Resistant Depression – Does Folic acid Prevent Lamotrigine From Working?

Recent study added lamotrigine to depressed subjects already under treatment. Folic acid supplementation appeared to prevent any improvement versus those not on supplementation.

Comparative evaluation of quetiapine plus lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in bipolar depression (CEQUEL): a 2 × 2 factorial randomised trial
John R Geddes et al.
The Lancet Psychiatry
http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366%2815%2900450-2/abstract

  • Randomized double blind control trial with 101 subject in each group
  • Used the QIDS-SR16 depression scale which has a range of  0-27 (veresus the beck depression inventory which goes from 0-63)
  • Lamotrigine alone added – got a 4.14 drop in the  QIDS-SR16 depression scale
  • Lamotrigine with folic acid got a drop of 0.12.
  • In Beck terms that might be a drop of 9.6 versus on Lamotrigine [one whole depression level (eg moderate – mild) versus 0.28 on lamotrigine and folic acid

Comment – these results startled the researchers who were forced to say “Folic acid seems to nullify the effect of lamotrigine“. This is unprecedented – in resistant bipolar depression cases, I always have the hope that lamotrigine will be their answer and have seen cases of response. Alarmingly, this means I will have to go over my non-responders to see if they were on folic acid. Problem is, would taking them off folic acid now make any difference?

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