Major Depressive Disorder
Conditions
Keywords
Depression, Combination therapy, antidepressant, Deplin, folate, methylfolate
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.
Interventions
DRUGL-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
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.
DRUGSerotonin 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.
Sponsors
Red Oak Psychiatry Associates, PA
Baylor Health Care System
Pamlab, Inc.
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| Absolute Count of Alterations in Therapy Required, Such as Dose Increases, Antidepressant Substitutions, or Addition of Augmentation Medications | 60 days | — |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Deplin + Antidepressant Deplin in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) | 95 |
| Antidepressant Alone SSRI or SNRI alone | 147 |
| Total | 242 |
Baseline characteristics
| Characteristic | Deplin + Antidepressant | Antidepressant Alone | Total |
|---|---|---|---|
| Age, Continuous | 45.5 years STANDARD_DEVIATION 11.9 | 41.4 years STANDARD_DEVIATION 11.7 | 43.0 years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 62 Participants | 98 Participants | 160 Participants |
| Sex: Female, Male Male | 33 Participants | 49 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 93 | 68 / 103 |
| serious Total, serious adverse events | 1 / 93 | 3 / 103 |
Outcome results
Primary
Improvement as Measured by Change in Clinical Global Impression of Severity (CGI-S) Rating From Baseline
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
Population: All participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deplin + Antidepressant | Improvement as Measured by Change in Clinical Global Impression of Severity (CGI-S) Rating From Baseline | 17 Participants |
| Antidepressant Alone | Improvement as Measured by Change in Clinical Global Impression of Severity (CGI-S) Rating From Baseline | 10 Participants |
Secondary
Absolute Count of Alterations in Therapy Required, Such as Dose Increases, Antidepressant Substitutions, or Addition of Augmentation Medications
Time frame: 60 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deplin + Antidepressant | Absolute Count of Alterations in Therapy Required, Such as Dose Increases, Antidepressant Substitutions, or Addition of Augmentation Medications | 135 Alterations in antidepressant therapy |
| Antidepressant Alone | Absolute Count of Alterations in Therapy Required, Such as Dose Increases, Antidepressant Substitutions, or Addition of Augmentation Medications | 263 Alterations in antidepressant therapy |
Secondary
Length of Time to Peak Response, as Determined by the Clinical Global Impression of Severity (CGI-S) Scale
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
Population: All participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deplin + Antidepressant | Length of Time to Peak Response, as Determined by the Clinical Global Impression of Severity (CGI-S) Scale | 177 Days |
| Antidepressant Alone | Length of Time to Peak Response, as Determined by the Clinical Global Impression of Severity (CGI-S) Scale | 231 Days |
Secondary
Number of Hospitalizations Due to MDD
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deplin + Antidepressant | Number of Hospitalizations Due to MDD | 1 Hospitalizations due to MDD |
| Antidepressant Alone | Number of Hospitalizations Due to MDD | 4 Hospitalizations due to MDD |