Sustained remission of positive and negative symptoms of schizophrenia following treatment with eicosapentaenoic acid.

Recently, a membrane phospholipid hypothesis of schizophrenia has been proposed(1) that not only provides an underlying explanation for those aspects of schizophrenia traditionally explained by the dopamine hypothesis, but also can account for many other clinical features. These include the inverse relationship between schizophrenia and some inflammatory disorders; the high resistance to pain shown by some patients; the dramatic remission of symptoms that may occur with pyrexia; the increased risk associated with exposure to viral infections or maternal malnutrition during fetal development; and the difference in severity and prognosis in different countries.(2) 

Recent biochemical, cerebral magnetic resonance spectroscopy, and molecular genetics findings suggest that schizophrenia is associated with a cell membrane deficiency of arachidonic acid and docosahexaenoic acid (DHA), arising from excess activity of 1 of the phospholipase A2 (PLA2) group of enzymes.(3- 7) Thus, there is mounting evidence for the membrane phospholipid hypothesis; however, an important issue for clinicians is whether it has any useful implications for treatment.

Atypical antipsychotics such as clozapine represent a considerable improvement over standard neuroleptics. However, the mechanism of action of clozapine has not adequately been explained on the basis of neurotransmitter actions, and it is therefore interesting that almost 2 decades ago it was suggested that the structure and pharmacological actions of clozapine are consistent with its being a prostaglandin E analog. The E prostaglandins are potent stimulators of cyclic adenosine monophosphate formation, and cyclic adenosine monophosphate inhibits PLA2.(8) Furthermore, pharmacotherapy with clozapine has recently been shown to be associated with a dramatic rise in erythrocyte membrane concentrations of certain polyunsaturated fatty acids.(9) These observations raise the possibility that clozapine may be a successful drug because its primary action is on membrane phospholipid composition.(7)

The phospholipid hypothesis leads to the prediction that treatment with PLA2 inhibitors should result in clinical improvement in schizophrenia.(7) Eicosapentaenoic acid (EPA) is a PLA2 inhibitor(10) which is also a constituent of brain phospholipids and a precursor of DHA. We report the case of an unmedicated patient with schizophrenia in whom treatment with EPA was associated with a dramatic and sustained reduction in both positive and negative symptoms.

REPORT OF A CASE

A 31-year-old man first came to the attention of our local psychiatric service at the age of 28 years when he was diagnosed as suffering from schizophrenia as defined by the DSM-IV. At that time he was suffering from daily auditory hallucinations and a complex delusional system, both of which started in his early teenage years. Although his profile had always been predominantly one of unremitting positive symptoms, more recently he had also begun to suffer from negative symptoms, including anhedonia and social anxiety and withdrawal. Furthermore, his basic skills in coping with the practicalities of life were not well developed. At the time of diagnosis he was prescribed sulpiride. He only ever took 1 tablet (200 mg) of sulpiride, and immediately discontinued the medication because of a severe extrapyramidal reaction. He refused neuroleptics thereafter, and so has otherwise remained free of antipsychotic medication.