New research on depression, and a new look at supplements for mood and sleep disorders

At the end of 2013, there was much buzz about new studies showing that curing insomnia in people with depression might double the chance of a complete recovery from depression. The studies, financed by the National Institute of Mental Health, were welcomed as the most significant advance in treating depression since the introduction of the “selective serotonin re-uptake inhibitor” (SSRI), Prozac, twenty-five years ago. In effect, the new research findings turn conventional wisdom on its head, since they suggest that insomnia can be a main cause of depression, rather than just a symptom or a side effect, as previously assumed. If you can successfully treat a depressed person’s insomnia, according to the new view, you eliminate one of the main factors causing the depressed state.

New research findings turn conventional wisdom on its head
suggesting that insomnia can be a main cause of depression
rather than just a symptom or a side effect as previously assumed

As we followed reports on this breakthrough research on insomnia and depression, we were especially encouraged to read comments like the one from Washington DC psychiatrist James Gordon, who has advocated an integrative approach to treating depression. Here’s his letter to The New York Times: 

I welcome a new report’s finding that cognitive behavioral therapy is improving the outcome for depressed people with significant insomnia (“Sleep Therapy Seen as an Aid for Depression,” front page, Nov. 19). 

It reminds us that changes in attitude and perspective, and a therapeutic relationship, can right biological imbalances — like disordered sleep — and significantly enhance the lives of troubled people. The study also puts the therapeutic role of antidepressant medication in perspective: the depressed participants who received behavioral therapy did equally well whether or not they were taking the drugs. 

I hope that these results will encourage the National Institute of Mental Health, researchers, clinicians and all of us to expand our horizons. 

There are a number of other nonpharmacological therapies, including meditation, physical exercise, dietary change and nutritional supplementation, acupuncture and group support, that show promise for improving clinical depression and enhancing brain function.

At NYBC we have long believed that non-prescription therapies, such as supplements, are valuable alternatives for treating mood disorders and sleep disorders When the Centers for Disease Control surveyed use of antidepressant drugs in 2008, it found that one in 10 Americans was taking an antidepressant, and many had taken these drugs for years. Over a period of ten years, antidepressant use in the U.S. had shot up by 400%! So the question arises: how much of this spectacular increase represented real gains in treatment, and how much was over-prescribing? As Dr. Gordon mentions in his letter above, in some cases behavioral therapy for depression has worked just as well whether people were taking antidepressants or not—hardly a strong argument for the value of the prescription drugs.

A well-publicized 2008 report in the New England Journal of Medicine
found that pharmaceutical companies had consistently reported

only the most favorable trial outcomes for their popular antidepressants

A well-publicized 2008 report in the New England Journal of Medicine found that pharmaceutical companies had consistently reported only the most favorable trial outcomes for their popular antidepressants, passing over evidence that suggested a more limited effectiveness. Furthermore, as with many drugs, especially those used over a long period, antidepressants have side effects. Higher bone fracture risk and multiple cardiovascular risks have been identified; sexual side effects are common with antidepressants in both men and women; and withdrawal symptoms for those tapering off antidepressants include a long list of problems, such as panic attacks, insomnia, poor concentration and impaired memory.

Turning to the alternatives, we describe below supplements that NYBC has highlighted over the years for sleep and mood disorders. Note cautions about their use, but also note that some of these products may actually carry added benefits, rather than unwanted side effects.

1. Melatonin is a hormone occurring naturally in the body, but some people who have trouble sleeping have low melatonin levels. Melatonin has been used for jet lag, for adjusting sleep-wake cycles for people doing shift work on varying schedules, and for insomnia, including insomnia due to high blood pressure medications called beta-blockers. It is also used as a sleep aid when discontinuing benzodiazepines (Klonopin, Xanax, etc.) and to reduce side effects when quitting smoking.

2. Fish Oil. Epidemiologists have noted that populations that eat fish regularly have low rates of depression. And research has found that omega-3 fatty acids in fish oil supplements can be of benefit in treating depression and bipolar disorder. Fish oil can also be taken with other anti-depressants as an adjunct therapy. Doses found effective in treating depression are quite high, 3 to 9 grams per day, so be aware of potential problems related to the supplement’s blood-thinning properties. Added benefit: fish oil can help manage cholesterol, and supports cardiovascular health.

3. Deficiencies in the B Vitamins, especially B12 and folate, can result in neurologic symptoms — for example, numbness, tingling and loss of dexterity — and the deterioration of mental function, which causes symptoms such as memory loss, confusion, disorientation, depression, irrational anger and paranoia. A number of studies have shown that vitamin B12 is deficient in a large percentage of people with HIV, and the deficiency can begin early in the disease. Supplementing with a B complex protects against deficiency and supports cognitive health and mental function.

4. Vitamin D deficiency has also been linked to depressed states. Lack of the “sunshine vitamin” may be especially associated with Seasonal Affective Disorder (SAD), the “winter blues.” Vitamin D also supports bone health, and may protect against colds and flus.

5. Theanine, an amino acid found in green tea, acts as a relaxing agent by increasing levels of certain neurotransmitters (=brain chemicals that shape your mood), including serotonin, dopamine, and GABA (gamma amino butyric acid). Human studies have been limited to date, but one small study showed that theanine decreases stress responses such as elevated heart rate. Another investigation compared theanine’s calming effect to that of a standard anti-anxiety prescription drug, and found that theanine performed somewhat better. Note that NYBC stocks Theanine Serene (Source Naturals), a combination supplement that includes theanine and GABA.

6. Probiotics. Very recent research has looked into the communication between the digestive system and the brain, with a goal of understanding how gut health may influence chronic conditions, including mood disorders like depression and anxiety. For example, it has been shown that certain probiotics promote production of the calming, anti-stress neurotransmitter GABA in the body, pointing to a direct influence of probiotics on mood. Other potential links between the gastrointestinal system’s microorganisms and brain function are currently being explored.

7. L-Tryptophan and 5-HTP (5-hydroxy L-tryptophan). These closely related supplements are converted in the body to serotonin and to melatonin. (Take L-tryptophan with carbohydrates to make it effective.) Their use as antidepressants has been studied, and they have also been found to aid sleep and suppress appetite. (To minimize appetite suppression, take the supplement an hour before bedtime.)  Although L-Tryptophan and 5-HTP are close relatives, people may respond somewhat differently to them, so it may be worthwhile to try the other if the first doesn’t produce an effect An added benefit: 5-HTP may also decrease symptoms of fibromyalgia and migraine headaches.

8. In research funded by the National Institute of Mental Health, DHEA (dehydroepiandrosterone) was found to be an effective therapy for mild-to-moderate or severe midlife depression, on par with some prescription drugs. Moreover, the research showed that taking DHEA promoted both a significant lifting of depressive symptoms and an improvement in sexual functioning. Note that dosing recommendations vary for men versus women, and DHEA is not recommended for those diagnosed with prostate conditions or cancer.

9. SAMe (S-adenosyl-l-methionine) is produced naturally in the body from the amino acid methionine. Supplementing with SAMe increases concentrations of the neurotransmitters serotonin and dopamine. Several studies show SAMe having an antidepressant effect comparable to that of some prescription drugs. SAMe should be avoided in people with bipolar disorder, and should be used cautiously with other antidepressants, because the combination may push serotonin levels too high. Taking a B-complex vitamin while using SAMe can counter build-up of homocysteine, which has been linked to heart disease SAMe may also support joint health and liver function. Caution: the National Center for Complementary and Alternative Medicine has posted a warning that SAMe may increase likelihood of pneumocystis infection in immune-compromised people. Note: see also Trimethylglycine (TMG), which includes the raw materials that the body uses to manufacture SAMe. TMG is much less expensive than SAMe.

10. St. John’s Wort is a widely used herb with clinically demonstrated (multiple, well-controlled studies, mostly in Europe) anti-depressant effects for mild to moderate depression – generally without the side effects of prescription antidepressants. High doses of the herb may cause a sensitivity to light (phototoxicity), so avoid direct sunlight or sunbathing while using. Do not take St. John’s Wort with 5-HTP, serotonin re-uptake inhibitors (like Prozac), or with protease inhibitors, as it may affect beneficial liver enzymes. St. John’s Wort may also have activity against Epstein-Barr and herpes infections.

11. Finally, we’ll mention another combination supplement that NYBC has stocked: GABA Soothe (Jarrow). The GABA in this supplement is the neurotransmitter that promotes calmness coupled with mental focus. Also included is theanine (see above for a description of its anti-anxiety effects) and an extract of ashwagandha, an herb which has long been used in the Ayurvedic tradition of India to reduce fatigue and tension associated with stress.

 

supplement-header-2014
This article from the Spring 2014 edition of SUPPLEMENT: Newsletter of the New York Buyers’ Club, available for download at http://www.NewYorkBuyersClub.org

 

References:

CDC statistics on antidepressant use in the US, 2005-2008: http://www.cdc.gov/nchs/data/databriefs/db76.htm

Turner, E et al. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. New England Journal of Medicine,  2008; 358:252-260 January 17, 2008 doi: 10.1056/NEJMsa065779

Logan, A.. Omega-3 fatty acids and major depression: A primer for the mental health professional. Lipids Health Dis. 2004; 3: 25; doi:  10.1186/1476-511X-3-25

Sudden cardiac death secondary to antidepressant and antipsychotic drugs, Expert Opinion on Drug Safety, March 2008; 7(2):1081-194

Alramadhan E et al. Dietary and botanical anxiolytics Med Sci Monit. 2012 Apr;18(4):RA40-8.

Rogers PJ, Smith JE, Heatherley SV, Pleydell-Pearce CW. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl) 2008;195(4):569–77.

Kimura, K et al. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007 Jan;74(1):39-45.

National Center for Complementary and Alternative Medicine at NIH. S-Adenosyl-L-Methionine (SAMe): An Introduction Accessed at http://nccam.nih.gov/health/supplements/SAMe

Carpenter, D J. St. John’s wort and S-adenosyl methionine as “natural” alternatives to conventional antidepressants in the era of the suicidality boxed warning: what is the evidence for clinically relevant benefit? Altern Med Rev. 2011 Mar;16(1):17-39.

Foster, J A et al. Gut-brain axis: how the microbiome influences anxiety and depression Trends in Neuroscience. 2013 May;36(5):305-12. doi: 10.1016/j.tins.2013.01.005.

Rao, A V & Bested, A. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009; 1: 6 doi:  10.1186/1757-4749-1-6

“Natural mood enhancer”: Trimethylglycine (TMG)

Trimethylglycine (TMG for short) has been described as a “natural mood enhancer” by Dr Hyla Cass, a practicing physician who’s long advocated for more integrative approaches to mood disorders. That’s because TMG provides the raw materials that the body can use to manufacture S-adenosylmethionine (SAMe). SAMe, as you might know from reading other entries on this Blog, is a well-researched supplement with antidepressant effects comparable in some studies to prescription antidepressants. TMG is also a lot cheaper than SAMe! Cautions: Dr. Cass stresses the importance of being under a doctor’s supervision if using TMG while taking prescription antidepressants, since an excessive build up of the neurotransmitter serotonin is possible. Also note cautions about TMG’s potential role in bacterial growth, which has led to the recommendation not to use during an infection.

For more information on TMG, including dosage recommendations, see

http://nybcsecure.org/product_info.php?cPath=50&products_id=97

Supplements have a role in treating depression/sleep disorders

As 2013 drew to a close, there was much buzz about new studies showing that curing insomnia in people with depression might double the chance of a complete recovery from depression. The studies, financed by the National Institute of Mental Health, were welcomed as the most significant advance in treating depression since the introduction of Prozac 25 years ago. In effect, the new research findings turn conventional wisdom on its head, since they suggest that insomnia may be a main cause of depression, rather than just a symptom or a side effect, as has usually been assumed. So, if you can successfully treat a depressed person’s insomnia, you may be eliminating one of the main factors causing the depressed state.

As we followed news stories about this breakthrough research on insomnia and depression, we were especially encouraged to read comments from Washington DC psychiatrist James Gordon, who has advocated for an integrative approach to treating depression. Here’s his letter to the New York Times:

I welcome a new report’s finding that cognitive behavioral therapy is improving the outcome for depressed people with significant insomnia (“Sleep Therapy Seen as an Aid for Depression,” front page, Nov. 19).

It reminds us that changes in attitude and perspective, and a therapeutic relationship, can right biological imbalances — like disordered sleep — and significantly enhance the lives of troubled people. The study also puts the therapeutic role of antidepressant medication in perspective: the depressed participants who received behavioral therapy did equally well whether or not they were taking the drugs.

I hope that these results will encourage the National Institute of Mental Health, researchers, clinicians and all of us to expand our horizons.

There are a number of other nonpharmacological therapies — including meditation, physical exercise, dietary change and nutritional supplementation, acupuncture and group support — that show promise for improving clinical depression and enhancing brain function.

It is time to undertake authoritative studies of integrative approaches that combine these therapies, perhaps as well as behavioral therapy, in the treatment of both depression and insomnia.

JAMES S. GORDON
Washington, Nov. 19, 2013
The writer, a psychiatrist, is the author of “Unstuck: Your Guide to the Seven-Stage Journey Out of Depression.”

We at NYBC have long been interested in exploring research on supplements and mood disorders, and supplements and sleep disorders. In fact, you’ll find these categories of supplements in a single section of our catalog, at

Supplements for Mood and Sleep Disorders

Please feel free to browse this section, and learn more about supplements such as melatonin, theanine, SAMe, DHEA, and others. There is considerable research on many of these already published, and we believe they will have a role to play in a new, more integrative treatment strategy for depression.

American Psychiatric Association Task Force on supplements for major depression

The American Psychiatric Association recently commissioned a task force to study the state of “alternative and complementary” therapies for major depression. This follows widespread interest from the scientific community and a considerable accumulation of research to date. The Task Force reported in a 2010 article that focused special attention on these supplements: omega-3 fatty acids (commonly taken as fish oil supplements), St John’s Wort (the botanical Hypericum), Folic acid (a synthetic form of folate, a B vitamin found in leafy green vegetables, citrus fruits, beans, and fortified breads and cereals), and S-adenosyl-L-methionine (SAMe).

We welcome this acknowledgment by the mainstream US medical establishment that supplements have a role to play in treating a disabling condition that affects millions of people per year, and is not always easily treatable. (Only one-third of adult patients newly diagnosed with major depression achieve complete symptom relief when taking one antidepressant, so there is often an extended search for the right combination of drug and other treatment needed for remission.)

Below is a brief recap of some of the latest thinking on these key supplements for depression. Of course NYBC recommends that you use these supplements in consultation with your healthcare provider. More information on these supplements can be found by following the links to the NYBC website.

Omega-3 Fatty Acids (fish oil) recommended as a stand-alone treatment for people concerned about side effects, such as those with multiple medical conditions. It has also been combined with other antidepressants as an adjunct therapy. Fish oil’s blood-thinning property makes it problematic for doses above 3g/day. Added benefit: fish oil supports cardiovascular health.

St. John’s Wort is an herb widely studied and used, especially in Europe, for mild to moderate depression, though it hasn’t proved effective for major depression. Those taking protease inhibitors or certain other drugs should avoid St. John’s Wort because it interferes with their action.

SAMe (S-adenosyl-l-methionine). Supplementing with SAMe increases concentrations of neurotransmitters that influence mood, and multiple studies have confirmed its antidepressant effect. A dose of 400-800mg/day has been studied for mild-to-moderate depression, and 800-1600mg/day for moderate-to-severe. Studied as a stand-alone treatment, or as an adjunct treatment. Added benefit: SAMe supports joint health and liver function.

When combined with an antidepressant, folic acid supplements can improve symptoms, particularly in women. However, folic acid supplements are not a stand-alone treatment for depression. The safe upper limit is 1,000 mcg per day.

Supplements for Depression

We’ve updated our info sheet on supplements and depression–see below. See the NYBC entries for further information on DHEA; 5-HTP; SAMe; St. John’s Wort;
Fish oil (Max DHA); Tryptophan.

In recent years there’s been a lot of well-designed scientific research about the effectiveness of dietary supplements for depression. The supplements studied have ranged from the herb St. John’s Wort, which has a long tradition of use, to molecules like SAMe, L-Tryptophan, and 5-HTP, which play a role in the body’s production of neurotransmitters (such as serotonin) connected with mood and cognitive function. Other developments in depression research involve the steroid DHEA and fish oil.

DHEA (Dehydroepiandrosterone). In a study sponsored by the National Institute of Mental Health, DHEA was found to be an effective therapy for mild to moderate or severe midlife depression, on a par with some prescription drug treatments. Moreover, the NIMH research showed that taking DHEA promoted both a significant lifting of depressive symptoms and an improvement in sexual functioning. (On the other hand, inhibition of sexual function remains one of the chief troublesome side effects of prescription anti-depressants). Note that dosing recommendations vary for men versus women, and DHEA is not recommended for those diagnosed with prostate problems or cancer.

SAMe (S-adenosyl-l-methionine). First studied by Italian researchers in the 1950s, SAMe is produced naturally in the body from the amino acid methionine. Supplementing with SAMe increases concentrations of the neurotransmitters serotonin and L-dopamine, which are related to mood. Several studies show SAMe having an anti-depressant effect comparable to that of some prescription drugs. A dose of 400-800mg/day has been studied for mild to moderate depression, and 800-1600mg/day for the moderate to severe condition. As of 2007, SAMe was being compared with the prescription drug Lexapro® in a 5-year NIH-funded study. SAMe generally has fewer side effects than prescription anti-depressants. However, it should be avoided in people with bipolar disorder, and should be used cautiously with other anti-depressants, because the combination may push serotonin levels too high. Taking a B-complex vitamin while using SAMe can counter build up of homocysteine, which is associated with heart disease. (It’s best to take them separately.) SAMe also supports joint health and liver function, so may have positive effects for overall health if taken over the long term.

St. John’s Wort is a widely used herb with clinically demonstrated (multiple, well-controlled studies, mostly in Europe) anti-depressant effects for mild to moderate depression – generally without the side effects of prescription antidepressants. High doses of the herb may cause a sensitivity to light (phototoxicity), so avoid direct sunlight or sunbathing while using. Do not take St. John’s Wort with 5-HTP, serotonin re-uptake inhibitors (like Prozac), or with protease inhibitors, as it my affect beneficial liver enzymes. St. John’s Wort may also have activity against Epstein-Barr and herpes infections.

L-Tryptophan and 5-HTP (5-hydroxy L-tryptophan): These closely-related supplements are converted in the body to serotonin and to melatonin. (Specifically, L-Tryptophan converts to 5-HTP, which then converts to serotonin or melatonin.) Their use as antidepressants has been studied, and they have also been found to aid sleep and suppress appetite. (To minimize appetite suppression, try taking the supplement an hour before bedtime.) Mild gastrointestinal side effects have been reported with both. For best absorption, take with water or juice, and separately from protein-containing foods and dietary supplements. Although L-Tryptophan and 5-HTP are close relatives, people may respond somewhat differently to them. Thus, if encountering unwanted side effects or lack of effect from one, it may still be worthwhile to try the other.

The suggested dosage for 5-HTP is wide, ranging from 50 and 500 mg daily. It can be used together with other anti-depressants, in which case an effective dose could be quite low. The best approach is to start at the low end of the range and increase as needed. Like 5-HTP, L-Tryptophan has been used in combination with other anti-depressants, and has also been employed with lithium for bipolar disorder. An added benefit: 5-HTP may also decrease symptoms of fibromyalgia and migraine headaches.

Fish Oil. Epidemiological studies have suggested that populations that eat fish regularly have low rates of depression. More recently, research has found fish oil supplements (omega-3 fatty acids being the significant component) of benefit in treating depression and bipolar disorder. It’s also worth noting that fish oil can be taken with other anti-depressants as an adjunct therapy. Doses found effective in treating depression are quite high, 3 to 9 grams per day, so be aware of potential problems related to the supplement’s blood-thinning properties. Added benefit: as has been widely reported, fish oil can have a beneficial impact on cholesterol regulation and in supporting cardiovascular health.
_____________________________________________________________________________References:
REFERENCES: Christian R. Dolder, “Depression,” in Natural Products: A Case-Based Approach for Health Care Professionals, ed. Karen Shapiro, published by the American Pharmacists Association, Washington, DC (2006), pp. 97-114.
Shaheen E Lakhan and Karen F Vieira. “Nutritional therapies for mental disorders” in Nutrition Journal (2008), 7:2doi:10.1186/1475-2891-7-2. Accessed 10/7/2009 at http://www.nutritionj.com/content/7/1/2
Schmidt PJ, et al. “Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression,” Archives of General Psychiatry (February 2005): Vol. 62, No. 2, pp. 154–62.
Hyla Cass, “Prescriptions for Depression,” in Supplement Your Prescription: What Your Doctor Doesn’t Know About Nutrition. Basic Health Publications (2007), pp. 113-128.

SAMe for osteoarthritis

We were interested to see in the recently published Mayo Clinic guide to alternative medicine a fairly strong statement supporting the use of SAMe (s-adenosylmethionine) for osteoarthrititis. So we checked with what regard as one of the best online resources for such questions, the University of Maryland Medical Center. Here’s their report, updated in 2009, which basically backs up the Mayo Clinic view:

A number of well-designed clinical trials show that SAMe may reduce pain and inflammation in the joints, and researchers think it may also promote cartilage repair, although they are not clear about how or why this works. In several short-term studies (ranging 4 – 12 weeks), SAMe supplements were as effective as nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen in adults with knee, hip, or spine osteoarthritis. SAMe was as effective as these medications in lessening morning stiffness, decreasing pain, reducing swelling, improving range of motion, and increasing walking pace. Several studies also suggest that SAMe has fewer side effects than NSAIDs. Another study compared SAMe to celecoxib (Celebrex), a type of NSAID called a COX-2 inhibitor, and found that over time SAMe was as effective as celecoxib in relieving pain.

From: http://www.umm.edu/altmed/articles/s-adenosylmethionine-000324.htm

Read more at the NYBC entry for SAMe:
http://nybcsecure.org/product_info.php?cPath=57&products_id=207

SAMe helps depression

While this is not a study involving people living with HIV, there is good reason to believe that SAMe may be helpful in the depression that may arise with HIV disease.

S-Adenosyl Methionine (SAMe) Augmentation of Serotonin Reuptake Inhibitors for Antidepressant Nonresponders With Major Depressive Disorder: A Double-Blind, Randomized Clinical Trial
George I. Papakostas, M.D., David Mischoulon, M.D., Ph.D., Irene Shyu, B.A., Jonathan E. Alpert, M.D., Ph.D., and Maurizio Fava, M.D.

Objective: Despite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-adenosyl methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development.

Method: Participants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM–D).

Results: The HAM–D response and remission rates were higher for patients treated with adjunctive SAMe (36.1% and 25.8%, respectively) than adjunctive placebo (17.6% versus 11.7%, respectively). The number needed to treat for response and remission was approximately one in six and one in seven, respectively. There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason (20.6% versus 29.5%, respectively), due to adverse events (5.1% versus 8.8%, respectively), or due to inefficacy (5.1% versus 11.7%, respectively).

Conclusions: These preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication.

Am J Psychiatrya 2010; 167:942-948
(published online July 1, 2010; doi: 10.1176/appi.ajp.2009.09081198)
© 2010 American Psychiatric Association