In the Journals

Clinicians guide to anti-inflammatory treatments for major depression

Targeting inflammation is a promising way to treat patients with major depressive disorder, according to a report in Journal of Clinical Psychiatry.

Prior research has shown a link between inflammation and greater depressive symptom severity as well as resistance to commonly used antidepressants in MDD, Manish Kumar Jha, MD, from the departments of psychiatry and neuroscience, Icahn School of Medicine at Mount Sinai, wrote.

After reviewing published reports and ongoing studies, Jha found that currently available anti-inflammatory agents that show potential in major depression include NSAIDs, nutraceuticals and anticytokine treatments.

Adjunctive celecoxib, the most widely studied NSAID for its antidepressant effect, was linked to higher rates of remission compared with placebo in a prior meta-analysis, but using celecoxib along with antidepressants was also discouraged in another prior report. NSAIDs also have poor clinical utility as antidepressant monotherapy, Jha wrote.

Nutritional supplements – such as l-methylfolate, curcumin and omega-3 fatty acids (especially eicosapentaenoic acid), have indicated antidepressant potential, especially in patients with major depression and increased levels of inflammatory biomarkers.

Jha also noted that monoclonal antibodies against proinflammatory cytokines, which allow precise and personalized way to target specific immune pathways, offer “the most intriguing anti-inflammatory treatments for depression.”

Targeting the tumor necrosis factor alpha, a proinflammatory cytokine that may be elevated in patients with treatment-resistant depression, has potential and a 2016 study found that anticytokine treatments significantly improved depressive symptom severity in patients with chronic inflammatory conditions, Jha wrote.

Interleukin-17 (IL-17), a proinflammatory cytokine, has also been implicated in pathophysiology of depression and antidepressant response, and two anti–IL-6 antibodies, sirukumab (Janssen) and siltuximab (Sylvant, Janssen), have also been shown to be effective in reducing depressive symptom severity among patients with rheumatoid arthritis. Future studies are needed to determine the clinical utility of minocycline augmentation in depression.

“While the utility of these anticytokine treatments in patients with MDD is currently limited, clinicians may consider them for their patients with comorbid autoimmune conditions such as psoriasis and rheumatoid arthritis,” he wrote.

New potential anti-inflammatory treatments for depression included leucine, infusion of mesenchymal stem cells obtained from human donors and sirukumab.

“As none of the anti-inflammatory treatments are approved by the FDA, clinicians should restrict their off-label use to patients for whom FDA-approved treatments are either ineffective or impractical,” Jha wrote. “In such cases, clinicians should use a measurement-based care approach to monitor improvement in depressive symptom severity along with any treatment emergent adverse events with these anti-inflammatory treatments and ensure that patients are not continued on ineffective treatments for too long.” – by Savannah Demko

Disclosure: Jha reports no relevant financial disclosures.

Targeting inflammation is a promising way to treat patients with major depressive disorder, according to a report in Journal of Clinical Psychiatry.

Prior research has shown a link between inflammation and greater depressive symptom severity as well as resistance to commonly used antidepressants in MDD, Manish Kumar Jha, MD, from the departments of psychiatry and neuroscience, Icahn School of Medicine at Mount Sinai, wrote.

After reviewing published reports and ongoing studies, Jha found that currently available anti-inflammatory agents that show potential in major depression include NSAIDs, nutraceuticals and anticytokine treatments.

Adjunctive celecoxib, the most widely studied NSAID for its antidepressant effect, was linked to higher rates of remission compared with placebo in a prior meta-analysis, but using celecoxib along with antidepressants was also discouraged in another prior report. NSAIDs also have poor clinical utility as antidepressant monotherapy, Jha wrote.

Nutritional supplements – such as l-methylfolate, curcumin and omega-3 fatty acids (especially eicosapentaenoic acid), have indicated antidepressant potential, especially in patients with major depression and increased levels of inflammatory biomarkers.

Jha also noted that monoclonal antibodies against proinflammatory cytokines, which allow precise and personalized way to target specific immune pathways, offer “the most intriguing anti-inflammatory treatments for depression.”

Targeting the tumor necrosis factor alpha, a proinflammatory cytokine that may be elevated in patients with treatment-resistant depression, has potential and a 2016 study found that anticytokine treatments significantly improved depressive symptom severity in patients with chronic inflammatory conditions, Jha wrote.

Interleukin-17 (IL-17), a proinflammatory cytokine, has also been implicated in pathophysiology of depression and antidepressant response, and two anti–IL-6 antibodies, sirukumab (Janssen) and siltuximab (Sylvant, Janssen), have also been shown to be effective in reducing depressive symptom severity among patients with rheumatoid arthritis. Future studies are needed to determine the clinical utility of minocycline augmentation in depression.

“While the utility of these anticytokine treatments in patients with MDD is currently limited, clinicians may consider them for their patients with comorbid autoimmune conditions such as psoriasis and rheumatoid arthritis,” he wrote.

New potential anti-inflammatory treatments for depression included leucine, infusion of mesenchymal stem cells obtained from human donors and sirukumab.

“As none of the anti-inflammatory treatments are approved by the FDA, clinicians should restrict their off-label use to patients for whom FDA-approved treatments are either ineffective or impractical,” Jha wrote. “In such cases, clinicians should use a measurement-based care approach to monitor improvement in depressive symptom severity along with any treatment emergent adverse events with these anti-inflammatory treatments and ensure that patients are not continued on ineffective treatments for too long.” – by Savannah Demko

Disclosure: Jha reports no relevant financial disclosures.