Table 3.

Anti-inflammatory treatment strategies.

Intervention type	Advantages	Disadvantages	Comments
Pharmacological interventions
Celecoxib and other NSAIDs	May be useful as a monotherapy, or in combination with antidepressant medication (152) Celecoxib is associated with better antidepressant efficacy (response and remission) than other NSAIDs (152)	Risk for gastrointestinal bleeding with chronic use, especially for older adults or those who use alcohol Increased risk of cardiovascular events Affects other pathways in addition to inflammation (e.g., glucocorticoid receptors, adhesion molecules)	Patients with higher initial inflammation experienced greater benefit from celecoxib than those with lower inflammation (152) Patients with comorbid pain- or inflammatory-related disorders responded better to NSAID treatment than those without similar disorders (152)
Cytokine inhibitors (e.g., infliximab)	Specifically targets individual inflammatory cytokines Treatment response can be monitored by assessing change in the targeted cytokine Can normalize sleep (75) Cytokine inhibitors have reduced depressive symptoms in people with psoriasis (194, 195), lessened fatigue during cancer treatment (196), and resolved MDD in Crohn’s disease patients (197)	Reduces the ability to fight infection; increases risk of death and reactivation of tuberculosis Not suitable for those with immunosuppressive conditions Patients with lower CRP responded better to placebo than infliximab, suggesting infliximab may not be appropriate for patients without inflammation-driven MDD (17)	Treatment-resistant MDD patients with high baseline CRP had substantially greater reductions in depressive symptoms than those with low CRP Cytokine antagonists and anti-inflammatory cytokines have reversed or reduced cytokine-induced sickness behaviors in rodents (34)
Omega-3 PUFAs	Higher fish consumption is associated with a lower prevalence of depression Few side effects Benefits extend to cardiovascular system (e.g., lowering triglycerides)	Less beneficial among individuals without an inflammatory profile (42, 102)	Omega-3 PUFAs attenuated both endotoxin and IFN-α-induced inflammation and sickness behavior in rodents and humans (109–113) EPA appears more beneficial than DHA (42, 100, 101) Patients with a lower inflammatory profile responded better to placebo than to EPA (42)
Prebiotics, probiotics, and antibiotics	Probiotics reduce gut leakiness and neuroinflammation in animal models May also impact obesity (53) Initial studies in humans suggest that probiotics improve mood among healthy adults and those with IBS and chronic fatigue syndrome (57)	More information is needed on the particular microbiota alterations in depressed patients that need to be addressed	Most of the treatment data comes from animal models
Lifestyle/behavioral interventions
Healthy diets (e.g., Mediterranean diet)	May confer additional benefits such as reduced cardiovascular disease risk Healthier diets offer some protection against the development of both depressive symptoms and depressive disorders (82, 83)	Dietary change and adherence can be a substantial obstacle Some people may have limited availability of nutritious foods due to cost and access	A Mediterranean diet may reduce inflammation among individuals with health risks (84) Can buffer the impact of depression on inflammation (86)
Caloric restriction/time restricted eating	Caloric restriction can simultaneously attenuate production of proinflammatory cytokines while enhancing anti-inflammatory pathways (88) Low-cost intervention	Implementation can be challenging Quite difficult to maintain long-term adherence Diet must be nutrient-dense to compensate for caloric restriction	Aged mice subjected to caloric restriction had the lower cytokine responses characteristic of young mice following immunotherapy, and were similarly protected from mortality (129)
Weight loss	Reduces multiple obesity-related health risks, including depression	A minority of people maintain a substantially lower weight long-term after weight loss	Weight loss reduces inflammation; those with greater weight loss have greater CRP reductions (198)
Exercise	Can result in substantial long-term benefits for morbidity and mortality	Regular exercise is required for continued benefit	When assessed objectively by maximal exercise testing, fitness is inversely associated with inflammation, even after adjusting for confounds including age, smoking, medications, and visceral fat (187)
Integrative medicine interventions	Can be adapted for those with physical limitations. May reduce inflammatory over-responsiveness to stressors (173–175) Yoga, tai chi, and mindfulness-based meditation improve sleep, another path to reduced inflammation (164, 199, 200)	Regular practice required for efficacy	Benefits are proportional to the time invested (174, 199) The specific active anti-inflammatory components of yoga, tai chi, meditation, and other integrative therapies are not known (e.g., the relative importance of breathing, meditation, movement, etc.)
Family intervention	Benefits may be long-lasting and could extend to parents and other siblings	Significant parental investment Can be costly Access may be limited (e.g., by lack of family support)	Family therapy buffered against elevated inflammation in at-risk youth (161)
Cognitive-behavioral therapy (CBT)	Can address multiple behaviors leading to inflammation (e.g., depression, sleep habits, pain, negative health behaviors) Long-lasting benefit possible	Requires the patient’s investment in change Significant time commitment Poorer outcomes among those with comorbid conditions Risk of relapse	CBT interventions addressing depression, sleep, and pain also lowered inflammation (55, 162, 164, 165, 167)