"One of the most common problems in treating depression is the number of people who are left with symptoms after initial treatment with a first-line antidepressant," said study leader Jonathan Alpert, from the Massachussetts General Hospital.

SAMe (S-Adenosy-L-Methionine) is found in all human cells and is also sold in synthetic form as a dietary supplement in the US. (In European markets however, it is classified as a medicine.) Although some reports had suggested the supplement might be useful in treating depression, few rigorous research trials have been carried out.

"Some previous trials have suggested that SAMe might have effects comparable to some antidepressants, but there has not been sufficient research on oral SAMe preparations or comparisons with available antidepressants."

Alpert's team aimed to investigate whether adding SAMe, provided by supplement maker Pharmavite, to antidepressant treatment could improve the results for patients for whom a single medication had not relieved symptoms.

They enrolled 30 participants who had continued to have significant depression after more than a month of treatment with drugs like Prozac, Paxil or Effexor.

During the six-week study, participants received SAMe along with their antidepressant, starting at 400 mg of SAMe two times a day and increasing to 800 mg twice a day after two weeks. Patients were free to stay at or return to the 400 mg dose level if they chose to, in consultation with their doctor.

At the end of the study period, analysis with several standard tools for measuring symptoms of depression showed that 50 per cent of participants had significant improvement in their symptoms and 43 per cent had complete remission of their depression. Although two participants dropped out because of treatment side effects, there were no reports of serious adverse events.

"This is the first study to look at the safety and efficacy of combining SAMe with antidepressant treatment after antidepressants had proven insufficient on their own," said Alpert. "Patients and physicians have been using these combinations without good supporting data, and these results are an initial step toward compiling the necessary scientific evidence."

The researchers note that the current study has many limitations – including its small size, the lack of a control group and the fact that participants knew they were taking an active dose of SAMe.

However they have received US government funding for a double-blinded, placebo controlled trial of SAMe in combination with antidepressant treatment.

A second National Institutes of Health-funded study will compare SAMe with standard antidepressants and with placebo as a single-drug therapy.