Combination of Medical Food and Antidepressants May Be Better Than Antidepressants Alone

Deborah Brauser

June 01, 2010

June 1, 2010 (New Orleans, Louisiana) — Combining an L-methylfolate prescription medical food supplement (Deplin, Pamlab) with a selective serotonin reuptake inhibitor (SSRI) or a serotonin norepinephrine reuptake inhibitor (SNRI) provides greater improvements in depressive symptoms of depression than monotherapy with an SSRI or SNRI, according to a large retrospective medical record review study.

The investigators, who also found that these improvements occurred 23% faster in the combination group compared with those treated with the monotherapy, presented the results here at the American Psychiatric Association (APA) 2010 Annual Meeting.

Dr. Lawrence Ginsberg

"We found that adding L-methylfolate to an antidepressant at the start of treatment has valuable benefits for these patients," principal investigator Lawrence D. Ginsberg, MD, from Red Oak Psychiatry Associates in Houston, Texas, said in a statement.

"The shorter time to improvement strongly implies that combination strategies right from the start may be a more time-efficient approach than antidepressant monotherapy," Dr. Ginsberg told Medscape Psychiatry.

New Approach Needed

According to Dr. Ginsberg, past studies show that nearly 70% of depressed individuals will not reach remission by taking 1 antidepressant alone, "so clearly a new approach is needed.”

He explained that up to 70% of people who have depression may have a specific genetic factor that compromises their ability to convert folic acid into L-methylfolate, "the only form of folate that can cross the blood-brain barrier and regulate serotonin, norepinephrine, and dopamine."

Deplin is a trimonoamine modulator that contains L-methylfolate in a tablet form.

For this study, Dr. Ginsberg and his team evaluated the medical records of 242 patients between the ages of 18 and 70 years (66% female; mean age, 43 years) who were seen at a single outpatient psychiatric clinic due to a major depressive episode.

All patients received at treatment initiation either Deplin, 7.5 to 15 mg, plus an SSRI or SNRI (the combination group, n = 95) or an SSRI or SNRI only (the monotherapy group, n = 147).

The primary outcome was improvement in MDD symptoms, shown by a 2-point decrease from baseline in the Clinical Global Impression–Severity (CGI-S) score.

"I set this bar pretty high," explained Dr. Ginsberg. "Most research considers a 1-point reduction an accomplishment, but we really wanted our patients to achieve this 2-point reduction. That was my goal; I was shooting for the rafters."

Quicker, Sustained Improvements

Results showed that significantly more of the combination-treated patients showed the 2-point CGI-S reduction at the 60-day time point compared with those receiving monotherapy (18.1% vs 7.04%; P < .01).

Although not statistically significant, there was also a trend toward symptom reduction at 30 days for those receiving the combination treatment compared with the monotherapy patients.

In addition, the time to major improvement was significantly shorter at a median of 177 days for all patients in the combination group vs a median of 231 days for the monotherapy group (P = .03). This major improvement was sustained throughout the 2-year study period.

"We also found that the number of hospitalizations in the monotherapy group was nearly 3 times greater than in the combination group," reported Dr. Ginsberg. However, this was not statistically significant (2.7% vs 1%).

For the subgroup of patients with the highest severity score at baseline (CGI-S = 5), 40% of those treated with the combination therapy showed a major improvement in symptoms at 60 days, whereas only 16.3% of the monotherapy group showed this improvement (P < .02).

Finally, although the overall rate of discontinuation of antidepressant therapy due to adverse events was 34% for the monotherapy vs 17.9% for the combination treatment (P = .0078), there were no significant differences in overall rates of adverse effects found between the 2 groups (P = .21).

"While all the findings were promising, this last one was unexpected," said Dr. Ginsberg. "Usually, when you have 2 agents, you expect more discontinuation. But we can say with confidence that the medication did not cause additional adverse events or discontinuation from adverse events."

"Overall, I'd tell clinicians that they can increase the ability to get people well by combining a traditional SSRI or SNRI with L-methylfolate, especially if the patient is in an at-risk population," he said.

Twice the Response

"Folate deficiency related to depression has been around since about 1975, with the speculation that if you didn't have enough folate absorbed through your foods, then the brain itself would not have enough folate to do its functions," cochair of the APA Scientific Program Committee Don Hilty, MD, professor of psychiatry and behavioral sciences at the University of California–Davis in Sacramento, told Medscape Psychiatry.

"It's interesting that in this study, the [investigators] discovered that patients who took an antidepressant and L-methylfolate, a product made with folate, had a little bit earlier response and did not have any noticeable side effects," added Dr. Hilty, who was not involved with the study.

"Although the [combination] group didn't have a huge response at about 18%, it was over twice the number of those who responded while taking an antidepressant alone," he noted. "While this finding is not proof by any means that this supplementation works, it definitely implies that more research should be done prospectively in this area with good sample sizes."

Dr. Hilty reported that a number of studies have been coming out in recent years looking at L-methylfolate. "So this is 1 more step in the process of getting a better snapshot of what's really going on with these supplements."

"The important takeaways are that we need to be mindful about folate deficiencies and should probably try medical foods in patients who haven't responded to traditional treatments. Also, even though there aren't any real clear side effects from supplements like this, we have to be mindful to watch and see if there are any interactions with prescribed medications," concluded Dr. Hilty.

This study was funded by Pamlab. Dr. Ginsberg reported having received research support from and participated in speaking engagements for Pamlab in the past. Dr. Hilty has disclosed no relevant financial relationships.

American Psychiatric Association (APA) 2010 Annual Meeting: Abstract NR3-46. Presented May 24, 2010.


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