Targeting the Immune System with Pharmacotherapy in Schizophrenia.

Abstract

The clinical manifestations of increased cytokine activity in individuals with schizophrenia have not been clearly delineated; thus, planning pharmacological interventions remains an entirely empirical endeavor. Although there are many preliminary findings regarding the use of adjunct pharmacotherapeutic strategies targeting the immune system, in most instances, clearly efficacious results require further validation. Antipsychotics remain the most effective pharmacological treatment approach in schizophrenia, and evidence suggests that they impact cytokine and immune cellular physiology in the patient, though this requires improved mechanistic understanding. Omega-3 polyunsaturated fatty acids (PUFAs) and statins may be a beneficial supplement in the situation where a patient with metabolic syndrome is a candidate for dietary modifications and/or control of LDL-cholesterol. Such an approach would require adjusting the diet and pharmacology towards a profile that could have antiinflammatory effects, especially considering that adiposity is a source of increased inflammatory activity. Another strategy would be the addition of the neurosteroid pregnenolone, which appears to be well tolerated. Non-steroidal antiinflammatory drugs (NSAIDS) are routinely prescribed for other clinical conditions; thus, their use in schizophrenia could be easily implemented; however, their efficacy is unclear, and side effects require careful monitoring. The use of tetracycline antibiotics such as minocycline or antiimmune drugs such as azathioprine or methotrexate should be left to an academic research group, where the outcome and molecular signatures can be monitored in a controlled manner. Ultimately, the benefit/risk ratio of each of these adjunct treatments should be considered on a case-by-case basis. Finally, lifestyle changes such as improved sleep, reduced smoking, and weight reduction strategies, all factors which are associated with increased inflammation, should not be overlooked when working towards an improved functional outcome.