Early psychosis intervention works, but can we move to prevention?

Many individuals at high familial risk of schizophrenia show cognitive and social impairment well before the illness onsets, according to a pioneering study in Denmark. This finding fuels efforts to enhance resilience. The Danish OPUS trial in first episode psychosis also contributes greatly to the convincing meta-analysis showing comprehensive early intervention brings both functional benefits to patients and savings for society. 

Compared with the wider population, individuals with one or both parents who had a diagnosis of schizophrenia:

  • Grow up under difficult circumstances. The home environment was judged inadequate – largely because of absence of stimulation – in 21% of cases. This was true of only 2% of families in the control group.
  • Were more likely to have had a delayed start to education (17% vs 7%)
  • Are significantly more likely to have been diagnosed with a childhood psychiatric disorder, mainly anxiety or ADHD
  • Have poorer cognitive function, language skills and fine motor control
  • Are more likely to have had psychosis-like experiences such as hearing voices or having visions
  • Show less awareness of others in a test of theory of mind.

All of these findings, presented by Merete Nordentoft (University of Copenhagen, Copenhagen, Denmark) during her plenary lecture at ECNP 2019, are from the seven-year assessment of children enrolled in the High Risk and Resilience Study which recruited 522 families, 202 with children where one or both parents have schizophrenia.

Some at-risk children are widely disadvantaged, others do well. We need to promote resilience

On the negative side, there is a group of children at risk of schizophrenia who show disadvantage across all domains of functioning. This proportion of multiply-disadvantaged children is greater than that seen in control families. But, to be more positive, around a third of at-risk children are doing quite well, Professor Nordentoft said.

 

A magnum OPUS
Another Danish initiative, the OPUS trial, is undoubtedly great work. But for Professor Nordentoft the name also has a specifically musical connotation. Given the heterogeneity among people with first episode psychosis, the assertive treatment program which the study compared against ‘treatment as usual’ (TAU) had to be pragmatic enough to play a range of tunes.

In the trial, 275 patients were randomized to OPUS and 272 to receive (TAU). All were offered standard treatment for another three years.

Comprehensive intervention brings functional benefits to patients and savings for society 

The coordinated, community-based program included social skills training, cognitive behavior therapy and treatment for substance abuse. Recognizing everyday practicalities, there was also counseling about debt. And central to the program was family psychoeducation.

In 90% of cases, families did in fact become involved. And the OPUS team consciously regarded them as the closest of partners, a resource that could not be matched and as co-sufferers whose mental health also needs to be protected. “Thank you for your engagement” was an acknowledgement frequently and sincerely used. 

The study also recognized that there was a delay before patients became engaged in healthcare. The mean duration of untreated psychosis was nine months.

 

Rewards personal and financial

Satisfaction with treatment was greater in the intervention group, and there was a larger decrease in psychotic symptoms overall. But perhaps the most pleasing outcome was the increased number of patients who were able to live independently at seven years.

There have also been health economic benefits.1 Due mainly to a reduced number of days spent in a hospital or an institution, the bottom line showed that OPUS intervention led to a 24,000 Euro saving per patient over the first five years.

Improved outcome following comprehensive early intervention is now evident in a meta-analysis of trials which included OPUS, RAISE in the United States and PIANO in Italy.2

Even so, long-term follow-up studies indicate that the prognosis of people with first episode psychosis is very diverse.3 Some have high levels of functioning and are able to stop taking antipsychotic medication. There are others for whom not taking medication poses a clear risk of relapse. And there are others still who experience chronic illness and need to be supported with aspects of daily life.

Mental illness is a severe public health problem, and we need to be correspondingly ambitious in our efforts at prevention

 

Be ambitious about prevention

We should be doing more to improve the prospects for people with mental health challenges in general, and for underserved schizophrenia patients in particular. Mental illness is a severe public health problem, and we need to be correspondingly ambitious in our efforts at prevention, said Professor Nordentoft.

Professor Nordentoft noted that other speakers have been correct in drawing a parallel with cardiology4 or, we might add, cancer. In terms of prevention, we in psychiatry are in some ways still at a stage equivalent to intervening only after a myocardial infarction, or the development of metastatic disease.

Early intervention in psychosis is key to the future of psychiatry, especially since Christoph Correll’s 2018 meta-analysis of ten trials demonstrating that early intervention is clearly superior to treatment as usual in improving symptoms, function and quality of life.2

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

1. Hastrup LH et al. Br J Psychiatry 2013;202:35-41.

2. Correll C et al. JAMA Psychiatry 2018; 75:555-565

3. Wils RS et al. Schizophr Res 2017;182:42-48.

4. Insel TR.  Nature; 11;468:187-93.

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