Outcomes in first episode manic psychosis

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It has already been a busy year for those of us who work in Early Intervention in Psychosis (EIP) services in England (Marwaha et al., in press).

In April, psychosis was the first mental disorder to have an NHS target, the Access and Waiting Time target. This target specifies that someone with suspected psychosis gets assessed, and if appropriate, will be allocated a care coordinator in EIP and started on NICE-concordant treatment within two weeks of referral.

In addition to this, services are now also working with those thought to be at clinical high risk for psychosis (Thompson et al., 2016) and many Trusts are expanding the age-range of EIP services to extend to all working age adults, up to 65, rather than the 14-35 age range to date.

The Mental Elf blog has covered many of the important developments in EIP of late:

In addition to improving the standards of EIP, there is increasing interest in expanding the EIP approach of service delivery not only to ‘prodromal states’ but also to disorders other than schizophreniform psychosis (Marwaha et al., in press). Traditionally, those with a new onset of an affective psychosis will come under the care of EIP and many of the arguments made for early intervention in schizophrenia also pertain to bipolar disorder.

Bipolar disorder is highly burdensome and the disorder typically begins in early adulthood (13-30 years). Response to pharmacological and psychological treatments is thought to be best earlier in the disorder (Bechdolf et al., 2010) and there is a step-wise decline in cognition, quality of life and employment with increasing numbers of episodes. Thus, as in the case of psychosis, early specialist treatment has the potential to change the outcomes of those affected. Specialist EI services for people with a first episode of bipolar disorder are limited within the UK context, though Danish evidence suggests they are clinically and cost-effective (Kessing et al., 2013).

More generally, it is increasingly clear that mood instability is important clinically, across diagnoses (Broome et al., 2015) and the Mental Elf has covered this topic as well as the relationship between cannabis use and mania.

The paper discussed here, Chang et al., (2016), presents a longitudinal 3-year follow up of first episode patients with mania with psychosis and those with a schizophreniform psychosis. This is an important study for those who work within Early Intervention in Psychosis services; although the majority of patients in such services will ultimately go on to have a diagnosis of schizophrenia, a substantial proportion will have an affective psychosis, presenting with either a depressive or manic episode, with psychotic features. Yet, most of the studies of first episode psychosis tend to be with patients with a diagnosis of schizophrenia; hence, this paper begins to fill an important aporia for clinicians and researchers interested in the early course of psychotic illness more generally.

Chang and colleagues helpfully summarise why understanding the early course of manic psychosis is important; despite an initially good treatment response, significant functional impairment may continue. Data suggests that prolonged duration of untreated bipolar disorder may result in elevated risk of recurrence and shortened inter-episode interval, declined response rate to both pharmacological and psychological interventions, and greater functional disability. This all points to the importance of early intervention in bipolar disorder, as well as in schizophrenia, and is a spur to further work in this area and the expansion of EI.

This study directly compared clinical and functional outcomes between first episode mania with psychotic features (FEMP) and first-episode schizophrenia (FES).

This study directly compared clinical and functional outcomes between first episode mania with psychotic features (FEMP) and first-episode schizophrenia (FES).

Methods

The study followed up a cohort of young Chinese patients presenting to a Hong Kong Early Intervention service, comparing those with first episode mania with psychotic features (FEMP) with those with first episode schizophrenia (FES) and their baseline pre-treatment status and the 3-year outcomes.

700 young people, between 15-25, were enrolled in the clinical service between 2001-2003, and of these 515 met ICD-10 criteria for FES or FEMP, with 420 completing 3-year follow up.

Case note information was used and data was extracted by research assistants. Baseline data included socio-demographic variables, age at onset of psychosis, and Duration of Untreated Psychosis (DUP), which was defined as time interval between onset of positive symptoms and first contact to psychiatric services. The final 3-year outcome included the clinical ICD-10 diagnosis. Positive and negative symptom were scored by the Clinical Global Impression – Severity of Illness Scale (CGI-S). Records of suicide attempts, violence, and substance abuse were recorded as was service utilisation, number and duration of inpatient stays, and receipt of financial welfare. Functional outcome was recorded by use of the Social Occupational Functioning Assessment Scale (SOFAS) and by vocational status. Functional remission was defined as attaining both sustained employment and SOFAS score of greater than 60 in the prior 12months.

The research group compared the baseline characteristics of study completers and non-completers, to assess for any possible bias in findings due to differential dropout. Group differences were compared, and multiple logistic regression analyses were performed to examine whether group membership predicted functional outcome.

Results

  • The main difference between study completers and non-completers was that study completers had shorter Duration of Untreated Psychosis (DUP) and lower baseline SOFAS.
  • Of the 420 completers, 374 (89%) had first episode schizophrenia (FES), and 46 (11%) had first episode mania with psychotic features (FEMP).
  • Comparing the groups at baseline, the FEMP were younger (mean of 19.7, FES 21.1), were more likely to be hospitalised (89.1%; 47.1% of the FES cohort), had shorter DUP, more severe positive symptoms, and lower SOFAS score.
  • However, at 3-year follow-up the FEMP patients had lower levels of positive symptoms, but a greater number of hospitalisations across the study period than the FES cohort.
  • At the end of the 3 years, the FEMP had higher rates of sustained employment, functional remission, and lower use of welfare.
  • The logistic regression analysis demonstrated that diagnostic group (FEMP or FES) predicted positive symptom score, SOFAS score, as well as sustained employment and functional remission.
First-episode mania with psychosis (FEMP) patients had better outcomes than first-episode schizophrenia (FES) patients.

First-episode mania with psychosis (FEMP) patients had better outcomes than first-episode schizophrenia (FES) patients.

Conclusions

Despite the seemingly positive findings, the authors conclude that:

less than half (45.7%) of FEMP patients achieved sustained employment and only 36.9% attained functional remission at the end of 3-year treatment indicate that FEMP is associated with pronounced functional impairment (Chang et al., 2016, p.3)

and that

our results highlight an unmet therapeutic need for developing specialized early intervention to FEMP patients to enhance their functional outcome in the initial, critical years of treatment (ibid, p.4).

This is an important conclusion to draw: those with first episode mania with psychotic features (FEMP) may do better in some respects than those with first episode schizophrenia (FES), but still have many hospitalisations and a significant proportion have a poor functional outcome, and present more unwell at baseline.

Some of this may be due to them being part of services that were initially designed for those with FES: hence, it is a genuine research question as to whether the prognosis can be improved further with bespoke EI bipolar services and an attention to the differences in care pathways and interventions required in the FEMP group. We should be optimistic that improved outcomes are achievable.

Diagnostic group membership of FEMP (vs. FES) predicted better 3-year outcomes even when baseline confounders were adjusted.

Diagnostic group membership of FEMP (vs. FES) predicted better 3-year outcomes even when baseline confounders were adjusted.

Strengths and limitations

The study has many strengths, including a large sample size, and a relatively high follow up rate. Further, the service from which the participants are drawn is geographically based, rather than being a specialist team or one with a complex set of referral criteria. Hence, the sample should be representative of the wider population and be epidemiologically representative.

However, there are some exclusion criteria that may result in a bias in the sample and limit the generalizability of the findings to other EIP teams. The group is younger than that seen in UK EIP services, 15-25 rather than 14-35, and excludes those who have already had one month of psychiatric treatment. Further, those with a substance-induced psychosis illness are also excluded; these latter two factors may lead to a selection bias against those with a less clear cut presentation (the FEMP perhaps becoming clearer after a month of treatment) or with comorbid substance use. Further, there is no discussion of how it was determined whether a substance induced psychosis is present. Diagnostic uncertainty is a key principle of EIP and one that clinicians should try and work with.

The variables studied seem to have been decided post hoc, rather than decided in advance and based upon clear hypotheses to be tested. This is an understandable limitation, given that the sample is drawn from a large clinical service, but it would be good to know which variables the authors would have examined ideally. Measures of mood symptomology are lacking, as are important indices of suicidal ideation and of substance misuse.

Although DUP is recorded, we don’t not know how long those with FEMP may have had mood problems prior to presentation and treatment. There is an absence of data on those who have presented with a first episode of depression with psychosis. In addition to hospitalisation, data on use of enhanced community support would be good to have included (such as use of crisis teams and home treatment) as would have been contact with police and other legal/court services.

An additional issue is the notion of employment as a dichotomous variable (employed or not), with the additional qualifiers as to whether sustained or full-time or part-time. However, what we don’t know is whether those with FEMP or FES participants returned to an occupation similar to that which they were in prior to their first episode. Hence, despite the apparently better functional outcome of those with FEMP, it doesn’t rule out that they may still have had an occupational decline. The authors appropriately note limitations to their study including variability in the quality of the documentation of the clinical records from which data is drawn, the low prevalence of FEMP in the sample, and the absence of data regarding mood symptoms.

Summary

Chang et al., (2016) present an important naturalistic follow-up of those with first episode schizophrenia (FES) and first episode mania with psychotic features (FEMP). The data presented suggests that those with FEMP have a better functional outcome than those with FES, but with more hospitalisations during their time with EIP services.

A strong case is made to develop Early Intervention services for those with Bipolar Disorder to improve these outcomes further.

These findings underscore the need to develop specialised early intervention services for FEMP to promote early functional recovery.

These findings underscore the need to develop specialised early intervention services for FEMP to promote early functional recovery.

Conflict of interest

Matthew Broome has worked in the area of mood instability and in Early Intervention in Psychosis service evaluation.

Links

Primary paper

Chang WC et al (2016) Three-year clinical and functional outcome comparison between first-episode mania with psychotic features and first-episode schizophrenia, Journal of Affective Disorders, Volume 200, August 2016, Pages 1-5, ISSN 0165-0327, http://dx.doi.org/10.1016/j.jad.2016.01.050

Other references

Bechdolf A, Nelson B, Cotton SM, Chanen A, Thompson A, Kettle J, et al. (2010) A preliminary evaluation of the validity of at-risk criteria for bipolar disorders in help-seeking adolescents and young adults. Journal of Affective Disorders 2010; 127: 316–20

Broome M.R., Saunders K.E.A., Harrison P.J., Marwaha S. Mood Instability: significance, definition, measurement. The British Journal of Psychiatry 2015; 207(4) 283-285.

Kessing LV, Hansen HV, Hvenegaard A, Christensen EM, Dam H, Gluud C, et al. Treatment in a specialised out-patient mood disorder clinic v. standard out-patient treatment in the early course of bipolar disorder: randomised clinical trial. Br J Psychiatry 2013; 202: 212–9.

Marwaha, S., Thompson, A., Upthegrove, R., Broome MR 15 Years On – Early Intervention for a New Generation. The British Journal of Psychiatry (in press).

Thompson, A., Marwaha, S., & Broome, M. R. (2016). At-risk mental state for psychosis: Identification and current treatment approaches. Advances in Psychiatric Treatment, 22(3), 186-193. doi:10.1192/apt.bp.115.015487

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Matthew Broome

Matthew is a Senior Clinical Research Fellow in the Department of Psychiatry, at the University of Oxford, Consultant Psychiatrist to the Oxford Early Intervention in Psychosis Service, Associate College Tutor for Oxfordshire, and Clinical Co-lead for the Early Intervention for the Oxford Academic Heath Sciences Network. Prior to his current post, he was Associate Clinical Professor of Psychiatry at the University of Warwick and Honorary Consultant Psychiatrist to the Coventry Early Intervention Team. He trained in psychiatry at the Maudsley Hospital, Bethlem Royal Hospital, and the National Hospital for Neurology and Neurosurgery and has a PhD in Psychiatry from the University of London and in Philosophy from the University of Warwick. Whilst in London, he worked with the Lambeth Early Onset Team (LEO) and set up the OASIS at risk service together with colleagues. He is a former chair of the Philosophy Special Interest Group at the Royal College of Psychiatrists and is series editor to the Oxford University Press series, International Perspectives in Philosophy and Psychiatry. He is an associate and handling editor for the British Journal of Psychiatry. Matthew’s research interests include the prodromal phase of psychosis, delusion formation, functional neuroimaging, the role of GABA in psychotic symptoms, mood instability, early intervention services, and the philosophy of psychiatry.

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