wandering, wondering, wunderink…

Posted on Wednesday 22 July 2015

If you read the blogs, you’re likely familiar with the Wunderink Clinical Trial [Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy]. It has been reviewed by many including NIMH Director Tom Insel [Antipsychotics: Taking the Long View], MedScape [Antipsychotics in First-Episode Psychosis: Less Is More], Sandra Steingard [A psychiatrist thinks some patients are better off without antipsychotic drugs], me [persistence…], and many others [see well worth reading…]. These three editorials in BJPsych Advances offer somewhat differing views on this study and its meanings:

  • Long-term effects of antipsychotics
    Joanna Moncrieff
    BJPsych Advances March 2015, 78-79. DOI: 10.1192/apt.bp.114.012591
  • Early schizophrenia: skilful management of medication
    John Cookson
    BJPsych Advances March 2015, 80-84. DOI: 10.1192/apt.bp.114.013359
  • Patients need reliable facts and figures about antipsychotics
    Stephen M. Lawrie
    BJPsych Advances March 2015, 85-87. DOI: 10.1192/apt.bp.114.013375
If I put the titles of these papers in Google®, and select the BJPA link, I get full text. But if I try to use the link, it takes me to their pay wall. I suggest you try my title·into·Google® method. The articles are short and make an interesting read as a trio.

Dr. Joanna Moncrieff is the co-chairman of the Critical Psychiatry Network, a foreign correspondant on Mad in America, and the author of The Bitterest Pills, The Myth of the Chemical Cure, and A Straight Talking Introduction to Psychiatric Drugs. Her writings are heavily referenced in the British Psychological Society‘s Report, Understanding Psychosis and Schizophrenia in the section on Medication. She regularly writes of her concern that long term use of antipsychotic medication can cause brain damage [see Antipsychotics and brain shrinkage: an update], a point she also emphasized in this editorial. After summarizing the results of the Wunderlink Trial, she concludes:
Antipsychotics can effectively reduce acute psychotic symptoms in many people, but evidence on the benefits of long-term treatment is more equivocal, and recent evidence underlines their potentially negative effect on brain volume, alongside other serious physical complications. NICE [2014] recommends more research into long-term outcomes of antipsychotic discontinuation. In the meantime, recent evidence suggests that a trial of supported antipsychotic discontinuation should be considered as one option in the routine treatment of people with psychotic conditions. This strategy may help some people to improve their functioning and quality of life, and reduce the risks to their physical health.
Dr.. Stephen Lawrie is a Neuro-Imaging researcher at thr University of Edinburgh who has done some industry-funded research. After reviewing the known risk/benefit profile of the antipsychotics and countering some of Dr. Moncrieff’s points, he presented a close reading of the Wunderink study, noting among other things that…
Only about 20% of those in the dose reduction/discontinuation group actually managed to discontinue their antipsychotic medication at all. There were no actual differences between the dose reduction/discontinuation and maintenance treatment groups in social function or quality of life, and the mean dose of antipsychotic over the previous 2 years was only about 1.5 mg different in haloperidol equivalents [~2 mg v. ~3.5 mg daily]. In the final analysis, only 8 individuals in the dose reduction/discontinuation group and 3 in the maintenance treatment group had sustained antipsychotic discontinuation during the 7-year follow-up.
He goes on to conclude…
What it actually shows is that antipsychotic discontinuation is rarely feasible and that slow tapering of the dose down to an average of about 2 mg haloperidol equivalents is associated with some measures of functional improvement. Indeed, the results are entirely in keeping with treatment guidelines which suggest that antipsychotic medication should be maintained for 2 years and then phased withdrawal attempted. What the trial suggests we really need is not new strategies for managing antipsychotic treatment after a first episode, but a way of identifying the small number of patients who can manage without antipsychotics.
Dr. John Cookson is a Consultant Psychiatrist at the The Royal London Hospital. He begins with…
The enthusiastic embrace by Moncrieff of Wunderink et al’s 7-year follow-up of a 2-year randomised controlled trial of treatment for first-episode psychosis is understandable. But any eagerness to dismiss the usefulness of long-term treatment with antipsychotics is premature. The results are counter-intuitive and seem to have puzzled the authors themselves and to invite speculative explanations.
He reviews the history of the studies supporting long term maintenance and Wunderink’s paper. I found this article’s logic harder to follow and summarize and leave it for  you to reach your own conclusions. He ends with…
The main finding of the Wunderink et al study is that after 7 years, 30 people from the original 128 with a first episode of non-affective psychosis were identified as being in recovery, with symptomatic and functional remission; of these, 25 were on no medication at that time. This group represented about half of the patients eligible for the study. The findings tell us that skilful management of medication is important in helping patients to achieve more complete remission of functional impairments after a diagnosis of schizophrenia-like illness.

It remains advisable for patients with a first episode of schizophrenia or other non-affective psychosis to continue on medication for at least 1 year after remission of the episode and/or discharge from hospital. A proportion of patients who remain well 1 year later may not require further antipsychotic medication, but there is no reliable way of identifying these, other than by a gradual discontinuation of medication. Those with a longer initial DUI or with comorbid substance misuse are less likely to remain well for long without medication. For those requiring medication to remain well, adherence is important; the medication is not effective unless it is taken, and side-effects must be recognised. The management of dosage, choice of antipsychotic and achievement of adherence require close clinician–patient relationships with skilful clinical management, as does advice to the families and carers. 
Wunderink is one of those studies that gets discussed and analyzed over and over – something of a Rorschach ink·blot for the pre-existing opinion of the reader. Those who  are opposed to maintenance antipsychotic treatment point to the greater functional recovery in the group of patients in the reduction/discontinuation group at seven years. Those who support maintenance antipsychotic treatment note that very few patients could actually get off of antipsychotics entirely in either group of this study. The patients in the reduction/discontinuation group were on a lower mean dose in the years following the original 18 month study, suggesting that the improved functional recovery might be related to the lower dosing regimens.

I must say that my own limited and anecdotal experience mirrors these results somewhat. I left training with the attitude that lower·dose or better-yet, medication·free, was the laudable goal, but wasn’t altogether able to bring it off. Getting people medication·free was invariable followed by relapse, and I settled for the lower·dose route unless directed otherwise by the patient’s choice. Those selecting medication·free either restarted medication or relapsed and ended up on a higher dose. In theory, perhaps, relapse is not necessarily a bad thing, but in practice, it was a major disruption in the interpersonal and vocational lives of the patients I followed. A couple sustained medication·free·ness, but it was way late in the game.

Wunderink’s study raises questions, but doesn’t necessarily answer them. It’s partially the reason I found that section [Section 12 on Medication] of the British Psychological Society‘s Report, Understanding Psychosis and Schizophrenia and Dr. Moncrieff’s editorial as more polemic than science-based. While I might share their sentiment, we don’t treat patients by sentiment. And one thing about Wunderink’s cohort – they were patients who came for follow-up unlike most other studies. By my reckoning, the studies that report on psychotic patients continuing on medications invariably show that most don’t [eg CATIE], in spite of what the various guidelines recommend. So while so many papers end with a call for further research, Wunderink’s final words are, in this case, mandatory in my book to adequately anchor any conclusions from this trial:
Of course, only one study indicating advantages of a DR strategy in patients with remitted FEP is not enough evidence in such an important matter. However, these results merit replication by other research groups.
    Bernard Carroll
    July 22, 2015 | 11:12 AM

    In earlier times, the Wunderink study would have been respectfully noted for what it is as well as for its limitations, and that would have been that. It would have set the stage for more definitive studies, in the normal manner of clinical science, and that would have been a good thing. Nowadays, however, the polemical fur flies around such modest reports as Wunderink. Many folks like Moncrieff over-interpret it in support of their pre-cooked agendas, and that is a bad thing. As I commented here a few days ago, no one clinical study will succeed in controlling for all possible confounds or in gathering all possibly important information. Our job is to see the forest for the trees and to refrain from straw-man caviling about minor issues in an effort to discredit entire studies. There is a useful message in the Wunderink report but it is not the touchstone that Moncrieff suggests.

    July 22, 2015 | 3:11 PM

    It’s strange how in these debates about more or less medication for psychosis – a debate which might not matter so much if not for the billions in profit to be made on these drugs – the issue of what cures schizophrenia is never mentioned.

    I recommend the reader to books like Rethinking Madness (Williams), Treatable the Untreatable (Steinman), Weathering the Storms: Psychotherapy of Psychosis (Jackson), and Psychotherapy of Schizophrenia: Treatment of Choice (Karon). In these books it can be seen that a loving long-term relationship, along with understanding how one’s delusions and other psychotic phenomena developed, provide the chance for real healing, renewed functioning and intimate relationships. Medication can help by making extreme distress manageable, but it cannot cure “schizophrenia.”

    If this sounds impossible to you, maybe you should read those books! The people behind that sad label “schizophrenia” are not just numbers in these studies, they are real people with hopes and dreams. Maybe we should direct more attention to what heals instead of maintains them.

    July 29, 2015 | 1:32 PM

    This may be a long comment but I am intending for it to my last comment in terms of offering my opinion about the current treatment of psychosis. (I may well continue to ask questions about particular studies to clarify my own thinking if that is okay). I feel that I have been treated politely here on this site, but I do feel like an ‘uninvited’ guest who has been trying to point out some serious flaws – only to realize that people here have already heard all these things but do not consider them to be particularly significant. (This of course is my opinion only and I know that I have no idea whatsoever what the silent readers actually think!)

    I am realizing that there is quite a divide between how I view many of these discussions and many of the comments here. When I read the passages you cite from Dr. Lawrie in your “wandering, wondering, wunderink” post, I hear an “antipsychotics for the treatment of psychosis are innocent until proven guilty” perspective , rather than what I would consider to be a “first do no harm” perspective.

    I had already read the comments of Dr. Stephen Lawrie elsewhere, and at that time was angered about passages similar to the ones you quoted. How can a study that shows such little overall recovery, particularly with the maintenance group be used to support current treatment guidelines?

    Dr. Lawrie says: “What it actually shows is that antipsychotic discontinuation is rarely feasible….. .Indeed, the results are entirely in keeping with treatment guidelines which suggest that antipsychotic medication should be maintained for 2 years and then phased withdrawal attempted.”
    The study does not compare people who were treated with or without antipsychotic medication during the first two years so why does he say that the ‘results are entirely in keeping with treatment guidelines which suggest that antipsychotic medication should be maintained for 2 years…..?
    As a lay person I used to think that if a psychiatrist made a comment that ”antipsychotic discontinuation ‘ is rarely feasible’ ” , it would be because the people being maintained on antipsychotics were doing pretty well, and when they were taken off the medication they stopped being well. However it seems that this is not what it means at all. What it seems to actually mean is that the people maintained on medication may indeed be very sick, but when they are taken off the medication, their psychotic symptoms become more florid. (Please correct me if this is wrong.) So when Lawrie says “Only about 20% of those in the dose reduction/discontinuation group actually managed to discontinue their antipsychotic medication at all.” – I say.. what on earth does that mean? The gross assumption – not backed up by any studies of long term recovery that anyone has pointed out to me – is that this means that the 80 % of the people who cannot ‘discontinue’ their medication are ‘better off’ than if they had not been put on it in the first place. How can such assumptions abound in the literature? Particular when those ‘20%’ who do manage to get off their medication fared better as a group in this study?

    This is the line that really makes my blood boil:“ What the trial suggests we really need is not new strategies for managing antipsychotic treatment after a first episode, but a way of identifying the small number of patients who can manage without antipsychotics.”
    Isn’t the `small’ number of patients Lawrie describes at least similar in number to the number who recovered with the maintenance medication?

    Instead of that comment, wouldn’t a comment like this be more appropriate: “Oh no! I thought I was giving my patients the best possible treatment and now am worried that in at least some cases, the treatment was making them worse! What can we do to make sure this doesn’t happen, and what does this tell us about the majority of our patients (I think 60% in this study?) who are maintained on medication and are not recovering.”

    There are some things from your ‘still around’ post that I also wanted to mention, You say
    “Wunderink’s study raises questions, but doesn’t necessarily answer them. It’s partially the reason I found that section [Section 12 on Medication] of the British Psychological Society‘s Report, Understanding Psychosis and Schizophrenia and Dr. Moncrieff’s editorial as more polemic than science-based. While I might share their sentiment, we don’t treat patients by sentiment.”I have reread the section you refer to and I just don’t understand why you consider it so problematic. It speaks very strongly about how medication is helpful for some people. I wonder what is the ‘science base’ that you think is missing or should be included, or what are the bits that you consider misleading? I wonder if you think that there are different approaches out there that are not mentioned here, that are more ’science based’ rather than ‘sentimental’ in terms of long term recovery? (These are real –not rhetorical questions) My hunch is that there are things that could be finetuned by people who understand the nuances of the research (e.g I wonder if people disagree with the comment ‘that the drugs appear to have a general rather than a specific effect’ for example????)….and what I really wonder/hope is that people like yourself could give specific feedback to the authors about this section to make it better. The report was so important to our family – we were able to take it to some very empathetic and good mental health workers who felt it was very empowering in terms of how they saw they could now help people in psychosis – and I think it would be such a travesty if it is ‘buried’

    Finally, what I think is that given there does not seem to be a research base for what approaches are best for long term recovery of psychosis, what psychiatrists have (some of them) is only clinical experience. When I say ONLY it is not to put down clinical experience – I am a very big believer in clinical experience and think that, in fact, it will be numerous case studies (of both medicated and nonmedicated subjects) that will ultimately lead to answers in such complicated illnesses. No, I say ONLY because it puts psychiatrists who have experience with people in psychosis at par with many other health professionals who also have experience with psychosis, not necessarily `superior to’ , (although it does make sense to me that those mental health practitioners who also have lived experience may well be able to trump everyone in terms of effective therapy). So I don’t disagree with you when you say the following things:

    “And a million times I’ve heard that an interest in psychotherapy doesn’t require a medical education – a wasted four years. But actually, I can’t personally imagine any better preparation than spending one’s life amid and among the suffering people that physicians attend daily. That’s what got me interested in the first place and where I learned much of what I know.
    ……… And that for many of our patients, psychotherapy of the kind I learned, practiced, and still practice is exactly what the doctor ordered. As for Whitaker’s thoughts about searching for a marketable skill or some new function. I guess I already have one, so I don’t need to ponder a Collaborative Care environment where I’m asked to be an expert consultant medicating patients I’ve never seen [which to me smells like malpractice].”

    -except that I would add that being effective in psychotherapy for people in psychosis requires great depth of experience, insight, understanding , respect and empathy which people with (or without ) a medical background might not have. I would also add that there are certain things about the current model of psychiatry in the hospitals –which is many people’s first introduction to psychiatry – that hinders recovery. These factors include the emphasis of ‘speed’ of assessing and commencing drug treatment , and how hospital environments can be unnecessarily stressful when stress exaberates illness (such as separating people in psychosis from people they trust).

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