Mood Support Protocol: A Resource for Practitioners


Written and medically reviewed by Fullscript’s Integrative Medical Advisory Team

Depression is a common mental disorder, affecting individuals of all ages. (25) In 2017, the World Health Organization (WHO) reported that depression affects over 300 million individuals worldwide, accounting for approximately 4.4% of the global population. (9)(24) Increasing 18% from 2005 to 2015, the prevalence of depression continues to rise. (24)

If left untreated, severe depression may lead to suicide. Suicide is the second leading cause of death in individuals aged 15-29 and accounts for almost 800,000 deaths globally every year. (25) Fortunately, effective interventions are available for depression.

What is depression?

Depression, also referred to as major depressive disorder or clinical depression, is a serious mood disorder that affects thoughts, feelings, and daily functioning. (1)(18) The condition is more common in women than men and typically emerges during the late teens to mid-20s. (1)

Certain forms of depression may be characterized by their unique symptoms or the circumstances in which symptoms are present, such as:

Persistent depressive disorder (dysthymia): depression persists for a minimum of two years, often characterized by episodes of major depression followed by less severe periods

Psychotic depression: severe depression occurs with some form of psychosis (e.g., delusions, hallucinations)

Bipolar disorder: disorder characterized by periods of major depression (bipolar depression) and periods of mania or hypomania

Postpartum depression: major depression occurring during pregnancy or after delivery, characterized by feelings of extreme sadness, anxiety, and exhaustion

Seasonal affective disorder: recurring depression corresponding with the same time each year, typically during the winter months when there are fewer hours of sunlight (18)

man sitting on couch looking sad holding head

Depression is a serious mood disorder that affects thoughts, feelings, and daily functioning.

Signs and symptoms

Depressive episodes may be mild, moderate, or severe, depending on the severity and number of symptoms present. (18) In order to be diagnosed as depression, symptoms must persist for a minimum of two weeks. (1)(18)

Symptoms of depression may include:

  • Sadness, depressed mood, or feelings of “emptiness”
  • Anxiety and/or irritability
  • Pessimism, feelings of hopelessness, worthlessness, and/or guilt
  • Loss of interest or pleasure in hobbies or activities once enjoyed
  • Fatigue (lethargy) or decreased energy
  • Restlessness
  • Poor concentration and/or memory
  • Difficulty making decisions
  • Changes in appetite and/or weight unrelated to dieting
  • Difficulty sleeping/waking up or oversleeping
  • Unexplained aches or pains, or unresponsive to treatment (e.g., headaches, digestive issues, cramps)
  • Suicidal ideation and/or attempts (1)(18)

Causes and risk factors

The pathogenesis of depression is believed to involve a complex interaction between genetic, biochemical, environmental, and psychological factors. While depression can occur in anyone, risk factors for the condition include:

  • Personal or family history of depression
  • Major life changes, stress, or traumatic events (e.g., unemployment, death of a loved one, exposure to poverty, violence, abuse, or neglect)
  • Use of certain pharmaceutical medications
  • Certain medical conditions (e.g., diabetes, cardiovascular disease, cancer, Parkinson’s disease) (1)(18)
  • Certain personality traits (e.g., low-self esteem, pessimistic, difficulty coping with stress) (1)

Integrative protocol for mood support

Depression is typically treated with antidepressant medication, psychotherapy, or a combination. Electroconvulsive therapy (ECT) and other brain stimulation therapies are often used in treatment-resistant cases. (1)(18) Research has also shown that certain nutrients and botanicals may be effective in improving symptoms of depression.

St. John’s wort extract plant form

The flowering tops of St. John’s wort can be used to make tea.

St John’s wort (Hypericum perforatum)

St. John’s wort (SJW) is a leafy herb with yellow flowering tops that grows in temperate regions of the world. The medical use of SJW dates back thousands of years to ancient Greece. (12)(17) Current research demonstrates the antioxidant and neuroprotective properties of SJW and the effectiveness of the herb has been examined for several health conditions, such as anxiety, inflammatory conditions, cancer, and bacterial and viral diseases. (12) Several studies have also demonstrated the effectiveness of SJW in the treatment of depression and have suggested that SJW may be similarly effective but produce fewer adverse effects compared to antidepressant medication. (3)(7) The therapeutic effects of SJW may be attributed to a number of active constituents, particularly hypericin and hyperforin. (12)

SJW is available in topical preparations, as well as tablets, capsules and liquid extracts. The flowering tops of the plant can also be used to make tea. (17) When prescribing St. John’s Wort, it’s important to account for possible interactions as St. John’s Wort has been shown to interact with several medications. (12)(17)

Research findings:

  • Hypericum perforatum demonstrated similar efficacy to SSRIs including criteria like remission rate, Hamilton-Anxiety Scale and depressive symptoms in patients with mild to moderate depression (3)(20)
  • Improvements in relapse rates, Hamilton-Anxiety Scale, Beck Depression Inventory time courses and greater overall improvement (Clinical Global Impressions (CGI) scale) were observed. In addition, Hypericum perforatum demonstrated a potential for prophylactic effect in patients with chronic depression or depression alone (11)(15)(22)

US: Search for Hypericum perforatum in the Fullscript catalog.
CAN: Search for Hypericum perforatum in the Fullscript catalog.

Omega-3 fatty acids

Omega-3 fatty acids, sometimes referred to as n-3s, play an important role in the structure of phospolipids, helping to maintain the structure and function of cell membranes in the body. Omega-3 fatty acids also provide the body with energy and produce eicosanoids. Eicosanoids are signaling molecules responsible for a number of functions within the immune, endocrine, cardiovascular, and pulmonary systems. While there a several different omega-3s, the most well-known and researched are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA is found primarily in algae and certain plant oils, such as flaxseed, soybean, and canola oil. EPA and DHA are found primarily in oily fish and krill. (19) EPA and DHA can be synthesized from ALA, however this process in limited to approximately 10-14% in men and women, respectively. (6)

In addition to dietary sources, omega-3 fatty acids may also be obtained through supplementation. Omega-3 formulations can be derived from a number of different sources, including fish, krill, cod liver, and vegetarian algae. It’s important to check the labels of omega-3 products as the composition and forms of omega-3s can vary significantly between products. (19) Research has demonstrated omega-3 fatty acid supplementation to be beneficial in the treatment of depression as a result of its anti-inflammatory effects and role in cell membrane composition and function. (4)

Research findings:

  • Dietary n-3 polyunsaturated fatty acids (PUFAs) were shown to lower the risk of depression (10)(16)(23)
  • Increased levels of red blood cell EPA, DHA and ratio were correlated with improved remission rate (5)

US: Search for Omega fatty acids in the Fullscript catalog.
CAN: Search for Omega fatty acids in the Fullscript catalog.

rhizome of R. rosea roots

Over 140 compounds have been isolated from the roots and rhizome of R. rosea.

Rhodiola (Rhodiola rosea)

Rhodiola rosea, also known as golden root, roseroot, and arctic root, was first used to improve physical performance and endurance, fertitility, and longevity in traditional European and Chinese medicines. It was also used as a remegy for certain health conditions, including fatigue, depression, altitude sickness, anemia, and cancer. (13)

Modern research has now isolated approximately 140 compounds from its roots and rhizome (e.g., flavonoids, glycosides, proanthocyanidins). Studies suggest that R. rosea may possess a number of therapeutic and adaptogenic properties, including anti-fatigue, neuroprotective, cardioprotective, anxiolytic, antidepressive, and nootropic effects. (21) The antidepressant effects of R. rosea are believed to be attributed to its ability to modulate the stress or hypothalamic-pituitary-adrenal (HPA) response and improve central neurotransmission. (13)

Research findings:

  • Cell response to stress was shown to be regulated by rhodiola, which in return, positively impacted overall mood (2)
  • Overall depression symptoms including insomnia, somatization and emotional instability were improved (8)
  • A decrease in the Hamilton-Anxiety Scale was observed with fewer adverse effects than sertraline (14)

US: Search for Rhodiola rosea in the Fullscript catalog.
CAN: Search for Rhodiola rosea in the Fullscript catalog.

Key takeaways

While depression is typically treated with antidepressant medication and psychotherapy, research has shown that certain nutrients and botanicals, such as St. John’s Wort, omega-3 fatty acids, and rhodiola may be effective in improving symptoms of depression. A protocol using natural supplements can be used therapeutically on its own or as an adjunct to existing treatment. When recommending nutrients or botanicals as an adjunct to treatment, be sure to check for possible interactions with pharmaceutical medications to prevent possible negative health outcomes in patients. If you are not an integrative healthcare provider, we recommend speaking with one to find out whether these supplements are right for your wellness plan.

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The Fullscript Integrative Medical Advisory team has developed or collected these protocols from practitioners and supplier partners to help health care practitioners make decisions when building treatment plans. By adding this protocol to your Fullscript template library, you understand and accept that the recommendations in the protocol are for initial guidance and may not be appropriate for every patient.

  1. American Psychiatric Association. (2017). What is depression?. Retrieved from
  2. Amsterdam, J.D., & Panossian, A.G. (2016). Rhodiola rosea L. as a putative botanical antidepressant. Phytomedicine, 23(7), 770-83.
  3. Apaydin, E. A., Maher, A. R., Shanman, R., Booth, M. S., Miles, J. N., Sorbero, M. E., & Hempel, S. (2016). A systematic review of St. John’s wort for major depressive disorder. Systematic Reviews, 5(1), 148.
  4. Burhani, M. D., & Rasenick, M. M. (2017). Fish oil and depression: The skinny on fats. Journal of Integrative Neuroscience, 16(s1), S115–S124.
  5. Carney, R. M., Steinmeyer, B. C., Freedland, K. E., Rubin, E. H., Rich, M. W., & Harris, W. S. (2016). Baseline blood levels of omega-3 and depression remission: a secondary analysis of data from a placebo-controlled trial of omega-3 supplements. The Journal of Clinical Psychiatry, 77(2), e138–e143.
  6. Cholewski, M., Tomczykowa, M., & Tomczyk, M. (2018). A comprehensive review of chemistry, sources and bioavailability of omega-3 fatty acids. Nutrients, 10(11), 1662.
  7. Cui, Y. H., & Zheng, Y. (2016). A meta-analysis on the efficacy and safety of St John’s wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults. Neuropsychiatric Disease and Treatment, 12, 1715–1723.
  8. Darbinyan, V., Aslanyan, G., Amroyan, E., Gabrielyan, E., Malmström, C., & Panossian, A. (2007). Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nordic Journal of Psychiatry, 61(5), 343-8.
  9. Friedrich, M. (2017). Depression is the leading cause of disability around the world. JAMA, 317(15), 1517.
  10. Grosso, G., Micek, A., Marventano, S., Castellano, S., Mistretta, A., Pajak, A., Galvano, F. (2016). Dietary n-3 PUFA, fish consumption and depression: A systematic review and meta-analysis of observational studies. Journal of Affective Disorders, 205, 269-281.
  11. Kasper, S., Volz, H.P., Möller, H.J., Dienel, A., & Kieser, M. (2008). Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression: A double-blind, randomized, placebo controlled long-term trial. European Neuropsychopharmacology, 18(11), 803-13.
  12. Klemow, K.M., Bartlow, A., Crawford, J., Kocher, N., Shah, J., & Ritsick, M. (2011). Medical attributes of St. John’s wort (Hypericum perforatum). In I.F.F. Benzie, & S. Wachtel-Galor (Eds.), Herbal medicine: Biomolecular and clinical aspects (2nd edition). Boca Raton, FL: CRC Press/Taylor & Francis.
  13. Mao, J. J., Li, Q. S., Soeller, I., Xie, S. X., & Amsterdam, J. D. (2014). Rhodiola rosea therapy for major depressive disorder: a study protocol for a randomized, double-blind, placebo-controlled trial. Journal of Clinical Trials, 4, 170.
  14. Mao, J. J., Xie, S. X., Zee, J., Soeller, I., Li, Q. S., Rockwell, K., & Amsterdam, J. D. (2015). Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial. Phytomedicine, 22(3), 394–399.
  15. Mannel, M., Kuhn, U., Schmidt, U., Ploch, M., & Murck, H. (2010). St. John’s wort extract LI160 for the treatment of depression with atypical features: A double-blind, randomized, and placebo-controlled trial. Journal of Psychiatric Research, 44(12), 760-7.
  16. Mocking, R. J., Harmsen, I., Assies, J., Koeter, M. W., Ruhé, H. G., & Schene, A. H. (2016). Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Translational Psychiatry, 6(3), e756.
  17. National Centre for Complementary and Integrative Health. (2017). St. John’s wort. Retrieved from
  18. National Institute of Mental Health. (2018). Depression. Retrieved from
  19. National Institutes of Health. (2019). Omega-3 fatty acids. Retrieved from
  20. Ng, Q.X., Venkatanarayanan, N., & Ho, C.Y. (2017). Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis. Journal of Affective Disorders, 210, 211-221.
  21. Panossian, A., Wikman, G. & Sarris, J. (2010). Rosenroot (Rhodiola rosea): Traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine, 17(7), 481-493.
  22. Singer, A., Schmidt, M., Hauke, W., & Stade, K. (2011). Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: A reanalysis of data from a controlled clinical trial. Phytomedicine, 18(8-9), 739-42.
  23. Sublette, M. E., Ellis, S. P., Geant, A. L., & Mann, J. J. (2011). Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. The Journal of Clinical Psychiatry, 72(12), 1577–1584.
  24. UN News. (2017). UN health agency reports depression now ‘leading cause of disability worldwide’. Retrieved from
  25. World Health Organization. (2018). Depression. Retrieved from