Can magnesium help depression – or is it just a placebo?

“Over-the-counter magnesium tablets significantly improve depression in just two weeks, new research reveals,” the Mail Online reports. A small study found that people taking the supplements – on top of their existing treatment – reported an improvement in depression symptoms.

However, because the study wasn’t blinded (people knew what they were taking) the improvements could have been down to the placebo effect; people get better just because they expect to get better.

Researchers asked 126 adults with mild or moderate depression to spend six weeks taking magnesium supplements and six weeks without magnesium supplements. People also continued with their usual depression treatment. Researchers monitored people’s depression symptoms with phone calls every two weeks.

Half the people took supplements straight away, and half took supplements after waiting six weeks. Depression symptoms improved by an average six points on a scale of 0 to 27 after people took magnesium for six weeks, compared to after six weeks not taking magnesium.

The potentially positive effect of magnesium on depression isn’t outside the realms of possibility. The element is thought to play a role in many of the biological processes involved in mood regulation.

It is therefore frustrating that a more rigorous study design wasn’t used to rule out the possibility of a placebo effect.

Where did the story come from?

The study was carried out by researchers from the University of Vermont and was funded by the Henry and Carleen Tufo fund of the University of Vermont. The study was published in the peer-reviewed journal PLOS One on an open-access basis, so it’s free to read online.

The Mail Online covered the study uncritically, not mentioning that it had no placebo group and was not blinded. They also stated, incorrectly, that people were untreated for depression while not taking magnesium – in fact, everyone in the study took magnesium in addition to continuing with their usual treatment.

What kind of research was this?

This was an open-label randomised cross-over clinical trial, with no placebo group. People knew when they were taking the treatment and when they were not, as did the researchers monitoring their symptoms.

This type of study can show whether people’s symptoms improved while they were taking treatment, but it can’t tell us whether those improvements were caused by the active ingredient, or whether they would have happened while taking anything – even a sugar pill.

What did the research involve?

Researchers contacted 1,340 adults identified by their primary care doctor as having mild or moderate depression. Of these, 126 people agreed to take part and were eligible for the study. People continued their usual treatment throughout the study.

Half were randomly assigned to start magnesium supplements immediately, followed by a six week ‘control period’ without magnesium. The other half were assigned to start magnesium after a six week control period. All participants were monitored for symptoms and side effects with phone calls every fortnight, throughout the 12 week study period.

People took four 500mg tablets of magnesium chloride daily.

Researchers looked at the average change in symptom score from start to end of the six weeks of magnesium treatment, and from start to end of the six weeks of control. They calculated the net difference (ie the difference in change in score between the two six week periods) and adjusted the figures to take into account use of SSRI medicines, the order in which people had been randomised, and their response during the control period.

Depression symptoms were measured using the standard Patient Health Questionnaire 9 (PHQ-9) which uses nine questions to diagnose and classify depression. Mild depression is a score of 5 to 9, moderate depression is 10 to 14, moderate to severe depression is 15 to 19 and 20 to 27 indicates severe depression. 

What were the basic results?

People scored on average six points lower on the depression scale while taking magnesium supplements (adjusted net difference -6.0, 95% confidence interval (CI) -7.9 to -4.2). This is seen as clinically important.

Analysis of the figures found that magnesium was effective regardless of age, gender, depression category and depression treatment. Perhaps surprisingly, it also suggested that adherence to treatment (whether people took at least 80% of the tablets) did not make a difference.

The most commonly reported side effect was diarrhoea, reported by eight people, but this was not more common when people were taking magnesium than when they were not taking it.

How did the researchers interpret the results?

The researchers say their results showed that “magnesium supplements may be a fast, safe and easily accessible alternative or adjunct [addition] to starting or increasing the dose of antidepressant medications.”

Addressing the issue of the lack of a placebo group, they claim it is “not useful when the research seeks to assess the presence and magnitude of the effect of an intervention.”

They add: “Whether magnesium works because it induces a physiological change in the subject, or only because of the placebo effect (or a combination of the two), it remains that subjects do report better levels of depression and anxiety when taking magnesium than when not.”

Conclusion

Depression is a serious illness that can cause a great deal of distress to those who have it, as well as to their friends and family. Current treatments – both medication and talking therapies – work well for some people but less well for others.

Antidepressants can have unwanted side effects. So, a new treatment for depression with few side effects would be very welcome.

Despite the researchers’ interpretations of their results, however, it’s hard to recommend a treatment when we don’t know whether a sugar pill would work just as well.

The lack of a placebo group in the study means we cannot be sure whether magnesium is a useful treatment for depression. We know that the placebo effect is real, and that it can bias results of clinical trials if not tested for by a placebo group in the study.

This study was relatively small (only 112 people provided data that could be analysed); lasted only 12 weeks and did not include a placebo group. It’s entirely possible that the results shown with magnesium pills are due to the placebo effect, and that they would have worn off with a longer study period.

Although the researchers say that magnesium is “safe”, high doses can cause diarrhoea. UK guidelines state that most people should be able to get sufficient magnesium through their diet, such as by eating more green vegetables, and that the effects of high-dose magnesium in the long term are unknown. Also, magnesium supplements are not recommended for people with a history of kidney disease.

This study seems to have been a wasted opportunity to find out whether magnesium is a useful supplement for people with mild to moderate depression.

Links To The Headlines

Over-the-counter magnesium tablets can banish the blues in just TWO WEEKS without the side effects associated with antidepressants. Mail Online, June 28 2017

Links To Science

Tarleton EK, Littenberg B, MacLean CD, et al. Role of magnesium supplementation in the treatment of depression: A randomized clinical trial. PLOS One. Published online June 27 2017