Shedding Light on Depression
Depression is a common mental disorder that presents with depressed mood, loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy, and poor concentration. These problems can become chronic or recurrent and lead to substantial impairments in an individual’s ability to take care of his or her everyday responsibilities. At its worst, depression can lead to suicide, a tragic fatality associated with the loss of about 850 000 lives every year.
Depression is the leading cause of disability as measured by YLDs and the 4th leading contributor to the global burden of disease (DALYs) in 2000.
Depression can be reliably diagnosed in primary care. Antidepressant medications and brief, structured forms of psychotherapy are effective for 60-80 % of those affected and can be delivered in primary care. However, fewer than 25 % of those affected (in some countries fewer than 10 %) receive such treatments. Barriers to effective care include the lack of resources, lack of trained providers, and the social stigma associated with mental disorders including depression.
Rx Depression Drugs
Many have made the commitment to try beat their chronic depression once and for all. Over the years some have tried every antidepressants drug available. Some provided temporary relief but none had really helped in a permanent way. And when the side effects became unbearable, people who stopped taking them suffered debilitating withdrawal symptoms like cramps, dizziness, and headaches.
20-plus years of research on antidepressants suggests that they are effective, from the tricyclics to the selective serotonin reuptake inhibitors (SSRIs) that target serotonin (Zoloft, Paxil, and Prozac) to even newer ones that also target norepinephrine (Effexor, Wellbutrin). The research had shown that antidepressants help a majority of the people with depression who take them. These findings have served as the basis for the common perception that there is no question that the safety and efficacy of antidepressants rests on solid scientific evidence.
But ever since a study in 1998, whose findings were reinforced by research in The Journal of the American Medical Association, that undisputed evidence has come with a big asterisk. The study, by Irving Kirsch, from the Department of Psychology at the University of Hull, was the first to examine both published and unpublished evidence of the effectiveness of antidepressant drugs.
Yes, it is true that the drugs lift depression in most patients. But that benefit is hardly more than what patients get if they had taken a dummy pill, a placebo. As more and more scientists who study depression and the drugs used to treat it are concluding, antidepressants are basically expensive Tic Tacs. The lion’s share of the drugs’ effect comes from the fact that patients expect to be helped by them, and not from any direct chemical action on the brain, especially for anything short of very severe depression.
The placebo effect is the benefit you get from a fake pill or other treatment. The foundation for the placebo effect rests on the holy trinity of belief, expectation, and hope. But telling this to someone with depression who thinks they are being helped by antidepressants threatens their emotional stability. To explain that it is all in their heads, and that the main reason they are benefiting is because of their imagination and expectations can be devastating new for them to swallow. So rather than to speak up and deliver heart breaking news to people who are already susceptible to emotional stress, many people take the easy route. They keep quiet and tow the politically correct line that “antidepressants work.” Some people may ask, “But isn’t it more important to know the truth?” Unfortunately, based on the reaction to the research so far, the answer is, “Not too many people.”
Antidepressant drugs have helped tens of millions of people, and doctors and researchers alike certainly do not advocate that patients suffering from depression to stop taking the drugs, although they are not necessarily the best first choice. Psychotherapy, for instance, works for moderate, severe, and even very severe depression, without the harmful side-effects and withdrawal symptoms.
By and large, the unpublished studies were those that had failed to show a significant benefit from taking the actual drug. This suggests that the effectiveness of the drugs may have been exaggerated in the past by drugs companies cherry-picking the best results for publication. The belief that antidepressants can cure depression chemically is simply wrong. Some researchers even wondered if antidepressants were “a triumph of marketing over science.”
In Britain, the agency that assesses which treatments are effective enough for the government to pay for stopped recommending antidepressants as a first-line treatment, especially for mild or moderate depression. But if experts know that antidepressants are hardly better than placebos, few patients or doctors do. Although some doctors have changed their prescribing habits, more reacted with anger and incredulity. Understandably. For one thing, depression is a devastating, underdiagnosed, and undertreated disease. Of course doctors were frightened at the idea that the drugs might be mirages. If that were true,their first line of defense would have been decimated.
Two other factors are at work in the widespread rejection of Kirsch’s (and, now, other scientists’) findings about antidepressants. First, defenders of the drugs scoff at the idea that the FDA would have approved ineffective drugs. There’s a simple explanation: the FDA only requires two well-designed clinical trials showing a drug is more effective than a placebo. That’s two, period. Even if many more studies show no such effectiveness. And the size of the “more effective” doesn’t matter much, as long as it is statistically significant. Second, doctors see with their own eyes, and feel with their hearts, that the drugs lift the black cloud from many of their depressed patients. But since doctors are not exactly in the habit of prescribing dummy pills, they have no experience comparing how their patients do on them, and therefore never see that a placebo would be almost as effective as a $4 pill. “When they prescribe a treatment and it works,” says Kirsch, “their natural tendency is to attribute the cure to the treatment.” Hence the widespread “antidepressants work” refrain that persists to this day.
As a spokesperson for Lilly (maker of Prozac) said, “Depression is a highly individualized illness,” and “not all patients respond the same way to a particular treatment.” A spokesperson for Pfizer, which makes Zoloft, also cited the “wealth of scientific evidence documenting antidepressants’ effects,” adding that the fact that antidepressants “commonly fail to separate from placebo is a fact well-known by the FDA, academia, and industry.” Other manufacturers pointed out that Kirsch and the JAMA authors had not studied their particular brands.
Even Kirsch’s analysis, however, found that antidepressants are slightly more effective than placebo pills. Perhaps antidepressants do have some non-placebo, chemical benefits. But the small edge of real drugs compared with placebos may not mean what it seems. The researchers said that the drug was more effective than a placebo in severely depressed patients but that this was because of a decreased placebo effect.
Consider how research on drugs works. Patient volunteers are told they will receive either the drug or a placebo, and that neither they nor the scientists will know who is getting what. Most volunteers hope they get the drug, not the dummy pill. After taking the unknown meds for a while, some volunteers experience side effects. Bingo: a clue they’re on the real drug. About 80 percent guess right, and studies show that the worse side effects a patient experiences, the more effective the drug. Patients apparently think, this drug is so strong it’s making me vomit and hate sex, so it must be strong enough to lift my depression. In clinical-trial patients who figure out they’re receiving the drug and not the inert pill, expectations soar.
That matters because belief in the power of a medical treatment can be self-fulfilling (that’s the basis of the placebo effect). The patients who correctly guess that they’re getting the real drug therefore experience a stronger placebo effect than those who get the dummy pill, experience no side effects, and are therefore disappointed. That might account for antidepressants’ slight edge in effectiveness compared with a placebo, an edge that derives not from the drugs’ molecules but from the hopes and expectations that patients in studies feel when they figure out they’re receiving the real drug.
But the question of whether antidepressants, which in 2008 had sales of $9.6 billion in the U.S., reported the consulting firm IMS Health, have any effect other than through patients’ belief in them was too important to scare researchers off. Proponents of the drugs have found themselves making weaker and weaker claims. Their last stand is that antidepressants are more effective than a placebo in patients suffering the most severe depression.
So concluded the JAMA study in January. In an analysis of six large experiments in which depressed patients received either a placebo or an active drug, the true drug effect, in addition to the placebo effect was “nonexistent to negligible” in patients with mild, moderate, and even severe depression. Only in patients with very severe symptoms was there a statistically significant drug benefit. Such patients account for about 13 percent of people with depression. “Most people don’t need an active drug,” says Vanderbilt’s Hollon, a coauthor of the study. “For a lot of folks, you’re going to do as well on a sugar pill or on conversations with your physicians as you will on medication. It doesn’t matter what you do; it’s just the fact that you’re doing something.” But people with very severe depression are different, he believes. “My personal view is the placebo effect gets you pretty far, but for those with very severe, more chronic conditions, it’s harder to knock down and placebos are less adequate.
Every scientist who has stepped into the treacherous waters of antidepressant research are keenly aware of the disconnect between evidence and public impression. “Prescribers, policy-makers, and consumers may not be aware that the efficacy of [antidepressants] largely has been established on the basis of studies that have included only those individuals with more severe forms of depression,” something drug ads don’t mention, they write. People with anything less than very severe depression “derive little specific pharmacological benefit from taking medications. Pending findings contrary to those reported here … efforts should be made to clarify to clinicians and prospective patients that … there is little evidence to suggest that [antidepressants] produce specific pharmacological benefit for the majority of patients.”
How could anti-depressants, especially those that raise the brain’s levels of serotonin, possibly have no direct chemical effect on the brain? Surely raising serotonin levels should right the synapses’ “chemical imbalance” and lift depression. But a new drug, tianeptine, which is sold in France and some other countries (but not the U.S.), turns out to be as effective as Prozac-like antidepressants that keep the synapses well supplied with serotonin. The mechanism of the new drug? It lowers brain levels of serotonin. “If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it,” says Kirsch, “it’s hard to imagine how the benefits can be due to their chemical activity.”
Perhaps antidepressants would be more effective at higher doses? Unfortunately, in 2002 Kirsch and colleagues found that high doses are hardly more effective than low ones It is hard to see the 72 percent who got much better on ersatz higher doses as the result of anything but the power of expectation: the doctor upped my dose, so I believe I’ll get better. It’s tempting to look at the power of the placebo effect to alleviate depression and stick an “only” in front of it, as in the drugs work only through the placebo effect. But there is nothing “only” about the placebo response. It can be surprisingly enduring, as a 2008 study found: “The widely held belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking,” scientists wrote in the Journal of Psychiatric Research.
All this being said, patients on antidepressants should not suddenly stop taking them. That can cause serious withdrawal symptoms, including twitches, tremors, blurred vision, and nausea, as well as depression and anxiety. Friends and colleagues who believe Kirsch is right ask why he doesn’t just shut up, since publicizing the finding that the effectiveness of antidepressants is almost entirely due to people’s hopes and expectations will undermine that effectiveness. Maybe keeping patients in the dark about the ineffectiveness of antidepressants, which for many are their only hope, is a kind act. Maybe ignorance is bliss. But then again, if my life and my emotional health were on the line, I would want every piece of information out there so I can make an educated decision on which treatments are best for me. I would want my friends and family to let me know the truth rather than to pity me and leave me in the dark, so to speak.
This view is gaining interest, s shown by the explicit criticism of drug companies by the authors of the recent JAMA paper, more and more scientists believe it is time to abandon the “don’t ask, don’t tell” policy of not digging too deeply into the reasons for the effectiveness of antidepressants. Maybe it is time to pull back the curtain and see the wizard for what he is. As for Kirsch, he insists that it is important to know that much of the benefit of antidepressants is a placebo effect. If placebos can make people better, then depression can be treated without drugs that come with serious side effects, not to mention high costs.
Another problem is that so few people get any decent treatment. A study from the University of Michigan, in the Archives of General Psychiatry, found that only one in five Americans with depression has received even one adequate course of treatment in the past year. The criteria for adequate treatment are modest: 60 days of an antidepressant with four doctor or nurse visits over the year or (for talk therapy) four mental health visits lasting 30 minutes or more.
Perhaps this is the story that matters. Most depressed people don’t get evaluated; most who are evaluated don’t get treated; and most who are treated are treated poorly. As for whether medication helps with minor depression, that question may be less important than another one. If we were to treat all patients well, if with the mildly or moderately depressed we were to start with psychotherapy and then, if that doesn’t do enough, weigh other options, in that situation, ought we to consider antidepressants? To my mind, the answer is still, “Yes.” But we are not there, far from it. Alternative treatments for depression, such as counselling or physical exercise should be tried first. For many, medication is successful. But talking therapies can have dramatic effects also. We have put a lot of emphasis on medication in the past and it is about time we redressed the balance and put more emphasis on less invasive treatments. The side effects of antidepressants often include emotional numbing, insomnia, nausea, sexual dysfunction and weight gain. In some cases, it can result in suicide. There are no such side effects from talk therapy, socializing, exercising and increasing your nutritional intake.
Treating Symptoms is Not Good Enough
“Depression” is simply a label we give to people who have a depressed mood most of the time, have lost interest or pleasure in most activities, are fatigued, can’t sleep, have no interest in sex, feel hopeless and helpless, can’t think clearly, or can’t make decisions.
But that label tells us NOTHING about the cause of those symptoms. In fact, there are dozens of causes of depression — each one needing a different approach to treatment. Depression is not one-size-fits-all disorder. Depression is a mere symptom of a deeper underlying problem. Treating the symptoms of depression do nothing to treat the root cause, and therefore can not possibly provide a permanent solution without a chemical dependence to Rx drugs, and their related side-effects. Understanding the true reason for your depression and resolving that issue is a much more practical and safer solution. This can be accomplished through therapy and counseling.
In The Depression Cure, Dr Steve Ilardi argues that the brain mistakenly interprets the pain of depression as an infection. Thinking that isolation is needed, it sends messages to the sufferer to “crawl into a hole and wait for it all to go away”. This can be disastrous because what depressed people really need is the opposite: more human contact.
The elements required for a permanent solution for depression are: meaningful activity (non-negative thoughts), social connectedness, regular exercise, a diet rich in omega-3 fatty acids, daily exposure to sunlight, healthy diet, and good quality sleep.
Deficiency in vitamin D can lead to depression. Supplement with at least 2,000 to 5,000 IU of vitamin D3 a day. Your brain is made of up this fat, and deficiency can lead to a host of problems. Supplement with 1,000 to 2,000 mg of purified fish oil a day. Vitamin B12 (1,000 micrograms, or mcg, a day), B6 (25 mg) and folic acid (800 mcg). These vitamins are critical for metabolizing homocysteine, which can play a factor in depression. Heavy metal toxicity has been correlated with depression and other mood and neurological problems. You may want to get checked for mercury poisoning, especially if you have tooth fillings or caps.
Our environment may have evolved rapidly but our physical evolution hasn’t kept up. “Our genome hasn’t moved on since 12,000 years ago, when everyone on the planet were hunter- gatherers,” he says. “Biologically, we still have Stone Age bodies. And when Stone Age body meets modern environment, the health consequences can be disastrous.”
To counteract this Ilardi focuses on the aspects of a primitive lifestyle that militate against depression. “Hunter- gatherer tribes still exist today in some parts of the world,” he says, “and their level of depression is almost zero. The reasons? They’re too busy to sit around brooding. They get lots of physical activity and sunlight. Their diet is rich in omega-3, their level of social connection is extraordinary, and they regularly have as much as 10 hours of sleep.”
“The devil is in the detail,” replies Ilardi. “People need to know how much sunlight is most effective, and at which time of day. And taking supplements, for example, is a complex business. You need anti-oxidants to ensure that the fish oil is effective, as well as a multivitamin. Without someone spelling it out, most people would never do it.” Overcoming depression is an important step toward lifelong vibrant health. These are just of few of the easiest and most effective things you can do to treat depression.
Nothing could be a crueler message than to tell those suffering from major depression that physiological amounts of vitamin D will cure it. Premature claims for a variety of nonprescription supplements have given suffering millions hopes that were soon dashed on the rocks of scientific reality. Even the supplements that may help such as SAMe, omega-3/omega-6 intake ratios, or lowering homocysteine with adequate methylating B vitamins/TMG are not cure-alls.
Perhaps raising false hopes of curing an illness as devastating as major depression is not as serious as some of psychiatry’s past crimes, such as telling mothers of schizophrenics that they caused their child’s illness or using false recovered memories of sexual abuse that destroyed innocent families. That said, we must not raise false hopes. Nevertheless, what do we know about major depression and vitamin D?
Vitamin D and Mood
In a 1998 controlled experiment, Australian researchers found that cholecalciferol (400 and 800 IU), significantly enhanced positive affect when given to healthy individuals. They concluded that vitamin D3 deficiency provides a compelling and parsimonious explanation for seasonal variations in mood.
In 1999, in an even more interesting study, vitamin D scientist, Bruce Hollis, teamed up with Michael Gloth and Wasif Alam to find that 100,000 IU of vitamin D given as a one time oral dose improved depression scales better than light therapy in a small group of patients with seasonal affective disorder. All subjects in the vitamin D group improved in all measures and, more importantly, improvement in 25(OH)D levels was significantly associated with the degree of improvement.
To further strengthen the case that vitamin D deficiency causes some cases of depression, evidence should exist that the incidence of depression has increased over the last century. During that time, humans have reduced their sunlight exposure via urbanization (tall buildings and pollution reduce UVB ), industrialization (working inside reduces UVB exposure), cars (glass totally blocks UVB), clothes (even light clothing blocks UVB), sunblock and misguided medical advice to never let sunlight strike your unprotected skin.
All these factors contribute to reduce circulating 25(OH)D levels. Klerman and Weissman’s claim that major depression has increased dramatically over the last 80 years is one of the most famous (and controversial) findings in modern psychiatry. Something called recall bias (a type of selective remembering) may explain some of the reported increase, but does it explain it all?
Is depression associated with other conditions thought to be associated with vitamin D deficiency, such as heart disease, diabetes, hypertension, rheumatoid arthritis, cancer, or osteoporosis? if depression were associated with heart disease, one would expect excess unexplained mortality in major depression, which is a well-established finding.
Remember that association does not mean causation. If A is associated with B, then A could cause B, B could cause A, or a third factor(s), C, could cause both A and B. Therefore, if heart disease is associated with depression then the possibilities are depression caused the heart disease, heart disease caused the depression, or an unknown factor(s), perhaps vitamin D deficiency, caused some portion of both the depression and the heart disease. “Perhaps” being the key word. Remember, most of the serious errors in psychiatry (and medicine) are made when associations are confused with causation; or when subsequence is confused with consequence.
heart disease, hypertension, diabetes, rheumatoid arthritis, cancer, and low bone mineral density are all associated with depression. One parsimonious explanation is that vitamin D deficiency causes some portion of all these illnesses. Remember, all these diseases are multifactorial, so we are only talking about the percentage of the illness possibly caused by vitamin D deficiency.
Evidence exists that major depression is associated with low vitamin D levels and that depression has increased in the last century as vitamin D levels have surely fallen. Evidence exists that depression is associated with heart disease, hypertension, diabetes, rheumatoid arthritis, cancer and low bone mineral density, all illnesses thought to be caused, in part, by vitamin D deficiency. Finally, vitamin D has profound effects on the brain including the neurotransmitters involved in major depression.
Therefore, vitamin D may help major depression. It is too early to say. However, it is not to early to heed the following advice: If you suffer from depression, get your 25(OH)D level checked and, if it is lower than 35 ng/mL (87 nM/L), you are vitamin D deficient and should begin treatment. If you are not depressed, get your 25(OH)D level checked anyway. If it is lower than 35 ng/mL (87 nM/L), you are vitamin D deficient and should begin treatment.