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April 14, 2013 by Sandra Steingard, MD

Optimal Use of Neuroleptics, Part 3: Duration of Untreated Psychosis

For the past 20 years, there has been a prevailing concern in psychiatry that psychosis is bad for the brain. The notion is that the psychotic process is in and of itself damaging and therefore every effort should be made to curtail this process in order to forestall further damage. This idea heightened the urgency to initiate drug treatment. When I read Anatomy of an Epidemic, this was one of my most pressing concerns; If I suggested to my patients that they pursue other treatments before starting drug treatment, was I helping or harming them?

I wondered how this concept could be reconciled with Whitaker’s suggestion that long term exposure to neuroleptics was associated with a worse outcome.  This seemed like an urgent question and it led me to review the literature on this topic. The research into what has been called “duration of untreated psychosis” (DUP) is extensive.  I have tried here to present a fair presentation of the data although I will admit that a full review is beyond the scope of this blog.

In 1991, Richard Jed Wyatt wrote a highly influential paper entitled, “Neuroleptics and the Natural Course of Schizophrenia” (Schizophrenia Bulletin 1991, 17 (2): 325 – 351).  Wyatt was the Chief of the Neuropsychiatry Branch of the National Institutes of  Mental Health. In this paper, Wyatt reviewed papers in which patients diagnosed with schizophrenia were treated with and without neuroleptics and then followed for a period of time often after the initial treatment phase ended. In his conclusion, he asks, “Is there something that is toxic to the individual beyond the immediate psychotic episode?”  Although he may not have been the first person to ask this question, his opinion carried much weight in the field.  He answers this question as follows, “The thrust of this article is that some patients are left with a damaging residual if a psychosis is allowed to proceed unmitigated.  While psychosis is undoubtedly demoralizing and stigmatizing, it may also be biologically toxic.”

The paper, however, does not prove this.  In fact there are articles cited that contradict this conclusion (see Schooler, 1967, Carpenter , 1977, Rappaport, 1978).  Wyatt finds flaws in the methodology of those studies that lead him to question their outcomes more than he does those of the studies whose conclusions concur with his hypothesis.   Although Wyatt also reports on at least one study (Falloon,1989) which reports on very good outcomes using low dose short-term neuroleptics in combination with family support, this message – that low dose neuroleptic was as or may be even more effective than higher doses – was quickly lost in the era promoting the safety of the newer neuroleptics.

This paper led to further research on the topic.  It led to the development of early intervention programs.  It also led to studies whose aim was to evaluate whether the outcome is improved if people get into treatment sooner.  In most but not all of these studies, treatment is synonymous with drug treatment.

A Finnish study by Pentilla et al (Schiz Res 143 (1); 3-10,2013) tracked 89 individuals for 20 years after they were given a diagnosis of schizophrenia.  Initially, they found that in the first two years those who had a longer DUP spent more time in the hospital and had a higher re-hospitalization rate.  However, by 10 years, longer DUP associated with decreased risk of disability pension, less time in hospital, more time at work in the long-term outcome.

In another long term study by Hill et al (Schiz Research 141; 215-221, 2012), which followed 170 people for 12 years, longer DUP was associated with greater positive and negative symptoms, lower GAF, lower QLS.  However, longer DUP was not associated with functional impairment (working, living independently).

It appears that fewer studies have examined DUP in a broader sense, i.e., defining treatment as more than neuroleptic treatment. Haan et al (Schizophrenia Bulletin, 29(2):341-348, 2003) did examine this question. A distinction was made between DUP, defined as time between onset of psychotic symptoms and initiation of drug treatment, and delay of intensive psychosocial treatment (DIPT). They did not find that DUP explained poor outcome but they did find that DIPT had a higher probability of negative symptoms at 6 years independent of the influence of DUP, duration of treated psychosis, age at onset, and gender.

In the Open Dialogue system of care, time between developing psychosis and entering treatment is not ignored.  However, although they do not use these terms, they do pay attention to DIPT and they find it to have an negative impact on outcome (Seikkula, J et al Journal of Constructivist Psychology, 14: 4, 267 — 284, 2009). When they examined their outcomes, they found that those who had a longer period of time before entering treatment had worse outcomes  in a paradigm of care in which neuroleptics are not considered first line treatment.  Those with a worse prognosis had significantly greater exposure to drug treatment.

Poor Prognosis Good Prognosis
Hospital days ** 47.5 (56) 9 (19.2)
Ongoing medications (%)** 52.9 19.7
No medications used (%) 47.1 80.3

Patrick McGorry is probably the psychiatrist who has the most experience with early intervention including early use of neuroleptics.  In his current study (J Clin Psych Nover 27, 2012), however, he has chosen to compare the use of risperidone to cognitive therapy to supportive psychotherapy in individuals considered at ultra high risk of developing psychosis.  At 12 months, he found that there was no advantage to the use of risperidone.

So there is consensus that early intervention is a good thing. However,  treatment does not need to be synonymous with neuroleptics.

In my final blog in this series, I will talk about the challenges of so-called “compliance” and I will discuss my conclusions.

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