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Low red cell folate levels are associated with poor response to nortriptyline in major depression

  • Ben Beaglehole (a1), Suzanne E. Luty (a1), Roger T. Mulder (a1), Martin A. Kennedy (a2) and Peter R. Joyce (a1)...



There has been a long interest in the relationship between folate and depression.


In this paper, we report baseline measures of red cell folate that were collected during a randomized trial of 107 patients with major depression. Red cell folate levels were examined for association with percentage improvement in depressive symptoms during treatment with fluoxetine or nortriptyline. The influences of possible confounding factors were assessed.


The low red cell folate group (defined in relation to the median) had a significantly poorer response to nortriptyline. This effect of red cell folate levels was not present in those treated with fluoxetine. No relationships were found between red cell folate levels and possible confounding factors of age, nutritional status, alcohol history, depression subtype, depression severity and chronicity of depression.


Response to nortriptyline was affected by red cell folate status. It may, therefore, be beneficial to consider folate augmentation in patients with major depression, particularly if treated with nortriptyline.


Corresponding author

Professor Peter R. Joyce, Department of Psychological Medicine, University of Otago, PO Box 4345, Christchurch, New Zealand. Tel: +64 3 3720 400; Fax: +64 3 3720 407; E-mail:


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