Friday, 3 September 2010

Are "Antipsychotics" Antipsychotics?

This is the question asked by Tilman Steinert & Martin Jandl in a letter to the journal Psychopharmacology.

They point out that in the past 20 years, the word "antipsychotic" has exploded in popularity. Less than 100 academic papers were published with that word in the title in 1990, but now it's over 600 per year.

The older term for the same drugs was "neuroleptics". This terminology, however, has slowly but surely fallen into disuse over the same time period.

To illustrate this they have a nice graph of PubMed hits. Neuroskeptic readers will be familiar with these as I have often posted my own and I recently wrote a bash script to harvest this data automatically. Now you too can be a historian of medicine from the comfort of your own home...

Why does it matter what we call them? A name is just a name, right? No, that's the problem. Actually, neuroleptic is just a name, because it doesn't mean anything. The term derives from the Greek "neuron", meaning... neuron, and "lambanō" meaning "to take hold of". However, no-one knows that unless they look it up on Wikipedia because it's just a name.

Antipsychotic, on the other hand, means something: it means they treat psychosis. But whether or not this is an accurate description of what "antipsychotics" actually do, is controversial. For one thing, these drugs are also used to treat many non-psychotic illnesses, like depression, and PTSD.

More fundamentally, it's not universally accepted that they have a direct anti-psychotic effect. All antipsychotics are powerful sedatives. There's a school of thought that says that this is in fact all they are, and rather than treating psychosis, they just sedate people until they stop being obviously psychotic.

Personally, I don't believe that, but that's not really the point: the point is that it's controversial, and calling them antipsychotics makes it hard to think about that controversy in a sensible way. To say that antipsychotics aren't actually antipsychotic is a contradiction in terms. To say they are antipsychotic is a tautology. Names shouldn't dictate the terms of a debate in that way. A name should just be a name.

The same point applies to more than just antipsychotics - I mean neuroleptics - of course. Perhaps the worst example is "antidepressants". Prozac, for example, is called an antidepressant. Implying that it treats depression.

But according to clinical trials, Prozac and other SSRIs are a lot more effective, relative to placebo, in obsessive-compulsive disorders (OCD) than they are in depression (though this is not necessarily true of all "antidepressants", yet more evidence that the word is unhelpful.)

So, as I asked in a previous post: "Are SSRIs actually antiobsessives that happen to be helpful in some cases of depression?" Personally, I think the only name for them which doesn't make any questionable assumptions, is simply 'SSRIs'.

ResearchBlogging.orgTilman Steinert and Martin Jandl (2010). Are antipsychotics antipsychotics? Psychopharmacology DOI: 10.1007/s00213-010-1927-3

17 comments:

Anonymous said...

As a psychiatrist, I agree with your statement that drugs with multiple purposes shouldn't be named for one of the effects. Also, a lot of people use the word "neuroleptic" specifically to mean first-generation antipsychotics, not second-generation ones, but even that is not consistent. One of the problems with this is when you want to use an antipsychotic in someone who's not psychotic. For example, Seroquel in bipolar depression. Then the patients run and google it and think you think they're "crazy." It's also a valid point that SSRIs are better anti-anxiety meds than antidepressants. That's another thing, when you want to start an SSRI on someone with panic disorder, for example, and they're like, "but I'm not depressed!"

Finally, the notion that antipsychotics (or D2 antagonists, as I prefer to call them) are simply sedating and have no antipsychotic action is just so obviously false that I'm not sure exactly how to respond to it. Other sedating meds have no antipsychotic effect. There were plenty of sedatives around before the 1950s, and thorazine was revolutionary because it did something that other sedating meds didn't. Also, not all antipsychotics are equally sedating. Abilify, for example, which is a functionally-selective partial agonist at D2 (yet still called an "antipsychotic" as if it were in the same class as D2 antagonists), is often activating and causes insomnia. Finally, patients who are on even highly sedating antipsychotics for long enough often adjust to the point where they're not obviously sedated at all, yet the antipsychotic effect persists.

Neuroskeptic said...

Right - patients are often the ones who are most confused by these names.

I was at the pharmacy once (to pick up some antidepressants, ironically) and the woman in front of me in the queue had just been prescribed citalopram for anxiety. She was concerned that she was being given "an antidepressant" and was very insistent that she was not depressed. Eventually she seemed to accept that citalopram was not an antidepressant in her particular case!

Re: antipsychotics being just sedatives, I agree that it's wrong, but it is a school of thought (if Peter Breggin and Thomas Szasz can be said to constitute a school). On the other hand I think the view that SSRIs aren't specific antidepressants, just "emotion-blunters", is more defensible.

ex-hedgehog freak said...

Given that the antipsychotics have such a wide variety of receptor-binding properties and psychopharmacologies, is it fair to even call them a class? I see a large number of reviews that lumps them all in together for discussion purposes; when the reality is one must distinguish between quetiapine, olanzapine, ziprasidone et al, because of their reported differences in efficacy for different disorders, as well as their differential propensity to cause side effects such as weight gain and sedation.

I think the notion has come about simply because these agents were first used in trials for schizophrenia. While we all know that schizophrenia is a complex disorder with different symptom domains, what are generally considered the most immediately debilitating are the positive symptoms like delusions (ie. psychoses). Drugs that are considered to have efficacy in schizophrenia are those that are 'anti-psychosis', even if they have limited ability to addres the negative symptoms of cognitive impairments; as such treatment of psychosis has become equated with treatment of schizophrenia.

The question really is, how would you redefine them if you are picking classes? They are more than just dopamine antagonists (or partial agonists in the case of aripiprazole)

Neuroskeptic said...

Well that's why I like "neuroleptic". They do seem to have something in common, but it's not limited to being anti-psychotic.

As you point out, they are more than just D2 antagonists. But D2 antagonism is what gives them their unique character. Which I would say is covered by the term "neuroleptic".

petrossa said...

To my mind it's long overdue that current DSM's where thrown out and completely redone by anyone but those that have followed formal training.

All the current system is, is circular reasoning taken to its extreme. One writes a book full of subjective, culture bound criteria based on which people get their training. Logically they'll always find that the book fits the problems people suffer from.

Most 'labels' are, except in the rare cases that a person by accident demonstrates perfectly the symptoms described, just that. Labels without real meaning.

At least when they cut off the wrong leg in hospital you'll notice one time or another.

Not so with mental problems. It would amaze me to find out that even half the people on treatment are treated for the right problem.

Added to that the God Syndrome is higher amongst neuro professionals since they can't be proven to be wrong.

A cardiac surgeon is less likely to get away with faulty diagnosis.

ex-hedgehog freak said...

Neuroskeptic:

But you would argue then that antidepressants (SSRIs, SNRIs, TCAs etc) are also neuroleptics? My sense is that this term would cover all psychotropic drugs without regard for the underlying pharmacology?

This seems to be a bigger question that the FGAs and SGAs themselves, but more of how we define the entire scope of psychotropics into classes and groups, either based on MOA or even disease states. I agree that using a general term such as neuroleptics is not necessarily a bad thing, particularly from the patients perspective; both you and the anonymous commenter #1 above gave the classic examples of patient reactions. The concern is that patients find out this info in the wrong places - (a) at home on the Web, and (b) in the pharmacy when they pick up the Rx. The conversation on what the drug in question does should have happened way before that back in the psych office.

Neuroskeptic said...

No, by "neuroleptic" I mean what we usually (nowadays) call "antipsychotics". But as I said, I prefer neuroleptic because it avoids the connotation that they are only useful in psychosis.

To be honest the terminology is what it is and it won't change any time soon, I will I'm sure continue to use the word antipsychotic because it's what we do, but it's important to remember that it's just a name.

reasonsformovi ng said...

And, of course, the idea that antipsychotics improve cognition (I'd like to see other sedatives do that!)

Paul said...

I think I agree with Dr Healy who suggests that the usefulness of neuroleptic drugs is down to their ability to induce feelings of apathy in patients. So where as a sedative would simply make a user less able to respond to delusions or hallucinations, a neuroleptic will simply make a user care less about their delusions or hallucinations. That is not to undermine the usefulness of these medications, though it would explain why they seem to be effective for a number of psychiatric conditions.

Jean said...

For a long time I have found it confusing that drugs called antipsychotics are not just given to treat psychosis. I was on antipsychotic medication 1968-1974 (eg. chlorpromazine, melleril) though I was never psychotic. Now when I say I was being treated for schizophrenia you might be forgiven for thinking, 'Oh, but that's a psychotic illness, so maybe you didn't realise you were psychotic'. But, no. I was diagnosed with a form of schizophrenia called 'simplex' and my 'symptoms' were only the so-called 'negative' ones: lethargy, lack of motivation, apathy and social withdrawal. I still can't understand why I was treated with drugs which have the same side-effects as the symptoms which they were supposedly meant to treat. I felt much better without any drugs at all and I only managed to get my life back when I came off them against medical advice. But, to get back to the subject of this post, yes, it is very confusing and misleading to call these drugs antipsychotics.

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Paul said...

Re antipsychotics and the hypothesised mechanism of action, what did you make of the Volz et al 2007 Cochrane review comparing them to benzos? The letter you link to cites this paper I think.

My reading of it was that the small amount of evidence available suggests not a lot of difference between the effectiveness of benzos and antipsychotics.

Anonymous said...

Neuro:
Au contraire, I think there is ample evidence for sedative hypothesis of "antipsychotics." And you can see this for yourself. All you have to do is give a medicated schizophrenic a Rorschach test. While they are behaviorally calmer, they will still yield thought disorder on this measure. Take them off their tranquilizers, and presto! they are rambling disorganized people again. The drug only masks the psychosis. It does not cure it. And antipsychotics are hardly "anti-thought disorder" agents, as if we have figured out the biochemistry of thinking!!!

Anonymous said...

Hell "antidepressants" may really be "anti-sexual" pills with "anti-anxiety" and anti-depressant" side effects!

Another Anonymous said...

"antidepressants" may really be "anti-sexual"

Yes, but alas Amineptine is gone...

pj said...

In medicine we use a number of medications for reasons other than the classical reason. So metoclopramide is a D2 antagonist (so a neuroleptic?) often used for nausea (so classically called an anti-emetic) which is also used as a GI pro-kinetic. Erythromycin is a macrolide antibiotic which is also used as a prokinetic. Carbamazepine is an anticonvulsant used for neuropathic pain. Aspirin is an NSAID used as an anticoagulant. This isn't a debate limited to psychopharmacology, it is just that the spehere of mental health has disproportionate issues over questions of nomenclature.

Otte said...

I would also vote for the name "neuroleptics" being a pragmatic solution that has the advantage of uncoupling medication from clinical effect and indication domain. In order to look at potential clinical effects I found it very usefull to handle them by their receptor affinity (Ki) and power profile as the clinical effects of receptor stimulation/blocking are rather well known.
Using scientifically sound principles, one can prevent the horror of polypharmacy leading to exagerated (and dangerous) high daily doses. I advice calculating the BNF (britisch national formularion) max daily dose equivalent taking into account pharmacodynamic effects on CYPD interactions by (often to) many other drugs. Polypharmacy is a big bump on the skin of many psychiatric prescriptions and should be eradicated if we truly care for patient safety. The principles are well known since many years, yet seem not to penetrate into daily practise. Often in the clinic we wittnes alchemic and heuristic symptom driven prescription patterns that violate every sound scientific principle and hence are the cause of (often hidden) but dangerous short or long term side effects (fi metabolic syndrome, QT problems, epileptic fits, EPS etc..)

Time has come that drastic change in the hearts and minds of prescribers is absolutely imperative.Imposing guidelines (although maybe not very sympathico) is a possible remedy to this unsafe heuristic. Knowing science is good, applying it is necessary.

Dr. G. Otte
neuropsychiatry