Does Longer Duration of Untreated Psychosis Cause Worse Outcomes?

New research counters the long-held assumption that a longer duration of untreated psychosis is associated with worse outcomes.

Ayurdhi Dhar, PhD
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Conventional wisdom in the treatment of psychosis suggests that the longer psychosis goes untreated, the worse outcomes people will have long term. This position is often used to support the use of antipsychotics early in the course of treatment. A new study, published in The American Journal of Psychiatry, challenges the evidence for this position.

The researchers, led by Katherine Jonas at Stony Brook University, find that past research documenting a relationship between the duration of untreated psychosis (DUP) and worse long-term outcomes is likely an illusion created by lead-time bias. Their study found that rather than untreated psychosis causing adverse outcomes, those with a shorter duration of untreated psychosis “are in an earlier stage and therefore appear to have better outcomes than those with a long DUP, who are in a later stage.”

Duration of untreated psychosis (DUP) is the time period between symptom presentation and treatment, and many define it as the time between the emergence of psychotic symptoms and the first psychiatric hospitalization. For decades, longer DUP has been related to worse prognosis, higher symptom severity, problems in remission, and worse recovery outcomes. Thus, early intervention approaches often suggest immediate psychiatric intervention at the first sign of psychosis.

These understandings have been challenged on numerous grounds. Some authors have criticized that early intervention can lead to increased antipsychotic prescriptions, severe side effects, and an increased likelihood of involuntary commitment. Others point out that the fear around the relationship between DUP and outcomes has led to doctors consolidating more authority and more frequently restrain patients at the slightest hint of psychosis.

The debate over whether to begin antipsychotics immediately is especially important as studies have related being off antipsychotics with better psychosocial functioning and higher employment rates. Additionally, positive social relationships, alternate forms of integrated care, and even the simple frequency of social interactions with friends have been linked to better recovery, especially for first-episode psychosis. These new investigations have called into question where it is necessary to use antipsychotics as the first line of treatment for first-episode psychosis.

Additionally, while early treatment for psychotic symptoms can be beneficial, treatment does not always mean medication. Additionally, the relationship between longer DUP and patient outcomes is complicated. Most experts associate it with worse outcomes, but others find that in the long run, it is associated with less hospitalization and lower chances of being on disability.

This new study begins by noting that longer DUP has been repeatedly linked to worse prognosis, symptom severity, and other adverse events. They also note that the mechanism behind this is unknown.

One popular hypothesis explaining the relationship between worse outcomes and long DUP suggests that a more extended period of untreated psychosis causes degenerative neurotoxicity, and thus a decline in thinking and resultant chronic deficiencies. The evidence for degeneration in brain function is inconclusive, with recent research showing that antipsychotics themselves can cause brain changes. Another popular hypothesis advances the idea that more prolonged untreated psychosis is itself a marker of a severe form of schizophrenia, which is resistant to treatment.

The theory forwarded by the authors of this study suggests that longer DUP simply means that the illness has progressed significantly and thus appears to be more debilitating. In effect, longer DUP does not predict a worse outcome.

The authors wanted to test if lead-time bias explains the relation between worse outcomes and DUP. This is a type of bias where early detection of a disease can make it appear that the patient survived longer when compared to a patient who was diagnosed later. Thus, even though the two patients survive for the same amount of time with a particular disease, it gives the appearance that the former survived longer and had a better prognosis simply because they were seen earlier by a doctor. Because they were diagnosed earlier, the time from diagnosis to death will appear longer.

The researchers gathered data from the Suffolk County Mental Health Project; this included people with first-admission for psychosis between the years 1989 to 1995. Follow-ups using personal interviews were carried out at six months, 24 months, 48 months, ten years, and 20 years. Patient psychosocial functioning was assessed at baseline and the 6-month follow-up period using the Premorbid Adjustment Scale and Global Assessment of Functioning Scale.

The premorbid phase of a disease is the period before symptoms present themselves. Psychosocial functioning scales assess sociability and withdrawal, relationships with peers, academic performance, adaptation to school, and social-sexual relationships.

The researchers found some associations between DUP and psychosocial functioning at first admission, and at six and twenty-four month after admission. But outside of this time period, DUP was not related to psychosocial functioning, either in premorbid cases or in long-term ones. In effect, they provide evidence to support the hypothesis that the much-hyped association between longer untreated psychosis and worse outcomes is not due to a more serious underlying disease or because of neurotoxicity, but because of lead-time bias.

In other words, people assessed for response to treatment in the early stages of disease (shorter DUP) appear to be doing better because they are in early stages. Given time, they will progress towards more severe symptoms. Since these patients are observed earlier in their disease stage, they look like they are responding positively to treatment. Patients with longer DUP are seen later in their disease stage and thus seem to be doing worse. The absence of early treatment and diagnosis is blamed for this when it is merely the result of being observed by experts at later stages of a disease. They write:

“Long-DUP patients are ahead of short-DUP patients in illness progression at given study timepoint, causing spurious differences between groups even though they are on the same trajectory.”

The researchers found that in follow-up periods, shorter DUP was positively related to a worse decline in psychosocial function after the onset of symptoms. When viewed against the time of the first admission in a psychiatric facility, longer DUP appeared to show worse outcomes. But once the psychosocial functioning of the individual was analyzed against the onset of symptoms (not first admission), any relation to DUP vanished.

Both long and short duration of untreated psychosis patients experienced diminishing psychosocial functions, but the longer DUP patients experienced these declines before they were admitted the first time, whereas the short DUP patients showed these deficits after their first admission.

This gives experts an illusion of positive treatment result – in earlier stages when researchers assess outcomes of a treatment they administer, they observe that the treatment works. That is, it leads to the appearance that early intervention for psychosis was effective despite the fact that in both long-term and short-term patients, the trajectory of the disorder remained the same – they were just evaluated at different time periods. The authors write:

“These findings suggest a potential for biased inferences in studies of first-episode psychosis. Studies that assess outcomes for a short period after the first admission may identify protective effects of early diagnosis or treatment that actually reflect differences in illness stage rather than changes in the illness course.”

Essentially, the authors found that when they included lead-time as a factor to consider in the relationship between longer DUP and disease trajectory, longer DUP failed to predict worse outcomes.

Overall, this article is another piece of evidence in the line of recent research that challenges the traditional understandings and treatment of psychosis.

 

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Jonas, K. G., Fochtmann, L. J., Perlman, G., Tian, Y., Kane, J. M., Bromet, E. J., & Kotov, R. (2020). Lead-Time Bias Confounds Association Between Duration of Untreated Psychosis and Illness Course in Schizophrenia. American Journal of Psychiatry. Published online first: 12 Feb 2020. https://doi.org/10.1176/appi.ajp.2019.19030324 (Link)

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31 COMMENTS

  2. Untill now, was proven that antipsychotics cause brain shrinkage. This is measurable science.

    Why do they speak about “neurotoxicity of untreated psychosis”, yet they refer to cognitive (psychosocial etc) manifestations?
    Why can’t they bring evidence about any negative impact of untreated psychosis on brain as a physical organ?

  3. The longer a tree falls to the ground, the more danger there is, because the more impetus it gains falling from its height, the more upon hitting it’s target there will have been gravity involved.

    This is why we should make sure to get hist (oops I mean hit) often as possible by many many missiles called asteroids, then the planet will have more gravity, and the tree won’t take so long to fall!

  5. “Others point out that the fear around the relationship between DUP and outcomes has led to doctors consolidating more authority and more frequently restrain patients at the slightest hint of psychosis.”

    That’s the problem the patients are so ‘cute” and the doctors are so…..

    And the answer probably isn’t taking a squirt gun into “therapy” and shooting the doctor with kool aid.

    Besides, the keys that will release you aren’t ones he can hold, that would be like Hollywood selling keys to the city, or to release Pegasus for a joy ride, or who knows what!?

  6. Remember that line from Jerry MacGuire? “Show me the money!”

    Show me the disease!

    The fact that recovery can occur without medical treatment should really make us question the bio model.

    For the sake of argument, even if psychosis is linked to a brain disease–until scientists can produce a bio marker they don’t know what’s wrong and can’t fix it. Assuming improved brain function is what they are after.

    • There is a substance (kryptopyrolle) that appears in the urine of certain patients. Psychiatry ignores it, because patients excreting large quantities of it don’t have consistent DSM diagnoses, despite the dysperceptions that all the group members have, and that B6 and zinc in proper quantities will successfully treat all the varied diagnoses inflicted on the patients. (see Carl Pfeiffer’s volumes for more detail on the subject).

  8. Since most of the “mental health” workers today have delusions that thoughts, gut instincts, and dreams are all “psychosis.” This all sounds like a bunch of “invalid” theories about the “invalid” DSM disorders.

    https://www.nimh.nih.gov/about/directors/thomas-insel/blog/2013/transforming-diagnosis.shtml

    And since the antipsychotics create “psychosis,” via anticholinergic toxidrome.

    https://en.wikipedia.org/wiki/Toxidrome

    Which, of course, none of the psychiatrists I’ve known claim to be aware, despite being taught this in med school. I’m quite certain early antipsychotic treatment = bad outcomes for the patients. But that’s good for the p$ychiatri$t$.

  9. I can prove that neuroscientists researching frantically for a cure for “schizophrenia” cannot tell the difference between akathisia and “Psychosis”.

    I can prove that these neuroscientists would sooner kill psychiatric patients than acknowledge recovery from non chemical means.

    I can prove what I say from my own historical and present day medical records.

  10. To be as honest as possible and try to squeeze a response in

    This whole thing is like saying that the amount of time it takes to make plans that work decides whether they will.

    Psychosis is simply finding what works, for that person who is going through it, you give a person that right and they will. But handing out what-works-for-others-not-going-through-psychosis to gain control so that those who are going through it are hampered, and then say time is involved in a negative way. Why is it negative? Who is stuck not seeing as negative? Is it negative? If it was positive would there be more of it?

    That I would go back now and believe all of whatever wasn’t allowing me to let go of what simply didn’t work, and put how CONFUSING it ended up being when discouraged from finding my own answer in a list of symptoms, as if there was no reason for me to be confused…..

    And now that I’ve gotten this far, it’s not about being a working member of society; it’s about miracles, which were happening the whole time, but in the background and now have stepped forward rather than further away or down under or hidden or anything like that.

    And yet I hear the birds come and cry at my window every day, because of what’s lost to them, thanks to how “man” cares for nature.

  14. Longer duration of going untreated does have worse outcomes-for psychiaytrists.

    Fewer pills=no lavish vacations called education, and no token gifts like fruit baskets woven from gold wires or diamond studded fountain pens.

    Your psychiatrist’s new 80 foot yacht won’t pay for itself.

  16. It is a selection bias.

    Suppose 1000 people are going through a psychotic crisis in families refusing psychiatric treatment.

    Suppose, 5 years later, 90% have recovered, and 10% have worsened.

    In desperation, the families of these 10% finally hospitalize them.

    In this case, we observe that 100% of people hospitalized have worsened in the last 5 years. Psychiatrists might observe that, in this group of chronic psychotics, the recovery rate is only 5%. But it is a selection bias: the original sample of this group was 1,000 people, and 90% of this group have recovered and will never go to psychiatry. They are therefore invisible.

    Now suppose 100 people are going through a psychotic crisis, but this time, in families following the recommendations of psychiatrists, and immediately hospitalizing their loved one.

    Suppose that with medication, 5 years later, 30% of people recover and 70% become chronic psychotics.

    Thus, according to psychiatric observations:

    30% of psychotics treated immediately recover, 40% become chronic;
    5% of psychotics treated 5 years later recover, 95% remain chronic.

    But according to the actual data:

    90% of psychotics never treated recover, 10% become chronic;
    30% of psychotics treated immediately recover, 70% become chronic.

    –

    Association ≠ causality.

    Sometimes a negative association can reveal positive causation.

  17. The solution is a lobotomy which is EXACTLY what the pills do.
    It does not fix, it cuts out, but it cuts out random all over the place and kills the whole body, just super slow. It causes a hundred more effects that the person originally had.
    It kills,
    So slow in fact that the person just walks slower and slower.

    Nice life.

  19. How the hell can psych drugs or any other form of “mental health” intervention AKA abuse address any bona fide medical conditions?

    It can’t. It can only worsen the underlying condition.

    Many more such as dehydration, lack of sleep, being in the toxic death trap called a hospital, being on a ventilator, Urinary tract infection, & adverse events to over 500 drugs are not even listed.

    Perpetuating myths and lies that depression, anxiety, psychosis being “mental illness” is CRIMINAL. Failure to include these facts, is disingenuous collusion, at best.

    • disorders causing delirium (toxic psychosis), in which consciousness is disturbed
    • neurodevelopmental disorders and chromosomal abnormalities, including velocardiofacial syndrome
    • neurodegenerative disorders, such as Alzheimer’s disease,[34] dementia with Lewy bodies,[35] and Parkinson’s disease[36][37]
    • focal neurological disease, such as stroke, brain tumors,[38] multiple sclerosis,[37] and some forms of epilepsy
    • malignancy (typically via masses in the brain, paraneoplastic syndromes)[37]
    • infectious and postinfectious syndromes, including infections causing delirium, viral encephalitis, HIV/AIDS,[39] malaria,[40] syphilis[41]
    • endocrine disease, such as hypothyroidism, hyperthyroidism, Cushing’s syndrome, hypoparathyroidism and hyperparathyroidism;[42] sex hormones also affect psychotic symptoms and sometimes giving birth can provoke psychosis, termed postpartum psychosis[43]
    • inborn errors of metabolism, such as Succinic semialdehyde dehydrogenase deficiency, porphyria and metachromatic leukodystrophy[44][45][46][47]
    • nutritional deficiency, such as vitamin B12 deficiency[8]
    • other acquired metabolic disorders, including electrolyte disturbances such as hypocalcemia, hypernatremia,[48] hyponatremia,[49] hypokalemia,[50] hypomagnesemia,[51] hypermagnesemia,[52] hypercalcemia,[53] and hypophosphatemia,[54] but also hypoglycemia,[55] hypoxia, and failure of the liver or kidneys
    • autoimmune and related disorders, such as systemic lupus erythematosus (lupus, SLE), sarcoidosis, Hashimoto’s encephalopathy, anti-NMDA-receptor encephalitis, and non-celiac gluten sensitivity[44][56]
    • poisoning, by therapeutic drugs (see below), recreational drugs (see below), and a range of plants, fungi, metals, organic compounds, and a few animal toxins[19]
    • sleep disorders, such as in narcolepsy (in which REM sleep intrudes into wakefulness)[19]
    • parasitic diseases, such as neurocysticercosis

  20. If DUP doesn’t predict outcome, because when in treatment the course is the same, I can only conclude that the treatment is not effective, and probably becomes the main cause of bad outcomes in the longer run.

    “The evidence for degeneration in brain function is inconclusive, with recent research showing that antipsychotics themselves can cause brain changes.”

    This was known in the 50s after haldol was beginning to be used. If tardive dyskenesia doesn’t hint at “brain change”, what causes it? A swarm of invisible ants biting you, causing the movement disorder?

      • When I was first escorted into a psych hospital for a prolonged stay many years ago, my mother asked why a lady sitting nearby had such uncontrolled movements in her legs. The psychiatrists response was: “Oh, don’t pay that any mind, they don’t even notice it”. I wonder what this shrink would say about parkinson?

        • I would also like to mention this psychiatrist had his own hobby (fetish). He would lay you down and with some magic balls he had, identify points in your head and pierce you with a piece of metal there, give you a magnet and tell you to stimulate the metal. There was also a Chinese (witch) doctor there who once gave me a potion of crushed scorpions that he said would be helpful. None of it did anything. Needless to say, psychotropic medication was standard and not discussed.

          • It is so very disgusting, yet you do realize that many people visiting a psychward simply look on, like people do when they see someone hobbling around with an injury.
            Many observers are aware, yet feel silenced or feel that is the way an MI looks.

            I remember years ago with my “postpartum” going to a friend’s/nurse/believer choice of “wonderful shrink” who happened to work in a unit.
            When I arrived for my appt, I was watching a woman walk down the hallway, (she had been outside) and as she slowly walked as if in slow mode, she dropped a glove, walked a few more steps until her brain realized she dropped a glove. She then turned around slow motion, and picked up her glove in slow motion.

            My whole appt I was only thinking about that woman, and I can’t remember if I asked about it, but I knew I would never have a second appt.
            It is so long ago, 27 years and I can’t remember ANYTHING about that appt, don’t remember what the good scientific doctor said, but to this day, I remember that woman.
            I knew she was being assaulted in unforgivable, unacknowledged, uncivil ways, in the disguise of chemicals they refer to as “medication”

            We should never refer to those chemicals as “medication”. They are simply chemical castration. But at that, not even successful.

            It is why they like to lock them away, so the public can’t put 2 and 2 together.

  21. There is a substance (kryptopyrolle) that appears in the urine of certain patients. Psychiatry ignores it, because patients excreting large quantities of it don’t have consistent DSM diagnoses, despite the dysperceptions that all the group members have, and that B6 and zinc in proper quantities will successfully treat all the varied diagnoses inflicted on the patients. (see the late Carl Pfeiffer’s volumes for more detail on the subject).

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