Pharmaceuticals Compared to Natural Supplements For Depression

Medications compared to natural supplementsDepression is a mental health condition that affects a significant portion of the population. It is estimated that it affects up to 15-20 percent of people some time in their life, and can have devastating effects on social, occupational, physical and educational function.

The mainstay treatments for depression include psychological therapies and pharmaceutical antidepressants. The most popular pharmaceutical antidepressants are classed as selective serotonin reuptake inhibitors (SSRIs) such as Prozac®, Zoloft® and Paxil®.

Interest in natural supplements for depression has increased over the past decade. This is because many pharmaceutical antidepressants are associated with several side effects. These include weight gain, nausea, drowsiness and headache.

So how do natural supplements compare to drug-based treatments for depression?

Although many mainstream doctors will argue that there is no research to support the efficacy of natural supplements for depression, this is simply untrue. Below we review some studies where there were head-to-head comparisons between a natural supplement and a pharmaceutical antidepressant.


There have been 3 studies now comparing the spice saffron to an antidepressant for the treatment of mild-to-moderate depression. In one study, saffron was compared to fluoxetine (Prozac®) in people with depression over an 8-week period. The results revealed that both treatments were equally effective in reducing depressive symptoms [1].

In another study, Saffron was compared to imipramine (Tofranil®) and the same results were found (i.e., equally effective) [2].

In a recent review paper published in Human Psychopharmacology, it was concluded that taking a saffron supplement was more effective than a placebo, and equally effective to antidepressant medications for the treatment of mild-to-moderate severity of depression [3].

S-Adenosyl Methionine (SAMe)

SAMe is a naturally occurring compound in our body that has several functions. In particular, it is involved in a process called methylation. Methylation is important for the production of mood-boosting neurotransmitters such as serotonin and dopamine.

There have been several studies supporting the benefits of SAMe supplements for the treatment of depression and some studies even showing that taking both pharmaceutical antidepressants and SAMe works better than taking antidepressants alone [4].

In a recent study it was shown that SAMe was just as effective as escitalopram (Lexapro®) for the treatment of depression… 36% of people responded on SAMe, compared to 34% on escitalopram (although a similar response rate of 30% occurred in people on a placebo). Depression remitted completely in 28% of people on SAMe and escitalopram, but in only 17% on a placebo [5].

St John’s Wort

St John’s Wort has undergone the most investigation as a natural treatment for depression. Overall it has been concluded that it is significantly better than a placebo for the treatment of adult depression. In comparison to antidepressant medication (SSRIs) is was concluded in a comprehensive review of all studies, that St John’s Wort was as effective but with less side effects [6]. The main problem with St John’s Wort is that it interacts with many medications such as the contraceptive pill, so caution is advised when using this supplement.

Overall the findings indicate that there are several natural options for the treatment of depression (mild-to-moderate severity). More research is required and there are other natural options available, but the findings so far are very promising.


1. Akhondzadeh, B.A. et al. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):439-42.

2. Akhondzadeh, S. et al. Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]. BMC Complement Altern Med. 2004 Sep 2;4:12

3. Lopresti, A.L. & Drummond, P.D. Hum Psychopharmacol. Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action. 2014 Nov;29(6):517-27.
4. Levkovitz Y. Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder. J Affect Disord. 2012 Feb;136(3):1174-8.

5. Mischoulon D, et al. A double-blind, randomized, placebo-controlled clinical trial of S-adenosyl-L-methionine (SAMe) versus escitalopram in major depressive disorder. J Clin Psychiatry. 2014 Apr;75(4):370-6.

6. Rahimi R, et al. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):118-27.