Neither Drugs Nor Therapy Prevent Psychosis

By Neuroskeptic | December 15, 2012 5:26 pm

Neither medication nor psychotherapy is effective in improving the prognosis for youngsters considered to be at high risk of developing psychosis, according to a major study just published.

The idea of identifying and treating young people at risk of becoming psychotic – because of a family history of schizophrenia, or because they’re showing some mild symptoms – has become very fashionable lately. But can we really do anything to pre-empt the disorder?

In this trial, 115 “ultra-high risk” Australian subjects were randomized to three different treatment conditions, or if they didn’t agree to treatment, they were just followed up to see what happened.

The treatments didn’t work. Here’s the smoking gun, showing the proportion who didn’t go psychotic over time:

This shows all four of the subject groups did pretty much the same in terms of their likelihood of becoming psychotic. Neither cognitive therapy, nor the antipsychotic drug risperidone (at a low dose) had any effect: those given ‘supportive therapy’ (basically: sympathetic chats) and a placebo pill did just as well.

There probably wasn’t even a placebo effect: none of the three treatment groups did better than people who got no treatment at all (monitoring group), although people weren’t randomly assigned to that group, so that’s a little less clear.

Is this a surprise? Yes, if you believed the early studies to examine this question which claimed great things for drugs and therapy. But the current findings are no shock if you’ve been following the (much larger) recent trials – for example the British one from earlier in the year, which found zero benefit of cognitive therapy.

Early small trials have a nasty habit of not working out in the long run.

The other lesson here is that even “ultra-high risk” folks usually don’t get psychotic: only about 10-20% of them, in fact, became ill in the first two years of this study; the British results I mentioned are very similar.

So is this really “ultra high”? Relatively, yes it is; even a 10% risk is far higher than the chance that a random person on the street would have. But in absolute terms, perhaps not.

A concern here is that rounding these folks up, labelling and ‘treating’ them might make their lives worse, or even increase the risk of psychosis. That’s not just my opinion: that’s what the very cognitive therapists who eagerly run these trials believe (or ought to, if they’re being consistent with their own theories).

One of the key ideas in cognitive accounts of psychosis is that the belief and fear that one is ‘going crazy’, or that you’re otherwise abnormal, is itself a major source of stress that actually leads to worsening of symptoms.

What could be scarier than being told you’re at “ultra high risk”?

Preventing psychosis is a great idea in theory. But most bad ideas are.

ResearchBlogging.orgMcGorry, P., Nelson, B., Phillips, L., Yuen, H., Francey, S., Thampi, A., Berger, G., Amminger, G., Simmons, M., Kelly, D., Thompson, A., and Yung, A. (2012). Randomized Controlled Trial of Interventions for Young People at Ultra-High Risk of Psychosis The Journal of Clinical Psychiatry DOI: 10.4088/JCP.12m07785

  • http://www.birmingham.ac.uk/staff/profiles/psychology/wood-stephen.aspx Stephen Wood

    I'm glad you're blogging about this research, but I think you're perhaps missing the full story, about intervention studies more broadly, and the UHR approach full stop.

    [disclaimer - if it wasn't obvious - I work in this field and have a long collaboration with the authors of this study]

    I was working in Melbourne during the recruitment period for this study, and I suspect that the low overall transition rate has a lot to do with the process of enrolling people into this clinical trial. I seem to remember it being a real slog, with the definite possibility that the slow recruitment resulted in people being less at risk than otherwise might be the case. Transition rates more generally have been dropping, for reasons that are still very unclear.

    With respect to intervention studies – this one is negative, for sure. But this one is positive. Twice the numbers, for what that's worth. NNT of 9. Importantly, the study was embedded within an enrichment pathway, which may be key to preventing recruitment of people who meet risk criteria but for whom psychotic symptoms are not the main reason for help-seeking.

    Which leads me to another point – that these young people are all help-seeking. No-one (to my knowledge) is suggesting going out into the general population, screening for psychosis risk, and intervening on that basis. The false positive rate would be huge – the whole point is indicated prevention. The people presenting to these UHR clinics are frequently very concerned about becoming psychotic (especially those who have family members with the disorder), so they already 'fear that they're going crazy' as you put it. Clinicians at UHR clinics are at least able to provide more evidence-based advice on the likelihood of such an outcome, and some intervention to reduce stress, substance use, and other potential triggers for a psychotic episode.

    But the part of your post that annoyed me was your throwaway last line (which isn't even a very good one – really, most bad ideas are good in theory? Presumably most good ideas are also good in theory). Clearly you think that preventing psychosis is a 'bad idea' but I'm not sure what you base this on. Would you elaborate?

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Hi Stephen, thanks very much for the comments.

    Re: the recruitment, I can well believe that recruitment of not-very-unwell people contributed to the results, but I'd say that was a) a point against the (current) UHR criteria, which, that implies, are too broad and b) a worrying sign in the future, because historically in psychiatry, interventions have always expanded their remit over time and I can't see this being different.

    I do see the point that maybe intervention would be helpful for the 'really' prodromal cases, quite possibly, that's what I meant about it being a good idea in theory – I wasn't being sarcastic. If it helps, it's good. But if, in practice, the great majority of people meeting criteria & getting these interventions aren't benefiting from it… then the theoretical benefits are not realized.

    As for the fact that they're help-seeking. Well, maybe in this trial, but in the British one, 45 people were referred to the trial and declined because they didn't want help. So that is not universal.

    And again, I really worry that in the future, if this becomes an accepted practice, people are going to get encouraged to seek help at the slightest sign of trouble.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    P.S. Having said that, it is a bit unfair to criticize a treatment on the grounds that it might be overused in the future; I read somewhere that back in the 50s some psychiatrists opposed lithium for bipolar, because they feared it would end up also being used in unipolar depression… which is clearly silly (and didn't happen, lithium is very rarely used in depression.)

    But I don't think what I'm saying is quite as silly because we're talking about a diagnose here really (“UHR”) and over the past 30 years so many psychiatric diagnoses have expanded that it's become the norm. ADHD, autism, bipolar are doing this as we speak (and schizophrenia with the “SCZ spectrum”), in the 90s it was depression…

  • http://www.blogger.com/profile/06845842769360018122 L. Paul Strait

    This is a little surprising, and I'd like to examine what the inclusion criteria were. There have been several clinics working on early interventions in psychosis over the last 15 years and they have fairly consistently found that about 30% of untreated high risk individuals develop frank psychosis within 2 years, and that number drops to less than 10% with either low dose antipsychotics (generally either risperidone or olanzapine), high dose omega 3 fatty acids (something in the neighborhood of 3 grams a day of a combination of EPA and DHA), or cognitive therapy.

    Interestingly, the 'false positive' rate tends to increase over time in every one of these clinics (generally I think because as they become well known they get more limit cases referred). I have 'false positive' in scare quotes because they are only false positives if you think you are diagnosing the prodromal phase of schizophrenia. If you are diagnosing a risk syndrome, the people who don't become psychotic still may have accurately been at risk.

    Even the individuals who don't develop frank psychosis do develop other serious mental illnesses — affective disorders, schizotypal personality disorder, etc., so even in those cases I think the fact that they have contact with a mental healthcare provider is positive.

  • http://www.psychologytoday.com/blog/unique-everybody-else Scott McGreal

    My initial response to reading about this study was disappointment that the treatment was ineffective. On the other hand though, I am relieved that that there is now no justification for giving antipsychotic drugs to people who might develop psychosis. Even though Risperidone is one of the newer “atypical” drugs, it can have unpleasant side-effects and potentially adverse health effects. I also find it encouraging to read about a study with no significant results being published, especially after there has been so much discussion recently about publication bias.

  • http://www.birmingham.ac.uk/staff/profiles/psychology/wood-stephen.aspx Stephen Wood

    Annoyingly a comment I wrote last night seems to be lost in the ether (stuck in the spam filter?).
    Anyway, briefly…

    Yes, diagnostic creep is a big issue – hence the fight over the inclusion of the risk syndrome in DSM-5. It looks like we won that battle for the time being. The breadth of the criteria is also a problem, there being at least three different approaches to this currently, to say nothing about differences of opinion over when someone can be said to 'transition'.

    Overtreatment is indeed a major problem as well. While antipsychotics might be helpful (there are two trials that are positive, for example), the cost-benefit ratio may well be unfavourable. A parallel can be drawn with mastectomy for breast cancer – it can be said to 'work' for early stage cancers, but it is now regarded as unnecessary because less radical interventions are as effective. I've made this argument in detail elsewhere.

    Finally, who should get intervention? Bear in mind that the kinds of interventions proposed to prevent psychosis overlap considerably with the kind of clinical care offered for the presenting problems (with the obvious exception of antipsychotics, which I agree should not be used). Therefore, provided we require people to have a clear need-for-care, there are probably few ethical reasons to deny people these kinds of treatments. Furthermore, even though the majority of the UHR group do not become psychotic, their outcomes tend to be poor. So while preventing psychosis might not be a good idea, perhaps preventing 'bad outcomes' would be?

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Scott McGreal: Yes, kudos to the authors for publishing, especially since the study got industry funding (from the makers of risperidone).

  • http://www.blogger.com/profile/11760248140027990471 Professor Keith R Laws

    Just a small point about the authors publishing a negative study. In fact, the vast majority of RCTs looking at interventions to “prevent transition to psychosis” are negative in outcome.

    The Omega study is a spectacular outlier in this regard.
    The recent Dutch study mentioned above (van der Gaag et al) was significant but not for the Intention to Treat analysis.
    The recent study by Morrison and colleagues using CBT was also negative and flawed (http://keithsneuroblog.blogspot.co.uk/2012/04/cbt-you-spin-me-round.html)
    Add negative outcomes for McGlashan et al 2006; McGorry et al., 2002 and Phillips et al., 2007; Morrison et al., 2004; Morrison et al., 2007

    And finally none of the studies following up at 24 and 36 months find a difference in transitions.
    So not sure if too much kudos to be accredited – as almost all are negative – kind of suggesting some likely problem with 'the enterprise'

  • http://www.blogger.com/profile/16938658278079810327 jamzo

    keep in mind that the ultra high risk for psychosis initiative is based on the assumption that a crisis of psychosis can be prevented

    and they are testing antipsychotic drugs and/or therapy as the means to do this

    maybe cancer, strokes, heart attacks, and other health crises can be prevented via similar means

  • Anonymous

    There is an intervention that has significant evidentiary support — raising the offspring of mothers with schizophrenia in healthy adoptive homes:

    “The age-corrected morbid risk (MR) for
    definite DSM–III–R schizophrenia in lowrisk
    adoptees reared in healthy families
    was 0% (no genetic risk and no environmental
    risk), whereas that in high-risk
    adoptees reared in healthy families was
    1.49% (genetic risk in the absence of environmental
    risk). Mean risk for schizophrenia
    was 4.84% in low-risk adoptees reared
    in dysfunctional families (environmental
    risk in the absence of genetic risk), but
    13.04% in high-risk adoptees reared in dysfunctional
    families, that is, families with
    both a genetic risk and an environmental
    risk present (Tienari et al., 2002).”

    Tienari, P., Wynne, L. C., Sorri, A., Lahti, I.,
    La¨ksy, K., Moring, J., et al. (2002). Genotype–
    environment interaction in the Finnish
    adoptive family study: Interplay between
    genes and environment? In H. Ha¨fner (Ed.),
    Risk and protective factors in schizophrenia
    (pp. 29–38). Darmstadt: Springer-Verlag.

  • Anonymous

    Why would anything mainstream psychiatry do “prevent” the extreme states of mind, breakdowns and problems in living that get labeled “psychosis”?

    Psychiatry's entire interpretive system and conceptual framework is nothing but an invalid medicalization of human distress.

    Therefore it should never surprise that these quacks can't “prevent” anything.

    I'm very lucky to have escaped psychiatry at great personal cost, and I'm very happy to have had the opportunity, too often robbed from young people, to find alternatives and to thoroughly understand the dangerous quackery that psychiatry is.

    To label someone “unwell” just because they experience crises and come to cleave to “bizarre” beliefs, and to have so many people literally believing they are literally dealing with a bona fide “medical disease”, has got to be the most destructive idea humanity has ever come up with in relation to “helping” people through the problems of the human experience.

    Having mastered my mind and my thoughts in spite of psychiatric quackery and violent human rights abusing interventions, my task is always to stay under the radar and ensure these brain rapists don't get their hands on my thinking organ ever again.

    Oh look, there's even talk of taking away my kids in the comment section. Typical, nothing but hate, quackery, and human rights abuses are ever on offer really.

    Labeling someone “psychotic” or “schizophrenic” or whatever quack name calling psychiatry invents next, is not helping somebody. It is mystifying personal problems, and holding innocent people hostage in psychiatry's quest to be seen as real doctors, which they are most decidedly not.

    No worthless quack who flushed his medical degree down the toilet by becoming a psychiatrist, has any insight into why I underwent periods of overwhelming crisis and troubling thoughts.

    I'm a very lucky to have been able to have escaped psychiatry. So many people linger and die stuck forever in an endless cycle of quackery and lies.

    • Brandy Nolan

      As a parent of a child who has early onset childhood schizophrenia, I can truly say that therapy and meds do help! My child has been Halluinations & delutions since age two, now age 12. Her father has the disorder and many other of his family members…they tend to to get help and they live a life of horror, whereas my child is living as normal as a life as she can due to the help I get her.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Ah, “problems in living”, brilliant stuff.

    Since all human problems are “problems in living” – no-one has any trouble dying or staying dead – we can shorten that to just “problems” and, bingo, it turns out that psychiatry is all rubbish, because in fact, people with problems just have “problems”!

    Mind you, you only spent a hundred words or so saying that; Szasz wrote whole books on that tautology.

  • Peter

    Come on now. You aren't seriously arguing that conceptualizing mental disturbances as medical problems doesn't have consequences?

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    No – and I said as much in my original post with my point about labelling experiences & hence making things worse.

    So I've been down the path of that argument, I've gone as far as is wise to go. I also know that if you go much further than I did you end up in error.

  • Anonymous

    “Since all human problems are 'problems in living' – no-one has any trouble dying or staying dead – we can shorten that to just 'problems' and, bingo, it turns out that psychiatry is all rubbish, because in fact, people with problems just have 'problems'!”

    Note the ever so predictable use of the word “just”, as in “just problems”. Problems can be severe, dramatic, terrible, horrible, and extreme, but they are still problems.

    I think the reason the “brain disease” fanatics hate the word problem, is because it doesn't soud science-ey enough for them.

    You can rubbish Szasz's carefully prosecuted more than half century exposition of psychiatry's error all you like.

    I'm a person who has experienced the often severe personal problems that get labeled “schizophrenia”, I don't take psychiatric drugs, and no physician ever examined my brain and proved it diseased, nor did they for any other person who got the same label.

    But by all means, continue to believe the severity of bizarreness of a train of thought proves the person's brain is diseased.

    And indoctrinating scared young people to believe they are passive victims of an active brain disease, which is what psychiatry in the context of this blog post is, IS rubbish.

    And catastrophically harmful rubbish at that.

    I reiterate, I could not be more thankful that I escaped the cult of psychiatry scientism.

    And it's not just rhetoric that enabled Szasz to connect with people who have actually experienced and beat these problems, there's other things too, like the fact psychiatry started the 20th century with nothing but a book of quack nosology holding it up, and here we are in the 21st century and again, nothing but a book of quack nosology holding it up.

    Critics of psychiatry don't deny the severity of the problematic situations, behaviors and thought that can arise in a human lifetime, we just don't see any compelling reason to take the leap of faith required to agree that psychiatry has “proven” that these problems are brain diseases.

    There tends to be a divide between people who spend their lives imbibing journal articles, and the common folkk who can see the obvious. The quack sitting behind a desk that doesn't even pick a up a single piece of medical equipment, has slapped a label on you, he hasn't diagnosed a brain disease.

    But I can see how total 24/7 immersion in the slowly built up creation story that plays out in the go nowhere conceptually flawed “research” could indoctrinate a fellow.

    Me? I'm just lucky to have escaped this menace.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    “Note the ever so predictable use of the word “just”, as in “just problems”. Problems can be severe, dramatic, terrible, horrible, and extreme, but they are still problems.”

    Read what I wrote – I said you're the one saying they are just/only/nothing but/etc. problems. Which is a diagnosis – you (and Szasz) are in the business of handing out psychiatric diagnoses no less than anyone else. Yours are just rather simpler.

    “There tends to be a divide between people who spend their lives imbibing journal articles, and the common folkk who can see the obvious.”

    Maybe so, but I think you don't like me because I'm someone who both knows the science and has personal experience on the receiving end of psychiatry – and still disagrees with you.

    I'm the Black Swan that shouldn't exist.

  • Anonymous

    “Maybe so, but I think you don't like me because I'm someone who both knows the science and has personal experience on the receiving end of psychiatry – and still disagrees with you.

    I'm the Black Swan that shouldn't exist.”

    So if you sit on the opposite of a desk of a quack who declares you “clinically depressed brain diseased” yet performs no test, and you “know the science” (read: imbibes journal articles), that makes you a “black swan”? I don't think so, there are multitudes like you, that's how the Ponzi scheme keeps itself going.

    And believe me, “on the receiving end” of psychiatry, as in voluntarily swallowing SSRI's doesn't even begin to become close to knowing the receiving end. And you know it. So don't even start, Mr. “I don't believe in scientism”.

    Wrong. I'm not in the business of “handing out psychiatric diagnoses”….

    Get this, when we don't consider human problems MEDICAL problems, the word “diagnosis” doesn't apply. Simple. But hard to get your head around after years of indoctrination I know, hence the hostility from you.

    When someone felt sad and got the “depression label” and bought the lie that their brain was diseased, they really ain't no “skeptic”.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    You seem to have a “problem in leaving” silly comments – that's my diagnosis.

  • Anonymous

    “You seem to have a “problem in leaving” silly comments – that's my diagnosis.”

    And you'd be just as “scientific” as any “diagnosis” you yourself have received.

    You're no skeptic, that's for sure!

  • http://www.blogger.com/profile/00187465138890222167 LokaSamasta

    Hey I managed to get psychosis unexpectedly, because of stress, and I survived without drugs* or psychiatrists and I really enjoyed it and now I'm fine.

    *apart from hashish, but that doesn't count.

  • Anonymous

    An angle that I feel failed to be explored were the devastating side effects and risks of antipsychotics (well-documented, not controversial). Seeing the impact on patients, it is frequently hard to justify administration even if it did help with psychosis. The fact that it may not makes the risk:reward ratio entirely unjustifiable to the point of horrific. Otherwise, great article. Thanks!

  • Anonymous

    ok, so we're not sure if preventative CBT works.

    but side effects are zero.

    so why not point people to it if they feel they have mental ill-health risk factors, and would like to do something to reduce those? e.g. https://docs.google.com/viewer?a=v&pid=sites&srcid=ZGVmYXVsdGRvbWFpbnxtZW50YWxoZWFsdGh0aGlua2luZ3xneDo4ZDQ2NjkzMGQyMGNmZWE

    Another very interesting prevention idea is of mothers not receiving child-related benefits until they have passed a parenting certificate. Attachment is such a key issue, as are equal sibling treatment and prevention of abuse. Some basic education to mothers-to-be could have enormous benefits. Such ‘conditional’ benefits systems are very common in Latin America and Africa. See e.g. https://docs.google.com/viewer?a=v&pid=sites&srcid=ZGVmYXVsdGRvbWFpbnxtZW50YWxoZWFsdGh0aGlua2luZ3xneDo2YzYzMmI0NDNhMjkzMWFm&pli=1

  • Anonymous

    very interesting and useful post, thank you

  • Anonymous

    preventative CBT may not work for psychosis, but does appear to work for depression and anxiety
    see refs. here http://en.wikipedia.org/wiki/Mental_disorder#Research

  • http://www.blogger.com/profile/11760248140027990471 Professor Keith R Laws

    Re Anonymous point about “CBT side effects are zero” – this is just not true – read
    http://www.ncbi.nlm.nih.gov/pubmed/22759932

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Neuroskeptic

No brain. No gain.

About Neuroskeptic

Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

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