|Amino Acid / Protein|| Tyrosine
| ||Particular precursors such as tyrosine, which increases dopamine and noradrenaline, show beneficial results in the treatment of mild depression.|
Tryptophan / 5 HTP
| ||Tryptophan is a precursor to serotonin, a neurotransmitter that is frequently imbalanced in cases of depression. Conventional antidepressants work to increase neurotransmitter levels by blocking their breakdown. Depression associated with menstrual cycles and postpartum depression sometimes respond very well to tryptophan supplementation. Postpartum women usually have high estrogen levels and it has been found that high estrogen levels increase the conversion of tryptophan to niacin. Progesterone and hydrocortisone decrease its conversion. Women on birth control pills, when given vitamin B6 and tryptophan, generally tend to metabolize tryptophan more normally.|
The therapeutic efficacy of tryptophan and tyrosine in the treatment of depression has been inconsistent. According to this review article, studies have shown that two subgroups of depressed patients can be delineated. The first subgroup (Group A) has low urinary levels of the norepinephrine metabolite MHPG (3-methoxy-4-hydroxyphenethylene glycol). This group fails to respond to amitriptyline, but shows a favorable response to desipramine or imipramine (which tend to raise norepinephrine levels rather than serotonin). They also exhibit mood elevation after receiving dextroamphetamine. The second group (Group B) has normal or high urinary MHPG levels, fails to respond to imipramine, but responds to amitriptyline (which tends to raise brain levels of serotonin, rather than dopamine or norepinephrine). These patients experience no mood elevation after dextroamphetamine. Group A would be expected to respond to L-tyrosine (a norepinephrine precursor) and group B should respond to L-tryptophan (a serotonin precursor). The biochemical separation of these subgroups may increase the therapeutic predictability of both L-tryptophan and L-tyrosine.
Comment: In my experience, L-tryptophan is effective against depression more often than is L-tyrosine. A careful history, however, may help to identify those cases in which L-tyrosine would be the appropriate amino acid to prescribe. I typically ask depressed patients what medications they have received and which ones have been helpful; I also ask whether they have taken amphetamines and how they have responded to them. It appears, as Buist has suggested, that the information obtained from those questions can help predict who will respond to which amino acid.
Buist RA. The therapeutic predictability of tryptophan and tyrosine in the treatment of depression. Int Clin Nutr Rev 1983;3(2):1-3.
| ||Phenylalanine can affect depression via three separate pathways.|
A number of double-blind clinical trials have demonstrated that dosages of DLPA, the form commonly found in supplements, at doses as low as 150mg per day is effective in the treatment of some forms of depression.
- D-phenylalanine (DPA) exerts antidepressant activity due to its metabolism to phenylethylamine (PEA).
- DPA inhibits the breakdown of the body's endogenous opiates thus producing a state of euphoria.
- Phenylalanine is an important precursor for the production of noradrenaline and adrenaline thus increasing the body's ability to cope with stress.
| ||Glutamine supplementation has been proven to help decrease depression and reduce anxiety.|
Fish Oil / Krill
St John's Wort (Hypericum perforatum)
| ||St. John’s Wort has been shown to have a 60% to 70% response rate in adult patients with mild-to-moderate depression. A 2001 study found St. John's Wort (300mg extract per day) effective in children with mild to moderate depression also. Ratings of "good" or "excellent" were found by physicians to be 72% after 2 weeks, 97% after 4 weeks and 100% after 6 weeks. The ratings by parents were 65% after 2 weeks, 93% after 4 weeks and 98% at 6 weeks. The medication was tolerated well. [Phytother. Res 2001; 15: pp.367-70]|
A large trial compared St. John's wort extract with sertraline (Zoloft) and placebo in adults with depression. The trial found that neither St. John's wort nor sertraline were more effective than placebo in treating major depression. Most successful trials with St. John's wort have focused on persons with milder forms of depression. St. John's wort should be used primarily in mild to moderate depression as well as dysthymia. [JAMA 2002;287: pp.1807-14]
Rarely, with high doses, there may be temporary withdrawal symptoms when St. John's Wort is stopped suddenly. [Ann Pharmacother 2003;37(1): p.151]
A combination product called Amoryn contains St. John's Wort, 5HTP, and small amounts of B6, B12 and folic acid.
Green / Oolong / BlackTea (Camellia sinensis)
| ||Previous studies have reported that green tea exerts a variety of beneficial effects on stress and inflammation, Kaijun Niu, from the Tohoku University Graduate School of Biomedical Engineering (Japan), and colleagues investigated the relationship between green tea consumption and depressive symptoms. Studying a group of 1,058 community living elderly Japanese individuals, ages 70 and over, the researchers surveyed green tea consumption and evaluated depressive symptoms via the Geriatric Depression Scale. They found that those study subjects who drank four or more cups of green tea daily were 44% less likely to have symptoms of depression (as compared to subjects who drank one or less cups). The team speculates that the amino acid theanine, present in green tea, which has a calming effect on the brain, may contribute to the beneficial effect seen on depression in this study.|
| ||Daily use of marijuana was associated with a 5-fold increased risk for later developing depression and anxiety among|
adolescent females in a study of 1,601 Australian students aged 14-15 years at baseline who were followed for seven years. Weekly or more frequent marijuana use was associated with a 2-fold increased risk. Depression and anxiety in
teenagers was not predictive of later cannabis use. [BMJ 2002;325(7374): pp.1195-8]
High Carbohydrate Diet
| ||A carbohydrate-rich diet helps the body produce serotonin - the "happy" hormone. Special serotonin foods include oats, whole wheat, bananas and other carbohydrate-rich foods.|
Specific Carbohydrate / GAPS Diet
Artificial Sweetener Avoidance
| ||Due to the purported L-tryptophan content of pumpkin seeds, their use has been suggested to help treat depression. Further research is needed before pumpkin seeds should be considered for this purpose.|
Conventional Drugs / Information
| ||Dosage problems with antidepressants.|
Doctors follow the guidelines in the drug company-written PDR. The PDR still advises 75 mg initially for Elavil® (amitriptyline), yet 10 mg or 25 mg is frequently enough for mild depressions or pain syndromes. Effexor® is recommended at 75 mg, but 37.5 mg or 50 mg often is enough initially. Zoloft® is recommended at 50 mg, but 25 mg works well for many mild depressions. Serzone is recommended at 100 mg twice-daily, but 50 mg once or twice daily is usually plenty initially.
Similar strategies apply to Paxil®, Wellbutrin®, Celexa®, Norpramin®, Pamelor®, imipramine, doxepin and just about every other antidepressant. "The sales representatives for most antidepressants are now giving out sample packs starting with half-strength doses," Dr. Anthony Weisenberger, a top psychopharmacologist, recently told me. "They lose so many sales because patients get side effects and quit treatment, the drug companies have finally caught on that the dose makes a big difference."
Why is this happening with drug after drug? One reason is that the standard doses of antidepressants are based on studies of major depression-a severe disorder that requires strong treatment. In contrast, the great majority of office patients with depression have mild disorders. Yet, no distinction is made about treating mild and severe disorders in the dosage guidelines of most antidepressants, so doctors prescribe the same doses to everyone.
Antidepressive drug use does seem to make a great difference in the lives of many who take them. To make an accurate diagnosis, for example to distinquish between depression and bipolar disorder, may require a doctor who specializes in this kind of work. Even with a skilled doctor, it may take a trial with several different medications before finding the one or combination of drugs that is right for you. However, the following article indicates that this may not be the case for everyone.
Antidepressants Proven to Work Only Slightly Better Than Placebo! (Excerpted from an article by Dr. Irving Kirsch, M.D.)
Although antidepressant medication is widely regarded as effective, a recent meta-analysis of published clinical trials indicates that 75% of the response to antidepressants is duplicated by placebo.
The authors analyzed the efficacy data submitted to the FDA for the six most widely prescribed antidepressants approved between 1987 and 1999: Prozac , Paxil, Zoloft , Effexor , Serzone, and Celexa. The FDA data constitutes the basis on which these medications were approved. Approval of these medications implies that the data is strong enough and reliable enough to warrant approval. To the extent that this data is flawed, the medications should not have been approved.
In order to generalize the findings of the clinical trial to a larger patient population, FDA reviewers sought a completion rate of 70% or better for these typically 6-week trials. Only 4 of 45 trials, however, reached this objective.
In clinical trials, the effect of the active drug is assumed to be the difference between the drug response and the placebo response. The data submitted to the FDA revealed a small but significant difference between antidepressant drug and inert placebo. This difference may be a true pharmacological effect, or it may be an artifact associated with the breaking of blind by clinical trial patients and the psychiatrists who were rating the severity of their conditions.
In any case, the difference was relatively small and its clinical significance was dubious. If there is a powerful antidepressant effect, then it is being masked by a nonadditive placebo effect. Conversely, if the drug effect is as small as it appears when drug/placebo differences are estimated, then there may be little justification for the clinical use of these medications.
The problem, then, would be to find an alternative, as the clinical response to both drug and placebo is substantial. Placebo treatment has the advantage of eliciting fewer side effects. However, the deception that is inherent in clinical administration of placebos inhibits their use. Thus, the development of nondeceptive methods of eliciting the placebo effect would be of great importance. [Prevention & Treatment Volume 5, Article 23, July 15, 2002]
March 22, 2004 — The U.S. Food and Drug Administration (FDA) has asked manufacturers of the several antidepressant drugs to include in their labeling a warning statement that recommends close observation of adult and pediatric patients treated with their agents for worsening depression or the emergence of suicidality
The antidepressant drugs are fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro), buproprion (Wellbutrin), venlafaxine (Effexor), nefazodone (Serzone), and mirtazapine (Remeron).
Several of these drugs are approved for the treatment of obsessive-compulsive disorder in pediatric patients (sertraline, fluoxetine, fluvoxamine). Only fluoxetine is approved for use in children with major depressive disorder. None of these drugs are approved as monotherapy in treating bipolar depression, either in adults or children, and fluvoxamine is not approved as an antidepressant in the U.S.
The FDA has been closely reviewing the results of antidepressant studies in children since June 2003, after an initial report appeared to suggest increased risk of suicidal thoughts and actions in the pediatric population, according to today's advisory.
Although it is unclear whether antidepressants contribute to the emergence of suicidal thinking and behavior, these interim actions are intended to draw more attention to the need for careful monitoring of patients being treated with these drugs, especially at the beginning of therapy and during dose changes.
Discontinuation of medication may be appropriate in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms. Therapy changes should be made under the guidance of a physician, as certain medications should be tapered rather than stopped abruptly.
| ||Researchers found that walking for 30 minutes each day quickly improved depressive symptoms faster than antidepressant drugs typically do. Another study compared exercise with antidepressants among older adults and found that physical activity was the more effective depression-fighter. [British Journal of Sports Medicine April 2001;35: pp.114-117]|
Previous studies have suggested that exercise is a potent mood-booster, and some research indicates that for some patients regular activity may be a better depression treatment than psychotherapy or medication. Exactly why is unclear, but exercise does influence certain mood-related hormones. And it is also believed to enhance people's sense of control over their lives.
The main conclusion to draw from studies conducted is that the practice of exercise shows a negative correlation with depression - in other words, the more you exercise, the less depressed you feel. Interestingly, any kind of exercise relieves the symptoms of depression.
Research has shown that listening to music while exercising not only improves mood, but may also boost cognitive levels. An example of this was seen in higher scores among cardiac rehabilitation patients on verbal fluency tests. The study looked at the effects of music combined with short-term exercise and found that people diagnosed with coronary artery disease had enhanced brainpower after listening to music while exercising. The study also had the participants fill out a 30-item checklist, which included adjectives to describe the patient’s current mood, before and after exercising as a way to assess their anxiety and depression levels. The study concluded that participants claimed they felt better both emotionally and mentally after exercising regardless if they listened to music or not. However, signs of improvement in the verbal fluency areas were more than doubled after listening to music compared to that of the non-music session. [EurekAlert! March 23, 2004]
More and more researchers and physicians are coming to the conclusion that exercise can be as effective as antidepressants in reducing the symptoms of major depression.
Research on the subject has demonstrated that:
*10 months of regular, moderate exercise outperformed a leading antidepressant (Zoloft) in easing symptoms in young adults
*30-minute aerobic workouts done three to five times a week cut depressive symptoms by 50% in young adults [Yahoo News November 6, 2005]
| ||DHEA is a plentiful adrenal steroid hormone whose quantity decreases with age and may have significant psychiatric effects. In one study, six middle-aged and elderly patients with major depression and low plasma DHEA or DHEA-S levels were openly administered DHEA (30-90mg per day for 4 weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings as well as aspects of memory performance significantly improved. |
One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. Improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. [Biol Psychiatry, 1997 Feb; 41:3, pp.311-8]
Another study evaluated the efficacy of very high doses of DHEA (450mg) in the treatment of midlife-onset dysthymia. In 15 patients who completed the study, a robust effect of DHEA on mood was observed compared with placebos. 60% of the patients responded to DHEA at the end of the 6-week treatment period compared with 20% on placebo. A significant response was seen after 3 weeks of treatment on 90mg per day. The symptoms that improved most significantly were anhedonia (failure to experience pleasure), loss of energy, lack of motivation, emotional "numbness", sadness, inability to cope, and worry. [Biol Psychiatry 1999 Jun 15; 45(12): pp.1533-41]
In a study conducted by S. S. C. Yen and associates at the University of California, San Diego, researchers found that 50mg a day of DHEA administered for 6-months restored levels of DHEA in both men and women. This DHEA replacement was associated with an increase in perceived physical and psychological well-being for both men (67%) and women (84%).
Another study at UCSD was conducted in which researchers considered the association between levels of DHEA and depression. Nine different hormones (including DHEA) were measured in 699 older women. Out of all of these hormones, only low levels of DHEA were linked with depression.
In studies conducted at Cambridge University in England, researchers discovered that children with major depression have abnormally low levels of DHEA accompanied by abnormally high levels of cortisol.
University of California San Francisco At the University of California, San Francisco, DHEA was given to people with depression to determine its antidepressant effects. After 6 weeks, psychological tests indicated that about half the participants responded to DHEA therapy, with an overall enhancement of mood scores by over 30%.
In another study conducted by the Department of Psychiatry at UCSF, DHEA was administered to six middle-aged and elderly patients with major depression. In patients who received extended treatment with DHEA for six months, depression ratings improved 48-72%.
In a study conducted by researchers at the National Institute of Mental Health, middle-aged people with dysthymia (a chronic, low-grade depression) were given 90 mg of DHEA a day for 3 weeks. This study concluded that this amount significantly alleviated the participants' depression.
DHEA is the only hormone besides cortisol and serotonin that has consistently been linked to depression. But unlike cortisol, where high levels increase depression – high levels of DHEA actually alleviate depression.
Researchers have different theories about how DHEA alleviates depression. DHEA and can cross the blood-brain barrier and interact with the brain directly. DHEA can affect serotonin, GABA receptors, and other brain factors. It might modulate the serotonin-signaling pathway. In addition, DHEA is the precursor for estrogen and testosterone, which also enhance mood.
DHEA also has antistress effects that may be part of its antidepressant action. Research shows that cortisol, the stress hormone, is elevated in major depression. DHEA counteracts cortisol. Calmness is also associated with higher levels of DHEA.
| ||On the basis of theoretical ideas about how melatonin works, some authorities specifically recommend against using it for depression, schizophrenia, autoimmune diseases and other serious illnesses, and in pregnant or nursing women.|
Some studies showing melatonin to be an effective treatment for depression were flawed. Melatonin is unlikely to produce significant positive effects in the treatment of depression in most patients, especially if the patient is not already melatonin-deficient. Badly timed use of melatonin can worsen depression. However, some patients with SAD (seasonal affective disorder, a form of depression associated with the shortening of the days in autumn and winter) have been shown to have disrupted melatonin cycles, and have been treated effectively with light therapy.
Test Amino Acid Profile
| ||Amino acid profiles done on blood can reveal imbalances seen in a variety of disorders including depression. Low tyrosine or phenylalanine levels can result in abnormal levels of mood-regulating chemicals in the brain, such as dopamine and catecholamines. Low tyrosine levels can also create subnormal levels of thyroid hormone - a well-known cause of depression. |
Methionine is the precursor of SAMe which is needed for proper functioning of catecholamines and may be low in patients with depression.
Tryptophan is the body's source material for producing the hormones serotonin and melatonin, which also influence sleep patterns and mood. Depletion of tryptophan can cause an increase in depressed mood states; lower tryptophan levels have been correlated with a higher depression score even in patients who were already under treatment with anti-depressant drugs. [Arch Gen Psychiatry 1990;47(5): pp.411-18]
Test Essential Fatty Acid Profile
| ||Because of its nerve and muscle support, magnesium may also be helpful for depression.|
| ||Dysthymic disorder is a relatively common illness that is often treated with antidepressants. Compared with the study of major depression, there has been little systematic study of potentiation strategies for antidepressant-refractory dysthymic disorder. METHOD: Following a patient's report of dramatic response to the addition of chromium supplementation to sertraline pharmacotherapy for dysthymic disorder (DSM-IV), the authors initiated a series of single-blind and open-label trials of chromium picolinate or chromium polynicotinate in the treatment of antidepressant-refractory dysthymic disorder. RESULTS: In a series of 5 patients, chromium supplementation led to remission of dysthymic symptoms. Single-blind substitution of other dietary supplements in each of the patients demonstrated specificity of response to chromium supplementation. CONCLUSION: Preliminary observations suggest that chromium may potentiate antidepressant pharmacotherapy for dysthymic disorder. Controlled studies are indicated to test the validity of these initial observations. [J Clin Psychiatry. 1999 Apr;60(4): pp.237-40]|
In a separate study, fifteen patients (aged 18-65 years) with major depression, atypical subtype, who had been off of psychotropic medication for 7-30 days, were randomly assigned to receive, in double-blind fashion, in a 2:1 ratio, chromium picolinate (n = 10) or placebo (n = 5) for eight weeks. The dose was 400 mcg/day for the first two weeks, then 600 mcg/day, of elemental chromium (the dose was clarified in personal correspondence, Connor KM, 3/19/03). A response to treatment was defined as a decrease of at least 66% on a modified version of the Hamilton Depression Scale (HAM-D), along with a marked improvement in the Clinical Global Impressions of Improvement Scale (CGI-I; i.e., a score of 1).
Remission was defined as a final HAM-D score of less than 8. The response rates were 70% (7 of 10) in the chromium group and 0% (0 of 5) in the placebo group (p = 0.02). The remission rates were 60% in the chromium group and 0% (0 of 5) in the placebo group (p = 0.04). Compared with baseline, the mean HAM-D score decreased (improved) by 59% in the chromium group and by 36% in the placebo group (p = 0.11 for difference between groups).
Comment: Atypical depression constitutes more than 20% of all cases of depression in a typical clinic population. It is characterized by mood reactivity, increased appetite and weight gain, excessive sleepiness, leaden paralysis, and sensitivity to interpersonal rejection. Atypical depression is associated with greater chronicity and disability and more suicidal ideation than are other forms of depression. Conventional treatment consists primarily of monoamine oxidase inhibitors. Although it is a more serious condition than dysthymia (described above), atypical depression is similar to it in some ways, and might therefore conceivably be related to blood-glucose dysregulation. The beneficial effect of chromium picolinate in the treatment of atypical depression may be related to its ability to improve glucose metabolism. Another study has shown that chromium picolinate supplementation causes postsynaptic downregulation of 5HT2A (serotonergic) receptors, an effect which might also account for its antidepressant activity. [Davidson JRT, et al. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53:261-264.]
Lithium (low dose)
| ||In some cases, lithium (as a drug) is even a successful treatment for those with unipolar depression, or those who have never had a manic episode. Individuals who respond to lithium for depression are often those who have not responded to tricyclic antidepressants after several weeks of treatment. When given lithium in addition to their antidepressants, some of these people have shown significant improvement. |
A limited amount of testimonial evidence exists in support of the use of lithium orotate (150mg per day) in this condition. There is no study support that we are aware of regarding the use of this OTC product for depression.
Based on its general neuroprotective effect, researchers have suggested that "the use of lithium as a neurotrophic/neuroprotective agent should be considered in the long term treatment of mood disorders, irrespective of the 'primary' treatment modality being used for the condition." Translation: Lithium should be used along with any patent medicine being used for depression, anxiety, or any other "mood-altering" reason, since it will protect brain cells against their unwanted toxic effects. The researchers didn't say so, but I will: Any list of "mood altering substances" should include alcohol, tobacco, caffeine, "uppers," "downers," and-for those who do inhale-marijuana. Harmless as some of them might seem, these substances can cause brain damage with medium to long-term abuse. [taken from an article by Jonathan V. Wright, MD]
EPA (eicosapentanoic acid)
| ||There is an increasing body of evidence that indicates that fish oils, in particular those with high EPA to DHA ratios, have a major role to play in helping people maintain good mental health and to avoid mood swings and mild depression. Currently the only available source of EPA without equal amounts of DHA being present is "EPA rich" fish oil.|
Ethyl-eicosapentaenoate (ethyl-EPA - 1gm per day), in addition to conventional antidepressant medication, improved measures of depression in a study of 70 patients with persistant depression despite ongoing treatment with conventional antidepressant drugs. Higher doses had no effect on measures of depression. [Arch Gen Psychiatry 2002;59(10): pp.913-9]
| ||DMAE reduces apathy and increases motivation in persons afflicted with depression.|
TMG (Tri-methyl-glycine) / SAMe
| ||The compound 5-adenosylmethionine (SAMe), potentially produced through the demethylation of TMG, has been shown to alleviate depression.|
Six weeks of oral SAMe at 1600mg per day improved depression scores similarly to oral imipramine at 150mg per day in a comparison study of 281 patients with major depression. Fewer adverse effects were observed in the patients treated
with SAMe. [Am J Clin Nutr 2002;76(5): pp.1172S-6S]
Emotional Freedom Technique (EFT)
Calming / Stretching Exercises
| ||A few studies have looked at the effects of yoga breathing exercises, practiced daily for several weeks, on depression. One study showed that breathing exercises produced faster improvement than no treatment. Another study found that breathing exercises were as effective as an antidepressant drug for patients who were severely depressed, but less effective than electroconvulsive therapy (ECT).|
| ||Psychotherapy, as well as medication, can be effective in treating depression. Certain types of psychotherapy, namely cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT), have been shown to be particularly useful.|
Vitamin B12 (Cobalamine)
| ||Research shows that those who suffer from depression respond better to their treatment if they have high levels of vitamin B12 in their blood. Over 100 outpatients experiencing depression were closely observed over a six-month period. The patients were grouped by how well they responded to the treatment of their depression. Researchers also measured the level of vitamin B12 in the patients’ blood. The measurements were recorded on the first day they came in, and again at their six-month checkup. This allowed the researchers to keep track of whether the level of the vitamin influenced each patient’s outcome.|
The study found that the patients who responded fully to the treatment had higher concentrations of vitamin B12 in their blood at both the beginning and end of treatment. [BioMed Central Psychiatry December 1, 2003;3: p.17]