia, hypersomnia, diarrhea) from subjects treated with placebo. This was measured by the number of adverse events (physical symptoms) emerging or worsening during 12 weeks of treatment.
Time frame: Change from Baseline to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Citalopram | Number of Adverse Events (Physical Symptoms) Emerging or Worsening During 12 Weeks of Treatment | 4.7 Number of events | Standard Deviation 4.4 |
| St. John's Wort | Number of Adverse Events (Physical Symptoms) Emerging or Worsening During 12 Weeks of Treatment | 5.0 Number of events | Standard Deviation 4.5 |
| Placebo | Number of Adverse Events (Physical Symptoms) Emerging or Worsening During 12 Weeks of Treatment | 3.4 Number of events | Standard Deviation 3 |