Raising the standard of care in the treatment of schizophrenia: Yes we can!

Abstract

Objective:

In response to evidence of deteriorating outcomes of people with schizophrenia we recently published a critical review in the journal concerning why outcomes for schizophrenia are not improving. A published commentary on our review raised criticisms that we aim to address herein.

Method:

Published data related to four issues raised in the commentary were reviewed.

Results:

There is a body of evidence that supports the possibility of dramatic improvements in treatment effectiveness, presented in our critical review, and these can be achieved within existing financial resources and present day understanding of the pathophysiology of schizophrenia. However, the commentary leads us to highlight four current obstacles to improving treatment effectiveness: (1) the belief of many psychiatrists that long-term antipsychotic medication raises the cardiovascular mortality rate in schizophrenia when the opposite is almost certainly the case; (2) the need to improve psychiatrist training in diagnostic and communication skills, especially with first episode presentations; (3) the requirement for comprehensive and structured assessment of the highly prevalent deficits in insight and decision making capacity associated with schizophrenia; and (4) the need for improved intervention design to minimise the impact of these deficits on treatment choice and refusal.

Conclusion:

With a sense of professional urgency, a genuinely respectful and caring partnership between clinicians, affected individuals and their families, and researchers, with relative little innovation, we conclude that the standard of care can definitely be raised now in the treatment of schizophrenia.

We were disheartened by the Siskind and Dark (2016) commentary on our call to arms in the cause of improving the appalling outcomes of people with schizophrenia, namely a median recovery rate of 13.5%, an apparently worsening morbidity rate and an elevated preventable mortality rate (Catts and O’Toole, 2016). We believe unintentionally Siskind and Dark offer a tacit apology for existing standards of care, by suggesting our ‘challenge’ might contribute to ‘honing services’, rather than offer a blueprint for radical re-engineering of services. You do not ‘hone’ your fire-fighting skills when your house is burning down. Our profession’s inability to agree on what constitutes best practice and deliver it is in stark contrast to fields such as oncology (Mukherjee, 2010); it’s our patients and their families who pay the price for our deficiencies. The commentary raised four specific issues we now want to rebut.

First, Siskind and Dark assert that we state that we cannot be sure relapse contributes to treatment resistance. As we note, there are no absolute certainties in the schizophrenia research field; however, we reviewed 15 sound independent studies showing an obvious association between relapse and treatment resistance, and cite one study that demonstrates that relapse prevention via high rates of medication adherence strongly predicts high long-term remission rates (Girgis et al., 2011). Another large sample study of Chinese patients with schizophrenia comparing those who were never treated with antipsychotic medication with those who were, at 14-year follow-up showed that those who received medication had higher remission rates, lower psychosocial morbidity and lower death rates, consistent with the conclusion that absence of long-term antipsychotic treatment, and extended periods of active psychotic illness, is causally associated with treatment resistance (Ran et al., 2015), as other studies have shown (Catts and O’Toole, 2016). Of course, for many of us clinical experience has been the best teacher of the value of relapse prevention in avoiding treatment resistance. The question arises as to how much quality evidence do we need before we will prioritise relapse prevention as the most powerful modifiable risk factor for long-term poor outcomes in schizophrenia?

Second, in support of the current practice of delay in making the diagnosis of schizophrenia Siskind and Dark assert that there is ‘diagnostic instability in people with early psychosis’, without providing any evidence that this instability affects the diagnosis of schizophrenia. Of course, there will be diagnostic instability if the non-diagnosis of ‘early psychosis’ is made, but published evidence indicates the diagnosis of schizophrenia is particularly stable, more than 90% of patients retaining their initial diagnosis at long-term follow-up (e.g. Salvatore et al., 2011). We purport that delaying the diagnosis of schizophrenia after the diagnostic criteria are met can be construed as malpractice. We also do not accept Siskind and Dark’s view that entry into a specialised early psychosis programme will ensure a long-term assertive approach to medication adherence, especially as the relevant clinical practice guidelines include neither evidence-based objective adherence monitoring interventions nor evidence-based multi-modal approaches to improving adherence to oral medication.

Third, Siskind and Dark assert that we ‘insufficiently highlight the cardio-metabolic adverse drug reactions associated with anti-psychotic medications’ despite the fact that we directly refer to the need for effective preventive physical health measures twice in the text, once in the Figure, and once in the Table. The point that Siskind and Dark miss, along with many of their colleagues, is that in schizophrenia the best way to reduce cardiovascular disease and death, and suicide, is to ensure long-term maintenance antipsychotic medication (Catts and O’Toole, 2016). All seven large cohort studies published to date indicate that the use of antipsychotics is associated with a lower risk of death, and a lower risk of severe health problems, when compared with no antipsychotic use (Tiihonen, 2016). Indeed, it is the first episode patient who has most to gain, antipsychotic medication reducing the relative mortality rate from a 10-fold increase over that of the general population to a twofold increase. Antipsychotic medication does not appear to contribute at all to the raised cardiovascular disease-related mortality rate in schizophrenia, implicating unhealthy life style behaviours (e.g. smoking) and poor preventive physical health care as the major culprits in this morality rate: assertively addressing these latter issues is a core component of our treatment algorithm. We completely reject the commentary’s conclusion that the cardio-metabolic risks of antipsychotic medication justify the 2016 Royal Australian and New Zealand College of Psychiatrists (RANZCP) guidelines (Galletly et al., 2016) around cessation of antipsychotic medication, which support consideration of cessation as early as 12 months after remission in schizophrenia.

Finally, Siskind and Dark raise complex issues by asserting that our advocacy for long-acting injectable antipsychotic (LAIA) medication use as soon as the diagnosis of schizophrenia is made (assuming no contra-indications) ‘neglects the importance of consumer choice, self-determination and shared decision-making’ also asserting that ‘extinguishing symptoms is not the only, and not necessarily the most important, facet of a consumer’s recovery journey’. These assertions raise multiple issues but at the outset we state that our advocacy for LAIA maintenance medication as best practice in no way impinges on the right of patient choice in those who retain decision making capacity (DMC); what we say is that patients who do not lose or who re-gain DMC should be made aware of the research evidence and advised that LAIAs offer them the best chance of avoiding re-hospitalisation and retaining long-term recovery. And if the patient with schizophrenia was to lack DMC then the substitute decision-makers ought to have strong reason to decide that the incompetent person with schizophrenia ought not to receive maintenance treatment in a LAIA formulation. These propositions bring into focus the critical issues of the assessment of DMC (e.g. Appelbaum, 2007) and its key predictor, lack of insight (e.g. Cairns et al., 2005). Lack of insight is the most prevalent symptom of schizophrenia affecting as many as 97% of first presentation patients (World Health Organization, 1973); given its impact on DMC one might think an instrumental assessment of insight (e.g. David, 2012) in schizophrenia would be recommended as best practice in the 2016 RANZCP guidelines (Galletly et al., 2016), but it is not. More importantly, given how crucial DMC is to involuntary treatment determinations, you might think an instrumental assessment of DMC (e.g. Appelbaum, 2007) would be recommended as best practice in the 2016 RANZCP guidelines, as it is in the United States (Kozlowski-Gibson, 2016), but it is not. Not even the teach-back method (White et al., 2013) is noted in the Guidelines. Rather than undermine the patient’s autonomy, our algorithm calls for vastly greater attention to how information about best practice is delivered to patients and their families, far greater recognition of the prevalence of deficits in insight even in patients with apparent DMC, far greater effort to validly and reliably assess deficits in insight and DMC and far greater effort in designing psychoeducation and treatment to minimise the impact of deficits in illness awareness (anosognosia) on patient refusal of treatment, as is done in neurology (Prigatano and Morrone-Strupinsky, 2010). In terms of Siskind and Dark’s view that our algorithm only focuses on ‘extinguishing symptoms’ (though we think this a worthy aim in its own right), this clearly is not the true scope of our algorithm. We think we can realistically aim at arresting the disease process in the large majority of our patients offering them the hope of sustained recovery from schizophrenia. But this will require change in practice and new tools and training for clinicians. We suggest that an initiative in this field could be led and auspiced by the RANZCP, in the first instance, by convening a working party to oversee the design and evaluation of innovative practice and service delivery. It’s time for Psychiatry to form a genuine alliance with patients and their families, as in oncology (Mukherjee, 2010), to defeat the worst aspects of this disease now.