LAS VEGAS – In the clinical opinion of Dr. David Mischoulon, certain complementary and alternative medicine therapies such as St. John’s wort and omega-3 fatty acids may benefit some patients with mild to moderate depression.
At the annual psychopharmacology update held by the Nevada Psychiatric Association, Dr. Mischoulon said more than 70% of people worldwide have used some form of complementary therapy at some point in their lives.
Dr. David Mischoulon
“They often don’t have as many severe side effects as synthetic medication,” he said. “However, the body of knowledge about these therapies is limited. We don’t have as much systematic research or rigorous clinical trials of these treatments, so as clinicians who are put in the position of making recommendations, we don’t know how effective these treatments are compared to placebo or standard therapies.”
Then there’s the common public misconception that just because something is “natural” or can be bought over the counter, it’s automatically safe. “That isn’t the case,” said Dr. Mischoulon, director of research for the Depression Clinical & Research Program at Massachusetts General Hospital, Boston. “There have been a number of cases of adverse reactions when these natural products are taken along with standard medications. Another problem is that these products have different manufacturers that may use different techniques for preparing them, so the purity may vary. Also, most of these natural therapies are not covered by health insurance.”
He highlighted the following natural agents that are used to treat depression:
• St. John’s wort. He described this as “probably the most popular herbal remedy for depression,” with about 40 published trials to date: 26 placebo controlled, and 14 with standard antidepressant comparators. Studies have been limited by short duration, he said, and appear to favor its use for mild to moderate depression. Hypericin, hyperforin, and adhyperforin contained in St. John’s wort are thought to be the key ingredients.
“It’s thought that they might interact with cytokine production through the [hypothalamic-pituitary-adrenal] axis,” Dr. Mischoulon explained. “Consequently, this interaction could result in decreased cortisol production, which may attenuate depression.”
Side effects from using St. John’s wort are similar to those found with antidepressants, including dry mouth, dizziness, and constipation. “It’s generally thought to be safe,” he said. Phototoxicity can be an issue for some, and using St. John’s wort with selective serotonin reuptake inhibitors is not advised because of the potential for developing serotonin syndrome. Several cases of colic, drowsiness, and lethargy have been reported in breastfed infants whose mothers were taking St. John’s wort, and low birth weight from in utero exposure has been demonstrated in animal studies.
Dr. Mischoulon noted that St. John’s wort induces CYP3A4 expression, which reduces the therapeutic activity of numerous drugs, including warfarin, cyclosporine, oral contraceptives, digoxin, zolpidem, and olanzapine. Caution is required in HIV-positive, cancer, and organ transplant patients. “Overall the results for St. John’s wort as reported in the literature are encouraging but with some inconsistencies,” he said. “The best individuals for St. John’s wort are individuals with mild to moderate depression, and less so individuals with more severe depression.” He recommends a dose of 900-1,200 mg per day, “but do remember that different preparations of St. John’s wort may vary in potency, so in some cases you may need to go to a higher dose.”
• S-adenosylmethionine (SAMe). Present in all living beings, this substance is required for neurotransmitter synthesis, and depends on folate and B12 levels to function optimally. According to Dr. Mischoulon, SAMe has been evaluated in more than 45 randomized clinical trials involving various routes of administration in doses of 200-1,600 mg/day. In eight placebo-controlled studies, SAMe was superior to placebo in six trials and had similar efficacy in the other two. In eight studies that compared SAMe with tricyclic antidepressants, six demonstrated similar efficacy with TCAs and one demonstrated benefit of SAMe over imipramine. The other trial, led by Dr. Mischoulon, compared SAMe with escitalopram and placebo in 189 patients in three treatment arms over a course of 12 weeks (J Clin Psychiatry. 2014;75[4]:370-6). The researchers observed a benefit in all treatment arms (a drop of 5-6 points on the 17-item Hamilton Depression Rating Scale [HDRS-17]), but no statistically significant differences were found between the groups. The most common side effect in the SAMe arm was related to gastrointestinal issues, mainly stomach discomfort and diarrhea.
One of the appeals of SAMe is that it’s safe to use in combination with other medicines, including tricyclic antidepressants (TCAs). “It may even boost and accelerate the effect of TCAs,” Dr. Mischoulon said. “It’s also been combined successfully with SSRIs and” [selective serotonin norepinephrine inhibitors]. In one study of 30 patients who were partial or nonresponders to SSRIs, augmentation with SAMe led to a response rate of 50% and a remission rate of 43% at 6 weeks (J Clin Psychopharmacol. 2004;24[6]:661-4), “which is very encouraging for our treatment-resistant population,” he said. In a 2010 trial, researchers investigated augmentation with SAMe 800 mg b.i.d. or placebo for 6 weeks in 73 serotonin reuptake inhibitor nonresponders with major depressive disorder (Am J Psychiatry 2010;167[8]:942-8). The response rate was 36.1% in the SAMe group, compared with 17.6% in the placebo group.