What drugs and supplements decrease neuroinflammation?

Drugs and Supplements That Decrease Neuroinflammation

Based on the strongest available evidence, NSAIDs (particularly selective COX-2 inhibitors like parecoxib) and acetaminophen demonstrate the most robust clinical evidence for reducing neuroinflammation, with parecoxib showing a 45% reduction in postoperative delirium (a marker of neuroinflammation) compared to placebo in surgical patients. 1

Evidence-Based Anti-Neuroinflammatory Agents

First-Tier: Medications with Direct Clinical Evidence

NSAIDs and COX-2 Inhibitors

• Parecoxib (selective COX-2 inhibitor) reduced postoperative delirium incidence from 11% to 6.2% (p=0.031) in patients undergoing total joint arthroplasty, suggesting direct anti-neuroinflammatory effects independent of pain control. 1
• The mechanism involves blocking central nervous system prostaglandin production, which directly reduces neuroinflammation rather than simply providing analgesia. 1
• NSAIDs are effective for musculoskeletal pain and back pain for 2-12 weeks, though they carry gastrointestinal, renal, and cardiovascular risks that increase with duration and dose. 1

Acetaminophen

• Scheduled intravenous acetaminophen for 48 hours postoperatively reduced delirium incidence from 28% to 10% (p=0.01) in cardiac surgery patients over 60 years, with effects attributed to blocking central nervous system prostaglandin production rather than opioid-sparing. 1
• Maximum daily dose is 3-4 grams to avoid hepatotoxicity; lower doses required in patients with chronic alcohol use or liver disease. 1, 2
• Acts on the cyclooxygenase pathway with putative blockade of central nervous system prostaglandin production. 1

Second-Tier: Neuropathic Pain Medications with Anti-Inflammatory Properties

Gabapentin and Pregabalin (α2δ Calcium-Channel Antagonists)

• Provide effective neuropathic pain relief for 5-12 weeks by binding to calcium channels (α2δ subunits) in the brain and spinal cord, inhibiting release of excitatory neurotransmitters involved in pain and inflammation. 1, 3
• Gabapentin is recommended as first-line oral treatment for neuropathic pain at 1800-3600 mg/day in divided doses. 2
• Pregabalin is FDA-approved for neuropathic pain conditions and fibromyalgia, with dosing starting at 75 mg twice daily and increasing to 150 mg twice daily. 1, 3
• Common side effects include dizziness, somnolence, sedation, and peripheral edema. 1

Duloxetine (SNRI)

• FDA-approved for diabetic neuropathy and fibromyalgia at doses of 20-120 mg/day, with strong recommendations for use in neuropathic pain. 1
• Dual mechanism of action provides both antidepressant and central analgesic properties through serotonin-norepinephrine reuptake inhibition. 1
• Common side effects include nausea, dry mouth, headache, decreased libido, dizziness, and somnolence. 1

Tricyclic Antidepressants (Amitriptyline)

• Provide effective analgesia for neuropathic pain conditions at lower dosages than required for depression treatment, with shorter time to onset of effect. 1
• Start at 10 mg at bedtime, increase by 10 mg weekly to target 25-50 mg nightly, monitoring for anticholinergic effects and morning sedation. 3
• The number needed to treat for 50% pain relief is 4.1, meaning only about one in four patients achieves substantial benefit. 3

Third-Tier: Disease-Modifying Agents for Specific Neuroinflammatory Conditions

Corticosteroids

• Methylprednisolone (1-1.6 mg/kg/day) improves neurological outcomes in retro-orbital inflammation and Tolosa-Hunt syndrome. 1
• Prednisolone (20-60 mg/day or 1.83 mg/kg/day) improves neurological and radiological outcomes in inflammatory orbital/sellar lesions. 1
• Not recommended for fibromyalgia or chronic pain conditions, as they lack efficacy and cause significant harm in these populations. 3

Immunosuppressants and Monoclonal Antibodies

• Rituximab, azathioprine, mycophenolate, and tocilizumab reduce relapse rates in neuromyelitis optica spectrum disorder involving the optic nerve. 1
• Ocrelizumab, alemtuzumab, and natalizumab demonstrate superior effects at decreasing brain atrophy accrual in multiple sclerosis, indicating anti-inflammatory effects on neurodegeneration. 1
• These agents are reserved for specific autoimmune neuroinflammatory conditions and require specialist management. 1

Nutritional and Lifestyle Interventions

Omega-3 Fatty Acids

• Doses of 1000 mg twice to three times daily may regulate inflammation and optimize health through increasing the ratio of omega-3 to omega-6 fatty acids. 1
• Clinical trials show improvement in tear break-up time and Schirmer's test results, with potential to decrease symptoms of hyperalgesia. 1
• The mechanism involves regulation of inflammation through modulation of inflammatory mediator production. 1

Magnesium

• Marginal magnesium deficiency stimulates oxidative stress and secretion of proinflammatory mediators from phagocytic cells, resulting in chronic inflammation. 1
• Dietary magnesium intake is inversely associated with cardiometabolic disease, metabolic syndrome, colorectal cancer, and serum C-reactive protein (a biomarker of inflammation). 1

Vitamin D

• Supplementation may decrease blood C-reactive protein levels in children with overweight and obesity and improve inflammatory markers in pediatric intestinal bowel syndrome. 1
• High intake in the absence of nutritional deficiency may lower inflammation in those with existing chronic disease. 1

Vitamin C

• Subclinical vitamin C inadequacy has been associated with inflammation, elevated C-reactive protein levels, and depressed immune function. 1

Folate and Vitamin B12

• Deficiency exacerbates inflammation associated with disease and infection, while folic acid supplements lower C-reactive protein blood levels. 1

Exercise

• Cardio-exercise for at least 30 minutes twice weekly inhibits pain pathways, improves allodynia and hyperalgesia, and diminishes neuro-immunologic signaling after nerve injury. 1
• Exercise increases neurotrophic factors in the CNS contributing to neuroplasticity and neuro-restoration. 1
• Exercise therapy reduces pain and improves function in osteoarthritis, low back pain, and fibromyalgia for at least 2-6 months. 1, 2

Critical Pitfalls and Contraindications

Medications to Avoid

• Strong opioids should not be prescribed for neuroinflammatory conditions like fibromyalgia, as they lack efficacy, cause significant harm, and may paradoxically increase neuroinflammation through opioid-induced hyperalgesia. 3, 4
• Skeletal muscle relaxants have insufficient evidence for efficacy in chronic pain management. 1

Drug Interaction Considerations

• Combining tricyclic antidepressants with SNRIs increases serotonin syndrome risk without clear evidence of superior efficacy. 3
• Pregabalin combined with other CNS depressants (opioids, benzodiazepines) requires careful monitoring due to warnings about serious breathing problems. 5
• Monitor for additive CNS depression when combining pregabalin with any CNS-active medication, including muscle relaxants. 5

Pseudoatrophy Effect

• Powerful anti-inflammatory drugs (natalizumab, fingolimod, ocrelizumab) can cause initial brain volume loss in the first year due to resolution of inflammatory activity and edema, followed by beneficial effects in the second year. 1
• This pseudoatrophy effect can be overcome by the beneficial effects of anti-inflammatory drugs on neurodegeneration in multiple sclerosis. 1