Gabor Szendi:
The antidepressant nuisance
There is something strange going on here that should catch everyone's eye, but the penny has dropped for only a few. There are very effective drugs for various depressive disorders, according to psychiatry, however according to the World Health Organization, depression is the second biggest cause for most days taken off work. In contrast, the history of diseases shows that once the antidote to something has been discovered, the disease becomes relatively rare.
If we think about it, an avalanche of questions follows.
Is it possible that antidepressants may not actually heal? For thirty years people have been told that depression is caused by lowered serotonin levels in the brain, but antidepressants restore it. However if the drugs don't work then is it possible that the whole theory is wrong? But if the theory is wrong, how is it possible that a healing approach can still be based on it? And if it's not serotonin deficiency, then what is the real cause of depression? And do all depressed people really have brain lesions? Or maybe there's a bunch of unhappy, dissatisfied, sad, lonely, poor, unemployed, divorced, heartbroken, mourning, mid-life crisis suffering - and so on - people among them?
Let's just take these questions in order!
Are antidepressants effective?
The proof of the pudding is in the eating. Let's for a moment ignore the many questions relating to antidepressants, because the ultimate question is whether these drugs have an antidepressant effect.
Professor of Psychology Irving Kirsch had been researching placebo effects for years, when his attention started to focus on the new antidepressants that appeared in the late 1980s, the SSRIs (Selective Serotonin Reuptake Inhibitors). Because of the overwhelming enthusiasm of the general public and the media for the 'happiness pill' that solved everything, he suspected that there would be a good amount of placebo effect in the studies. He didn't expect that he would find only placebo effect. Antidepressant clinical trials conducted by the pharmaceutical industry in 1998 were re-analyzed with his statistician colleague and to their great surprise, it was revealed that antidepressants have no real drug effect, and these drugs work merely as a placebo. Others have also shown that the 'healing effect' was proportional to the number and severity of the side effects observed by patients, which is typically a feature of placebo response (Szendi, 2018). After all, this is how humans work: faith in healing is strengthened by suffering, in the hope of healing. The inner circles of the pharmaceutical industry and psychiatry knew exactly what Kirsch's analysis showed in reality, but the professionals, who were paid to defend their multi-billion-dollar market, tried to defuse the destructive truth.
At this point, Thomas Moore drew Kirsch's attention to the fact that half of antidepressant trials were not published because of their failure, and these results were sitting in the cabinets of the United States Food and Drug Administration. Kirsch obtained the unpublished studies and once again confirmed that antidepressants are simply a placebo. The title of Moore and Kirsch's analysis was 'The Emperor's New Drugs.' Since then, several analyzes have confirmed Kirsch's result. In 2008, Eric Turner and his associates proved that half of antidepressant studies refute the claimed antidepressant effects, only these studies were not published either, giving practitioners, as well as the general public, a much more positive view of these drugs. More recently in 2017, a combined analysis of 131 studies again confirmed the ineffectiveness of antidepressants (Szendi, 2018). However the lay public knows nothing of these frauds, and hundreds of millions continue to take ineffective drugs that are very rich in side effects.
According to the rules, two positive tests are enough to register a drug, while the number of unsuccessful examinations is unlimited. It is as if for some, only the bull's eye counts at a shooting competition. But in many cases, even the two successful tests required for registration cannot be 'produced', therefore, for example, reboxetine (Endronax) is not yet approved in the US, but is available in many other countries. In a pooled analysis of several studies, reboxetine was found to be an ineffective and harmful drug (Eyding et al., 2010). But by the logic of science, no antidepressant should have been allowed, when half of the studies refute its effectiveness. If it were ever to happen, anywhere in the world, that a dropped object would not fall to the ground, the law of free-fall gravity would immediately lapse. However even if an antidepressant is proven to be ineffective twenty times, if it is able to produce statistically significant results from two studies, then the drug is accepted as effective. Of course this will not make it effective, but healthcare authorities and people around the world spend 16 billion dollars annually on these ineffective, but not harmless drugs.
Is the serotonin hypothesis of depression false?
The serotonin hypothesis of depression theory has never been proven by anyone, and in fact many have proved it false. Psychiatrists however explain to their patients that low serotonin levels are the cause of their depression.
The simplest refutation is the ineffectiveness of the drugs just discussed. As soon as one person takes even one antidepressant, serotonin levels quickly rise in the brain. If serotonin deficiency causes depression, it should therefore be relieved within a few hours - but that's not what's happening. Most people do not recover even after 3-4 weeks, although psychiatry says that by this time the drugs should have had an 'effect'.
The serotonin hypothesis is also contradicted by the fact that in most subtypes of depression, serotonin levels in the brain are not low, but high (Andrews et al.,2015), as well as in social phobia (Frick et al.,2015), in which antidepressants are also used to treat patients.
At least two compounds are known to be potent antidepressants, although they lower serotonin levels. One is reserpine (a compound extracted from Indian snakeroot) that was used in the 1950s as an antihypertensive, before being found to cause depression, so extensive use was stopped. Since it lowers serotonin, it is considered as one piece of evidence of the serotonin hypothesis. Reserpine has now been shown to have antidepressant effects (Baumeister et al., 2003). This is similar to the serotonin-lowering tianeptin (Coaxil), which was found to be a great antidepressant in animal studies, where the placebo effect is out of question.
Another counter-argument is that if the brain's serotonin level is influenced artificially by an amino acid cocktail, nothing happens. Elevated serotonin levels do not eliminate depression (Soh and Walter, 2011), and no one will become depressed due to a lowered level (Ruhé et al., 2007).
However, there is one compound, ketamine, used during surgical anesthesia, that relieves depression within 1-2 hours, but does not affect the serotonergic, but rather the glutamatergic system (Abdallah et al.,2015). Ketamine is not yet available as a drug, but it is a strong rebuttal to the theory of depression that is spread by all means possible.
They do not work, but they are not harmless
If antidepressants were merely ineffective, they should still not be used, since the problem for which they are given remains untreated, and thus worsens. Over the years, serious side effects have come to light such as increasing the risk of suicide by 2 to 3 times, bringing out aggression in many people, causing metabolic disorders (such as fattening, and the risk of diabetes increasing by 2-3 times). Emotional detachment can also be caused (Szendi, 2005), and infertility in men can result (Riggin et al., 2015). Combined with a non-steroidal anti-inflammatory drug, it increases the risk of intestinal bleeding twelve-fold (de Jong et al., 2003). Due to withdrawal symptoms when antidepressants are discontinued, many people are unable to leave these agents (Szendi, 2005).
But what causes depression then?
Even if we did not know what causes depression, there would still be no reason for the serotonin theory. What's more, we do know the reason, except billionaire interests prevent it from becoming widely known.
Depression is caused by molecules that produce inflammation in the brain (cytokines, interleukins). Anyone who has had flu knows that infectious diseases are accompanied by somnolence, disinterest, and loss of appetite. This is called disease behavior, and its evolutionary point is that reduced activity during infection, physical injury, or mental trauma promotes physical and mental regeneration. In the 1980s, it was noticed that depression was extremely common in all inflammatory diseases, and even when the inflammatory response of the immune system was stimulated for medical purposes, patients still had severe depressive symptoms (Szendi, 2010). It has also been shown that psychological stress is associated with inflammation, and even depressive personality traits such as pessimism, results from higher levels of inflammation.
The test of a theory is always putting it into practice. Numerous studies have already been conducted showing that anti-inflammatory drugs can really improve depressive conditions (Köhler et al., 2016). Unfortunately, taking current non-steroidal anti-inflammatory drugs (NSAIDs), which have been used in most of these studies, also presents serious risks (infarction, internal bleeding), so they are unsuitable for the treatment of depression. However they support the inflammatory theory of depression.
In my book 'Unhappiness and Evolution', published in 2010, I introduced the inflammation theory, and showed the important causes of the ever-growing depression epidemic (Szendi, 2010). When, in the 1950s, the first compound believed to be antidepressant (today it is known to have no such effect) was produced, the company had been sitting on it for three years because they thought there were so few depressed people, that marketing the drug was not worth it (Szendi, 2005). Today, 10.5% of the Hungarian population (Eurostat, 2017) is considered depressed. Over the past 70 years, Western populations, including Hungarians, have gradually become obese. Obesity causes a so-called systemic inflammation, which is a serious risk factor of depression. Several studies have shown that in contrast to the Western diet, a less refined carbohydrate diet halved the risk of depression. Another important factor is that sports performed on foot (running, aerobics, etcetera) have anti-inflammatory effects, but a sedentary lifestyle is a feature of the Western world.
The main cause of the depression epidemic is therefore the inflammatory lifestyle. The number of depressed people is increased because psychiatry - not considering the underlying causes - considers every depressed state as 'depression'. And being depressed because of any social problem, natural life situation or unrecognized physical illness (such as thyroid malfunction), people themselves seek shelter through psychiatrists, because sick-pay allowance is only granted to those with a recognized state of illness, which usually requires obedient taking of medication.
References
Abdallah CG, Averill LA, Krystal JH. Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Ann N Y Acad Sci. 2015 May;1344:66-77.
Andrews, P. W. et al.. Is serotonin an upper or a downer? Te evolution of the serotonergic system and its role in depression and the antidepressant response, Neurosci Biobehav Rev, 2015, 51:164-188.
Baumeister, A. A. - Hawkins, M. F. - Uzelac, S. M. 2003. Te myth of reserpine-induced depression: Role in the historical development of the monoamine hypothesis, J Hist Neurosci, 12(2):207-220
De Jong JCF, van den Berg PB, Tobi H, de Jong-van den Berg LTW. Combined use of SSRIs and NSAIDs increases the risk of gastrointestinal adverse effects. British Journal of Clinical Pharmacology. 2003;55(6):591-595.
Eurostat: Do you feel depressed? 2017. http://ec.europa.eu/eurostat/web/products-eurostat-news/-/DDN-20170324-1?inheritRedirect=true
Eyding D, Lelgemann M, Grouven U, Härter M, Kromp M, Kaiser T, Kerekes MF, Gerken M, Wieseler B. Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ. 2010 Oct 12;341:c4737.
Frick, A. et al.. Serotonin synthesis and reuptake in social anxiety disorder: A positron emission tomography study, JAMA Psychiatry, 2015, 72(8):794-802.
Köhler O, Krogh J, Mors O, Benros ME. Inflammation in Depression and the Potential for Anti-Inflammatory Treatment. Curr Neuropharmacol. 2016;14(7):732-42.
Riggin L, Koren G. Effects of selective serotonin reuptake inhibitors on sperm and male fertility. Canadian Family Physician. 2015;61(6):529-530.
Ruhé, HG; Mason, NS; Schene, AH: Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry, 2007, 12(4):331-359.
Soh NL; Walter G: Tryptophan and depression: can diet alone be the answer? Acta Neuropsychiatrica 2011, 23: 3-11.
Szendi G: Unhappines and evolution. Jaffa, 2010.
Szendi G: Depression industry. Sík, 2005.
Szendi G: Misleading medicine. In the trap of dogmas. Jaffa, 2018.