Antipsychotics lead to worse outcomes in first-episode psychosis

What happens when you give antipsychotic drugs at the first sign of psychosis? Worse results, according to a new study Schizophrenia Bulletin Open.

People who did not receive antipsychotic medications within the first month after being diagnosed with a first episode of psychosis were, on average, almost twice as likely to be in recovery after five years as those who received medications immediately. According to the researchers, this means that there are many patients who do not need antipsychotics, at least not immediately.

The authors of the study were Tommi Bergström of Jyväskylä University and the Wellbeing Services County of Lapland, Finland, and Tapio Gauffin of the Wellbeing Services County of Lapland, Finland.

After controlling for observable confounders, immediate antipsychotic medication was associated with a worse 5-year outcome compared with 1-month antipsychotic postponement. These findings align with previous research on need-adapted approaches and recent controlled trials, which suggest that there is a significant subgroup of patients with acute psychosis who do not require immediate antipsychotic treatment, and who may benefit from postponing medication. can help in identification, especially in first-episode cases. Those patients, he writes.

Bergström and Goffin used the Finnish National Health Registry to identify all people who met the study criteria. It involved 3714 adolescents aged 13–20 who had been diagnosed with a psychotic disorder between 2003 and 2013 and had never previously taken antipsychotic medications. Researchers followed their records for up to five years (or until death). During the first month after diagnosis, 1549 (42%) did not receive antipsychotics. Over five years, 29% never took medications.

The researchers found that, on average, those 1549 people were 1.8 times more likely to be cured after five years.

In this study, those who recovered were defined as those who were still alive and had not received any type of psychiatric treatment, supportive housing or disability allowance over five years. Researchers say these services are provided to the entire population as needed and are recorded in the registry based on their universal health care system.

Next, the researchers wanted to see whether the delay resulted in worse performance for those taking antipsychotics. That is, is there a subgroup of patients who need to be given the medications immediately and who would be harmed by waiting a month?

To test this, Bergstrom and Goffin looked only at patients who took the medications until the end of the study and compared those who started taking the medications immediately versus those who took the medications later.

They found that there were no differences in recovery and mortality rates for most outcomes, but people who started medications immediately were more likely to receive disability payments and die at a younger age than those who delayed taking medications.

The researchers write:

Since there may still be a subgroup of patients with psychosis who require immediate or preventive antipsychotic treatment to prevent a worsening course [first-episode psychosis]It was hypothesized that deferral of antipsychotics for those who ultimately used antipsychotics would be associated with worse outcomes. However, the findings do not support this hypothesis. There was no indication that antipsychotics started before a formal diagnosis of psychosis or immediate antipsychotic treatment for those who ultimately require antipsychotics would improve treatment outcomes.
They say, in fact, contrary to our hypothesis, the time after death [first-episode psychosis] It was found that treatment was significantly longer for individuals whose antipsychotic medication was postponed. Furthermore, after controlling for confounding factors in both sub-samples, immediate antipsychotic medication was associated with significantly higher disability proportions at the end of the 5-year follow-up period.

One argument often made against these types of studies is that they are misleading by indicating that the people with the most severe baseline symptoms are the ones who receive the drugs and are also the ones who are expected to have the worst outcomes. . Thus, people who receive medications will have worse outcomes not because of the medications but because of baseline severity.

To account for this, the researchers used a statistical model called stationary inverse probability of treatment weighting (SIPTW) to control for these potential confounds. After their analysis, all of their results remained the same, indicating that the findings were not due to confounding by signal.

This latest study builds on Bergström’s previous work, specifically a 2020 study that looked at the cumulative risk of antipsychotics for all patients with first-episode psychosis over 19 years. That study also found that people who took the most medications for the longest period had worse outcomes, including higher mortality rates. And the researchers controlled for confounding by indication in that study as well.

They wrote in that 2020 study that moderate and high cumulative exposure to antipsychotics within the five years before FEP was consistently associated with a higher risk of adverse outcomes during 19 years of follow-up, compared with low or no risk.

Researchers have found that cognitive-behavioral therapy without antipsychotics is just as effective for first-episode psychosis, with the addition of medications providing no additional improvement.

Previous research has also found that interventions including antipsychotic medications may lead to worse outcomes for people at high risk for psychosis.

And decades of research by luminaries like Wunderink, Harrow, and Jobe have shown that people who stop taking antipsychotics have better long-term outcomes.

Researchers have identified childhood trauma as the primary cause of psychosis, even as biological theories involving dopamine and genetics have been rejected. This is consistent with previous studies that found that experience of childhood trauma, but not heredity, was associated with psychosis.

Thus, interventions that focus on healing from trauma and that promote empathy, empowerment and human connection and respect for those with lived experience may be a more successful path to recovery.

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Bergström, T., and Goffin, T. (2023). Association of antipsychotic deferral with 5-year outcomes of adolescent first-episode psychosis. Schizophrenia Bulletin Open, 4(1), sgad032. https://doi.org/10.1093/schizbullopen/sgad032 (link)

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