Drug Therapy to Treat Minor Depression

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00048815
• Collaborator: National Institute of Mental Health (NIMH) (NIH), National Center for Complementary and Integrative Health (NCCIH) (NIH), Office of Dietary Supplements (ODS) (NIH)
• Enrollment: 73
• Locations: 3
• Arms: 3
• Duration (Months): 49.9
• Patients Per Site: 24.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Citalopram; Drug: St. John's Wort; Drug: Placebos	N/A

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Pharmacotherapy for Minor Depression
• Study Start Date: Feb 1, 2003
• Actual Primary Completion Date: Apr 1, 2007
• Actual Study Completion Date: Apr 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: citalopram Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks.	Drug: Citalopram; Established Selective Serotonin Reuptake Inhibitor antidepressant; Other Names: Celexa, Cipramil
Experimental: 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.	Drug: St. John's Wort; Natural extract from the St. John's Wort plant.; Other Names: Hypericum
Placebo Comparator: Placebo Subjects in this arm received double-dummy (look-alike) placebo for 12 weeks.	Drug: Placebos; Placebo pill

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	University of Pittsburgh, Western Psychiatric Institute and Clinic	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institute of Mental Health (NIMH)
• National Center for Complementary and Integrative Health (NCCIH)
• Office of Dietary Supplements (ODS)

Investigators

• Principal Investigator: Andrew A. Nierenberg, M.D., Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here to view the "Treatment for Minor Depression" NIH news release.

Publications

None provided.

• Responsible Party: Andrew A. Nierenberg, MD, Director Bipolar Clinic and Research Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00048815
• Other Study ID Numbers: R01MH061758; R01MH061758; R01MH061757; R01MH061394; DSIR AT-SO; NCT00043524; NCT00050544
• First Posted: Nov 13, 2002
• Last Update Posted: May 11, 2018
• Last Verified: May 1, 2018

• Keywords provided by Andrew A. Nierenberg, MD, Director Bipolar Clinic and Research Program, Massachusetts General Hospital: Minor Depression; St. John's Wart
• Additional relevant MeSH terms: Depression; Depressive Disorder; Citalopram

Study Results

Participant Flow

Arm/Group Title	Citalopram	St. John's Wort	Placebo
Arm/Group Description	Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks.	Subjects in this arm received 810 mg/day of St. John's Wort taken orally (in three tablets of 270mg each) for 12 weeks.	Subjects in this arm received double-dummy (look-alike) placebo for 12 weeks.
Period Title: Overall Study
STARTED	24	26	23
COMPLETED	18	22	19
NOT COMPLETED	6	4	4

Baseline Characteristics

Arm/Group Title	Citalopram	St. John's Wort	Placebo	Total
Arm/Group Description	Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks.	Subjects in this arm received 810 mg/day of St. John's Wort taken orally (in three tablets of 270mg each) for 12 weeks.	Subjects in this arm received double-dummy (look-alike) placebo for 12 weeks.	Total of all reporting groups
Overall Participants	24	26	23	73
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.3 (12.5)	42.2 (14.1)	51.4 (16.6)	48.1 (15.0)
Sex: Female, Male (Count of Participants)
Female	13 54.2%	13 50%	11 47.8%	37 50.7%
Male	11 45.8%	13 50%	12 52.2%	36 49.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 8.3%	0 0%	1 4.3%	3 4.1%
Not Hispanic or Latino	22 91.7%	26 100%	22 95.7%	70 95.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	24 100%	26 100%	23 100%	73 100%

Outcome Measures

1. Primary Outcome

Title	Efficacy Assessed Using the Inventory of Depressive Symptomatology - Clinician Rated (IDS-C)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Citalopram	St. John's Wort	Placebo
Arm/Group Description	Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks.	Subjects in this arm received 810 mg/day of St. John's Wort taken orally (in three tablets of 270mg each) for 12 weeks.	Subjects in this arm received double-dummy (look-alike) placebo for 12 weeks.
Measure Participants	24	26	23
Least Squares Mean (Standard Error) [units on a scale]	-11.47 (1.36)	-9.35 (1.23)	-10.49 (1.37)

2. Primary Outcome

Title	Number of Adverse Events (Physical Symptoms) Emerging or Worsening During 12 Weeks of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Citalopram	St. John's Wort	Placebo
Arm/Group Description	Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks.	Subjects in this arm received 810 mg/day of St. John's Wort taken orally (in three tablets of 270mg each) for 12 weeks.	Subjects in this arm received double-dummy (look-alike) placebo for 12 weeks.
Measure Participants	24	26	23
Mean (Standard Deviation) [Number of events]	4.7 (4.4)	5.0 (4.5)	3.4 (3.0)

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	The Patient-Rated Inventory of Side Effects (PRISE; Rush et al., 2004) was administered at baseline and all subsequent visits. This obtained information not only about the presence or absence of 32 specific adverse events (and the opportunity to write in "others"), but whether those were present at a tolerable or distressing level or constituted a serious adverse event. Vital signs and medication compliance were also assessed at each visit during treatment.
Arm/Group Title	Citalopram		St. John's Wort		Placebo
Arm/Group Description	Subjects in this arm received 20mg/day of citalopram taken orally for 12 weeks.		Subjects in this arm received 810 mg/day of St. John's Wort taken orally (in three tablets of 270mg each) for 12 weeks.		Subjects in this arm received double-dummy (look-alike) placebo for 12 weeks.
All Cause Mortality
	Citalopram		St. John's Wort		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Citalopram		St. John's Wort		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/26 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Citalopram		St. John's Wort		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/24 (95.8%)		22/26 (84.6%)		18/23 (78.3%)
Cardiac disorders
Palpitations	3/24 (12.5%)	3	3/26 (11.5%)	3	4/23 (17.4%)	4
Dizziness on standing	5/24 (20.8%)	5	4/26 (15.4%)	4	3/23 (13%)	3
Chest Pain	1/24 (4.2%)	1	1/26 (3.8%)	1	4/23 (17.4%)	4
Ear and labyrinth disorders
Ringing in ears	3/24 (12.5%)	3	1/26 (3.8%)	1	0/23 (0%)	0
Eye disorders
Blurred vision	5/24 (20.8%)	5	6/26 (23.1%)	6	4/23 (17.4%)	4
Gastrointestinal disorders
Diarrhea	8/24 (33.3%)	8	8/26 (30.8%)	8	1/23 (4.3%)	1
Constipation	6/24 (25%)	6	8/26 (30.8%)	8	3/23 (13%)	3
Dry Mouth	6/24 (25%)	6	6/26 (23.1%)	6	0/23 (0%)	0
Nausea/Vomiting	6/24 (25%)	6	7/26 (26.9%)	7	4/23 (17.4%)	4
Nervous system disorders
Headache	10/24 (41.7%)	10	6/26 (23.1%)	6	11/23 (47.8%)	11
Tremors	4/24 (16.7%)	4	4/26 (15.4%)	4	0/23 (0%)	0
Poor coordination	1/24 (4.2%)	1	3/26 (11.5%)	3	1/23 (4.3%)	1
Dizziness	3/24 (12.5%)	3	4/26 (15.4%)	4	5/23 (21.7%)	5
Difficulty sleeping	10/24 (41.7%)	10	13/26 (50%)	13	7/23 (30.4%)	7
Sleeping too much	7/24 (29.2%)	7	5/26 (19.2%)	5	1/23 (4.3%)	1
Psychiatric disorders
Anxiety	5/24 (20.8%)	5	5/26 (19.2%)	5	9/23 (39.1%)	9
Poor concentration	6/24 (25%)	6	7/26 (26.9%)	7	7/23 (30.4%)	7
General malaise	7/24 (29.2%)	7	2/26 (7.7%)	2	5/23 (21.7%)	5
Restlessness	3/24 (12.5%)	3	8/26 (30.8%)	8	6/23 (26.1%)	6
Fatigue	10/24 (41.7%)	10	3/26 (11.5%)	3	5/23 (21.7%)	5
Decreased energy	9/24 (37.5%)	9	5/26 (19.2%)	5	5/23 (21.7%)	5
Renal and urinary disorders
Frequent urination	2/24 (8.3%)	2	3/26 (11.5%)	3	1/23 (4.3%)	1
Menstrual irregularity (females)	2/13 (15.4%)	2	0/13 (0%)	0	3/11 (27.3%)	3
Reproductive system and breast disorders
Loss of sexual desire	7/24 (29.2%)	7	4/26 (15.4%)	4	5/23 (21.7%)	5
Trouble achieving orgasm	8/24 (33.3%)	8	5/26 (19.2%)	5	5/23 (21.7%)	5
Trouble with erections (male)	5/11 (45.5%)	5	1/13 (7.7%)	1	2/12 (16.7%)	2
Skin and subcutaneous tissue disorders
Rash	2/24 (8.3%)	2	2/26 (7.7%)	2	1/23 (4.3%)	1
Increased perspiration	4/24 (16.7%)	4	1/26 (3.8%)	1	1/23 (4.3%)	1
Itching	1/24 (4.2%)	1	2/26 (7.7%)	2	2/23 (8.7%)	2
Dry skin	2/24 (8.3%)	2	3/26 (11.5%)	3	1/23 (4.3%)	1

Limitations/Caveats

Stringent inclusion criteria may have yielded a sample who depression was too mild to show added benefit for either active treatment beyond general therapeutic effects of study participation

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.