The 2016 Royal Australian and New Zealand College of Psychiatrists guidelines for the management of schizophrenia and related disorders

Schizophrenia is a disorder characterised by symptoms that are positive (delusions and hallucinations), negative (social withdrawal, restriction of affect and paucity of thought) or disorganised (disordered form of thought and disorganised behaviours).1 In addition, many people with schizophrenia also have cognitive problems that further affect their functioning.1 According to the large-scale 2010 Australian National Survey of High Impact Psychosis (SHIP), the 1-month prevalence for schizophrenia and schizoaffective disorder in Australia was 2.1 per 1000 population aged 18–64 years.2 The SHIP study included patients in contact with treatment services; 81.6% of the patients were taking antipsychotic medications and, of these, 74.0% were on atypical agents (Box 1), 16.4% were on clozapine and 15.2% were on typical antipsychotics.3 Despite high rates of antipsychotic use, many participants in the SHIP study continued to experience delusions (41.3%) and hallucinations (37.5%), and most had an illness characterised by multiple episodes with partial recovery (31.8%) or continuous chronic illness (30.5%).3

The publication of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines for the management of schizophrenia and related disorders4 provides an opportunity to reflect on how the field of psychiatry has changed since the release of the previous guidelines in 2005.5 The new guidelines also allow us to bring Australian and New Zealand psychiatrists and general practitioners up to date regarding new treatment approaches, and to contextualise the management of schizophrenia in the prevailing health provision arrangements of the two countries.

This summary outlines the process of establishing the current guidelines, provides an overview of the scope of the final version, and gives some details about specific aspects of care most pertinent to general practice. The full guideline4 is available at https://www.ranzcp.org/Files/Resources/Publications/CPG/Clinician/CPG_Clinician_Full_Schizophrenia-pdf.aspx.

Background

The schizophrenia and related disorders guidelines are part of a suite of guidelines sponsored by the RANZCP across various psychiatric disorders, which aim to provide current, evidence-based recommendations for clinical care and to outline best practice. The guidelines are informed by recent research — including randomised clinical trial data — and incorporate clinician and researcher expert opinion. As such, they reflect clinical reality and are therefore responsive to the needs of clinicians in everyday practice. The current guidelines reflect the prevailing zeitgeist of staged care and the recovery paradigm, and place particular emphasis on the management of physical health problems pertinent to schizophrenia — an area of increasing concern, given the dramatically reduced life expectancy among patients with schizophrenia.6

Method

The RANZCP supported the establishment of a writing group that comprised eight psychiatrists working in a range of jurisdictions across Australia and New Zealand, a psychologist expert in youth-based services and an expert mental health pharmacist.4 After reviewing the existing international guidelines and the 2005 RANZCP schizophrenia guidelines,5 the group members agreed on the overarching scope and structure of the current guidelines and were allocated specific writing tasks based on their areas of expertise. Other experts were invited to assist with the drafting of particular components when there were evident gaps, and the process was overseen by the writing group through regular teleconferences and iterative cross-review of all the collated materials. The recommendations included the National Health and Medical Research Council (NHMRC) levels of evidence (Box 2), and were classified as evidence-based recommendations (EBRs) or consensus-based recommendations (CBRs).7 EBRs are based on clinical trial evidence, while CBRs are expert consensus encompassing all available evidence, including clinical experience; CBRs are thus arguably softer but more reflective of everyday clinical practice.

A draft version of the document was submitted for review to a wide range of organisations and individuals with an interest in mental health — RANZCP committees, cognate professional bodies, special interest groups and individual practitioners — and consumer and carer input was specifically sought. After consultation with an independent expert advisory group, the guidelines were then published in the Australian and New Zealand Journal of Psychiatry.4

Recommendations

The guidelines are structured as an introduction and six sections. The introduction provides an overview of the schizophrenia construct and key concerns regarding its epidemiology, neurobiology, longitudinal course and socio-economic costs. Much of this section was informed by publications from the second Australian SHIP study conducted in 2010.2,3,8

The stages of schizophrenia as a framework for clinical care

Section 1 introduces the stages of schizophrenia — pre-psychotic or prodromal stage; first episode psychosis; a stage of incomplete remission, recurrence or multiple relapses; and severe, persisting illness — as an overarching framework for the guidelines. This approach allows treatment to be targeted to an individual’s stage of illness. Section 1 covers the ultra-high risk state, where the patient shows certain subthreshold symptoms and disability; watchful monitoring and cognitive behavioural therapy (CBT) are recommended (EBR; NHMRC level I), but antipsychotics should be withheld until and if the person develops frank positive psychotic symptoms enduring for at least a week, or when CBT is ineffective or the individual is at risk of self-harm or aggression (EBR; level III-1). CBT is recommended because it seems to have some benefit for the patient in terms of ability to deal with symptoms and delay, and potentially reduce, transition rates; it has no obvious adverse effects.9 Antipsychotic agents are not recommended in the ultra-high risk stage, as the evidence for their efficacy in preventing transition to a full-blown psychosis is less unequivocal, and all have side effects, which may be distressing and cause physical health problems (such as weight gain).

In addition to recommending a thorough physical health check (Box 3), the guidelines give prominence to the treatment of a first episode of frank psychosis as it is a very sensitive part of the illness journey, and one in which getting it right is particularly important for patient and family engagement and for determining the longitudinal trajectory of the illness. Early treatment using the lowest effective dose of an antipsychotic is recommended (EBR; level II), and the choice of medication should take account of specific target symptoms and potential longer term side effects (EBR; level I). Use of second generation antipsychotics is suggested, although the clinician is reminded that this is a broad grouping of rather disparate drugs with differing pharmacodynamics and pharmacokinetics (Box 1). First-line options include daily doses of amisulpride (start with 50–100 mg; initial target dose 300–400 mg), aripiprazole (start 5–10 mg; initial target 15–20 mg), quetiapine (start 25–50 mg; initial target 300–400 mg), risperidone (start 0.5–1.0 mg; initial target 2–3 mg) or ziprasidone (start 40–60 mg; initial target 80–120 mg). Olanzapine is not recommended for first-line use, owing to its potential metabolic side-effect burden. Medications should be monitored carefully for efficacy and side effects (EBR; level II).

In the first episode, as in other illness stages, a comprehensive, multifaceted treatment plan encompassing psychological and psychosocial aspects of care (eg, vocation, studies and relationships) and including families wherever possible should be considered (EBR; level II). GPs are seen as a linchpin of the treatment team (CBR); as the individual moves further along the stages of illness, it is important to implement a recovery plan that is negotiated with the patient and open to regular review (EBR; level II). Peer workers with lived experience of mental illness are increasingly being deployed and may be highly effective in the delivery of recovery-oriented care (EBR; level III-2), and GPs should also be part of any such planning (CBR). Ongoing medication adherence is pivotal and should be subject to continuous attention (EBR; level II). Early use of long-acting injectable forms of antipsychotics should be considered and offered, particularly when there is a high risk of non-adherence to oral agents (EBR; level II).

Emphasis should be placed on psychological interventions (Box 4), and family psycho-education should also be offered routinely (EBR; level I). Returning to work or studies is an important focus of the disease management, as this remains a major deficiency of current service provision in Australia and New Zealand, where evidence-based interventions are not widely available (EBR; level I).

If treatment is not progressing satisfactorily, a second psychiatric opinion should be sought (CBR). Moreover, if the person adheres to the prescribed medication but remains psychotic, distressed and disabled by their illness, contributory factors such as substance use need to be managed.10 Strategies with some support in the literature include motivational interviewing and CBT, but this is acknowledged as a particularly difficult clinical situation, and it is recommended to refer patients to specialist clinicians (CBR).

Combination of antipsychotics should generally be avoided, but it may be justified in particular circumstances, with careful monitoring (EBR; level II). If there is treatment resistance — generally considered as non-response to adequate doses of at least two antipsychotics for 4–6 weeks each — the early introduction of clozapine should be considered (EBR; level I). There is also evidence that electroconvulsive therapy may be helpful for some individuals who are resistant to antipsychotic medications, including clozapine, or are acutely aroused and distressed by their symptoms and cannot be managed with medication alone (EBR; level II).

Comorbid substance use, treatment and physical health

The writing group gave particular prominence to the medical care of people with schizophrenia and provided recommendations for metabolic monitoring (Box 5). This is an important area for GPs, who often have oversight of the physical care of such patients. All people with schizophrenia should be advised about the benefits of exercise and a healthy diet (EBR; level III-3). Moreover, the choice of antipsychotic medication should take account of the individual’s risk of metabolic side effects, and alternative agents should be offered if weight gain and other metabolic problems accrue (EBR; level II). In particular, aripiprazole, amisulpride, asenapine, lurasidone and ziprasidone tend to be associated with less weight gain than other agents, although all of these medications may cause weight problems in some people. The use of metformin should be considered in individuals who are required to take antipsychotics with a high metabolic burden, as this can reduce insulin sensitivity and result in modest weight loss. Metformin is usually well tolerated and may be used in the longer term (EBR; level II).

Tobacco smoking is very common in people with schizophrenia and rates have not changed much in this group over the past decade.11 Medical practitioners need to ask all individuals with schizophrenia about their smoking habits and offer appropriate interventions to help patients reduce, and ultimately cease, tobacco use (EBR; level III-3).

Sleep problems — in particular, obstructive sleep apnoea — are more common among people with schizophrenia than the general population, and are less likely to be detected, in part due to the assumption that symptoms such as lethargy and fatigue are a consequence of the negative symptoms of schizophrenia.12 Therefore, this is another area where GPs play an important role by arranging appropriate tests and enabling interventions as necessary (CBR). Poor dentition, exacerbated in many instances by psychotropic medications that reduce saliva in the mouth, is another concern in patients with schizophrenia,13 and mental health clinicians and GPs should advocate for their patients in terms of good dental care (CBR).

Schizophrenia may present with other comorbid psychiatric problems that need to be managed (EBR; level III-2). Depression and anxiety are common in people with schizophrenia and are all too often missed, because some of the symptoms associated with those disorders may overlap with those of schizophrenia (EBR; level III-3).14 It should be carefully considered whether antipsychotic medication may be contributing to such symptoms; for example, a number of antipsychotics — clozapine in particular — may induce or exacerbate obsessive compulsive disorder. Appropriate psychological therapies should therefore be offered (EBR; level II) to target depression and anxiety symptoms; if the symptoms persist, antidepressant and other pharmacological strategies should be deployed (EBR; level II). It is important to avoid adding to the side-effect burden associated with antipsychotic agents (eg, sexual dysfunction with some antidepressants) (EBR; level IV) and minimising pharmacokinetic interactions (eg, fluvoxamine increases blood levels of clozapine) (EBR; level IV).

Trauma of many kinds (eg, early trauma, including sexual abuse; later childhood trauma; trauma associated with domestic violence; trauma associated with hospitalisation, including restraint and seclusion; and victimisation) is regrettably all too common for people with schizophrenia.15,16 There is an emphasis on trauma-informed care with awareness of the potential for post-traumatic stress syndromes to add to the burdens associated with schizophrenia (CBR).

Specific populations and circumstances

Section 5 of the guidelines provides suggestions about the particular sensitivities and cultural issues pertinent to caring for people with schizophrenia who are of Aboriginal and Torres Strait Islander descent in Australia or of Maori or Pacific Islander descent in New Zealand. These sections are especially important, as most of the mental health workforce is not from those communities and their understanding of cultural matters is vital if they are to deliver appropriate and nuanced care. Particular guidance is also provided in dealing with refugees and migrants.

Schizophrenia in women raises a number of clinical and psychosocial concerns.17 The guidelines advocate for gender-specific approaches to diagnosis and management (CBR) and provide guidance regarding the use of medications in pregnancy and breastfeeding (EBR; level III-3). Women generally require lower doses of antipsychotics than men, and medications associated with increased prolactin levels (eg, typical agents, amisulpride, risperidone and paliperidone) may affect the menstrual cycle and fertility and patients need to be warned about these problems. The role of hormone replacement therapy in the management of schizophrenia is also discussed in the guidelines (EBR; level II).

Older people with schizophrenia require particular care, and as medical comorbidities are common and the medications for these problems may interact with psychotropic agents (EBR; level III-2), lower doses of antipsychotics are suggested wherever possible (EBR; III-2). These patients are particularly susceptible to delirium, notably in association with medications that have strong anticholinergic properties; hence, antipsychotics without prominent anticholinergic activity (such as risperidone) may be preferred. Moreover, there is a heightened risk of cerebrovascular events associated with antipsychotics in older people. The RANZCP guidelines endorse strong advocacy for multidisciplinary team involvement in the care of older people with schizophrenia (EBR; level I) and recommend offering appropriate psychological therapies, as this is often not considered relevant for older people, even though they may benefit greatly from them (CBR).

Other considerations

Section 6 deals with homelessness, psychiatric comorbidities, trauma, violence, suicide and victimisation. Some of these problems are managed as part of the consideration of comprehensive care models. Homelessness is a particularly fraught problem and requires interdisciplinary assessment, and an occupational therapy assessment of the ability of people who are homeless to live independently should be offered where appropriate (EBR; level I).

This section of the guidelines covers research and evaluation, with a plea for the routine use of validated and standardised outcome measures pertinent to clinical practice (CBR), as well as attention to monitoring service delivery in key areas, such as time to first treatment, rates of seclusion and absconding, and measures of individuals’ participation in their care planning.

Conclusion

The 2016 guidelines provide an update for clinicians on the optimal care of people with schizophrenia. They adopt a staged approach to care and emphasise patient and carer involvement in determining the best individualised care model compatible with the recovery paradigm. GPs play a vital role, particularly in terms of monitoring and treating physical health morbidities and risk factors in people with schizophrenia and related disorders.