well worth reading…

Posted on Wednesday 20 August 2014

This is not really a blog post – more like a library of selected readings. Over the last year, there has been a dialog about the use of maintenance antipsychotic medication in the long term treatment of schizophrenic patients scattered around in various publications that hinges on an article published in JAMA Psychiatry last summer. It’s a Dutch Study that followed patients with First Episode Schizophrenic illness for 7 years. First the abstract of the article and an excerpt from the accompanying editorial [both behind a paywall]:
Long-term Follow-up of a 2-Year Randomized Clinical Trial
by Lex Wunderink, MD, PhD; Roeline M. Nieboer, MA; Durk Wiersma, PhD; Sjoerd Sytema, PhD; and Fokko J. Nienhuis, MA
JAMA Psychiatry. 2013 70[9]:913-920.

Importance: Short-term outcome studies of antipsychotic dose reduction discontinuation strategies in patients with remitted first-episode psychosis [FEP] showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before.
Objective: To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction discontinuation [DR] vs maintenance treatment [MT] trial.
Design: Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR.
Setting: One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million–population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission.
Participants: After 7 years, 103 patients [80.5%] of 128 patients who were included in the original trial were located and consented to follow-up assessment.
Intervention: After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician.
Main Outcomes and Measures: Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy [MT or DR] was controlled for baseline parameters.
Results: The DR patients experienced twice the recovery rate of the MT patients [40.4% vs 17.6%]. Logistic regression showed an odds ratio of 3.49 [P = .01]. Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates.
Conclusions and Relevance: Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice.
By Patrick McGorry; Mario Alvarez-Jimenez; and Eoin Killackey
JAMA Psychiatry. 2013 70[9]:898-899.

…It now seems probable for patients who achieve clinical remission from FEP that as many as 40% can achieve a good longterm recovery with use of no or low-dose antipsychotic medication. It is important to identify these patients at an early stage. Combining DR strategies with proactive psychosocial recovery interventions maximizing early functional recovery, delivered in specialized, optimistic systems of early psychosis care, is likely to further increase the percentage of full functional recovery. Physical health would also be expected to improve through reduction of antipsychotic load and greater levels of social inclusion and employment.

The crude use of antipsychotic medications, the delay in building evidence to guide their use, the ideological storms that continue to distort the discussion, and the tendency of human beings to seek either/or solutions to problems have combined to cause us to pose the wrong questions. In moving to a more personalized or stratified medicine,we first need to identify the probably very small number of patients who may be able to recover from FEP with intensive psychosocial interventions alone.  For everyone else, we need to determine which medication, for how long, in what minimal dose, and what range of intensive psychosocial interventions will be needed to help them get well, stay well, and lead fulfilling and productive lives. These factors have rarely been the goal in the real world of clinical psychiatry — something we must finally address now that we are armed with stronger evidence to counter poor practice. Antipsychotic load is a key concept that takes us beyond polarized views stoked by alarmists on the one hand and hard neurobiological reductionists on the other…
At the time of publication, there were two commentaries, one in Medscape and a blog post by Tom Insel MD, Director of the National Institute of Mental Health [The remainder of these references are available online]:
Sandra Steingard MD, Medical Director at the Howard Center in Burlington Vermont and blogger on Robert Whitaker’s Mad in America, wrote a piece in the Washington Post later last year that discussed the findings of Wunderlink et al and some of her experience in her clinic.
The first response article came from E. Fuller Torrey MD, founder of the Treatment Advocacy Center and Associate Director of the Stanley Medical Research Institute. [To read some of the articles cited below, you will need to register on the Psychiatric Times site. It’s free and in-so-far as I can see, painless].
And was followed by one from Joseph M. Pierre, M.D., Co-Chief of the Schizophrenia Treatment Unit at the VA Greater Los Angeles Healthcare Center and Clinical Professor of Psychiatry at UCLA.
While I have thoughts of my own about some of the issues mentioned in these articles, I’ll save them for later. I thought this was a conversation that needed to be collected in a single place. There is no disagreement that it is desirable to use the lowest effective dose of medications. In my day in this particular arena, that was what I was taught and practiced. The "medication for life" injunction certainly has its proponents, but is hardly a specialty-wide injunction. But previously, the central reason was preventing harm – avoiding the specter of Tardive Dyskinesia. The study by Wunderlink et al and some others suggests something further, that patients who can be maintained on either low dose or no medications are able to achieve a better functional recovery. Many of us have felt that intuitively, but this study adds the weight of a controlled trial. While there’s no clear consensus in this discussion, this is a high level dialog of pros and cons among experts of the hands-on variety, well worth reading…

Update: Here’s a critical analysis of the Wunderlink et al study written by George Dawson shortly after it was published:
    August 20, 2014 | 6:10 PM
    August 20, 2014 | 6:44 PM

    Thanks George,

    I took the liberty of adding it to the post…

    August 20, 2014 | 7:37 PM

    Thank you! To a lot of college educated persons, just questioning the use of any psyche drug puts the questioner in the category of being unscientific like people who won’t vaccinate their children. There is ample evidence that some of these drugs aren’t helping a lot of people a lot of the time.

    August 20, 2014 | 7:37 PM

    This is going in my library.

    August 20, 2014 | 8:04 PM

    Considering the crap shoot that is diagnostic labels at times, since many people only have one episode of psychosis in their whole lives and then live without medication and do fine, isn’t it precipitous to prescribe antipsychotics for life for a person after a first episode of psychosis? And though John Nash may be an exception— he had many episodes of psychosis— as an example of someone who recovered without meds, does it make sense for a movie about his life to suggest that he recovered with newer meds in order to not encourage anyone on antipsychotics to stop their meds? Is the culture of meds for life justified? Must any episode of psychosis be treated like a lifelong disability? Is that scientifically prudent? Is this paternalism evidence-based?

    berit bryn jensen
    August 21, 2014 | 6:30 AM

    May I point to Western Lappland, Jaakko Seikkula and Open Dialogue once more, producing recovery and health, best results compared to standard treatment in our medicalized, drug-dependent americanized, western culture.
    I do not think dr Nardo has forgotten. I’m eagerly awaiting his take on the otherwise excellent overview you presented above.
    As for long term results, clearly exposited by science journalist Robert Whitaker and professor Peter Gøtzsche, together expected to Oslo 25th of November, there are economic profit for Big Pharma in life long treatment with harmful drugs, no benefits to public health and the public purse.
    While patients with somatic illnesses have increased their lifespan, patients in psychiatry – in the same period here in Norway – have sharply reduced lifespan, coinciding with the increase in legally prescribed psychotropic drugs, coercive interventions and early death. So many young lost, killed by corruption, greed and ignorance. It has to stop. We must stop this abomination!

    Steve Garlow
    August 23, 2014 | 2:13 PM

    Your presentation of and discussion of these results is somewhat disingenuous. To fully understand the results reported in this article, you must first understand the results of the original treatment discontinuation protocol. In that analysis only a very small number of patients were successfully discontinued from antipsychotics and maintained off the antipsychotics for any length of time. Posted below is the first paragraph of the discussion from the original article.

    The main result of the study is that only a minority of remitted first-episode patients can be taken off treatment with antipsychotic drugs successfully. Roughly speaking, of all patients assigned to the discontinuation strategy, only 50% were actually taken off treatment with antipsychotic drugs, 30% had to restart antipsychotics because of recur- rent symptoms, and only the remaining 20% were able to stay off antipsychotic drugs successfully during the remain- ing observation period. If the observation period had been longer, the number of successfully withdrawn patients very likely would have been even smaller. However, the mean discontinuation time of successfully withdrawn patients was significantly longer than in patients who had to resume antipsychotic treatment, suggesting the relapse risk in suc- cessfully withdrawn patients levels off with survival time.

    The interesting thing is that there is a small group of people who have psychotic symptoms who are able to stop antipsychotics after and initial course of treatment. But this is a small group of patients, on the order of 20% or less. The vast majority of patients with schizophrenia and chronic psychotic disorders will require chronic use of antipsychotics for indefinite periods. But this does point out the heterogeneity of the condition we recognize as schizophrenia and that the idea of a group of conditions with similar outward symptoms but different fundamental biologies is supported by these results.

    August 23, 2014 | 5:00 PM

    Mr. Garlow, I do not think the questions being addressed are only about stopping the drugs. There is also an important question about optimal dose.When Wunderink analyzed his data according to dose – comparing those from both groups who were stabilized on 1 mg of haloperidol a day or less vs those on higher doses, he found that significantly more of those on lower doses had better outcomes. I understand the common response is that this is due to the underlying heterogeneity of the condition and not an effect of drugs. I agree this may play some role. However, why do we see this effect in the group randomized to DR? And why do we see a similar outcome in the other two studies I have identified that were also RTC’s? there is a similar pattern of more frequent relapses over the first two years that then abates. I think it is reasonable to continue to have discussions with people over many years about minimizing dose. You conclude that the longer one looks, the higher the rate of relapse but this is not supported by the study – the relapse rate slows down over time.

Sorry, the comment form is closed at this time.