Supplements as a First-Line or Adjunct Treatment to Depression
Depression is so much more than just persistent low mood. It is the loss of interest and pleasure in activities, hopelessness, apathy, social withdrawal, weight changes, insomnia, and other symptoms that disrupt normal functioning (1) (2). Depression can vary in severity from mild to moderate to severe, where at its most severe, it can be a life-threatening condition involving suicidal ideation and self-harming behaviours. According to the Canadian Mental Health Association (CAMH), approximately 8% of Canadian adults will experience an episode of major depression at some point in their lives (3). We can only assume that that number has increased in recent months with the current state of events in the world.
Depression is thought to be caused by a multitude of factors from genetic to acquired vulnerabilities from significant emotional to environmental and social factors. This frequently quoted statement summarizes it perfectly: “Genetics loads the gun and environment pulls the trigger” (4). Just as the cause is multifactorial, so should the treatment approach, with a focus on modifying the environmental parameters within our control. In this case, supplements would only be one of the many prongs in a multi-pronged approach to the natural treatment of depression.
Whether using supplements as a first-line option or as a complementary approach to pharmaceutical medications, remember that you must still address the underlying root cause of your mood disruption. Supplementation is always intended to be just that, a supplement to other treatment approaches, mainly lifestyle and dietary modifications including sleep optimization, nutritional diet, daily movement, and stress management. This also means leveraging all the support you can get from your community, friends and family and your healthcare team.
Conventional first-line treatment options commonly involve selective serotonin reuptake inhibitors (SSRIs) such as Prozac, Zoloft, and Paxil. These can be a viable option and very effective therapeutically for many patients with depression. As a Naturopathic Doctor, I love to meet a patient where they are at. Whether that means supporting their use of pharmaceutical medications with additional natural health strategies or finding a first-line treatment alternative. At the end of the day, both are external tools that we can leverage to help lower the symptoms that a patient with depression is experiencing, in order to enable them to engage with dietary and lifestyle modifications to address the root cause. Addressing the mind, body, and spirit is vital for mood disorders. Supplements can be a great resource to help alleviate the burden of depression to allow for the practice of some long-term, sustainable health strategies.
St. John’s Wort (SJW)
St. John’s Wort (SJW) is usually the number one botanical herb used as a first-line natural treatment approach for mild-to-moderate major depressive disorder (MDD). A multitude of studies have shown its effect in therapeutically improving mood, while decreasing symptoms of anxiety and insomnia as well (5) (6) (7) (8) (9). SJW is as effective as several first-line pharmaceutical medications such as several SSRIs (10) (11) (12) including fluoxetine (Prozac) (13) (14), sertraline (Zoloft) (15), and paroxetine (Paxil) (16). The depression response and remission rates of SJW are over 60% (17) and comparable to medications, with fewer reported adverse effects (18). Although this herb may be better tolerated by patients in the treatment of their depression, St. John’s Wort still has commonly reported adverse effects including headaches (19), photosensitization, skin reactions, and allergies (20). It also has some well-known interactions with common medication such as the oral contraceptive pill, statins, warfarin, and more (18). Caution should be used when considering this herb as a treatment option for major depressive disorder.
5-Hydroxytryptophan (5-HTP) is the precursor to serotonin, a neurotransmitter involved in sleep, appetite, temperature, sexual behaviour, pain, mood and aggression (21). Supplementing with 5-HTP can improve symptoms of depression within 8 weeks of use and has even shown remission rates up to 65% (22). Not only has 5-HTP supplementation been shown to be comparable to conventional antidepressants such as fluoxetine (Prozac) (23), but it also makes some medications more effective when used in conjunction (24). This supplement can be of particular use in those who suffer from sleep disturbances, changes in appetite and libido as part of their depressive picture, as 5-HTP helps to address all of these functions and more.
Similarly to 5-HTP, SAMe has shown benefit both as a first-line monotherapy or as an adjunct treatment to conventional antidepressants. SAMe is often added to treatment plans when patients with depression are not responding well to conventional pharmaceutical approaches. For every 7 non-responsive patients with depression treated by adding SAMe to their medication, one patient went into remission (25). Impressively, SAMe seems to enhance the function of SSRIs in particular, which is the usual conventional first-line treatment approach used by medical doctors.
Saffron is commonly known as a spice in cooking but can yield some powerful antidepressant benefits when supplementing with a concentrated extract. Interestingly, saffron supplementation can improve not only symptoms of depression but also those of anxiety and stress, within only 4 weeks of use compared to placebo (26).
Supplements, as important of a role as they may play in helping to regulate and balance your mood, are only one part of a holistic treatment approach. They are still an external source that we may rely on to address a much more internal state. These should always be used in conjunction with dietary and lifestyle modifications. In fact, they can help to lower the threshold of your current symptoms and allow for you to implement these in a more impactful, consistent and efficacious manner.
- Patel, K. Depression. Examine.com. [Online] Examine.com, March 2, 2020. [Cited: September 17, 2020.] https://examine.com/topics/depression/.
- Coryell, W. Depressive Disorders. MERCK MANUAL. [Online] Merck Sharp & Dohme Corp., March 2020. [Cited: September 17, 2020.] https://www.merckmanuals.com/professional/psychiatric-disorders/mood-disorders/depressive-disorders?query=depression.
- Fast Facts about Mental Illness. Canadian Mental Health Association. [Online] Canadian Mental Health Assocation, National. [Cited: September 17, 2020.] https://cmha.ca/fast-facts-about-mental-illness.
- Gene-Environment Interactions in the Development of Complex Disease Phenotypes. Ramos RG, Olden, K. 1, North Carolina : Int J Environ Res Public Health, 2008, Vol. 5. doi: 10.3390/ijerph5010004.
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- A systematic review of newer pharmacotherapies for depression in adults: Evidence report summary. Williams JW, Mulrow CD, Chiquette E, et al. 9, San Antonio, USA : Ann Intern Med, 2000, Vol. 132. doi: 10.7326/0003-4819-132-9-200005020-00011..
- Cluster analysis of symptoms during antidepressant treatment with Hypericum extract in mildly to moderately depressed out-patients. A meta-analysis of data from three randomized, placebo-controlled trials. Kasper S, Dienel A. 3, Wien, Austria : Psychopharmacology (Berl), 2002, Vol. 164. doi: 10.1007/s00213-002-1203-2..
- St John's Wort for depression. Linde K, Mulrow CD, Berner M, Egger M. CD000448., Munich, Germany : Cochrane Database Syst Rev, 2005, Vol. 2. doi: 10.1002/14651858.CD000448.pub2..
- St John's wort for major depression. Linde, K., Berner, M. M., and Kriston, L. CD000448., Munich, Germany : Cochrane.Database.Syst.Rev., 2008, Vol. 4. doi: 10.1002/14651858.CD000448.pub3..
- Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Rahimi, R., Nikfar, S., and Abdollahi, M. 1, Tehran, Iran : Prog.Neuropsychopharmacol.Biol.Psychiatry, 2009, Vol. 33. doi: 10.1016/j.pnpbp.2008.10.018..
- Comparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis. Asher GN, Gartlehner G, Gaynes BN, et al. 12, Chapel Hill, North Carolina : J Altern Complement Med., 2017, Vol. 23. doi: 10.1089/acm.2016.0261..
- Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. Harrer G, Schmidt U, Kuhn U, Biller A. 4, Salzburg, Germany : Arzneimittelforschung, 1999, Vol. 49. doi: 10.1055/s-0031-1300417..
- Equivalence of St. John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. E., Schrader. 2, Pohlheim, Germany. : Int Clin Psychopharmacol, 2000, Vol. 15. doi: 10.1097/00004850-200015020-00001..
- Comparison of an extract of Hypericum (LI 160) and sertraline in the treatment of depression: A double-blind, randomized pilot study. Brenner R, Azbel V, Madhusoodanan S, et al. 4, New York, USA : Clin Ther , 2000, Vol. 22. doi: 10.1016/S0149-2918(00)89010-4..
- Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. . Szegedi A, Kohnen R, Dienel A, Kieser M. 7490, Berlin, Germany : BMJ , 2005, Vol. 330. doi: 10.1136/bmj.38356.655266.82..
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- S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Papakostas GI, Mischoulon D, Shyu I, et al. 8, Boston, MA, USA : Am J Psychiatry, 2010, Vol. 167. doi: 10.1176/appi.ajp.2009.09081198.
- Affron® a novel saffron extract (Crocus sativus L.) improves mood in healthy adults over 4 weeks in a double-blind, parallel, randomized, placebo-controlled clinical trial. Kell G, Rao A, Beccaria G, et al. Toowoomba, Australia : Complement Ther Med. , 2017, Vol. 33. doi: 10.1016/j.ctim.2017.06.001..