Chronic depression has been described as the disease of modern times. It afflicts 121 million people worldwide, which equates to around one in 10 adults, while one out of every 13 Europeans is currently taking an SSRI (selective serotonin reuptake inhibitor) antidepressant such as Prozac to counter it.
Tragically, they are all being poorly served by medicine, which is working with an unproven, and flawed, theory of the causes of depression, and with drugs that are doing more harm than good.
Instead, a new theory is developing that suggests that depression is the byproduct of the body's natural inflammatory response to infection. If true, an anti-inflammatory would be a better drug therapy than an SSRI, and this is supported by the evidence, which has found that the SSRI drugs are ineffective in around two-thirds of depressed people (Am J Geriatr Psychiatry, 2011; 19: 839-50).
As with the equally flawed theory that LDL (low-density lipoprotein) cholesterol is 'bad' (see WDDTY vol 22 no 4, July 2011), so serotonin-a neuro-transmitter-has been wrongly associated with depression. The 'chemical imbalance' theory maintains that low serotonin levels are a major cause of depression. Although it has never been proved, it spawned the massive SSRI drugs market, which generates around $14 billion (lb8.75 billion) in sales every year. Around 10 per cent of European adults regularly take an antidepressant, according to one review and, as co-author Andrew Oswald observed, "An awful lot of people are relying on chemical happiness" (Oswald A. 'Antidepressants and Age'. IZA Discussion Paper No. 5785, June 2011).
However, SSRIs aren't delivering happiness because serotonin has nothing to do with depression. Instead, they are causing a wide range of serious side-effects, including even death.
Just as LDL cholesterol has a vital role to play in the healthy functioning of our body and brain, and especially as we age, so serotonin helps to regulate emotion, development, neuronal growth, the blood-clotting process, attention, electrolyte balance and reproduction. SSRIs interfere with the natural balance of serotonin, and cause bleeding, stroke and death, especially in the elderly.
To support the theory that depression is a byproduct of inflammation, evolutionary biologists point to several factors.
- Depression is a common indicator of future heart disease, which is invariably the result of inflammation.
One study of 866 people, aged around 60 years or older, discovered that people who suffered from bouts of depression and mood swings were twice as likely to suffer a heart attack as non-depressed people (Psychophysiology, 2011; 48: 1605-10). According to another study, young people who suffer from depression are far more likely to die from heart disease after the age of 40. In a study that tracked the health of 7641 people aged 17 to 39, women with a history of depression were three times more likely to die from cardiovascular disease and 14 times more likely to die from a heart attack. Men were 2.4 times and 3.5 times more likely to die, respectively. After taking into account unhealthy lifestyle factors such as smoking and poor diet, the researchers said that depression increases the risk of heart disease through physiological mechanisms such as inflammation (Arch Gen Psychiatry, 2011; 68: 1135-42).
- Depression is closely related to C-reactive protein (CRP), an indicator found in the blood that inflammation is somewhere in the body.
However, researchers from Duke University were unable to decide whether inflammation caused depression or depression caused the rise in CRP markers (Biol Psychiatry, 2012; 71: 15-21).
- Depression is also a risk factor for diabetes, itself an inflammatory disease.
In a 10-year study of 65,381 women aged between 50 and 75, those who reported that they suffered from depression were 17 per cent more likely to develop type 2 diabetes, whereas the rate rose to 25 per cent among those who had been diagnosed by a doctor and were taking an antidepressant. Conversely, women with diabetes were 29 per cent more likely to develop depression, and this rose to 53 per cent among women whose diabetes was more severe, and who were medicating with insulin (Arch Intern Med, 2010; 170: 1884-91).
- Omega-3 fatty acids are natural anti-inflammatories that can counter depression.
In one study of 432 adults with major depression, those who took a fish-oil supplement for eight weeks reported a significant improvement in their condition compared with those given a dummy capsule, or placebo (J Clin Psychiatry, 2011; 72: 1054-62).
- The omega-3s can also help to ward off depression in new mothers, who can be susceptible to post-natal depression.
Women in the last stage of pregnancy experience a sudden increase in inflammation, which researchers at the University of New Hampshire say is a top contributor to depression after the birth. Breastfeeding the newborn lowers stress, so the body's inflammatory response is not triggered. However, the risk is lowered even further if the new mother also supplements with omega-3s, they say (Int Breastfeed J, 2007; 2: 6).
As with breastfeeding mothers, so with all of us: stress triggers the body's inflammatory response which, in turn, leads to depression, according to the new theory. Evolutionary biologists Andrew Miller and Charles Raison, both of whom are from the University of Arizona in Tucson, point out that depressed people often have higher levels of inflammation even when they are not fighting an infection. This suggests that there is a genetic component to depression, that somehow it is embedded in our genes and is triggered following stress. "Most of the genetic variations that have been linked to depression turn out to affect the function of the immune system. This led us to rethink why depression seems to stay embedded in the genome," said Miller (Mol Psychiatry, 2012; doi: 10.1038/ mp.2012.2).
Another evolutionary biologist-Paul Andrews from McMaster University in Ontario, Canada-takes up the theme. Not only is depression a byproduct of inflammation, but medicine's current theory that low serotonin levels causes it is also hopelessly wrong and dangerous (Front Evol Psychol, 2012; doi: 10.3389/fpsyg. 2011.00159).
Serotonin is a chemical that is vital to many of the body's processes, and its levels naturally rise and fall, but eventually stabilize in a process known as 'homeostasis', the body's natural system of self-regulation.
However, SSRIs interfere with homeostasis and prevent serotonin levels from normalizing. This suggests that the long-term use of SSRIs can damage all of the functions that serotonin naturally helps to regulate, and this is supported by clinical trials into the safety of these drugs.
- Gut problems. SSRIs cause stomach pain, diarrhoea, constipation, indigestion, bloating and headache. The effects are experienced by between 13.8 per cent and 22.9 per cent of patients (J Clin Psychiatry, 2010; 71: 484-90).
- Clotting. Blood-clotting is affected by SSRIs, which interfere with blood platelet production (Thromb Res, 2010; 126: e83-7). As a result, the drugs can also increase the risk of abnormal bleeding. People taking the drug are more likely to need hospital treatment for excessive bleeding and lose more blood during surgery. SSRI users are also more likely to suffer bleeding in the stomach, and the risk increases when an SSRI is taken with a drug such as an NSAID (non-steroidal, anti-inflammatory drug) (Clin Gastroenterol Hepatol, 2009; 7: 1314-21).
- Heart problems. Although some studies have shown positive or neutral effects, others have demonstrated that SSRIs increase the risk of heart problems such as myocardial infarction (Heart, 2005; 91: 465-71).
- Stroke. SSRIs have anticoagulant qualities that prevent the blood from thickening. While they appear to protect against blood clots in the lungs, they cause stroke, or brain haemorrhage (Cochrane Database Syst, 2008; 4: CD000024).
- Suicidal behaviour. Depression can lead to thoughts of suicide or even committing suicide, but so, too, can SSRIs. One meta-analysis of 702 trials, involving more than 87,000 patients, concluded that the drugs increase the risk of suicide (CNS Neurosci Ther, 2010; 16: 227-34).
- Death. Older people who take an SSRI are at greater risk of dying, a major study of 60,746 depressed patients aged 65 and older has discovered. Indeed, many symptoms associated with ageing-such as stroke, falling and fractures-are, in fact, caused by the SSRI, say researchers from the University of Nottingham. Interestingly, the same effects were not seen with the older-generation antidepressants, which do not target serotonin levels (BMJ, 2011; 343: d4551).
If a lowered serotonin level isn't the cause of depression, it isn't surprising that SSRIs-which promote serotonin production-have almost no positive effect, and certainly none that is greater than with a placebo.
One measure of the severity of depression is the Hamilton Depression Rating Scale (HDRS), and one study discovered that people taking an SSRI saw a 9.6-point reduction in their HDRS score-but those given a placebo reported a 7.8-point reduction. This 1.8-point difference was not considered statistically significant and, were it not for the fact that SSRIs were being measured, it would not be a therapy that the UK's NICE (National Institute for Clinical Excellence) would recommend for depression (PLoS Med, 2008; 5: e45).
Indeed, the placebo effect may have a significant role in the treatment of depression, possibly more so than in other conditions. In a study of 89 depressed patients, brain responses-as seen by EEG (electro-encephalography)-were similar in both those given a placebo and in others taking an SSRI (Neuropsycho-pharmacology, 2012; doi: 10.1016/j.euroneuro.2012.02.005).
In his analysis, McMaster's Paul Andrews says that SSRI limited benefits, and range of side-effects, suggest that they do more harm than good. The SSRI patient is also much more likely to suffer another major bout of depression later, he says.
Overall, people who have taken SSRIs are twice as likely to suffer depression again as someone who works through their depression without resorting to the drugs. People who didn't take the drugs have a 25-per-cent chance of having a later depressive episode, while those who took an SSRI run a 42-per-cent risk of a relapse (Front Psychology, 2011; 2: 159; doi: 10.3389/ fpsyg.2011.00159).
A new understanding
New theories about depression are beginning to break through, and none suggests that serotonin levels are a factor. The most promising links it to inflammation, but other researchers see that as part of the story, and that our own personal environment plays a significant part, too.
Researchers from the University of Notre Dame near Chicago believe that an inflammatory response could also be triggered by early traumatic experiences, such as parents who reject a child, in a theory they have called 'G x E (genetic and environmental) design'.
To test the theory, they studied 177 adolescents at a juvenile detention centre in Russia. Many were suffering from depression, and the researchers
were able to measure the extent of the depression in relation to the severity of their childhood experiences, such as punishment, hostility, parents' unjustified criticism and lack of respect (Psychol Sci, 2008; 19: 62-9).
Depression is projected to be the second leading cause of disability worldwide by 2020. The time is long overdue when the problem should be taken out of the hands of the drugs industry, with its discredited-and never proven-chemical-imbalance theory, and instead passed to those who do not stand to gain financially from helping the depressed.
Factfile: Hiding the evidence
Drug companies have been deliberately concealing evidence that their best-selling antidepressants don't work. The companies have deliberately hidden around a third of the research studies they carried out on a dozen SSRI (selective serotonin reuptake inhibitor) antidepressants because the findings concluded that the drugs were not effective. Instead, they published the few that had favourable results in order to get their drugs approved by America's drugs regulator, the Food and Drug Administration (FDA).
Of the studies that were published, 94 per cent concluded that SSRI antidepressants helped in cases of chronic and acute depression-but when the unpublished studies were included, the ratio of positive studies dropped to just 51 per cent.
The drug companies were forced to hand over the studies to researchers from Oregon's Health and Science University under US Freedom of Information legislation. When the Oregon researchers included the results of the 'hidden' papers, they discovered that the drugs had a positive effect ranging from just 11 per cent-which was worse than a placebo, or sugar pill-up to 69 per cent. The average effect was 32 per cent, which was roughly similar to that of a placebo. They also noted that some of the papers that had been published had a positive outcome that was not justified by the actual results-in other words, the researchers had lied in their conclusion, often the only part of any research paper that doctors actually read (N Engl J Med, 2008; 358: 252-60)
Factfile: Mind-body therapies for depression
- Cognitive behavioural therapy (CBT). 'Talking therapy' has strong evidence to suggest that it is as effective as drugs, especially for chronic depression. In one study of 316 adolescents aged between 13 and 17 years, it did even better: those who had received CBT reported fewer symptoms and depressive episodes than those who were given antidepressants (JAMA, 2009; 301: 2215-24).
- Spirituality. Worshipping a higher power and regularly attending church services are powerful antidotes to depression. One study of 918 churchgoers discovered that they were 30-per-cent less likely to suffer depression than would a non-churchgoer (Psychol Med, 2009; 39: 1009-17).
- Positive thinking. Also known as 'positive activity interventions' (PAIs), this can be just as effective as drugs, especially when antidepressants stop working. In a review of previous studies, researchers have discovered that simple PAIs, such as counting one's blessings, practising optimism and performing acts of kindness, can all help to lift depression (J Altern Complement Med, 2011; 17: 675-83).
A similar technique, called 'concrete thinking', can lift depression in just two months. Concrete thinking asks the depressed person to be more specific in his thinking to keep a sense of perspective, improve problem-solving, and reduce worry and brooding (Psychol Med, 2011; 16: 1-13).
- Tai Chi. This slow-motion exercise regime from China helps the elderly overcome their depression. Drugs don't work in two-thirds of older patients, but the exercise does. In one study of 112 elderly adults, those whose antidepressant wasn't effective were also assigned to a 10-week course of either Tai Chi or a health-education class. Around 65 per cent of those in the Tai Chi group said their depression had lifted compared with 51 per cent in the health class (Am J Geriatr Psychiatry, 2011; 19: 839-50).
- Mindfulness meditation. This type of meditation-which focuses on every sensation in the present moment-helps with depression and post-traumatic stress disorder (PTSD). After six months, one study group reported significant improvements in their depression, and 47 per cent had clinically significant improvements in their PTSD scores (J Clin Psychol, 2012; 68: 101-16).
Factfile: Other, physical causes of depression
While inflammation may be the general underlying condition behind depression, other more specific conditions-some directly associated with inflammation-appear to coexist with it.
- Household mould. Depressed people might turn to the homes they live in for a clue as to their condition. Damp and mouldy environments appear to play a part in bringing on the condition-although researchers aren't sure whether it is the mould itself, or being sick from the mould and feeling powerless to prevent it.
- Hypothyroidism. One in five sufferers of chronic depression also has hypothyroidism, where the thyroid glands produce too little thyroxine, a hormone that helps to regulate heart rate, body temperature and the processing of food.
- Reactive hypoglycaemia (low blood sugar). Diabetes is associated with depression, so it is not surprising that low blood sugar-brought about by eating sweet or starchy foods-is also linked. People who regularly eat fast food and/or processed baked products such as cakes and doughnuts are 51-per-cent more likely to develop depression (Public Health Nutr, 2011; 15: 424-32).
- Low vitamin D. This works both ways: people with high levels of vitamin D usually don't get depressed, while those with low levels do. The vitamin may affect neurotransmitters, inflammatory markers and other factors that relate to depression.
- Irritable bowel disease (IBD). Gastrointestinal problems are often the third side of a triangle that also includes anxiety and depression. About a third of people with Crohn's disease also suffer from headaches, eye problems and depression.
- Low testosterone. Older men with low levels of testosterone are more likely to have depression. In one study of 3987 men, those with the lowest levels were three times more likely to suffer depression compared with men who had the highest levels. Low hormone levels may be affecting neurotransmitters and other hormones in the brain (Arch Gen Psychiatry, 2008; 65: 283-9).
- Belly fat. There's some connection between 'central adiposity'-or belly fat-and depression. Researchers have found that people-and women in particular who were overweight or obese-with visceral fat around their middle are much more likely to suffer from depression.
- Multiple sclerosis (MS). Up to half of MS sufferers also have depression that is unrelated to the psychological impact of the disease.
- Stroke. This is also closely associated with depression-and it could be because of the SSRI drugs. Up to half of all stroke victims become seriously depressed afterwards, although it is not always detected, and often mistaken as a late symptom of the actual stroke episode.
- Coeliac disease. Depression often accompanies coeliac disease, where eating wheat, rye, oats or barley damages the inner lining of the small intestine.
Factfile: Alternatives to SSRIs
- St John's wort (Hypericum perforatum). The king of herbal antidepressants, St John's wort is "significantly more effective" than Prozac, according to one study of 135 people with major depression. When they were given the herb, the drug or a placebo, St John's wort was more effective than the other two (J Clin Psychopharmacol, 2005; 25: 441-7).
- SAMe (S-adenosylmethionine). There's some evidence to suggest that SAMe supplements help to ease depression, possibly by improving the functioning of the brain's neurotransmitters (Am Fam Physician, 2000; 62: 1051-60).
- Acupuncture. This form of traditional Chinese medicine is better than a placebo for major depression, and was of greater benefit than an antidepressant for people suffering from depression following a stroke ('An Overview of Complementary and Alternative Medicine Therapies for Anxiety and Depressive Disorders'. VA Evidence-based Synthesis Program Reports. Washington, DC: Department of Veterans Affairs, 2011).
- Omega-3 fats. Supplements of this fatty acid help to ease major depressive disorders, say researchers after analyzing 13 studies. The results were mixed, but the overall response suggests a "small and significant" benefit (Mol Psychiatry, 2011; doi: 10.1038/mp.2011.100).
- Vitamin supplements. The B vitamins, including biotin and B6, vitamin C, calcium, iron, copper, magnesium, potassium and omega-6 fatty acids, and especially evening primrose oil, all have some evidence of having a positive impact on depression.