A combination of the supplement S-adenosylmethionine (SAMe) and the probiotic bacteria Lactobacillus plantarum (L. plantarum) HEAL9 may rapidly alleviate symptoms of depression and anxiety, new research suggests.
A team of Italian investigators randomly assigned 90 patients with subthreshold or mild-to-moderate depression to receive either SAMe plus L. plantarum HEAL9 or placebo for 6 weeks and found significant reductions in depression, anxiety, and cognitive symptoms as early as 2 weeks following treatment initiation.
"The effect of this novel product is independent from the severity of the symptoms, unlike traditional antidepressants available on the market that have minimal benefits for subthreshold or mild-to-moderate symptoms," write the investigators, led by Alberto Saccarello, MD, a physician in private practice in Genova, Italy.
The findings were published online recently in Primary Care Companion CNS Disorders.
Similar to SSRIs?
Antidepressant drugs are considered to be standard of care for depression treatment and superior to placebo, but their use in subthreshold depression is "controversial" and the effect size of these agents is "strictly associated with the baseline severity of symptoms," the researchers write.
SAMe has been studied as an adjunctive therapy to antidepressant drugs and psychotherapy for mild-to-moderate depression, with its putative antidepressant effects possibly "due to its capability to attenuate oxidative and nitrosative stress that is partially similar to that of selective serotonin reuptake inhibitors (SSRIs)," they add.
Extensive research has also shed light on the role of microbiota in patients with depressive disorder, suggesting a role for probiotic supplementation. A probiotic called L. plantarum 299v has been found to have a significant effect on stress markers, such as cortisol levels.
The current study compared the effects of a combination of SAMe and L. plantarum HEAL9, which is a probiotic strain similar to L. plantarum 299v, with placebo in patients between the ages of 18 and 60 years (n = 90; mean age, 48.1 years; 82% female) with subthreshold or mild-to-moderate depression.
Most patients were white (95.5%) and employed (70.8%), and roughly half (56.2%) were married.
Patients were excluded if they had one or more psychiatric disorders, such as a substance use or psychotic disorder, or were being treated with psychotropic drugs or other food supplements except for multivitamins, salts, and trace elements.
Participants were required to meet ICD-10 diagnostic criteria for mild-to-moderate depression and were selected if their total score on the Zung Self-Rating Depression Scale (Z-SDS) was between 41 and 55.
They were randomly assigned to receive placebo (n = 44) or 200 mg of SAMe plus L. plantarum HEAL9 1 × 109 CFU (n = 46).
Although change in the Z-SDS score from baseline to treatment week 6 was the primary outcome, researchers also analyzed changes in other scales related to insomnia, anxiety, irritable bowel syndrome, and health status.
Superior to Placebo
Compared with patients in the placebo group, those in the treatment group showed greater reductions in Z-SDS total score at 2 weeks (–2.78; 95% CI, –5.33 to –0.23, P = .0330) and at 6 weeks (–3.55; 95% CI, –6.43 to –0.67; P = .0165).
Additionally, improvement was shown at 6 weeks in the core depression subdomain of the Z-SDS (–1.64; 95% CI, –3.07 to –0.22; P = .0247).
At 2 weeks, participants showed significant reductions in the cognitive and anxiety subdomains of the Z-SDS. The Zung Self-Rating Anxiety Scale (Z-SAS), a separate anxiety questionnaire that participants completed, likewise showed a superior reduction in anxiety symptoms (P = .0345).
Researchers also found a greater reduction among those in the treatment group compared with the placebo group on the Birmingham IBS (B-IBS) symptom questionnaire, but it did not reach statistical significance.
In addition, the combination treatment was safe, with no treatment-related adverse effects.
"The superiority of the new product versus placebo is expressed by the statistically significant difference of the mean absolute change of the Z-SDS total score...from baseline to the end of treatment after 6 weeks," the investigators write.
They note that study limitations include the relatively small number of participants and the short treatment period, "hence no long-term conclusions can be drawn."
They recommend that further randomized controlled studies with "prolonged follow-up" be conducted to investigate the effect of the combination treatment in more severe forms of depression or with antidepressants.
"Proof of Concept"
Commenting on the study for Medscape Medical News, Richard Brown, MD, associate professor of clinical psychiatry, Columbia University, New York City, said it "addresses the specific need for what one can do for patients with mild-to-moderate outpatient depression because what we know from research is that the antidepressants work for the more moderate-to-severe cases."
For milder cases, "which is a lot of what GPs see, having a treatment that is minimal in side effects and also works fast is great," said Brown, who was not involved with the study.
Moreover, "increasing research suggests that the microbiome plays a role in depression but so far no one has conducted a good study that shows changing the microbiome by giving probiotics helps depression significantly," he noted.
"The fact that [the researchers] showed an effect using this particular probiotic in combination with SAMe is an exciting proof of concept that if we work on the microbiome, we can get a positive effect in depression and maybe other psychiatric disorders," Brown said.
He noted that the "bowel needs a lot of SAMe, which is important in the gut, but we don't know how SAMe and the probiotic are working together, which is an interesting line of research for the future."
Investigators' disclosures are listed in the article. Brown has reported no relevant financial relationships.
Prim Care Compan CNS Disord. Published online June 25, 2020. Abstract
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Cite this: Supplement Plus Probiotic May Improve Depressive Symptoms - Medscape - Aug 12, 2020.