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November 13, 2017 by Sandra Steingard, MD

Duration of Untreated Psychosis Revisited: Response to the Goff Paper

Earlier this year, the American Journal of Psychiatry published a paper, “The Long-Term Effects of Antipsychotic Medications on Clinical Course in Schizophrenia.” This was a response to the concerns that have been raised that these drugs negatively impact long-term outcomes. The authors conclude, albeit in a somewhat lukewarm way, that overall, the “evidence for a negative long-term effect of initial or maintenance antipsychotic treatment is not compelling.” Robert Whitaker and Joanna Moncrieff, whose work was cited by the authors, have written critiques of this paper.

Even if one accepts the paper’s conclusions at face value, there is little argument regarding some serious long-term risks such as movement disorders and weight gain. One of the most compelling reasons why these authors support long-term care is related to the relapse data: when one is started on these drugs, the relapse rate is higher when they are stopped than when they are continued (at least over the first two years). However, there is general consensus that there are some individuals who will recover and not need medications long-term. In fact, there is even consensus that some can recover without drugs; the dispute is over numbers.

For me, this raises an urgent question about initial treatment. Doesn’t it make sense to try to capture all of those individuals who might get through a psychosis without drugs? Doesn’t it make sense to invest heavily in interventions that do not rely on drugs as a first-line treatment? At least then we can protect that group — be it 20% or 80% — from the cycle of relapse that seems to begin once the drugs are introduced.

However, this approach has not been carefully evaluated within the mainstream of psychiatry. This is because of the hypothesis — almost elevated to accepted doctrine — that a delay in starting antipsychotic drugs increases the likelihood of a poor long-term outcome. This notion has been around for almost thirty years. If one is interested in offering approaches, such as Open Dialogue, that do not insist on early use of drugs, this is a pressing concern. I addressed the history of this concept — often referred to as Duration of Untreated Psychosis (DUP) — in an earlier blog and I concluded that while there is strong evidence that intervening early with people experiencing psychosis is helpful, the intervention did not have to include drugs. So I read with interest the section in the Goff paper on DUP and I review that here.

Goff and colleagues only devote one paragraph to this topic and cite three papers. They conclude, “The efficacy of antipsychotics for the initial treatment of psychosis is well established. Early initiation of antipsychotics may improve long-term course of the illness, although this has not been established by randomized trials.”

The first paper they cite by Pentilla and colleagues was a meta-analysis of studies that evaluated the association between DUP and long-term outcome. They found that the longer the time before the development of psychotic symptoms and the initiation of treatment, the worse the outcome. However, in this paper, treatment was not synonymous with drugs. Treatment was defined as “antipsychotic medications, psychosocial treatment, contact with treatment services or first hospital admission.” It seems, therefore, impossible to form any conclusion from this paper on the relative merits or drawbacks of the drugs.

The second paper studied was by Melle and colleagues. These authors assessed the impact of an early detection (ED) program designed to help identify and treat individuals who were experiencing psychosis. In this study, the program was effective in identifying individuals and connecting them with a treatment that included not only medication but also significant psychosocial supports. The group in the ED area were less ill at the outset, and, over time, they remained less impaired. There was no difference among the groups in exposure to antipsychotic drugs and there is no specific analysis comparing the duration between initial symptoms and initiation of drug. It seems that what one can conclude from this study is that if individuals are identified early, they tend to be less impaired and they remain so over time. It is hard to know if intervention of any kind had much effect. Again, this paper does not offer any specific information to inform us about impact — negative or otherwise — of the drugs.

The final paper is a thorough literature review of studies that analyzed the association between duration of untreated psychosis — and in this paper, treatment appears to be synonymous with initiation of drug — and various outcomes. They found that those started on drugs earlier had a more robust reduction of psychotic symptoms. They did not find conclusive evidence that the drugs had any impact on function or quality of life. They did not assess long-term outcomes.

It seems hard to support, based on these three studies, the assertion that “early initiation of antipsychotics may improve long-term course of the illness.”

This is not without import.

A frightened individual and his family comes in to my office. They want the best. In our current climate, there can be enormous pressure put on young people already in distress to try the drugs. They often do not like them and when they stop, well-meaning families may implore them to resume. This comes out of fear for the future. This can lead to alienation and a rupture between people who can be so critical to a person’s recovery.

We need to be honest with individuals and their families about what we do and do not know. It does not seem that there is adequate evidence to insist on the drugs as a way to improve long-term outcome and my own experience suggests this insistence can do harm.

I will be discussing this in my lecture on the MIACE course on Psychiatric Drug Withdrawal.


s-steingardDr. Sandra Steingard is Medical Director at HowardCenter, a community mental health center where she has worked for the past 21 years. She is also clinical Associate Professor of Psychiatry at the College of Medicine of the University of Vermont. For more than 25 years, her clinical practice has primarily included patients who have experienced psychotic states. Dr. Steingard serves as Board Chair of the Foundation for Excellence in Mental Health Care.

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