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Long-term recovery and treatment resistance in first episode psychosis

PhD candidate Kristin Fjelnseth Wold

Picture of Kristin Fjelseth Wold

Kristin Fjelnseth Wold. Photo: Private.

Many people who experience mental illness wonder how the illness will affect their lives. This also applies to people with psychotic disorders. Psychotic disorders are often severe disorders that affect people's lives and functioning. The disorders contribute to high levels of personal distress, vast societal costs and significant reductions in life expectancy [1]. A diagnosis of psychotic disorder is however not a clear indication of a negative long-term outcome, as studies show a heterogeneous illness course. As much as 80% of first-episode psychosis (FEP) patients experience full symptom remission after the first episode, a subgroup of 10-20% do not relapse and some of these eventually stop treatment without negative effects [2]. However, more than 50% of individuals with a diagnosis of first-episode psychosis experience intermittent, but long-term, psychiatric problems and around 20% develop chronic symptoms and disability despite adequate treatment [2]. The wide range of possible outcomes of the disorders, including the “extreme” outcomes (comprising those with good outcomes who do not need further treatment or those who will not respond to treatment) reduce statistical power in treatment studies, hamper the development of new treatments and reduce the ability to personalize treatments.

Treatment resistance - when established treatment does not help

Approximately one third of patients with psychotic disorders do not respond to standard antipsychotic medication. It is well established that patients who do not respond to traditional antipsychotic treatment should be offered treatment with Clozapine [3,4]. Although Clozapine can be effective for some of these patients, there is usually a long delay before it is used, and for about half of these patients, even Clozapine seems to be ineffective. Some of these non-responding patients continue to be exposed to sometimes unwanted and often disabling side effects, with little if any clinical benefit. This happens because we do not have any other treatment options. Treatment-resistance is thus associated with particularly poor clinical outcomes and presents a major therapeutic challenge [5].

It is still not clear whether the group of treatment resistant patients is a categorically distinct subgroup or whether they represent the most severe cases on a continuum [6]. There is also a problem with being able to perform new treatment studies without having identified this group of patients, because approximately one third of participants in the new studies probably will be non-responders to the treatment tested and this will lead to reduced study power.

Recovery - who get better and what can we learn from this?

In recent years, studies have shown that more people get better after a psychotic episode than we previously thought. There is a group of first episode patients who seem to recover quickly after the first episode, or early in the course of the disease [7]. This is an important research area, because knowledge about this group can contribute to reducing stigma and bring hope, and give important information about how to provide better prognosis and outcome. If we are able to identify modifiable factors that can be associated with good outcome, we can focus on changing these factors and thus have the opportunity to increase the proportion of patients who get a better outcome [8].

Early and efficient treatment

There is reason to believe that risk and vulnerability factors related to the development of psychotic disorders also predict treatment response and long-term outcome. Studies show that early course characteristics may give indications of longer-term outcome [8]. The early clinical phases of the disorders provide an important window to our understanding, since symptoms and functioning will be less confounded with the effects of treatment and non-response. There is still a lack of long-term outcome studies, including longitudinal studies focusing on the treatment resistance and recovery groups.

In my doctoral project, we will therefore try to identify and investigate the groups of patients who seem to recover quickly and those who do not seem to respond to the treatment they receive. We want to investigate whether these groups have any specific clinical characteristics, risk factors or genetic common features. We will investigate how these patient groups change over a ten-year period. In the project, we will also focus on childhood trauma as a specific risk factor for treatment response, long-term course and outcome of first-time psychosis.

We think it is important to identify risk factors leading to more serious and long-term course in order to be able to provide the right treatment early on for each individual patient. If we can say something about who need what kind of treatment earlier in the course of illness, we might be able to prevent more serious course and outcome of the disorders, be able to better distribute resources in the health care system and make it possible to adapt personalized treatment.


  1. Whiteford HA et al., (2013) Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010, The Lancet, 2013;382(9904):1575-86.
  2. Owen MJ, Sawa A, Mortensen PB., (2016) Schizophrenia, The Lancet, 2016;388(10039):86-97.
  3. Lally J, Gaughran F., (2019) Treatment resistant schizophrenia - review and a call to action, Ir J Psychol Med, 2019;36(4):279-91.
  4. National Collaborating Centre for Mental Health (Great Britain), National Institute for Health and Care Excellence (Great Britain). Psychosis and schizophrenia in adults: treatment and management. Updated edition 2014. ed.
  5. Howes OD et al., (2017), Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology, Am J Psychiatry, 2017;174(3):216-29.
  6. Gillespie AL, et al., (2017) Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review, BMC Psychiatry, 2017;17(1):12.
  7. Simonsen C., et al. (2017) Early clinical recovery in first-episode psychosis: Symptomatic remission and its correlates at 1-year follow-up, Psychiatry Res, 2017;254:118-25.
  8. Austin SF., et al. (2013), Predictors of recovery in first episode psychosis: the OPUS cohort at 10 year follow-up, Schizophr Res, 2013;150(1):163-8.




Published Feb. 25, 2021 12:05 PM - Last modified Feb. 26, 2021 5:48 PM