Resources for Codependency and Depression

By Karta Purkh S. Khalsa, AD, DN-C, RH.

You, like just about everyone else, probably have the occasional attack of the blues or funky mood, when things just don’t seem to be going all that well and life isn’t letting you be all you could be. Don’t fret – feeling a bit down is a normal response to struggling with loss or tarnished self-esteem. 

When the low feelings persist, you’re in trouble. If they deepen over time no matter what you do to change them, you’re truly depressed. True depression is a loss of interest in nearly everything that once gave you pleasure, replaced instead by an all-consuming feeling of emptiness or numbness. 

But clinical depression is another matter. An intense feeling of sadness, lasting for long periods of time and preventing someone from leading a normal life, is a treatable medical condition called major depressive disorder, one of a number of depressive illnesses and characterized by persistent and sometimes severe feelings of worthlessness, guilt, sadness, helplessness and hopelessness. Maybe there’s also disturbance in sleeping or eating patterns, anxiety, regret, shame, grief, diminished ability to think and concentrate and repetitive suicidal thoughts. Officially, five or more of these symptoms for two weeks or longer constitutes clinical depression. Practically, however, there are broad shades of gray- from low moods all the way to major depressive episodes.

Dysthymia (chronic depression) is less severe depression that lingers chronically for a long period of time, sometimes years, with people functioning adequately, but seeming consistently unhappy. Bipolar depression or “manic-depressive” disease causes people to have severe high and low moods. In between mood swings, a person may experience normal moods. Seasonal depression (seasonal affective disorder or SAD) rounds out the group.Depression may be the most disabling disease in the world, according to a recent global study published in Lancet. More than 245,000 people from 60 countries participated in WHO’s World Health Survey. After accounting for socioeconomic factors and health conditions, researchers confirmed that depression had the greatest effect on worsening health compared with angina, arthritis, asthma and diabetes. People with depression plus one or more chronic diseases were in the worst health of all the disease states studied.1

An estimated 19 million American adults are living with major depression.2 About 20%-25% experience an episode of major depression at some point during their lifetimes. Women apparently suffer approximately twice as much as men from major depression.

Suicide, strongly connected to depression, is the third leading cause of death in 10- to 24-year-olds.3

Sadly, most depressed people never seek treatment. Undiagnosed and untreated, depression can worsen, lasting for years and causing untold suffering. Up to 15% of people with major depression die from committing suicide.

Major depression is a life threatening illness, and should be treated by medical experts. There is no medical test- blood, X-ray, or laboratory- that can diagnose major depression. It is important, however, to rule out any other medical problems, such as hypothyroidism, that have symptoms similar to those of depression. Depression is conventionally treated with medications and counseling. Studies have shown that antidepressant drug therapy combined with psychotherapy appears to have better results than either therapy alone. A 2004 study in General Hospital Psychiatry shows that primary care depression treatment fails half the time.4 As of March 2004, the FDA ruled that 10 antidepressants must carry stronger suicide warnings on their labels. The package insert must now encourage close observation for worsening depression or the emergence of suicidal thinking and behavior in both adult and pediatric patients. 

Depression is a complex condition. Natural remedies can be very effective, especially mild forms of the disease. In addition, many nutritional, environmental and lifestyle factors may be involved. It is important to recognize that they are important in our total life and heath, not just in depression. Generally speaking, getting people healthy gets them less depressed. So far, there is no scientific evidence that any alternative treatment is effective for treating moderate to severe depression.

Remedy 1. Lithium orotate. A Safer Lithium.

Lithium, in the carbonate form, is a prescription drug for bipolar disorder. But lithium is a simple mineral, with profound benefits for the nervous system for improving mood and cognition. Lithium research goes back decades and show dramatic positive effects on brain health. Nontoxic lithium orotate is thought to be such an efficient delivery form for this mineral that very low doses are necessary, and blood levels of lithium remain extremely safe. Jonathan Wright, MD, is a big fan of this one.5

Remedy 2. Fatty Acids. Something fishy goin’ on.

Evidence for omega-3 fats in depression has been accumulating for years.6 Patients with depression have low levels of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), a primary structural component of the brain. Proper DHA levels are essential for proper functioning of the neurotransmitters- deficiency is linked to memory loss and depression. Subjects treated for six months with 90 mg per day DHA showed substantial improvement in apathy and social withdrawal symptoms.

Remedy 3. Play it again, SAM-e

S-adenosylmethionine (SAM-e) is a molecule that naturally occurs in the cells of plants and animals. In some studies, it worked well as an antidepressant in treatment of major clinical depression. It doesn’t cause side effects for most people. Clinical trials have shown that, at doses of 200-1600 mg per day, it is as effective as tricyclic antidepressants, and may have a faster onset of action. 

One study compared injected SAM-e to imipramine for major depression. It was as effective as the drug, with far fewer side effects. A recent study from Yale found a favorable and significant effect and that there appears to be a role for SAMe in the treatment of major depression in adults.

Lithium orotate Tablet120-480 mg per dayLightens mood rapidly
Omega-3 Fatty AcidsCapsule4 grams fish oil per dayFish oil or other sources
SAM-eCapsule800-1600 mg per dayCan be expensive

KP Khalsa, Natural Healing Specialist. Learn more about KP Khalsa at

  1.   Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. 2007 Sep 8;370(9590):851-8
    Department of Measurement and Health Information Systems, World Health Organization, Geneva, Switzerland.
    BACKGROUND: Depression is an important public-health problem, and one of the leading causes of disease burden worldwide. Depression is often comorbid with other chronic diseases and can worsen their associated health outcomes. Few studies have explored the effect of depression, alone or as a comorbidity, on overall health status. METHODS: The WHO World Health Survey (WHS) studied adults aged 18 years and older to obtain data for health, health-related outcomes, and their determinants. Prevalence of depression in respondents based on ICD-10 criteria was estimated. Prevalence values for four chronic physical diseases–angina, arthritis, asthma, and diabetes–were also estimated using algorithms derived via a Diagnostic Item Probability Study. Mean health scores were constructed using factor analysis and compared across different disease states and demographic variables. The relation of these disease states to mean health scores was determined through regression modelling. FINDINGS: Observations were available for 245 404 participants from 60 countries in all regions of the world. Overall, 1-year prevalence for ICD-10 depressive episode alone was 3.2% (95% CI 3.0-3.5); for angina 4.5% (4.3-4.8); for arthritis 4.1% (3.8-4.3); for asthma 3.3% (2.9-3.6); and for diabetes 2.0% (1.8-2.2). An average of between 9.3% and 23.0% of participants with one or more chronic physical disease had comorbid depression. This result was significantly higher than the likelihood of having depression in the absence of a chronic physical disease (p<0.0001). After adjustment for socioeconomic factors and health conditions, depression had the largest effect on worsening mean health scores compared with the other chronic conditions. Consistently across countries and different demographic characteristics, respondents with depression comorbid with one or more chronic diseases had the worst health scores of all the disease states. INTERPRETATION: Depression produces the greatest decrement in health compared with the chronic diseases angina, arthritis, asthma, and diabetes. The comorbid state of depression incrementally worsens health compared with depression alone, with any of the chronic diseases alone, and with any combination of chronic diseases without depression. These results indicate the urgency of addressing depression as a public-health priority to reduce disease burden and disability, and to improve the overall health of populations. ↩︎
  2.  Depression Health Center. WebMD Health. ↩︎
  3. Depression Basics. WebMD Health. ↩︎
  4. Sherbourne, C. General Hospital Psychiatry, March/April 2004; vol 26: pp 106-114. Wells, K.B., The Journal of the American Medical Association, Jan. 12, 2000; vol 238: pp 212-220. News release, Health Behavior News Service. 
    Sherbourne C, Schoenbaum M, Wells KB, Croghan TW. Characteristics, treatment patterns, and outcomes of persistent depression despite treatment in primary care. Gen Hosp Psychiatry. 2004 Mar-Apr;26(2):106-14.
    RAND, 1700 Main Street, Santa Monica, CA 90407-2138, USA.
    We examine the sociodemographic and clinical characteristics of depressed primary care patients who receive at least minimal standards of evidence-based treatment, comparing those who remain depressed with those who recover; and their subsequent treatment patterns and other outcomes. We used observational data from a subset of 542 treated patients participating in a group-level randomized controlled trial of quality improvement interventions for depression conducted in six managed care organizations. Nonresponse to treatment was defined as having at least minimally appropriate treatment for at least two of three 6-month periods but continuing to have probable depression. Our definitions of depression and appropriate treatment are broader than those used in clinical trials, but relevant to primary care settings. Many of the factors predictive of treatment resistance in clinical trials predict nonresponse to guideline concordant care among diverse primary care, depressed patients. The main unique predictors of nonresponse to treatment include a clinical factor (suicide ideation) requiring clinician assessment and intervention, a social/economic factor (unemployment) usually not addressed by medical interventions, and medication nonadherence. Nonresponders used more adjunctive therapies and combination medications, suggesting clinicians and patients were searching for solutions. High rates of service use and poor outcomes emphasize the urgency of new research to find solutions for these patients. ↩︎
  5.  Jonathan V. Wright, M.D, The Misunderstood Mineral, ↩︎
  6.  Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-61.
    Department of Psychiatry, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
    OBJECTIVE: Evidence has indicated an association between depression and low dietary intake of omega-3 polyunsaturated fatty acids (PUFAs). However, clinical trials examining the therapeutic benefit of omega-3 PUFAs in depression showed inconsistent results. The goal of this study is to systematically evaluate the antidepressant efficacy of omega-3 PUFAs by using meta-analytic method. DATA SOURCES: MEDLINE, Embase, and PsycINFO databases were searched from 1966 through August 2006 using the key words (depression OR depressive disorder OR mood disorder) AND (omega-3 OR EPA OR DHA OR poly-unsaturated fatty acid OR fish oil). The search was limited to literature in English and clinical trials. STUDY SELECTION: Ten double-blind, placebo-controlled studies in patients with mood disorders receiving omega-3 PUFAs with the treatment period lasting 4 weeks or longer were included. DATA EXTRACTION: Effect size (ES) of each individual study was derived by computing the standardized mean difference. A random-effects model was used to pool the ESs of all included studies. DATA SYNTHESIS: When pooling the results of 10 included studies (N = 329), we found a significant antidepressant effect of omega-3 PUFAs (ES = 0.61, p = .003). Likewise, omega-3 PUFAs significantly improved depression in patients with clearly defined depression (ES = 0.69, p = .002) or with bipolar disorder (ES = 0.69, p = .0009). The dosage of eicosapentaenoic acid (EPA) did not change the antidepressant efficacy significantly. However, significant heterogeneity among these studies and publication bias were noted. CONCLUSIONS: Although our meta-analysis showed significant antidepressant efficacy of omega-3 PUFAs, it is still premature to validate this finding due to publication bias and heterogeneity. More large-scale, well-controlled trials are needed to find out the favorable target subjects, therapeutic dose of EPA, and the composition of omega-3 PUFAs in treating depression. Severus WE. Effects of omega-3 polyunsaturated fatty acids on depression. Herz. 2006 Dec;31 Suppl 3:69-74.
    Ludwig-Maximilians-University, Department of Psychiatry, Munich, Germany.
    Depression is characterised by depressed mood or/ and the loss of interest or pleasure in nearly all activities for a substantial period of time, causing significant distress. Depression is a potentially life-threatening disease. It is a major risk factor for suicide as well as coronary artery disease (CAD) and sudden cardiac death (SCD). It also may be associated with impaired endothelial dysfunction and decreased heart rate variability (HRV). Both conditions seem to persist in patients with depression despite successful antidepressant treatment. During the last few years epidemiological studies as well as clinical trials have suggested a significant role of omega-3 fatty acids in the pathogenesis of depression. As omega-3 fatty acids have been demonstrated to also beneficially influence many of the conditions depression is a risk factor for (CAD, SCD) or may be associated with (decreased HRV, endothelial dysfunction), they may well represent a major advance in the treatment of depression. However more large randomized clinical trials are clearly needed to substantiate that claim. Su KP, Huang SY, Chiu CC, Shen WW. Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol. 2003 Aug;13(4):267-71.
    Department of Psychiatry, China Medical College Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan.
    Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs), including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents (red blood cell membrane, plasma, etc.) and dietary intake. However, more evidence is needed to support its relation. In this study, we conducted an 8-week, double-blind, placebo-controlled trial, comparing omega-3 PUFAs (6.6 g/day) [corrected] with placebo, on the top of the usual treatment, in 28 patients with major depressive disorder. Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group (P < 0.001). From the preliminary findings in this study, omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder.  Cenacchi T, et al. Cognitive decline in the elderly. A double-blind placebo-controlled multicenter study on efficacy of phosphatidyl serine administration. Aging Clin Exp Res 1993;5:123-33.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 Nov;76(5):1158S-61S. Harvard Medical School, Depression Clinical and Research Program, Massachusetts General Hospital, Boston 02114, USA.
    Major depression remains difficult to treat, despite the wide array of registered antidepressants available. In recent years there has been a surge in the popularity of natural or alternative medications. Despite this growing popularity, there is limited evidence for the effectiveness of many of these natural treatments. S-adenosyl-L-methionine (SAMe) is one of the better studied of the natural remedies. SAMe is a methyl donor and is involved in the synthesis of various neurotransmitters in the brain. Derived from the amino acid L-methionine through a metabolic pathway called the one-carbon cycle, SAMe has been postulated to have antidepressant properties. A small number of clinical trials with parenteral or oral SAMe have shown that, at doses of 200-1600 mg/d, SAMe is superior to placebo and is as effective as tricyclic antidepressants in alleviating depression, although some individuals may require higher doses. SAMe may have a faster onset of action than do conventional antidepressants and may potentiate the effect of tricyclic antidepressants. SAMe may also protect against the deleterious effects of Alzheimer disease. SAMe is well tolerated and relatively free of adverse effects, although some cases of mania have been reported in bipolar patients. Overall, SAMe appears to be safe and effective in the treatment of depression, but more research is needed to determine optimal doses. Head-to-head comparisons with newer antidepressants should help to clarify SAMe’s place in the psychopharmacologic armamentarium. ancheri P, Scapicchio P, Chiaie RD. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuropsychopharmacol. 2002 Dec;5(4):287-94.
    III Clinica Psichiatrica, Universita ‘La Sapienza’, Viale dell’Universita 30 (00185), Rome, Italy.
    S-adenosyl-L-methionine (SAMe) is a natural substance which constitutes the most important methyl donor in transmethylation reactions in the central nervous system. Several clinical trials have shown that SAMe possesses an antidepressant activity. This multicentre study was carried out to confirm both efficacy and safety of SAMe in the treatment of major depression. SAMe was given intramuscularly (i.m.) at a dose of 400 mg/d, double-blind, vs. 150 mg/d oral Imipramine (IMI) in patients with a diagnosis of major depressive episode, with a baseline score on the 21-item Hamilton Depression Rating Scale (HAMD) of >or=18. A total of 146 patients received SAMe whereas 147 received IMI for a period of 4 wk. The two main efficacy measures were endpoint HAMD score and percentage of responders to Clinical Global Impression (CGI) at week 4. Secondary efficacy measures were the final Montgomery-Asberg Depression Rating Scale (MADRS) scores and the response rate intended as a fall in HAMD scores of at least 50% with respect to baseline. The analysis of safety and tolerability was conducted in all treated patients. SAMe and IMI did not differ significantly on any efficacy measure, either main or secondary. Adverse events were significantly less in patients treated with SAMe compared to those treated with IMI. These data show 400 mg/d i.m. SAMe to be comparable to 150 mg/d oral IMI in terms of antidepressive efficacy, but significantly better tolerated. These findings suggest interesting perspectives for the use of SAMe in depression.  Williams AL, Girard C, Jui D, Sabina A, Katz DL. S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clin Invest Med. 2005 Jun;28(3):132-9. ↩︎

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