
- Vol 40, Issue 7
Analyzing SSRIs and Gut Microbiota in Major Depressive Disorder
What is the association between the gut microbiome and response to SSRIs in patients with depression?
CASE VIGNETTE
“Mr Richards” is a 55-year-old white male with a 20-year history of recurrent and severe major depressive disorder (MDD) with psychotic features. At his outpatient visits, his mood is chronically depressed, and he has a chronic delusion that he suffers from gastrointestinal candidiasis. He takes a probiotic formulation that he orders online from an overseas supplier to treat the candidiasis. He frequently reports various gastrointestinal symptoms.
Mr Richards is only partially adherent with his psychotropic medications and will often adjust the dose of, or altogether stop, medications without consulting his psychiatrist. He has reportedly failed 2 previous trials of selective serotonin reuptake inhibitors (SSRIs). He asks his psychiatrist about other probiotics he can take for his MDD.
Many patients who have MDD do not respond to treatment with SSRIs.1 There is some evidence for alterations in the gut microbiota of patients with depression versus controls.2,3 One study found that transplantation of the feces of patients with MDD into the guts of mice could induce depression-like behaviors.4
Outside of depression, gut microbiota can influence the effectiveness of medications via pharmacokinetic changes.5 There is also some evidence in animal models that SSRIs can influence gut microbiota.6,7
The Current Study
Gao and colleagues8 explored the association between the gut microbiome and response to SSRIs in patients with depression. They recruited 62 antidepressant-naïve patients aged 18 to 55 years with first-episode DSM-IV MDD. Participants were followed for 8 weeks of treatment with SSRIs. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17).
Study authors also recruited 41 matched healthy controls who had no history of mental disorders, an HDRS-17 score of less than 8, and were not being treated with antibiotics or probiotics at the time. Exclusion criteria were acute or chronic diseases or infections, pregnancy or lactation, antibiotic or anti-inflammatory treatment in the previous month, and history of digestive diseases.
Patients were treated with such SSRIs as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram. Response to SSRIs was defined as a ≥ 50% reduction in HDRS-17 score from baseline to week 8. Fecal samples were collected before SSRI treatment. Gut microbial communities were identified using a 16S ribosomal RNA gene sequence analysis.
Correlation coefficients were calculated for gut microbiome and clinical data. Binary logistic regression and receiver operating characteristic (ROC) curves were used to analyze the response to SSRIs and related bacteria.
There were significant differences in the gut microbiome composition of SSRI responders, SSRI nonresponders, and controls in the alpha-diversity analysis. The relative abundance of 12 genera were increased in the control group, of
5 were increased in responders, and of 2 were increased in nonresponders (
Regarding beta-diversity, there was a significant difference in the gut microbial community between SSRI responders—but not nonresponders—and controls. Three genera (Blautia, Bifidobacterium, and Coprococcus) were significantly correlated with the reduction in HDRS-17 scores. After controlling for age, sex, and education, the area under the ROC curve for SSRI response based on these genera was 0.93, with a sensitivity of 0.88 and a specificity of 0.92.
Study Conclusions
The authors concluded that gut microbiota—specifically the genera Blautia, Bifidobacterium, and Coprococcus—was associated with increased response to SSRIs in MDD. These 3 bacterial groups are related to the production of short-chain fatty acids.9
Study strengths include that participants were experiencing their first episode of depression and were antidepressant-naïve. Study limitations include modest sample size, absence of a placebo group, and the failure to control for dietary habits, which could influence the gut microbiome.
The Bottom Line
The diversity of the gut microbiome and the relative abundance of Blautia, Coprococcus, and Bifidobacterium are potential biomarkers of response to SSRIs in patients with MDD.
Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the editorial board of Psychiatric Times® and serves as schizophrenia section chief. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.
References
1. Zhao B, Li Z, Wang Y, et al.
2. Chen Z, Li J, Gui S, et al.
3. Jiang H, Ling Z, Zhang Y, et al.
4. Kelly JR, Borre Y, O’Brien C, et al.
5. Weersma RK, Zhernakova A, Fu J.
6. Ramsteijn AS, Jašarević E, Houwing DJ, et al.
7. Lukić I, Getselter D, Ziv O, et al.
8. Gao M, Tu H, Liu P, et al.
9. Sorbara MT, Littmann ER, Fontana E, et al.
Articles in this issue
about 2 years ago
Gender Differences in ADHD and Their Clinical Implicationsabout 2 years ago
Postpartum Psychosis: Improving the Likelihood of Early Interventionabout 2 years ago
Disparities and Opportunities in Mental Health Care for Womenabout 2 years ago
Adolescent Substance Use: Reasons for Optimism and Concernabout 2 years ago
What a Dying Woman Sawabout 2 years ago
New Research, Treatment Issues Featured at Annual Meetingabout 2 years ago
Determination and Imaginationabout 2 years ago
Dementia Treatment: An Unmet NeedNewsletter
Receive trusted psychiatric news, expert analysis, and clinical insights — subscribe today to support your practice and your patients.