Jason Biscamp Herbal and Supplemental therapies for the treatment of Depression Fifteen to twenty percent of the American public will be depressed at some point in their lives. Extreme guilt, inability to concentrate, inability to sleep, and anhedonia take an enormous toll on the life of the person who is depressed. Countless days of work and school are missed each year due to depression. There are several classes of conventional pharmaceuticals used to treat depression: Tricyclic antidepressants and Selective Serotonin Reuptake Inhibitors are the two most commonly used. However, some patients are reluctant to take these medications for a variety of reasons. One is the stigma of taking a psychiatric medication. The other is the side effect profiles of these medications ranging from nausea, sweating, dry mouth, tachycardia, arrythmias, and erectile dysfunction. It is no wonder that patients turn to herbal remedies and supplements, but do they work? St. John’s Wort is the first herb we will look at. St. John’s Wort was known to be used in ancient times for diseases other than depression. However, it has been found to have some active compounds that increase the level of the neurotransmitters dopamine, norepinephrine and serotonin – similar to how pharmaceutical antidepressants work. In an article that was a meta-analysis of twelve studies of St. John’s Wort, seven studies found St. John’s Wort to be superior to placebo. Four studies found St. John’s Wort to be as efficacious as another pharmaceutical drug1. In a study of six through sixteen year olds diagnosed with major depressive disorder, St. John’s Wort was administered for eight weeks. Participants in the study were evaluated weekly and the researchers found that scores on a common test used to evaluate depression in the pediatric population trended downward each week. At the end of the study, ninety-three percent of the participants chose to keep taking St. John’s Wort2. St. John’s Wort has relatively few side effects with the most common being stomach upset followed by fatigue, restlessness, anxiety, dry mouth, and skin rash3. St. John’s Wort does interact with medicines metabolized by the p450 3A4 by inducing that enzyme, although this effect is not seen until about ten days of administration. The Cyp 3A4 system is responsible for metabolizing more than half of the drugs currently sold4. In conclusion, this drug is probably safe and effective for the treatment of depression as long as the patient is not taking any of the other drugs with which it interacts.
S-adenosylmethionine (SAMe) is another supplement which is marketed as a treatment for depression as well as arthritis. SAMe is an enzyme found naturally in the body that is important in the synthesis of the neurotransmitters serotonin and dopamine, hormones, and other endogenous chemicals such as phosphotidylcholine5. One review article cites six studies that say SAMe was superior to placebo, six more comparison studies that claim SAMe is as good as or better than tricyclic antidepressants. The same article also cites studies that show patients treated with SAMe alone or combined with tricyclic antidepressants combined had faster remission of symptoms than those treated with tricyclics alone6. A large, multi-center study was performed to compare intramuscular SAMe versus imipramine and oral SAMe versus imipramine in patients with major depressive disorder. This study was double-blinded and had five hundred seventy-one participants. The study found both intramuscular and oral SAMe to be at least as effective as imipramine as determined by comparing baseline versus treatment Hamilton Depression Rating Scales. The study also found SAMe in both forms to be superior to imipramine in terms of patient tolerance of side effects7. The main side effect of SAMe is gastrointestinal upset followed by dry mouth and constipation. One study of SAMe for osteoarthritis followed 108 patients who were given 400mg daily for two years reported no adverse effects8. It has no known interactions with medications other than a theoretical risk when given with tricyclics. However, the cost of SAMe can easily run in the two hundred dollar range for the commonly recommended dosages. In summary, this drug is probably safe and probably effective as a treatment for depression and should be considered in patients who are reluctant to take conventional antidepressant medications. The next supplement to look at is 5-hydroxytryptophan (5-HTP.) 5-HTP is another chemical normally found in the body that is used as a precursor to serotonin. It has been marketed as a treatment for depression as well as insomnia and fibromyalgia. A meta-analysis of 5-HTP was performed on one hundred eight studies. The authors of this study found that of the initial one hundred eight studies, only two studies with a total number of sixty-four patients were actually well-done studies. The others were excluded because they did not use 5-HTP as monotherapy or were treating illnesses other than unipolar depression or did not compare to placebo. Of the two studies that made the cut, they found only that 5-HTP might be as good as placebo. Side effects experienced by these patients include dizziness and gastrointestinal upset 9. 5HTP has also been implicated to occasionally cause eosinophilia myalgia syndrome – a potentially fatal disease, although this is thought to be due to a
contaminant in the manufacturing process. This supplement is also known to have interactions with several medications including most of the antidepressants and anti-parkinsonian drugs. This supplement has never been shown to be better than any antidepressant medication and due to the possible toxic effects should probably not be recommended for patients. Ginkgo biloba is an herb that is mostly marketed for treating symptoms of dementia as well as boosting “brain power” or “memory” power. Ginkgo has not been well studied as a treatment for depression. One study enrolled twenty seven patients to determine if gingko could be used to prevent seasonal affective disorder, or seasonal depression. Fifteen patients were given gingko biloba extract and twelve patients received placebo and were followed for two years. The study concluded that there was no significant difference between those taking placebo and those taking gingko in preventing seasonal depression requiring other treatments. The authors did note in their study that with such a small sample size, there was an increased risk of a Type 2 statistical error10. However, another study looked at healthy patients’ subjective mental health and quality of life after four weeks of taking gingko biloba or placebo. The study was again relatively small with only sixty-six participants, but they did find that those who took the gingko reported higher assessments of their own mental health and quality of life and performed better on cognitive tests than those taking placebo 11. The most common side effects seen with Gingko biloba therapy is stomach upset, headache, and nausea. More serious but less frequently occurring are bleeding tendencies and insulin resistance. Gingko has several known drug interactions. It interferes with the action of most diabetes medications. Coadministration with blood thinners leads to a higher incidence of internal bleeding. Gingko can also be used to treat the sexual side effects common with most SSRI’s. In summary, there is not enough evidence to say that Gingko can or can not treat depression. It may have value in treating symptoms of depression such as inability to concentrate and feelings of low quality of life. This herb might be tried on a patient who refuses to take a conventional antidepressant, but should probably not be used as first-line or monotherapy for depression. Lavender has traditionally been used to treat depression and anxiety as it is thought to be a mood enhancer and have calming effects. Lavender can be administered in many ways including tincture, inhalation, and as a tea. One study of lavender for depression broke patients into three groups. Group A was treated with a tincture of lavender plus a placebo pill. Group B was treated with a
placebo tincture and one hundred milligrams of imipramine. Group C was treated with tincture of lavender and one hundred milligrams of imipramine per day. Results were measured by comparing weekly Hamilton Depression Scale scores. The group that received the tincture of lavendar and placebo imipramine saw some remission of symptoms. The group that received imipramine and placebo tincture did better than the previous group. However, the group that received both the tincture of lavendar and the imipramine did much better than the other two groups12. Unfortunately, there were only about 14 people in each group so these results are not too significant. The only significant side effect of Lavendar is constipation. There are no known drug interactions. Lavendar is probably a safe treatment for depression. However, effectiveness is a little less certain so should probably not be used as first-line or monotherapy, but as an adjunct with something else. Integration of all these methods into the standard of care for treatment of depression is feasible, but only after there are more quality studies performed on them. Some doctors feel that placebo effect is a good enough reason to recommend a therapy or to “give permission” to a patient to use them. Other doctors will never recommend or endorse these therapies until they pass rigorous clinical testing. The likelihood of these treatments ever becoming rigorously tested is low because there is not a lot of money to be made from most of these therapies. Does this mean we should let these possibly safe and effective remedies fall by the wayside? I would suggest the slow integration of these elements into clinical practice. Tell the mildly depressed patient to try gingko along with the Lexapro you will send him out the door with. In a more seriously depressed patient who can afford it, recommend she try some SAMe. Of course, this is after they are told that the evidence really is not there to support those recommendations. Perhaps if physicians can generate enough case studies someone will get excited enough to do a large multicenter study of the kind to definitively answer the questions of do these therapies work.
References 1. Gupta RK, Moller HJ. St. John's Wort. An option for the primary care treatment of depressive patients? Eur Arch Psychiatry Clin Neurosci. 2003 Jun;253(3):1408. 2. Findling RL, McNamara NK, O'Riordan MA, Reed MD, Demeter CA, Branicky LA, Blumer JL. An open-label pilot study of St. John's wort in juvenile depression. J Am Acad Child Adolesc Psychiatry. 2003 Aug;42(8):908-14. 3. Hammerness P, Basch E, Ulbricht C, Barrette EP, Foppa I, Basch S, Bent S, et al. St John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics. 2003 Jul-Aug;44(4):271-82. 4. Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003 Sep 17;290(11):1500-4. 5. Fetrow CW, Avila JR. Efficacy of the dietary supplement S-adenosyl-Lmethionine. Ann Pharmacother. 2001 Nov;35(11):1414-25. 6. Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr 2002;76(suppl):1158S–61S. 7. Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr. 2002 Nov;76(5):1172S-6S. 8. Nguyen M, Gregan A. S-adenosylmethionine and depression. Aust Fam Physician. 2002 Apr;31(4):339-43. 9. Shaw K, Turner J, Del Mar C. Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis. Aust N Z J Psychiatry. 2002 Aug;36(4):488-91.
10. Lingaerde O, Foreland AR, Magnusson A. Can winter depression be prevented by Ginkgo biloba extract? A placebo-controlled trial. Acta Psychiatr Scand. 1999 Jul;100(1):62-6. 11. Cieza A, Maier P, Poppel E. Effects of Ginkgo biloba on mental functioning in healthy volunteers. Arch Med Res. 2003 Sep-Oct;34(5):373-81. 12. Akhondzadeh S, Kashani L, Fotouhi A, Jarvandi S, Mobaseri M, Moin M, et al. Comparison of Lavandula angustifolia Mill. tincture and imipramine in the treatment of mild to moderate depression: a double-blind, randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Feb;27(1):123-7.