Changing the course of schizophrenia: biology, psychology and livelihood

Shelter from the storm

Professor Eduard Parellada (Hospital Clinic of Barcelona, Spain) opened the meeting by posing the question: “Can we alter the trajectory of schizophrenia?” He focused on the so-called ‘glutamate storm’ as a possible mechanism for neuroprogression. At critical periods in the disease process, this excitatory ‘storm’ may trigger neurotoxicity, producing selective apoptotic effects on dendrite pruning and therefore on synaptic plasticity. This, in turn, can lead to deficits in learning and memory for patients. Such changes have been indicated at the biochemical level, where increased levels of apoptotic markers have been demonstrated in patients with first-episode schizophrenia,¹ and at the clinical level, where longer durations of relapses show positive correlation with brain-tissue loss.² 

Early and continuous use of second-generation antipsychotics, and strategies to prevent relapse, may afford patients protection against this damaging increase in apoptosis and dendrite pruning

Prof Parellada went on to discuss potential ways to mitigate these effects of the disease process. Early and continuous use of second-generation antipsychotics, and strategies to prevent relapse, may afford patients protection against this damaging increase in apoptosis and dendrite pruning. In addition, inhibitors of glutamate release have been studied in a mouse model for their potential to reduce glutamate toxicity at early or prodromal disease stages.

Using national data to understand the disease burden

A key aspect of the current disease trajectory was discussed by Prof Jari Tiihonen (Karolinska Institute, Stockholm, Sweden and University of Eastern Finland, Kuopio, Finland). He presented data on a 30-year follow-up of nearly 80,000 people in Finland. This showed that, although survival has improved overall in this time, the risk of mortality for patients with schizophrenia is still substantially higher than that in the general population.³

The risk of mortality for patients with schizophrenia is still substantially higher than the general population

Meta-analyses of randomized controlled trials and observational studies have all demonstrated that antipsychotics produce a reduction in mortality compared with placebo treatment. In addition, long-acting injectable antipsychotics have shown positive outcomes. Prof Tiihonen also presented results from a 20-year nationwide follow-up in Finland of patients with a first episode of schizophrenia.⁴ Those patients who took an antipsychotic throughout the follow-up showed only a 5% rate of mortality overall – a figure close to that of the general population. Strikingly, however, people who had been discharged after their first episode and never taken antipsychotic medication after that showed much higher rates of mortality than those who continued taking treatment. Thus, these patients did not need antipsychotic treatment to prevent relapses (as they had not been re-hospitalized), but arguably would have benefited from medication to prevent this excess mortality.

When patients were asked to give their reasons for adherence to their antipsychotic medication, fulfilment of their life goals was high on the list

Putting life in your days

How to discuss treatment with patients, and improve their functional outcomes was the issue discussed by Professor Rebekka Lencer (University of Münster, Germany). She described what can often be a frustrating mis-match between the physician’s conviction about the benefits of medication, and the patient’s expectations and desired outcomes from their treatment. When patients were asked to give their reasons for adherence to their antipsychotic medication, fulfilment of their life goals was high on the list. This also featured as a reason for non-adherence (if the drug was interfering with the patient achieving their goals). So, Prof Lencer asked the audience whether they were aware of their patients’ life goals? Did that feature in their therapeutic decision-making?

Do you know the life goals of your patients? Does it feature in your therapeutic decision-making?

Prof Lencer also discussed some of psychological effects of schizophrenia that could have an impact on treatment. Many patients, when asked what they wanted from treatment, stated that they wanted to improve their self-esteem.⁵ She linked this to patients’ self-concept of their own competence – many patients might doubt their competence to negotiate difficulties in their lives. Patients’ self-concept was enhanced by subjective well-being, and reduced by trait anxiety. A reduced self-concept was, in turn likely to lead to self-stigmatization – internalization of the stereotypes that are commonly held against patients with psychiatric disorders – and a reduced quality of life and adherence to medication (as the need to take medication may reinforce self-stigmatization).

Include patients’ goals in therapeutic decision-making

Include patients’ goals in therapeutic decision-making; so that patients’ goals, and the physician’s goals of treatment can be aligned

A new patient-centered approach to consultations

Prof Lencer therefore set out some steps that physicians could take to help counteract these negative psychological effects, and to include patients’ wishes in a meaningful way within therapeutic decision-making. She advocated asking patients about their life goals at an early stage, so that patients’ goals, and the physician’s goals of treatment can be aligned. The role of medications can then be explained in terms of supporting patients to achieve their life goals and enhance their competence. Physicians could also assess patients’ self-concept of their competence: ask what activities they like, what hobbies they have and are successful in, what in their life are they proud of? Each consultation could then be an opportunity to boost the patient’s confidence and competence, by asking such questions and complimenting the patient on their achievements.

The information presented by all three of these speakers points towards early and consistent engagement with patients, to allow effective and consistent use of treatments, designed to provide neuroprotection, increased survival and achievement of patients’ life goals.

Educational financial support for this symposium was provided by Janssen