Some anti-inflammatory drugs such as aspirin, estrogen and the antioxidant Fluimucil (N-acetylcysteine) can improve the efficacy of existing schizophrenia treatments, new research shows.

For some time, it has been suggested that helping the immune system may benefit the treatment of schizophrenia, but until now there has been no conclusive evidence that this would be effective. However, a comprehensive meta-analysis of all robust studies on the effects of adding anti-inflammatories to antipsychotic medication, conducted by researchers at the University of Utrecht in the Netherlands and presented at the European College of Neuropsychopharmacology (ECNP) conference in Berlin, provides significant evidence that some, but not all, anti-inflammatories can improve symptoms in schizophrenia patients.

Aspirin, estrogens (in women) and Fluimicil show particularly promising results, but other anti-inflammatoriess - including celecoxib, minocycline, davunetide and fatty acids - have no significant effect, says the analysis, which pulls together data from 26 double-blind randomised controlled trials.

The immune system is linked to certain psychiatric disorders such as schizophrenia and bipolar disorder, and schizophrenia in particular is linked to the HLA gene system, which is found on chromosome 6 in humans and controls many of the characteristics of the immune system.

Schizophrenia affects around 24 million people worldwide, but treatment has not changed much in over 50 years and largely relies on correcting the regulation of dopamine in the brain. This has been shown to help systems such as hallucinations and delusions, but has been unable to help many other symptoms such as decreased energy, lack of motivation and poor concentration. 

Also, 20%-30% of all patients do not respond to antipsychotic treatment, but co-treatment with anti-inflammatories holds the possibility of improving patients’ response to treatment, say the researchers, led by Iris Sommer of the department of psychiatry at Utrecht University’s medical centre.

“This study makes us realise that we need to be selective about which anti-inflammatory we use. Now that we know that some effects are replicated, we need to refine our methods to see if we can turn it into a real treatment,” said Prof Sommer. 

Studies such a multicentre trial which has just started, using simvastatin to reduce inflammation in the brain of schizophrenia patients, will provide the proof of concept for targeting the immune system in schizophrenia, she added.

Commenting on the findings for ECNP, Celso Arango of the Gregoria Maranon University General Hospital in Madrid, Spain, noted that inflammation and oxidative stress seem to be important factors in different mental disorders. Animal models and clinical trials have shown that antioxidants and anti-inflammatory drugs could not only reduce symptoms associated with the disorders but also prevent the appearance of neurobiological abnormalities and transition to psychosis if given early during brain development.

The Utrecht study “is a step towards the possibility of better treatment, but we need more research in this area, especially with younger subjects where we might expect more brain plasticity,” said Prof Arango.