Doctors usually prescribe several medications to patients with mental disorders to treat the various symptoms. For example, a person with bipolar disorder may be prescribed one drug to treat mania and another to treat depression. But there is little evidence on how drug combinations interact or how diet and nutrition influence their effects. Our study on the effects of psychiatric drug combinations and a common dietary supplement had surprising results – results that show just how poorly understood and understudied this area is.
We found that the combination of drug therapies has long-term benefits for treating depression in patients with bipolar disorder. However, taking a folic acid supplement could interfere with the therapeutic effect of the drugs.
Real world effects
Although treatment of mental health disorders with multiple drugs is the norm, there is not much evidence about which combinations help keep patients healthy over the long term, and how these may be affected by food and nutritional supplements.
Our study addressed these issues by examining whether a combination of commonly used drugs is really better than using a single drug. We also investigated whether the action of these drugs is influenced by a vitamin supplement.
We showed that patients receiving a combination of drugs commonly used to treat bipolar disorder (quetiapine and lamotrigine) had fewer symptoms of depression and were less likely to relapse, compared with those receiving quetiapine alone. These results make sense because quetiapine acts relatively quickly, while lamotrigine takes longer to reach full effect.
Unexpectedly, our study also suggested that taking folic acid, a vitamin routinely given to pregnant women and fortified with certain foods, may block the benefits of combination therapy, at least initially. This discovery was unexpected. Folic acid was included in the trial because it improves symptoms in patients with major depressionand because patients are often more inclined to take a vitamin supplement than a prescribed drug.
If the finding is replicated, it suggests doctors may need to find alternative treatments for depression in women with bipolar disorder planning to have a child. More broadly, it also highlights the need to consider the role diet can play in influencing how patients respond to medication.
Diet and Medications
Our study is not the first to suggest that diet and supplements can influence the effects of prescribed medications. For example, organic compounds in grapefruit can increase circulating levels of a variety of prescribed drugs, make side effects more likely. In the same way, St. John’s worta herbal supplement often used to treat mild depression, may interfere with the actions of a number of prescribed medications, including reducing the effectiveness of oral contraceptives and causing side effects when used in conjunction with certain prescribed antidepressants.

Of note, the effect of folic acid in our study was the opposite of what was predicted – it made patients’ symptoms worse. This surprising finding raises the possibility that there are many other foods and supplements that may influence the effects of prescribed medications.
Effects like this are rarely, if ever, captured by drug trials. But they could prevent prescribed medications from working as intended or cause additional side effects. To add an extra level of complexity, it seems likely that genes could also affect these relationships. For example, there are a number of genetic variants that influence the actions of folic acid. These genetic variants could probably influence the action of certain drugs. We will examine some of these possibilities in our data set, in further study.
We tend to think of vitamins and dietary supplements as natural, so we assume their effects are beneficial. However, like prescription drugs, the nutrients and supplements we take are ultimately just chemicals and can have profound effects on our bodies, both positive and negative.
Our results show that our diet can influence the effect of prescribed medications and show how the beneficial effects of medications can be missed without knowledge of the diet and supplements used by patients in clinical trials. It will be difficult to capture this information in future trials, but our results underscore the importance of this information and the little understanding we have of the interaction between drugs and diet.