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<h3 class=”subheadMIstyles”>Case study</h3>
‘Rachel’ is a 20-year-old arts student at a university in Dublin. She is the eldest of three sisters, has supportive parents and has been in a good relationship for the past year. Her uncle has well-managed bipolar disorder, but otherwise there is no family history of mental illness. She plays Gaelic football in her spare time and enjoys music and cinema. She reluctantly admits to smoking ‘the odd joint’ of cannabis at weekend music festivals with friends, but never around exam time. She drinks three or four glasses of wine on Friday and Saturday nights.
As the autumn college term approaches, Rachel begins to hear unfamiliar voices talking to each other about her. They remark relentlessly that she will never amount to anything in life. Rachel tries everything to distract herself from these voices — vigorous exercise, loud music, watching DVDs, drinking alcohol and so forth — but nothing seems to work. As the voices become more persistent, Rachel becomes gradually more frightened. She wonders if they might emanate from a computer chip implanted in her ear. She becomes suspicious of her iPad and of the Internet in general. She believes the man reading the news on television is trying to warn her about the dangers of artificial intelligence. She suspects the CIA computer system is monitoring her through the electronic devices in her vicinity.
In response, Rachel insists on unplugging all communication devices in her house. She retreats to her room and rarely ventures outside, believing this to be the only way she can stay safe. She defers her return to college and ignores her boyfriend’s phone calls. In fact, she wonders if he might be involved in the conspiracy. Rachel’s worried parents call the family GP, who refers her for a specialist assessment. After much toing and froing, Rachel eventually agrees to keep her appointment, whereupon a detailed assessment leads to a diagnosis of first-episode psychosis and a suspicion that she may have evolving schizophrenia. Understandably, Rachel and her parents have many questions: ‘What is psychosis?’ ‘What is schizophrenia?’ ‘How on earth did this happen to our daughter?’ ‘Will she recover?’
Schizophrenia is more common than many people think; the lifetime risk is estimated at around 1 per cent, with symptoms generally first appearing between the ages of 15 and 40 years. Around one-in-five psychiatric admissions in Ireland is for the treatment of schizophrenia (making it second only to depressive disorders), while psychosis is the most common reason for involuntary admission. Often profoundly debilitating for the individual, schizophrenia is also expensive for society. Behan and colleagues (2008) estimated the cost (both direct and indirect) of schizophrenia to the exchequer to be over €460 million in 2006. This sum is likely to have increased in the intervening decade.
According to the <em>International Classification of Diseases</em> (<em>ICD-10</em>; WHO, 1993), schizophrenia is a severe psychotic illness not attributable to: (a) Organic brain disease; (b) substance intoxication, dependence or withdrawal; or (c) diagnosable mania or depression. For a diagnosis to stand, psychotic symptoms must be present on most days for at least a month, and must include one or more of the following: (a) Thought echo, insertion, withdrawal or broadcast; (b) passivity delusions (in which the individual believes their actions, impulses or feelings are controlled by an outside force) or delusional perception (in which a delusion is triggered by the perception of something real); (c) auditory hallucinations (usually third-person or running commentary); and (d) persistent delusions not already mentioned.
Even if a patient does not show evidence of one of the above, they can still be diagnosed with schizophrenia if they have two or more from a long list of less-specific symptoms. These include: a) Other types of hallucination; b) thought disorder (where the link — or ‘association’ — between one thought and the next becomes loosened); c), catatonic behaviours (for example, unconscious physical posturing or mutism); and d) negative symptoms (for example, emotional blunting or incongruity, paucity of speech, social withdrawal and general ambivalence about taking part in normal day-to-day activities).
Patients and relatives often ask what causes schizophrenia, but alas, there is no single easy answer.
There remains an emphasis on the stress-vulnerability model, a theory in which biological factors (a complex interaction between genetics and disrupted early development of the nervous system) predispose us to developing psychosis as we mature and encounter the rigours of life.
Obstetric factors, stressors in childhood and adolescence (leading to dopaminergic dysregulation) and social adversity (leading to negative cognitive biases in relation to everyday experiences) all likely increase the risk that a psychotic illness will emerge.
This risk is further heightened by the use of illicit substances, especially cannabis, which can increase the lifetime risk of schizophrenia by six or more times. Relapse of psychosis is more likely with interpersonal conflict and high expressed emotion in the family setting.
<h3><strong>Clinical practice guidelines</strong></h3>
Several sets of clinical practice guidelines (CPGs) exist in relation to the management of schizophrenia. These include those of the British Association for Psychopharmacology (BAP), the South London and Maudsley NHS Trust, the Scottish Intercollegiate Guidelines Network (SIGN), the schizophrenia Patient Outcomes Research Team (PORT) and others. The UK’s National Institute for Health and Care Excellence (NICE) published its updated guidelines in February 2014, and placed an emphasis on more recovery-orientated language, comprehensive multidisciplinary assessment, early intervention, care planning, a collaborative approach to prescribing, physical health monitoring, and phase-specific interventions such as carer information and support, cognitive behavioural therapy (CBT) and vocational rehabilitation.
But which CPGs are the best? This was the question posed by Keating and colleagues in a recent study published in the <em>BMJ Open</em>. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to compare CPGs in terms of quality and applicability to first-episode schizophrenia. Some 3,300 records were screened to find 10 CPGs that met the inclusion criteria. Recommendations varied in terms of the choice of antipsychotic, however side-effects (rather than efficacy) were usually deemed to be the key consideration. While maintenance of remission using antipsychotics was universally recommended, CPGs generally identified a paucity of evidence to guide the duration of maintenance treatment. The guidelines that scored best overall (using AGREE II) were the SIGN and NICE guidelines, and the <em>Clinical Practice Guidelines for Schizophrenia and Incipient Psychotic Disorder</em> published by the Spanish Ministry of Health and Consumer Affairs.
So, how does it work in practice? Specialist referral is almost always needed for someone with a suspected psychosis. Admission to hospital is sometimes (but not always) indicated, depending on mental state examination, assessment of safety and the likelihood of the admission requiring the Mental Health Act. Still, admission involves a safe environment for assessment and treatment, while providing carers with a brief period of respite, the opportunity to give collateral information and a resource for information and support.
Broadly speaking, antipsychotic medication is divided into first- and second-generation varieties. They used to be termed ‘classical’ and ‘atypical’ neuroleptics, respectively. First-generation antipsychotics have been available since the early 1950s. They include haloperidol, chlorpromazine and zuclopenthixol and are considered effective in the treatment of hallucinations, delusions and thought disorder, but less so for negative symptoms or functional outcome. Nevertheless, they represented the first line in psychosis management during the latter half of the 20th century.
Enter clozapine in the 1970s, the first of the second-generation antipsychotics. To this day, it is unrivalled in terms of efficacy, although initial claims about its usefulness in treating negative symptoms were probably overstated.
Its side-effects include potentially-fatal agranulocytosis, however a vigilant clozapine patient-monitoring service has allowed for clozapine’s ongoing use for treatment-resistant schizophrenia. Other side-effects include hypersalivation, sedation, weight gain, polyuria and an increased risk of cardiomyopathy and seizures. Since the early 1990s, newer second-generation antipsychotics have become available, including risperidone, olanzapine, amisulpride, quetiapine, aripiprazole, ziprasidone and others.
The theme (highlighted by Keating et al) of antipsychotic choice being governed by tolerability rather than efficacy is mirrored in a recent systematic review and pairwise meta-analysis by Yikang Zhu and colleagues, published in <em>Lancet Psychiatry</em>. The authors examined various first- and second-generation antipsychotics tested in 19 randomised, controlled trials involving 2,669 participants with first-episode schizophrenia. Interestingly, haloperidol performed poorly in comparison to most second-generation antipsychotics, but there were few other differences between the medications examined. As the evidence cited by the authors was considered to be generally poor in quality, they asserted that the choice of treatment should be guided principally by the side-effect profile.
And this is often the case in clinical practice. Potential side-effects include sedation, extrapyramidal symptoms (such as dystonia, Parkinsonism, akathisia and tardive dyskinesia), raised prolactin, QTc prolongation and weight gain. Indeed, as second-generation antipsychotics make up a large proportion of prescriptions in Ireland, cardio-metabolic side-effects are a particular issue for patients. According to the WHO, individuals with schizophrenia have a reduced life expectancy of between 10 and 25 years. Suicide only accounts for a small fraction of this.
Heavy smoking is two-to-six times more common among people with schizophrenia, while 45-to-55 per cent are obese, 10-to-15 per cent have type 2 diabetes and 19-to-58 per cent are hypertensive. In parallel, individuals with schizophrenia receive poorer medical care for their physical problems than do members of the general population. Diagnostic overshadowing frequently occurs and delayed diagnosis often prevents effective care.
This is naturally of concern to international organisations such as IEPA Early Intervention in Mental Health, whose members continually draw attention to the importance of good physical healthcare in the management of schizophrenia. IEPA has endorsed the Healthy Active Lives (HeAL) declaration, inherent in which is the need to intervene at the start of psychosis treatment to monitor physical health and manage cardio-metabolic risk. The importance of daily exercise and basic education in diet, shopping and cooking cannot be overemphasised, while it is no longer unusual to prescribe metformin prophylactically for individuals treated with clozapine or olanzapine. Indeed, some of the CPGs make clear reference to this approach.
So, let’s return to the case study at the opening of this article. How might Rachel be guided towards recovery? Engagement is the first challenge. There is ample scientific evidence to guide the advice offered by the doctor, but it is equally important that Rachel retains a clear sense of her own autonomy. Wherever possible, the choice of medication should be a collaborative process involving Rachel, taking carers’ (in this case her parents) views into account if she agrees. Naturally, every patient is unique, but the aim should be to utilise medication algorithmically in line with one of the CPGs, titrating to the minimum effective dose, adjusting according to response and tolerability and assessing over four-to-six weeks. Long-acting injections remain an option, while most guidelines suggest that clozapine should be considered where patients are unresponsive to two different antipsychotics, at least one of which is second-generation. It is important to bear in mind that failure to respond to any medication may be explained by inadequate dosage, non-adherence, misdiagnosis or substance misuse.
But Rachel’s recovery cannot rely purely on medication. Avoidance of illicit substances (such as cannabis) is essential. Numerous studies show that CBT yields both symptomatic and functional improvement. Psycho-education for carers and family members also has a strong evidence base.
Some time has passed since Brown and colleagues originally theorised on expressed emotion in the domestic setting, describing how high levels of hostility, critical comments and emotional over-involvement can increase the likelihood of relapse. In this context, numerous studies have highlighted the importance of providing accessible information and support for carers and families.
Initiatives such as the DETECT Early Intervention Service for Psychosis (and other similar early-psychosis services in Ireland) offer phase-specific interventions like CBT and carer psycho-education.
Similarly, occupational therapy and vocational rehabilitation initiatives such as Reach and the National Learning Network play an important role in recovery. Relapse prevention strategies are also incorporated into the Wellness and Recovery Action Plan (WRAP) groups run in locations across the country, while organisations such as Shine (formerly Schizophrenia Ireland) and the Hearing Voices Network offer a range of supports.
Successfully managing schizophrenia is about so much more than simply resolving symptoms. Recovery should remain the goal. Indeed, researchers such as Ashok Malla and colleagues (in Canada) assert that the right approach to first-episode psychosis can result in 70 per cent and 80 per cent of individuals returning to work by the end of years one and two, respectively. Collaborative and recovery-focused treatment that is in line with international best practice will provide individuals like Rachel with the realistic hope of an enjoyable, useful and fulfilling life.<strong> </strong>
www.stjohnofgodhospital.ie [includes link to Choice of Medication Website]
<strong>References available upon request</strong>
<h3 class=”subheadMIstyles”>Seven ingredients for Rachel’s recovery</h3> <p class=”listnumberedallotherlinesMIstyles”>Well-chosen medication will help Rachel to overcome her symptoms. However, she is entitled to be fully involved in any decisions about her medication.
<p class=”listnumberedallotherlinesMIstyles”>Avoidance of illicit substances such as cannabis will improve Rachel’s prospects of recovery. She might also consider giving up alcohol.
<p class=”listnumberedallotherlinesMIstyles”>CBT has a growing evidence base, while progressive muscular relaxation and mindfulness meditation may also be useful. There are useful self-help books and websites available.
<p class=”listnumberedallotherlinesMIstyles”>Carer psycho-education also has a growing evidence base. Well-informed and caring family members are often the best resource individuals with schizophrenia have.
<p class=”listnumberedallotherlinesMIstyles”>A well-structured lifestyle involving a defined daily routine will help Rachel to remain well. This might include occupational therapy, vocational rehabilitation (eg, Reach), further education (eg, the National Learning Network), voluntary work or a part-time job. A healthy diet and regular exercise are also important in promoting good mental health and preventing cardio-metabolic problems.
<p class=”listnumberedallotherlinesMIstyles”>Relapse-prevention strategies involve Rachel attending the outpatients department, keeping in touch with her specialist team and knowing the early signs of relapse specific to her. Her family can help in this regard. Courses such as WRAP are worth considering.
Advocacy — Rachel might consider joining a mental health advocacy group or her local service users’ forum. There is often good support available from those who have experienced psychosis before, while Rachel might even help to shape the delivery of a better mental health service for others in the future.
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