Anti-Inflammatory Agents

Increased proinflammatory markers have been found in the blood and cerebrospinal fluid of patients with schizophrenia, as compared to healthy controls. Given the role of inflammation in schizophrenia, anti-inflammatory medications might be helpful therapies.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

  • The rationale for investigating aspirin as a potential treatment for schizophrenia is that aspirin inhibits the production of inflammatory proteins, thromboxanes, and prostaglandins by altering the enzymatic activity of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2).2 A trial of aspirin found a decrease in total PANSS scores after 12 weeks, as compared to placebo.10 However, there was no change in cognitive functioning. Data regarding treatment with celecoxib, a COX-2 inhibitor, are “mixed.”2
  • Minocycline, a second-generation tetracycline with anti-inflammatory properties, exerts neuroprotective effects through inhibition of microglial activity, modulation of glutamate transmission, and anti-apoptotic action.2 Findings of several trials have been promising. For example, a 16-week trial comparing minocycline to placebo in 92 patients with early-stage schizophrenia found significant improvement in the SANS and the PANSS total, negative, and general scores.11
  • Statin drugs are thought to have anti-inflammatory properties. A randomized 12-week trial of pravastatin in patients with schizophrenia (n=60) found significant improvement in the PANSS positive symptoms scale at six weeks, but the improvement was no longer significant at 12 weeks.12 A statin combined with ondansetron (a serotonin 5-HT3 receptor agonist) is also being investigated as a potential treatment for schizophrenia.2

Vitamins

Schizophrenia is associated with vitamin deficiencies, both during prenatal development and after illness onset, suggesting potential utility for vitamin supplementation.2

B Vitamins

B vitamins are involved in cellular metabolic processes and oxidation reactions.  Individuals with schizophrenia often have low vitamin B levels.2 Two B vitamins (folic acid and vitamin B12) are particularly promising interventions in patients with genotypes for common, functional variants in the folate pathway (MTHFR [rs1801133] and FOLH1[rs202676]).12 Further studies of methylfolate are underway.2