Depressive illness is a chronic and recurrent illness. It is also a lethal disease as more than 70% of the 5300 suicides that occur in the UK each year are related to depression. To put the mortality in perspective, it is over twice the number of those killed in road traffic accidents.
In addition to the increase in mortality by suicide, the life of these patients is severely disrupted; their working capacity is weakened and the effect on their matrimonial and social life is severe. Depressive disorders are episodic and usually commence in the third or fourth decade of their life. Episodes of illness commonly last 6 to 18 months, but their extent is variable. Depressive illness is commoner in women, but suicide is more frequent in men.
Antidepressants, both new and old, are weak therapeutic agents. In a recent trial of fluoxetine (20mg daily) carried out for 10 weeks, only 40% of female patients showed a satisfactory response. Patients in the other arm of the trial, who were given 20mg of fluoxetine plus 500 microgram of folic acid, showed a response rate of 72%. Men showed a poor response with or without folic acid. Folic acid has also been shown to improve the response to prophylactic lithium in patients.
Before folic acid is biologically active, it must be metabolised to L-methylfolate, a slow process in humans and particularly so in depressive patients. It is therefore logical to give L-methylfolate instead of folic acid to the patients. L-methylfolate is readily available in the USA but not in the UK or most other European countries. My suggestion is that all patients who have been prescribed an antidepressant should also receive 400 micrograms of methylfolate.
Because of difficulties of compliance it would be desirable to incorporate the L-methylfolate in the same capsule or tablet as the antidepressant.
Low folate has been associated with increased heart disease and stroke. Low folate has also been linked with age-related macula degeneration, autoimmune disease and it is routine to give folic acid in the early months of pregnancy.
Initially, the first step is to make L-methylfolate available in the UK, so it can be prescribed by doctors. I would limit the size of tablets to 400 micrograms and discourage the use of large doses. I think it is urgent that we carry out further double blind trials using L-methylfolate in doses of 400 micrograms together with an antidepressant versus an antidepressant alone.
I can see no hope of reducing the mortality and morbidity of depressive illness with the medication now available to us.
Alec Coppen
Email: acoppen@hotmail.co.uk
References:
Coppen, A. Bailey, J. Enhancement of the antidepressant action of fluoxetine by folic acid: A randomized control trial J. Affect. Disorder 2000; 60:121-130.
Stahl, S.M. 2007 Novel therapeutic for Depression: L-methylfolate as a Trimonoamine Modulator and Antidepressant- Augmenting Agent. CNS Spectr;12(10):739-744
