Rational Prescribing Article Series

Article 3: 5-HTP for Depression – A rational prescribing approach

Depression has become one of the most common chronic diseases in the world. It affects more than 10% of the world’s population, and prescription drug treatment is inadequate in more than half of cases. While the stress of the pandemic has made mental illness a higher priority than ever, many people still struggle with the stigma attached to these disorders. That is unfortunate, because there are many other treatment options that address the brain, mind and body. The specialized fields of neurology and psychiatry are still worlds apart, making an integrative perspective of brain health more important than ever.

If you are struggling with depression, you should consider a trial of 5-HTP. This natural antidepressant has been safely used for decades. It is backed by some decent evidence, and unlike prescription drugs, a trial only takes a few days. A rational prescribing approach, ideally one that is supervised by your doctor or another healthcare professional, will allow you to do this safely and responsibly. As an integrative medical doctor grounded in science, I believe that rational prescribing is the best way for evidence-based integrative medicine to find its place in global healthcare.

How It Might Work

5-HTP is short for 5-hydroxytryptophan. The brain uses 5-HTP to make serotonin and makes its 5-HTP from tryptophan, an essential amino acid found in many foods. Serotonin is one of the key neurotransmitters in the body, and low levels of serotonin have been linked to depression. Prozac was the first antidepressant in a class of drugs called selective serotonin reuptake inhibitors (SSRIs), and it ushered in a revolution in psychiatry that persists to this day. While it is still unclear exactly how they work, we know they increase serotonin levels in the brain.

Tryptophan is also needed to make melatonin, the sleep hormone, and to make hormones that are part of the stress response. Intense or prolonged stress may divert this tryptophan to handle this stress, using what is called the kynurenic pathway, and this can deprive the brain of the tryptophan it needs to make serotonin. This process is not yet fully understood, but it may be why depression is linked to cardiovascular disease, diabetes and metabolic syndrome. These disorders are also linked to stress and the chronic inflammation that often goes with it, making depression one key symptom of an inflamed brain.

Commercially available 5-HTP supplements are made from the seeds of an African shrub called Griffonia simplicifolia. The plant was named after Marie-Théophile Griffon du Bellay, a Navy doctor who first described its medicinal use in Gabon, and was a pioneer in the study of sleeping sickness and the African entheogen Iboga, source of the alkaloid ibogaine.

Griffonia is one of the only naturally-occurring sources of 5-HTP, making this plant a growth industry in many tropical countries. Interestingly, China is now the world’s leading exporter of Griffonia seeds, and prior to the pandemic their global exports totalled nearly $1 billion.

Published Evidence

There have been many published reports on the successful use of 5-HTP to treat depression in adults. In a recent systematic review, the authors researched 141 publications, and they found 13 studies that met their criteria, involving 413 patients. As with many natural health products, the evidence was inconclusive because most of the trials were not designed to exclude the risk of bias. They also varied in terms of the type of extract, the dose used, and the types of depression treated, and sample sizes in most studies were small. Only three of the studies were placebo-controlled.

The benefit of a systematic review is that sometimes the data from individual studies can actually be combined, and this larger sample size yields more reliable data. In this case, the authors were able to pool the data from seven of these 13 trials, and the combined results indicated that “65{1071260361a6591b2768c24687f2d69ce8520c71da1d587858ed261d75abb6f4} of patients achieved marked remission following 5-HTP treatment.” In the six controlled trials that used the Hamilton Depression Rating Scale, patients reported a 12.7-point decrease — a very impressive improvement.

The dose used in these studies ranged from 50mg to over 3000mg daily, but the average daily dose was 100-300mg. The duration of treatment in these studies ranged from five to 56 days. There was no toxicity reported in any of the studies.

How to Try 5-HTP for Yourself: A Rational Prescribing Approach

Doctors typically only recommend treatments that have been proven effective in randomized controlled trials. This approach is called evidence-based medicine, and while it has major benefits, patients find themselves on their own when these options don’t work. Randomized controlled trials can provide evidence that a treatment is better than a placebo in a large group of people, but it does not confirm that it will work for you. If you are struggling to get a good night’s sleep, you can use a process that the World Health Organization calls rational prescribing to find out if 5-HTP works for you.

Rational prescribing is an approach that is taught to medical students worldwide. It is a useful way to improve prescribing for any treatment or therapy, whether it is a pharmaceutical drug, a natural health product, or any other therapy or self-care practice. Rational prescribing is about structuring every new prescription as a therapeutic trial in six steps:

  • Selecting the problem you want to treat
  • Choosing a treatment goal
  • Selecting a treatment
  • Defining the parameters of the trial
  • Taking the medicine or performing the treatment, and
  • Assessing the outcome and deciding next steps

One reason to consider 5-HTP is that a therapeutic trial only takes a few days. I typically start patients at about 50mg twice daily, and advise them to increase their dose by 50mg every two to three days until they reach 300mg. At that point, if there is no benefit, it may be worth trying something else. In most cases, this takes less than two weeks.

Because depression is a subjective feeling, it can be useful to track your progress using a daily journal. You may notice a change in the way you feel, but the change may be easier to note in terms of what you do. Improvements in function are often more meaningful, objective and clear. Side-effects may include headaches, an upset stomach or fatigue.

When taken on its own, 5-HTP is extremely safe. Excessively high levels of serotonin in the brain can cause serotonin syndrome, which can lead to heart problems, anxiety and shivering. This is well-known to emergency physicians, who see it in people who take too many antidepressants. While I was unable to find any case reports of serotonin syndrome linked to 5-HTP, you should not use it on your own if you are taking antidepressants. To do so, you should be supervised by a medical doctor who can provide close follow-up during your trial.

If 5-HTP works for you, the improvements in mood, sleep and overall well-being will likely be quite obvious. If it doesn’t work for you, there are many other options you can consider. The integrative treatment of depression can include exercise, more sunlight, getting a pet, addressing social isolation, cognitive-behavioural therapy, mindfulness practices, acupuncture, an anti-inflammatory diet, a gluten-free diet, St. John’s wort, vitamin B12 or folic acid.

Rational Prescribing and Integrative Medicine

While some practitioners prescribe several things at once, trying one thing at a time can help you identify what works and what doesn’t. Rational prescribing is a safer, more responsible and structured way to explore complementary and alternative medicine therapies. By structuring your wellness journey as a series of trials, you can build a personalized regimen that will improve your life.

If we can find a way to crowdsource all of this data, learning from people like you what works, what doesn’t, and why, perhaps we can take a step toward more evidence-based integrative medicine. As an integrative MD grounded in evidence and science, I have used this kind of real-world data to help many people improve their lives. I hope it helps you.