How to Prescribe Natural Medications? Part 1

Last updated: April 8, 2019

Host: Wegdan Rashad, MD

Today’s question is: Should you prescribe natural medications?

Here is a summary of this episode:

  • St. John’s wort and Rhodiola rosea have been found to cause serotonin syndrome when combined with SSRIs.
  • St. John’s wort, SAM-e and omega 3 fatty acids may cause switching to hypomania and mania in patients with bipolar disorder.
  • Correcting the ratio of omega-6 to omega-3 seems to correlate with the degree of improvement in depression. The omega-3s are found primarily in fish oil and in certain types of algae.
  • Rhodiola rosea functions as an adaptogen. It is taken at doses ranging from 100 to 680 mg per day.


Hello! I’m Dr. Wegdan Rashad and you are listening to the Psychopharmacology Institute podcast. We’ll be discussing topics that matter to you, the mental health clinician, in your practice, sharing expert opinions and the latest research.

Today, we will be talking about natural medications in psychiatry, they are also known as complementary or alternative medicines. You may come across patients who take these over-the-counter agents to self-treat their anxiety or depression. Today, we find out just how effective they are and how they come into psychotropic prescribing. We have with us Dr. David Mischoulon who is a clinical professor of Psychiatry at Harvard Medical School and the Director of the Depression Clinical and Research Program at Massachusetts General Hospital. He gave a lecture entitled “Natural Medications” available on our website.

In the last episode, I shared with you a case about a 35-year-old man taking sertraline for depression and then he started taking St. John’s wort. Afterward, he got diarrhea, sweats, and tachycardia. I asked you about the potential cause of these symptoms. Thank you for your answers, we received many correct responses. And in fact, yes, the answer is serotonin syndrome. Did you get the answer right?

Dr. Mischoulon elaborates further on how this can happen.

Dr. Mischoulon:
It is not considered safe to combine St. John’s wort with other antidepressants. St. John’s wort has a mild monoamine oxidase inhibition activity similarly to an MAOI antidepressant and when combined with other antidepressants, it can produce serotonin syndrome. This can be a very dangerous side effect that if untreated can result in death. This interaction can also occur with other medications if combined with St. John’s wort, for example, cold remedies. So the person taking St. John’s wort has to be very careful if they are considering taking another drug because there are many adverse interactions that can occur.

So St. John’s wort may indeed cause serotonin syndrome when combined with an SSRI. In fact St. John’s wort is not the only herbal agent to produce this, as we will see later in this podcast.

At the end of this episode, I will share with you another case, so stay tuned.

St John’s wort is one of the better studied natural antidepressants. It is effective for mild to moderate forms of depression. So perhaps you can consider prescribing it if a patient is has a milder form of illness and is willing to cover its costs out-of-pocket. But what about dosing and interactions?

Dr. Mischoulon:
The recommended dose of St. John’s wort runs between 300 and 1800 mg a day. Typically, it’s dosed on a two- or three-times-a-day basis and the most common dose used is about 900 mg a day. The practitioner and the consumer should keep in mind that different preparations of St. John’s wort may vary with regard to potency depending on how they are manufactured. St. John’s wort is thought to work by interacting with the hypothalamus-pituitary-adrenal axis with an effect of reducing cytokine production which in turn may dampen depression. St. John’s wort is thought to be a very safe natural product. Its side effects tend to be mild. Most commonly, we’ll see dry mouth, dizziness, and constipation. However, there are some more serious side effects that may occur, for example, phototoxicity which is extreme sensitivity to sunlight and also cycling to mania in patients with bipolar disorder.

Now Dr. Mischoulon raised a very important point and that is cycling to mania. This can happen with St. John’s wort and other herbal remedies, so you need to do some proper assessment for bipolarity before you proceed with prescribing these.

Like St. John’s wort, S-adenosyl methionine or SAM-e can also cause switching to hypomania or mania in patients with bipolar depression. If you’ve not heard of SAM-e before, it is basically an antidepressant that works through donating methyl group.

Dr. Mischoulon:
One advantage of using SAM-e for depression is that it may bypass any MTHFR polymorphisms. MTHFR is the enzyme methylenetetrahydrofolate reductase which is very important in the reaction shown in the diagram. A person with this deficiency may not be able to metabolize folate properly and thus result in lower levels of SAM-e and hence in less synthesis of the neurotransmitters such as dopamine, serotonin, and acetylcholine as well as others. So by giving SAM-e, we continue to stimulate synthesis of these key neurotransmitters and this may be how it exerts its antidepressant effect.

For patients who do have the mutation, another good option could be to take Deplin which is the commercial name for 5-methyltetrahydrofolate. My Psychopharmacology Institute colleague Dr. Dana Wang investigates further.

Dr. Wang:
How effective is SAM-e in comparison with methylated folate such as Deplin?

Dr. Mischoulon:
Right now, there are no studies comparing SAM-e against Deplin head to head. There are about 40 or so studies of SAM-e in depression that mostly support its efficacy. There are, on the other hand, fewer studies of folate usually in different preparations supporting its effect as an adjunctive antidepressant agent. Our group has done a study that showed that Deplin was effective as augmentation for people who were partially responding to antidepressants. The evidence for SAM-e is generally stronger because there is a larger number of studies published supporting its efficacy.

So, SAM-e is a good option as monotherapy or as an adjunct to antidepressants. What about its safety and interactions?

Dr. Mischoulon:
The recommended doses of SAM-e based on the literature are between 400 and 3200 mg a day. SAM-e can be combined safely with other drugs since it doesn’t have very many interactions. It has been combined with tricyclic antidepressants, serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors. SAM-e appears to be a very safe drug. Most of the side effects reported tend to be mild. These include insomnia, loss of appetite or anorexia, constipation, nausea, dry mouth, sweating, dizziness, and anxiety.

So, it is generally safe and without major interactions. It is worth considering indeed.

Now we will move on to a natural medication that has had a little bit of hype in the psychiatric and cardiovascular health community. Can you guess?

If you guessed omega-3 and 6 fatty acids then you are indeed correct. At some point, these essential fatty acids were widely prescribed by clinicians based on claims that they significantly improved cardiovascular health but later, Cochrane review studies have debunked some of these claims. How about essential fatty acids and mental health?

Dr. Mischoulon:
In some of our depression studies, we have found that correcting the ratio of omega-6 to omega-3 seems to correlate with the degree of improvement in depression. This suggests that in humans there may be an optimal ratio of omega-3 and omega-6 that we need to strive for through the diet. The omega-3s are found primarily in fish oil and in certain types of algae. These omega-3s are specifically EPA, eicosapentaenoic acid, and DHA, docosahexaenoic acid. Another omega-3, alpha-linolenic acid or ALA, can be found in flaxseed oil and in some other vegetable oils. The omega-6 fatty acids are found primarily in vegetable oils. It doesn’t really matter where you get your omega-3 or omega-6. The omega-3s are actually the same but some people may prefer one over the other. For example, individuals who follow a strict vegan diet may be more comfortable consuming omega-3 preparations that come from algae rather than from fish. But the benefits should be about the same.

Interesting, so there is some evidence to suggest that essential fatty acids can help in treating depression. In studies, omega 3 was mainly used as an adjunctive agent rather than monotherapy for depression, however.
They sound like healthy agents to take, but are there any safety concerns with omega-3s?

Dr. Mischoulon:
The omega-3s are thought to be quite safe. The most common side effects are mild and include stomach upset or fishy taste in the mouth. In the past, there have been concerns about the omega-3s causing bleeding usually at doses greater than 3 grams a day. However, more recent evidence suggests that these initial concerns were exaggerated and that the omega-3s are safe from the standpoint of bleeding. Nonetheless, many practitioners will still advise caution. There have been cases of cycling to mania occurring in patients with bipolar disorder. In the treatment of bipolar disorder with omega-3s, many of the studies have used very high doses between 6 and 10 grams a day. This may be one contributor to cycling. Again, caution is advised in bipolar patients who wish to use omega-3s.

So that’s the third agent today that we mentioned that could potentially cause switching to mania; St. John’s wort, SAM-e and omega-3 fatty acids.

Now let’s move on to our fourth and last alternative medicine, Rhodiola.

Now, Rhodiola rosea is a plant that is thought to be an adaptogen. What that basically means is that it makes you a little more like Superman i.e. it increases the body’s resistance to chemical, biological and physical stressors. It is also said to alleviate stress and sexual dysfunction. Hmmm, sounds great, really. Now let’s see what the evidence says.

Dr. Mischoulon:
Rhodiola has been studied for more than 40 years mostly in Russia and Scandinavia. Many of these studies have unfortunately not been translated to English. There are at least four controlled clinical trials that support efficacy for depression, anxiety, and cognition. Doses used have ranged from 100 to 680 mg a day. Rhodiola contains many potentially active ingredients. The adaptogenic chemicals are called rosavins and tyrosols. It also contains antioxidants such as flavonoids. It’s thought to have a monoamine modulation activity as well as monoamine oxidase A and B inhibition and opioid-like effects. All of these may contribute to antidepressant and anti-anxiety benefits.

So doses range from 100 to 680 mg per day. Rhodiola is best taken on an empty stomach at least 30 minutes before meals and preferably early in the day. One of its side effects includes vivid dreams so this might interfere a bit with sleep.

Dr. Mischoulon:
It can be combined with tricyclic antidepressants and in those cases, it may even reduce some of the side effects that occur with TCAs. On the other hand, there is one case of a mild serotonin syndrome reaction occurring when Rhodiola was combined with paroxetine. So we need to be careful with this combination.

That is the second agent that can cause serotonin syndrome with SSRIs beside St. John’s wort. So watch out for that.

And that’s about it for part one on using natural medications in psychiatry practice. I hope you picked up something new today. Now we arrive at the summary, also known as the key points.

Key Points

  • The most common dose of St. John’s Wort is 900 mg per day and it has been found to be effective for mild to moderate depression.
  • St. John’s wort and Rhodiola rosea have been found to cause serotonin syndrome when combined with SSRIs.
  • St. John’s wort, SAM-e and omega 3 fatty acids may cause switching to hypomania or mania in patients with bipolar disorder.
  • SAM-e acts as a methyl donor and can be helpful in patients with MTHFR deficiency.
  • Correcting the ratio of omega-6 to omega-3 seems to correlate with the degree of improvement in depression. The omega-3s are found primarily in fish oil and in certain types of algae.
  • Rhodiola rosea functions as an adaptogen taken at doses ranging from 100 to 680 mg per day, best taken on an empty stomach.

Before we go I’d like to share a case with you.

A 67-year-old man with early Alzheimer’s disease is having trouble sleeping. He and his caregiver prefer a natural medication to help him sleep. You do a full work up to exclude secondary causes of insomnia and find none. What natural medication could you prescribe in this patient?

Do you know the answer? Send us your response at and we will discuss the answer in the next episode.

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Do you have suggestions, questions or you know the answer to the case? Email us at

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The following people participated in this episode: Dr. Flavio Guzman as the general editor, Mark Young as the audio engineer, Pamela Gonzalez as the project manager and myself, Dr. Wegdan Rashad as the host. We’d also like to thank Dr. David Mischoulon, and Dr. Dana Wang, for being with us.

Thank you for joining us in today’s podcast until the next episode, goodbye!


  1. Mischoulon, D., & Rosenbaum, J. F. (Eds.). (2008). Natural medications for psychiatric disorders: considering the alternatives. Lippincott Williams & Wilkins.
  2. Maher, A. R., Hempel, S., Apaydin, E., Shanman, R. M., Booth, M., Miles, J. N., & Sorbero, M. E. (2016). St. John’s Wort for Major Depressive Disorder: A Systematic Review. Rand health quarterly, 5(4).
  3. Sharma, A., Gerbarg, P., Bottiglieri, T., Massoumi, L., Carpenter, L. L., Lavretsky, H., … & Mischoulon, D. (2017). S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research. The Journal of clinical psychiatry, 78(6), e656.

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