Can anti-inflammatory agents augment antipsychotic effects? Schi Bulletin. Jan.2014

16.01.2014

Role of inflammation in schizophrenia was first suggested by Torrey and Peterson  in their Lancet article in 1973.It is currently thought that genetic vulnerability interacts with stress,trauma, nutrition and infection to produce a pro inflammatory state in the brain.This is associated with a reduction in neurotrophic function.The neurotoxicity of pro inflammatory factors (TNF alpha, free radicals, complement factors etc) lead to reduced connectivity and tissue loss.They also trigger changes in neurochemical system.These ideas are supported by the fact that strongest genetic association with schizophrenia is found in the major histocompatibility complex genes including loci that influence the immune response.Prevalence of auto immune disorders are more among those with schizophrenia and their first degree relatives. Most antipsychotics, SSRI, lithium and  valproate have some anti-inflammatory action as well.

Can anti inflammatory agents reverse the above process? There is some evidence to suggest that anti-inflammatory agents can reduce symptoms. There is no evidence to show that they help resume  the neurotrophic function.

Iris E. Sommer, Roos van Westrhenen, Marieke J. H. Begemann, Lot D. de Witte, Stefan Leucht, and René S. Kahn describe current evidence regarding the efficacy of various anti-inflammatory agents as augmenting agents in schizophrenia.The review identified 26 studies.

Results

1.Two studies of Aspirin ( 1000mg, total 270 patients)  showed a mean weighted effect size of 0.3.

2.Estrogen, 7 studies, at doses 05 mg/d (patch) to 2mg/d (orally) showed a mean weighted effect size of 0.51

3. NAC: only one study, 2 g of NAC for 6 months produced a mean weighed effect size of 0.45 .

4. Celecoxib, Davunetide, Fatty acids such as eicosapentaenoic acids (EPA) and docosahexaenoic acids (DHA), Minocycline: No significant effect.

Three agents ( Aspirin, NAC, Estrogen) are promising as augmenting agents. Safety of these  three  need to be looked in to. Aspirin has other additional benefits but need to be cautious of GI bleeding. Estrogens are not safe for periods longer  than 1–2 months, unless combined with progesterone and  are  not suitable for men. NAC has no significant side effects.

Conclusions: The field is still in infancy. Some beneficial effects observed for aspirin, oestrogen and NAC. These three agents have properties other than anti-inflammatory actions. The existing evidence does not allow any firm conclusions.

Summary of the article:

Efficacy of Anti-inflammatory Agents to Improve Symptoms in Patients With Schizophrenia: An Update. Sommer IE, van Westrhenen R, Begemann MJ, de Witte LD, Leucht S, Kahn RS. Schizophr Bull. 2014 Jan;40(1):181-91

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