Sunday 20 October 2019

Covert drug dependence - or how prescribed drugs that create an illness are credited with curing it

In some ways, the editorial I wrote on Covert Drug Dependence was the most important-but-completely-ignored article that I ever wrote!

Covert drug dependence should be the null hypothesis for explaining drug-withdrawal-induced clinical deterioration: The necessity for placebo versus drug withdrawal trials on normal control subjects. Bruce G. Charlton. Medical Hypotheses. 2010; 74: 761-763.

(The core ideas are all drawn from David Healy - articulated in an adjacent article from the same issue of Medical Hypotheses - what I provided was the expression.)

Some edited excerpts:

Just as a placebo can mimic an immediately effective drug, so chronic drug dependence may mimic an effective long-term or preventive treatment...

The discovery of the placebo had a profound result upon medical practice. After the placebo effect was discovered it was recognized that it was much harder to determine the therapeutic value of an intervention than previously assumed.

An analogous recognition of the effect of drug dependence is now overdue, especially in relation to psychoactive drugs.

Just as placebo controlled trials of drugs are regarded as necessary to detect ineffective drugs, so drug withdrawal trials on normal control subjects should be regarded as necessary to detect dependence-producing drugs.

Nowadays the placebo effect is routinely assumed to be the cause of patient improvement unless proven otherwise. Placebo effect is therefore the null hypothesis used to explain therapeutic improvements.

The first aim of drug evaluation is now to show that measured benefits cannot wholly be explained by placebo.

This has led to widespread adoption of placebo controlled trials which compare the effect of the putative drug with a placebo. Only when the drug produces a greater effect than placebo alone, is it recognized as a potentially effective therapy.

The effect of withdrawing a drug upon which a subject has become dependent can be regarded as analogous to the placebo effect, in the sense that drug dependence resembles the placebo effect in being able to mislead concerning clinical effectiveness.

It may routinely be assumed that if a patient gets worse when drug treatment is stopped, then this change is due to the patient losing the beneficial effects of the drug, so that the underlying disease (for which the drug was being prescribed) has re-emerged.

However, this naïve assumption is certainly unjustified as a general rule because drug dependence produces exactly the same effect.

When a patient has become dependent on a drug, then adverse consequences following withdrawal may have nothing to do with revealing an underlying, long-term illness. Instead, chronic drug use has actually made the patient ill, the drug has created a new but covert pathology...

The body (including brain) has adapted to the presence of the drug and now needs the drug in order to function normally such that the covert pathology only emerges when the drug is removed and body systems are disrupted by its absence.

Eliminating drug dependence as an explanation for withdrawal effects cannot be achieved in the context of normal clinical practice, nor by the standard formal methodologies of controlled clinical trials. Just as eliminating the possibility of placebo effects requires specially designed placebo controlled therapeutic trails, so eliminating the occurrence of covert drug dependence requires also specially designed withdrawal trials on normal control subjects.

Our existing clinical evaluation procedures are not capable of detecting withdrawal effects. 

Even worse, current procedures misattribute the creation of dependence and harm following withdrawal, as instead being evidence of drug benefit with implication of the necessity for continued treatment of a supposed chronic illness.

The currently prevailing practices and assumptions systematically favours new drugs about which little is known.

Lack of evidence of dependence is interpreted as evidence of no dependence - perpetuating ignorance, and favouring new drugs about which we are ignorant.

In other words, as things stand; a drug that creates chronic dependence will instead be credited with curing a chronic disease.

Our current practice is precisely equivalent to chronic alcohol treatment being regarded as a cure for alcoholism - on the evidential basis that delirium tremens follows alcohol withdrawal, and alcohol can be used to treat delirium tremens!


Note: The prime example of covert drug dependence is psychiatric drugs - especially (so called) antidepressants, antipsychotics and mood stabilizers.

For instance antidepressants cause serious withdrawal symptoms that mimic the illness for which they were prescribed. This is interpreted as some kind of chronic depression or other illness. And that person may be recommended to stay on the drug.

Whenever the patient tries to stop taking the antidepressant, he gets depressive symptoms. The longer he stays on the antidepressant, the worse the withdrawal depression becomes. He may take the antidepressant forever, on the assumption he has chronic depression and that the drug is doing him good.

Thus people who want to stop taking antidepressants - either because they don't want to take drugs forever, or because the drugs have bad side effects on them (such as emotional blunting and demotivation, sexual dysfunction, or intermittent suicidal impulses) find they can't stop taking them. As a result, antidepressant prescriptions have been going up and up.

Big Pharma makes tens of billions of dollars per year by causing covert drug dependence then selling it as long term, preventive treatment.


dearieme said...

Do you have any views on the hypotheses on opiate addiction put forward by Theodore Dalrymple in this short book?

Bruce Charlton said...

@d - I haven't read it; and I don't know whether the blurb is an accurate description of his views. I used to know him slightly (by phone) from our association with the Social Affairs Unit. As Anthony Daniels we debated about antipsychotics once in the pages of the Quarterly Jounral of Medicine (QJM).

In general I don't agree with many people wrt psychopharamcology, except David Healy - my mentor in this and other matters psychiatric. IMO the field is riddled with false preconceptions.

I used to teach that drug dependence (including addiction) on several factors in addition to the substance itself. One factor is the motivation of the drug taker - for example whether opiates are being taken to relieve pain, or to get 'high'.

On top, tow major factors are the concentration of the drug, and the speed of absorption. Tincture of dilute opium taken by mouth (eg. laudanum) was so slowly absorbed as to be almost non-addictive unless it was used as a euphoriant (like Coleridge and De Quincey).

When a concentrated and rapidly absorbed form such as intravenous (or more so inhaled) heroin is invented, it gives an instant and very high dose - which is much more addictive, due to the 'hit'.

Another example is smoking a pipe compared with cigarette - with a pipe the nicotine is slowly absorbed through the small surface area of the mouth; with cigarettes the nicotine is absorbed instantly by the massive surface area of the lungs. Hence tobacco addiction wasn't much of a problem until cigarettes were invented.

So, the drug is only one element - but of course it is a vital element. Nobody gets addicted to drugs that make you feel bad - like most antidepressants (a few are euphoriant) or antipsychotics.

But such non-addictive drugs produce (often severe) 'negative dependence' by making people get ill when they stop taking them (eg stopping high dose chronic antipsychotics abruptly often causes a full blown, hospitalised psychosis - even if the person never had a psychosis before - this was known by the 1960s).

Negative dependence may be subjectively worse than addiction. eg. it would probably be preferable to be dependent on a euphoriant than a dysphoriant. In the 1980s people were addicted to Valium which made them feel good; in the 2000s many more people are negatively dependent on antidepressants that make them feel bad (demotivated, intermittently suicideal, emotionally blunted...).

dearieme said...

Thanks, BC.

Lucinda said...

This distinction between addiction and negative dependence seems analogous to Luciferic and Ahrimanic evil.

Bruce Charlton said...

@L - I think you are right. The Ahrimanic negative dependence is less 'obviously' and positively evil than Luciferic addiction; but in the end the Ahrimanic leaves a person with no satisfaction in life at all - just despair, nihilism and self-hatred.

Addicition is diminishing pleasure for escalating harm; with negative dependence there never was any pleasure, just more and more harm.