Are relapse prevention and functioning sufficiently prioritized in the treatment of schizophrenia?

Schizophrenia is a progressive disease characterized by multiple psychotic relapses. In addition to causing acute distress and disruption to patients and carers, relapses contribute to cumulative deterioration in occupational and social functioning.^1,2 Risk of relapse is high, reaching 16% within one year of a prior episode of psychosis and over 50% within two years.³

That said, there are differences between patients in the course of disease.⁴ And optimizing treatment, so that risk of relapse is reduced i.e., LAI treatment and hence functioning is preserved, can make a positive difference for people living with schizophrenia.

Relapse fuels disease progression, so the priority is prevention

Early intervention brings benefits

Effective management begins with early detection and intervention, Charlotte Emborg (Opus Clinic, Aarhus University Hospital, Denmark) emphasized. According to the Treatment and Intervention in Psychosis Study, early detection of first episode psychosis (FEP) is associated with significantly improved chances of recovery, independent living and full-time employment at ten years when compared with patients whose FEP was detected using standard procedures.⁵

This finding is complemented by evidence that shorter duration of untreated illness predicts superior functional outcome⁶ [see also https://progress.im/en/content/strategies-reducing-duration-untreated-psychosis] and by data showing that risk of hospitalization is significantly reduced (32% vs 42%) when early intervention services are compared with treatment-as-usual for people with early-phase psychosis.⁷

Clinical and functional remission go hand in hand, and both are needed to achieve a good therapeutic result, Philip Gorwood (Institute of Psychiatry and Neuroscience of Paris, Paris France) told at the Satellite symposium. This is probably most evident in the first decade of the disorder.

The importance of relapse prevention

Early treatment and maximizing adherence are the most important challenges in managing schizophrenia, he continued. But if we are successful in reducing relapses, there will be less stigma; and patient autonomy, social integration and self esteem will be reinforced – all of which facilitate functional remission.

Crucially, we also know from long term imaging studies that longer duration of relapse correlates with loss of total cerebral volume and volume of frontal white matter.⁸

Outcome can also be optimized by encouraging good adherence with treatment, said John Kane (Donald and Barbara Zucker School of Medicine, Hempstead, New York, USA). This may be aided by the use of LAIs, he continued. Yet, despite real-world evidence of improved clinical outcomes and the availability of a number of options for treatment with an LAI, this treatment strategy is still used sparingly.

Professor Kane further argued that LAIs should be offered to all patients who need treatment with an antipsychotic medication, including those with early-stage schizophrenia. To help this happen, all clinical staff should be aware of the rationale for using LAIs. They should also understand the best way of communicating this treatment option to patients and their families.

Acceptance can be encouraged by emphasizing that LAIs have been shown to contribute to the achievement of patient goals. Explaining the case requires time, patience and persistence. 

Putting a persuasive case

Communicating the case for LAIs needs understanding, patience and persistence; but can improve outcome for all concerned

The speakers noted several aspects pertaining to use of LAIs in practice, including data noting that medication is effective in preventing relapse, with a number needed to treat (NNT) as low as three.⁹ They also noted that many patients do not take oral medications as prescribed: in a large Finnish study involving 2588 patients, more than half either failed to collect a prescription on discharge or did not use their medication for more than thirty days.¹⁰ However, lack of adherence is difficult to predict in individual patients and the most frequent reason for relapse or hospitalization is inadequate adherence. A study showed that stopping medication was associated with a five times greater risk of first or second relapse than continuing therapy.³ The use of LAIs has also been shown to enhance adherence and reduces rehospitalization when compared to oral antipsychotic medication.^10,11 

Working with patients to enhance adherence

Recommending that a patient takes their medicine as prescribed is one way of attempting to improve adherence. Daily reminders may also be beneficial. However, providing the medicine in a long-acting formulation may be more effective. Patients do not necessarily hold negative views about LAIs, and there is evidence that their under-use is due more to ambivalence among psychiatrists,¹² Professor Kane said.

By way of encouragement, he cited very recent evidence from a study showing that it is possible to obtain agreement to receive injections in a high proportion of eligible patients even in the early phase of the disease.¹³

In this trial, outpatient centers have been randomized to treatment-as-usual or a program encouraging use of an LAI. This involved training staff in shared decision-making and how to discuss LAIs with patients and families. Of 576 patients who were potentially eligible, only 14% declined to participate in the trial because they would not consider taking an LAI. Of the final population of 234 participants, 91% accepted at least one long acting injection during their first three months in the study.

Given that patients and clinicians have the joint aim of improving function and quality of life, can our assessment of these outcomes be improved? Matthew Taylor (University of Oxford Medical Sciences Division, UK) posed this question. Typically, personal and social functioning has been assessed by unstructured clinical interview, but patient and clinician perceptions may be poorly correlated.¹⁴

More objective assessments such as the Global Assessment of Functioning (GAF) have become available. Professor Taylor also looked forward to technological advances which will enable us to obtain richer detail on patients’ assessment of their own state of health in the real world.¹⁵

Educational financial support for this Satellite Symposium was provided by H. Lundbeck A/S.