TNF blockers like Enbrel and infliximab can lower depression independent of improvements with physical symptoms. 62% of patients with treatment resistant depression saw improvement on infliximab versus 33% with standard therapies. Infliximab also improved sleep, allowing patients to stay asleep longer. Infliximab successfully improved depression symptoms in patients with inflammatory disease as well as controls who had elevated CRP and TNF but not on controls with normal CRP and TNF. Patients who were not effectively treated with SSRIs were found to have higher IL-6 and TNF.
Chronic inflammation can cause structural and functional changes in the brain, interfering with its ability to make new connections and damaging existing function. Activation of microglial cells in the nervous system is associated with maladaptive behaviors and decreased brain function seen in bipolar disorder, major depressive disorder and other mood conditions. They also protect neurologic function in multiple sclerosis, Huntington’s and Alzheimer’s. Minocycline, an antibiotic, also has significant anti-inflammatory and neuroprotective effects.
In some encephalitis models, DMARDs can actually restore stem cells of the nervous system, reducing tissue and myelin damage. DMARDs, often used for autoimmune diseases, improve mood symptoms in rheumatoid arthritis patients. They can also mitigate hyperactivity from amphetamines. Clinical trials are currently investigating the full effects of these medications on psychiatric conditions.
Mood stabilizers often have anti-inflammatory effects. In bipolar disorder patients, lithium and valproate decreased IL-6. Medications that act on serotonin and dopamine receptors decrease production of inflammatory molecules like TNF, IL-6 and PGE2. Escitalopram, an SSRI antidepressant, can decrease cortisol production and IL-11. ACTH production can be induced by fluoxetine.
References:
Furtado M, Katzman MA. Examining the role of neuroinflammation in major depression. Psychiatry Research 2015: 229, 27-36.
Rosenblat JD, et al. Inflamed moods: a review of the interactions between inflammation and mood disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2014; 53, 23-34.