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Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy: Long-term Follow-up of a 2-Year Randomized Clinical Trial. JAMA Psychiatry . 2013 Sep 1 ; 70(9):913-20. PubMed Abstract

Comments on Paper and Primary News
Primary News: Less Is More: Antipsychotic Dose After First-Episode Psychosis

Comment by:  Robin Emsley (Disclosure)
Submitted 2 August 2013 Posted 7 August 2013
  I recommend this paper

The article by Wunderink et al., like the original paper, is thoughtful and informative. However, the results are a bit surprising and will hopefully not encourage clinicians to discontinue maintenance antipsychotic treatment. My own view is that we should be taking relapse very seriously, as it may play a critical role in disease progression, in addition to the obvious associated psychosocial risks. An earlier Dutch cohort study with a 15-year follow-up found accruing morbidity and identified relapse as a critical factor. After each relapse, a subset of patients experienced persistence of positive and negative symptoms (Wiersma et al., 1998).

Given the very strong association between treatment discontinuation and relapse (Robinson et al., 1999), our inability to accurately identify early warning signs of relapse, and the failure of rescue medication to abort relapse, together with additional evidence for emergent treatment refractoriness in a subset of patients after relapse (  Read more

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Primary News: Less Is More: Antipsychotic Dose After First-Episode Psychosis

Comment by:  Martin HarrowThomas JobeRobert Faull
Submitted 14 August 2013 Posted 14 August 2013

While the empirical data on short-term studies of antipsychotics has produced considerable positive results, there is very little evidence on the long-term (four years or longer) efficacy of antipsychotics. Leucht and colleagues have noted “nothing is known about the effects of antipsychotic drugs compared to placebo after three years….” (Leucht et al., 2012).

Since multiyear (four years or longer) double-blind, drug-placebo studies of schizophrenia cannot be done, the relative lack of firm, long-term evidence on antipsychotic medications makes it more important that evidence from other types of studies be considered more carefully. This includes the long-term outcome of lower-dose and non-medicated schizophrenia patients from the seven-year Wunderink study and our 15- to 20-year naturalistic research finding more favorable long-term outcomes for unmedicated schizophrenia patients than those continuously prescribed antipsychotics (Harrow and Jobe, 2007;   Read more

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Primary News: Less Is More: Antipsychotic Dose After First-Episode Psychosis

Comment by:  Stephen Marder, SRF Advisor
Submitted 16 August 2013 Posted 16 August 2013

This is an important contribution that has a number of important implications:

First, outcomes such as relapse and remission seem very crude to me, and they tell very little about what is of interest to many people with schizophrenia. An advantage of this study is that the authors used a sophisticated functional measure. I agree with Cenk Tek that patients who have a recurrence when the dose of antipsychotic is too low or medications have been stopped can become better managers of their illnesses (see Cenk Tek's full comment). I also believe that one of the goals of early treatment should be to educate patients to self-manage symptoms when they occur so that a minor exacerbation can be successfully managed.

Second, this study reminds us of an older literature from the 1980s, including my work (Marder et al., 1984), which documented that living with excessive dopamine blockade can be a personal burden that is...  Read more

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Primary News: Less Is More: Antipsychotic Dose After First-Episode Psychosis

Comment by:  Clive AdamsStephanie Sampson
Submitted 14 August 2013 Posted 20 August 2013

One swallow does not necessarily indicate summer has arrived.

Shortly after publishing a Cochrane review on intermittent drug techniques for schizophrenia (Sampson et al., 2013), we were pleased to see Lex Wunderink and colleagues publish these new findings from their five-year follow-up. This current review includes the initial data of Wunderink et al. from the two-year study demonstrating double the relapse rates in their dose-reduction strategy relative to the maintenance treatment group. These data must be considered within the totality of all similar evidence, or there is risk of overextrapolating results from small trials. However, along with five other important and pioneering trials, the two-year findings by Wunderink et al. are entirely consistent (I2 = 0 percent) with other results (RR Relapse 2.46 95 percent CI 1.7-3.5), with Wunderink and colleagues' data contributing 42 percent of the weight to the finding. At around two years, maintenance treatment does seem to avoid more relapses than a variety of intermittent...  Read more

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