Psychiatric Drugs and Pharmacogenomics              (You Tube presentation on pharmacogenomics)

 

In the 1950’s the American Psychiatric Association was facing an existential crisis. Faith in psychiatry had diminished, poor outcomes were increasingly evident, and the rise of applied psychology was threatening the dominance which psychiatry had enjoyed for many decades. Staring down the barrel of oblivion, American psychiatry chose to hitch its wagon to the pharmaceutical industry in a desperate bid for survival. The marketing branches of ‘Big Pharma’ (note: not the scientific research branches) came to the rescue by literally inventing various chemical imbalance theories to explain forms of human distress, such as ‘clinical depression’, ‘schizophrenia’, ‘bi-polar disorder’, which had remained perplexing at best, and poorly explained by rudimentary psychoanalytic theories at worst. The American psychiatric dream of treating all of life’s vicissitudes with pharmaceutical drugs began in earnest, and the social-psychological-political realities which are well known to cause human distress were sidelined, ignored and denied. A massive marketing exercise was undertaken by biological psychiatry/Big Pharma to convince firstly all prescribers (psychiatrists and GPs) that depression was caused by not enough serotonin; schizophrenia was the result of aberrant levels of dopamine; bi-polar was presumably caused by not enough lithium- and of course, all such problems in living were set in motion by faulty genes. All of these serious problems in living (now defined as ‘mental illnesses’) could be treated with one psychiatric magic bullet or another.

The most persistent psychiatric marketing push, which has been intensively pursued over the last 30 years, is the notion that depression is caused by inadequate serotonin levels, treatable with Selective Serotonin Reuptake Inhibitor drugs, or SSRIs. Prozac was simply the first of these released in the late 1980s, but there are now many more on the market.

Both research and disciplined observation over the last 30 years reveals some very significant problems with SSRIs, as well as the serotonin deficiency theory on which they are based (most notably, the lack of supporting evidence, and the existence of contradicting evidence). British Professor of Psychiatry, Dr David Healy presents research which indicates that the risk of suicide increases as a result of the drugs, with probably 10 suicide attempts for every completed suicide- these are suicides and attempts that would not be happening were the person merely depressed rather than being depressed and on an SSRI. Around half of the people on SSRIs report to feeling emotionally dulled, while the other half report to feeling more anxious since going on the drug. Around 60% of people find the effects so uncomfortable that they take themselves off it within the first few weeks. Of those who remain on the drug, a significant proportion experience an intense form of physical and psychological agitation, referred to as akathisia. It is this agitation, when combined with the hopelessness which usually accompanies depressed mood which increases the risk of suicide.  Mild to moderate depression is not associated with an increased risk of suicide. Most SSRIs are prescribed to people who suffer mild to moderate depression, despite the fact that there is no research evidence that SSRIs are effective in treating mild to moderate depression. Regardless of how intense the depression is, people remain just as vulnerable to the adverse side effects of akathisia. Those who were at no risk of suicide- ie. most people who are prescribed SSRIs- become at risk of suicide simply because they are more likely to experience akathisia due to the SSRI.

But surely it is a risk worth taking, as the drugs are known to effectively treat depression? Well, actually, no. American Professor of Psychology Dr Irving Kirsch extensively researched the strength of placebo effects with SSRIs. He reports that double blind controlled studies show that SSRIs perform only slightly better than placebo tablets (the differences are statistically significant, but not clinically significant, ie. not different enough to make a felt difference to a person’s suffering). Further research reveals that the slight advantage of SSRIs over placebos can be explained by the ‘boosted placebo effect’, which results from subjects in the study being able to tell most of the time, because of the adverse effects, that they are on the real drug and not on the placebo. As such, the ‘blind’ is broken and the placebo effect again becomes very powerful. Apparent therapeutic effects of the SSRIs disappear when the enhanced placebo effect is taken into account.

But the drugs do ‘work’ for some people, even if only because of a placebo effect. Some people honestly report that SSRIs, or other psychiatric drugs such as benzodiazepines, lithium, anti-psychotics, are helpful for them, perhaps because the emotional dulling impact is welcome relief. Other people honestly report that the drugs nearly killed them, either psychologically or physically, or both. Neither groups of people are lying. How can the same drug result in such wildly different responses? The answer lies in the study of pharmacogenomics (aka phamacogenetics). This is the scientific study of the inherited capacity to break down (metabolise) and expel various chemicals. When applied to psychiatric drugs, pharmacogenetics explains the role of a specific group of liver enzymes (the CYP450s, the amounts of which we inherit from both parents) in the expulsion of drug chemicals. We all differ in our loading of these specific liver enzymes, whose only role is to metabolise and expel drugs which effect the functioning of the brain (psychoactive substances). This includes all psychiatric drugs such as SSRIs, as well as nicotine, caffeine, cannabis, alcohol, amphetamines, psychedelics, opiates, etc. The evidence of this can be seen in some people who appear to be hardly affected by a particular drug, while another person appears to have no tolerance of it at all.

Within the small collection of CYP450 liver enzymes, we can be either:- poor metabolisers (with virtually none of the required enzymes); intermediate metabolisers (a semi loading of the enzymes); adequate metabolisers (a full loading of the enzymes); or ultra-rapid metabolisers (more than the full loading). In regards to any particular drug, the poor or intermediate metobolisers can be expected to experience adverse side effects (either quickly or over time), while the adequate and ultra-rapid metabolisers can be expected to not suffer these. That 60% of people take themselves off SSRI antidepressants within the first few weeks suggests that the inability to break down and expel the chemicals in the drug is a relatively common experience. When not being well metabolised and expelled, the chemicals build up to a high concentration in the blood supply and adversely affect the brain. The results can be worsening depression, anxiety and panic; intense agitation; urges to self-harm; increased suicidal feelings, ideation, and behaviour; hypomania and mania (often then misdiagnosed as ‘bi-polar); and even psychosis. Where prescribers are not aware of pharmacogenomics and the reality of adverse effects of the drugs, they can often be tempted to increase the dosage level; add different psychiatric drugs to the cocktail, eg. valium, mood stabilisers, even anti-psychotics; and to misdiagnose the increased distress and confusion as being evidence of more and more psychiatric disorders, such as bi-polar disorder, generalised anxiety disorder, personality disorders, and sometimes psychosis. The typical response to each of the new diagnoses is- you guessed it- more psychiatric drugs. It is no wonder that some people simply spiral downwards as a result of their engagement with the mental health system.

When one in every five Americans is on a psychiatric drug, it is fair to call the mass drugging of the citizenry an American cultural phenomenon. Australia seems to be in a frenzy to embrace all things American. Some of this is welcome- is there anyone who does not enjoy at least some American music, literature, or movies? But a mature culture is able to selectively choose what imports work for us, and reject those which are simply toxic. It is evident that America is not a very well adjusted culture. A heady mix of the pursuit of happiness with free market capitalism in the form of Big Pharma has resulted in one in ten Americans being on an antidepressant drug. I suggest that the desire to drug nearly every human problem out of existence, while obscuring the causes with phoney theories is a toxic cultural import which we need less of, not more. Following the American example, our prescribers have been ‘educated’ by drug company reps to view human problems in living, human reactions to adverse life events, as ‘symptoms’ of ‘illnesses’ which require ‘treatment’ with ‘medications’. These terms are all euphemisms, words which legitimately belong in medicine but which have dubious validity in the realms of human emotional and psychological suffering.

Decades of research have long ago solved the mystery regarding human distress and puzzling behaviour- in a word, trauma. Adverse life events (childhood abuse, neglect; violence; poverty; insecure housing; sexism, racism, ageism, homophobia, etc) are the common causal factor underlying the vast bulk of psychological distress and disturbance.

My advice for anyone considering going onto a psychiatric drug, such as an antidepressant, is to undertake the relevant pharmacogenetic test first. The test (MyDNA- mental health medications) is relatively inexpensive- details can be found via this link. The test reveals your inherited loading of the CYP450 liver enzymes, and can suggest which drugs your body can cope with, as opposed to those it can’t. No one is able to determine your genetic capacity to metabolise and expel drugs by just talking with you. As such, prescribing in the absence of pharmacogenetic data is more akin to Russian roulette than any scientific enterprise. The MyDNA test is able to provide a rational basis to prescribing choices, if your preference is for psychiatric drugs.

If you are currently on psychiatric drugs and would like to not be, don’t panic! There are a range of withdrawal protocols available in credible books (e.g by American psychiatrist Dr. Peter Breggin- ‘Your Drug May be Your Problem’, and ‘The Antidepressant Fact Book’), and the more credible sources on the Net. UK Professor of Psychiatry, Dr David Healy provides an SSRI withdrawal protocol. Most withdrawal protocols emphasise the need to withdraw slowly, taking months if necessary- not the weeks. Where people are suffering from adverse life events, either historical trauma or current stressors, finding support and addressing those issues are most likely to be helpful. Our society offers a plethora of non-pharmacological options and alternatives, many of which are very viable.