Combination Deplin® and Antidepressant Therapy for a Major Depressive Episode (MDE)- a Retrospective Analysis

• Sponsor: Pamlab, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01001559
• Collaborator: Red Oak Psychiatry Associates, PA (Other), Baylor Health Care System (Other)
• Enrollment: 242
• Location: 1
• Duration (Months): 22
• Patients Per Site Per Month: 11

Study Details

Study Description

Brief Summary

This is a retrospective chart review study to determine if Deplin® 7.5mg-15mg combined with an antidepressant is better than an antidepressant alone in adults with major depression.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: L-methylfolate; Drug: Selective serotonin reuptake inhibitor (SSRI); Drug: Serotonin and norepinephrine reuptake inhibitor (SNRI)

Study Design

• Study Type: Observational
• Actual Enrollment: 242 participants
• Observational Model: Case-Control
• Time Perspective: Retrospective
• Official Title: Combination Deplin® and Antidepressant Therapy Compared to Antidepressant Therapy Alone for an Episode of Major Depression- a Retrospective Analysis
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Deplin + antidepressant Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)	Drug: L-methylfolate; Subjects must have been on their respective therapies for a minimum of 60 days. L-methylfolate dosing was 7.5 mg or 15 mg daily; Other Names: Deplin ; Drug: Selective serotonin reuptake inhibitor (SSRI); Subject must have been on their respective therapy for a minimum of 60 days. Because this was an observational retrospective analysis, dosing of SSRI/SNRI varied on a per patient basis.; Drug: Serotonin and norepinephrine reuptake inhibitor (SNRI); Subject must have been on their respective therapy for a minimum of 60 days. Because this was an observational retrospective analysis, dosing of SSRI/SNRI varied on a per patient basis.
Antidepressant alone SSRI or SNRI alone	Drug: Selective serotonin reuptake inhibitor (SSRI); Subject must have been on their respective therapy for a minimum of 60 days. Because this was an observational retrospective analysis, dosing of SSRI/SNRI varied on a per patient basis.; Drug: Serotonin and norepinephrine reuptake inhibitor (SNRI); Subject must have been on their respective therapy for a minimum of 60 days. Because this was an observational retrospective analysis, dosing of SSRI/SNRI varied on a per patient basis.

Outcome Measures

Primary Outcome Measures

1. Improvement as Measured by Change in Clinical Global Impression of Severity (CGI-S) Rating From Baseline [60 days]

   The Clinical Global Impression of Severity (CGI-S) Rating evaluates the severity of individual symptoms and treatment response in patients with mental disorders. The CGI-S is a 7-point scale that that requires the clinician to rate the severity of the patient's illness at the time of assessment. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms. Number of patients with an improvement in CGI-S scores as demonstrated by a reduction in ≥2 points (major improvement) from baseline.

Secondary Outcome Measures

1. Length of Time to Peak Response, as Determined by the Clinical Global Impression of Severity (CGI-S) Scale [60 days]

   The Clinical Global Impression of Severity (CGI-S) Rating evaluates the severity of individual symptoms and treatment response in patients with mental disorders. The CGI-S is a 7-point scale that that requires the clinician to rate the severity of the patient's illness at the time of assessment. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms. Median times to peak response. Peak response defined as the first improvement of two or more in the CGI-S from initial visit, and measured the time to the occurrence.

2. Number of Hospitalizations Due to MDD [60 days]

   Number of hospitalizations due to MDD during treatment were assessed during this retrospective analysis of L-methylfolate plus SSRI/SNRI at treatment initiation (n=95) and SSRI/SNRI monotherapy (n-147) from patient charts

3. Absolute Count of Alterations in Therapy Required, Such as Dose Increases, Antidepressant Substitutions, or Addition of Augmentation Medications [60 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females age 18-70

• The active arm (Arm #1) includes randomly selected 100-125 charts of patients with a primary diagnosis of major depression and a CGI-S of ≥4 who began Deplin and SSRI or SNRI therapy at the same time beginning in January 2007 to the present; and, Control group (Arm #2) includes randomly selected 125-150 charts of patients with a primary diagnosis of major depression who began SSRI or SNRI therapy matched in severity (CGI-S of ≥4)

Exclusion Criteria:

• Folic acid >400 mcg taken at any time during the study

• Psychotic features in the current episode or a history of psychotic features

• Any bipolar disorder (current or past) or any psychotic disorder (current or past)

• Current or past treatment with vagus nerve stimulation, ECT, or transcranial magnetic stimulation

• Antipsychotic therapy in conjunction with their antidepressant currently or in past 4 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Red Oak Psychiatry Associates, PA	Houston	Texas	United States

Sponsors and Collaborators

• Pamlab, Inc.
• Red Oak Psychiatry Associates, PA
• Baylor Health Care System

Investigators

• Principal Investigator: Lawrence D Ginsberg, MD, Red Oak Psychiatry Associates, PA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pamlab, Inc.
• ClinicalTrials.gov Identifier: NCT01001559
• Other Study ID Numbers: Pamlab D-005
• First Posted: Oct 26, 2009
• Last Update Posted: Dec 19, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by Pamlab, Inc.: Depression; Combination therapy; antidepressant; Deplin; folate; methylfolate
• Additional relevant MeSH terms: Depressive Disorder; Depressive Disorder, Major; Norepinephrine; Serotonin; Serotonin Uptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors

Study Results

Participant Flow

Recruitment Details	Single site, retrospective chart review of subjects administered a combination of Deplin and an SSRI or SNRI. The 242 subjects were 18-70 years of age (inclusive) and received their respective therapies between January 2007 and September 2009.
Pre-assignment Detail	Criteria that excluded patients were folic acid supplementation >400mcg, current or a history of psychotic features, bipolar disorder, a history of vagus nerve stimulation, electroconvulsive, or transcranial magnetic stimulation therapy. Any concomitant antipsychotic therapy in the most recent 4 weeks.

Arm/Group Title	Deplin + Antidepressant	Antidepressant Alone
Arm/Group Description	Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)	SSRI or SNRI alone
Period Title: Overall Study
STARTED	95	147
COMPLETED	95	147
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Deplin + Antidepressant	Antidepressant Alone	Total
Arm/Group Description	Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)	SSRI or SNRI alone	Total of all reporting groups
Overall Participants	95	147	242
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.5 (11.9)	41.4 (11.7)	43.0 (11.9)
Sex: Female, Male (Count of Participants)
Female	62 65.3%	98 66.7%	160 66.1%
Male	33 34.7%	49 33.3%	82 33.9%

Outcome Measures

1. Primary Outcome

Title	Improvement as Measured by Change in Clinical Global Impression of Severity (CGI-S) Rating From Baseline
Description	The Clinical Global Impression of Severity (CGI-S) Rating evaluates the severity of individual symptoms and treatment response in patients with mental disorders. The CGI-S is a 7-point scale that that requires the clinician to rate the severity of the patient's illness at the time of assessment. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms. Number of patients with an improvement in CGI-S scores as demonstrated by a reduction in ≥2 points (major improvement) from baseline.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Deplin + Antidepressant	Antidepressant Alone
Arm/Group Description	Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)	SSRI or SNRI alone
Measure Participants	95	147
Number [Participants]	17 17.9%	10 6.8%

2. Secondary Outcome

Title	Length of Time to Peak Response, as Determined by the Clinical Global Impression of Severity (CGI-S) Scale
Description	The Clinical Global Impression of Severity (CGI-S) Rating evaluates the severity of individual symptoms and treatment response in patients with mental disorders. The CGI-S is a 7-point scale that that requires the clinician to rate the severity of the patient's illness at the time of assessment. A rating of 1 is considered normal, or with the least severe symptoms, a rating of 7 is extremely ill, or the worst symptoms. Median times to peak response. Peak response defined as the first improvement of two or more in the CGI-S from initial visit, and measured the time to the occurrence.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Deplin + Antidepressant	Antidepressant Alone
Arm/Group Description	Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)	SSRI or SNRI alone
Measure Participants	95	147
Median (Inter-Quartile Range) [Days]	177	231

3. Secondary Outcome

Title	Number of Hospitalizations Due to MDD
Description	Number of hospitalizations due to MDD during treatment were assessed during this retrospective analysis of L-methylfolate plus SSRI/SNRI at treatment initiation (n=95) and SSRI/SNRI monotherapy (n-147) from patient charts
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deplin + Antidepressant	Antidepressant Alone
Arm/Group Description	Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)	SSRI or SNRI alone
Measure Participants	95	147
Number [Hospitalizations due to MDD]	1	4

4. Secondary Outcome

Title	Absolute Count of Alterations in Therapy Required, Such as Dose Increases, Antidepressant Substitutions, or Addition of Augmentation Medications
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deplin + Antidepressant	Antidepressant Alone
Arm/Group Description	Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)	SSRI or SNRI alone
Measure Participants	95	147
Number [Alterations in antidepressant therapy]	135	263

Adverse Events

Time Frame	AE reporting occurred between January 2007 and September 2009
Arm/Group Title	Deplin + Antidepressant		Antidepressant Alone
Arm/Group Description	Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI)		SSRI or SNRI alone
All Cause Mortality
	Deplin + Antidepressant		Antidepressant Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Deplin + Antidepressant		Antidepressant Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/93 (1.1%)		3/103 (2.9%)
General disorders
Hospitalization	1/93 (1.1%)	1	3/103 (2.9%)	3
Other (Not Including Serious) Adverse Events
	Deplin + Antidepressant		Antidepressant Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/93 (60.2%)		68/103 (66%)
Gastrointestinal disorders
Nausea	9/93 (9.7%)	9	9/103 (8.7%)	9
Constipation	7/93 (7.5%)	7	4/103 (3.9%)	4
Dry Mouth	1/93 (1.1%)	1	2/103 (1.9%)	3
General disorders
Fatigue	5/93 (5.4%)	5	2/103 (1.9%)	2
Nervous system disorders
Somnolence	12/93 (12.9%)	12	12/103 (11.7%)	12
Dizziness	3/93 (3.2%)	3	7/103 (6.8%)	7
Psychiatric disorders
Insomnia	4/93 (4.3%)	4	6/103 (5.8%)	6
Agitation	3/93 (3.2%)	3	6/103 (5.8%)	6
Decreased Appetite	1/93 (1.1%)	1	5/103 (4.9%)	5
Reproductive system and breast disorders
Sexual Dysfunction	11/93 (11.8%)	11	15/103 (14.6%)	15

Limitations/Caveats

[Not Specified]

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.