Psychosis and schizophrenia: importance of early referral

Psychosis is a ‘disturbance in the perception of reality, evidenced by hallucinations, delusions, or thought disorganization’.¹ It affects 4-5% of the population and occurs in a variety of psychiatric illnesses (see Table 1).^1,2 It is characterised by hallucinations (auditory hallucinations are the most common subtype), delusions (ie. false fixed beliefs), thought disorganisation, agitation and aggression.²

Schizophrenia affects 1% of the population. It is a chronic psychiatric illness with periods of active psychosis combined with a decline in day-to-day function.⁴ Symptoms are divided into: positive, negative, cognitive and affective. Positive symptoms are synonymous with active psychosis (ie. hallucinations, delusions and disorganised behaviour and thinking); where auditory hallucinations occur in 40-80% of patients.⁴ Negative symptoms consist of affective flattening, alogia, apathy and asociality/anhedonia (see Table 2). These moderately correlate with functional impairment and tend to be resistant to treatment.³

Cognitive symptoms correlate with loss of function and usually precede the onset of positive symptoms.^1,4 Areas that are affected include processing speed, attention, visual learning and memory, executive function, verbal comprehension and social cognition. Lastly, affective symptoms (mainly depression) occur in over half of patients throughout the course of their illness.

The American Psychiatry Association updated the diagnostic criteria for schizophrenia in 2013 and Table 3 summarises these criteria.

Schizophrenia is one of the most debilitating and economically catastrophic medical disorders.^4,5 Life expectancy is reduced by 10 years and only 10% will make a recovery allowing them to function completely independently within society.⁵ The duration of untreated psychosis correlates to poorer outcomes and it is associated with resistance to treatment, increased relapse rates, faster cognitive decline, increased risk of depression and substance abuse and increased incidence of behavioural problems.⁵ As such, early referral is crucial and re-enforces GPs’ pivotal role in early recognition of the disease.^5,6

Delayed diagnosis occurs more frequently in men, with earlier age of onset, and in those with a prolonged prodromal phase and fewer early positive symptoms.⁶ Studies have shown that 68% of patients present insidiously and attend their GP five to six times in the prodromal phase prior to accurate diagnosis.⁵ Better understanding of the natural course of this illness may help early detection (see Figure 1).

Early detection is understandably difficult as the symptoms at this stage are usually non-specific.⁵ Patients may present, or usually are brought in by a relative prior to the development of positive symptoms. A decline in hygiene or grooming and a reduction in psychomotor activation may precede the active psychotic phase.⁴ Such changes are important to note and can aid early diagnosis. Negative, cognitive and affective symptoms occur earlier in the course of the illness, so one should always think of screening for psychotic symptoms in anyone presenting with these types of symptoms. 

It is important to take into account risk factors for developing psychosis such as family history of schizophrenia, history of intermittent psychotic symptoms, social isolation, and history of intra-uterine or perinatal complications.^5,7

When a patient presents with features suggestive of psychosis, it is essential to fully investigate any possible underlying causes, as per common medical work-up:

• Bloods: FBC, U+E, LFT, TFT, B12, Ca, folate, VDRL (if indicated), urine C+S, toxicology screen, HIV (if suspected) 
• Other investigations to consider: CT brain or MRI, EEG, lumbar puncture (if indicated), heavy metal screen, rheumatologic work-up, hormone levels.⁸

Any underlying causes should be treated. Use of antipsychotic should be commenced where relevant and in some instances benzodiazepines may be used for symptom management in consultation with psychiatric services. 

Agitated patients should be evaluated for risk of harm to themselves or others and one should consider whether an involuntary admission under the Mental Health Act 2011 is appropriate. A rapid-acting first generation antipsychotic (eg. haloperidol) and/or a rapid-acting benzodiazepine (eg. lorazepam) should be used in severely agitated patients with acute psychosis.

Treatment of schizophrenia should take into account biological, psychological and social factors involved with the disease. Antipsychotic drugs, when taken regularly, protect against relapse in the short- and long-term. 

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Pharmacotherapy

With the exception of clozapine, systemic reviews and meta-analysis have not found convincing evidence that any of the antipsychotics are more effective than any other for acute schizophrenia.⁹ Large non-industry funded studies (CATIE and CUTLASS) have shown that second generation antipsychotics, olanzapine and risperidone, are marginally better tolerated and have a lower discontinuation rate compared to other antipsychotics, despite significant side-effects.¹⁰

NICE guidelines suggest initial treatment with oral second generation antipsychotic medication, the choice of which should be made in collaboration between the clinician and patient based on benefits and side-effect profile.¹⁰ Long-acting depot preparations should be used where there are likely to be issues with compliance.

Clozapine should be considered in treatment-resistant schizophrenia that has failed to respond to trials of at least two other antipsychotics (at least one of which is a second generation antipsychotic).

Physical health monitoring 

Antipsychotic medications can have a number of side-effects, including extrapyramidal symptoms (ie. Parkinsonism and akathesia), metabolic side-effects (including weight gain) and other side-effects (including unpleasant subjective experiences). Physical health monitoring is therefore extremely important in those on these medications. The following investigations should be undertaken: 

• Weight (plotted on a chart), waist circumference, pulse and BP, fasting blood glucose, HbA1c, blood lipid profile and prolactin levels, assessment of any movement disorders, nutritional status, diet and level of physical activity
• Blood tests: baseline and yearly: FBC, U+E, LFT, lipids, glucose, prolactin, CPK.  

When initiating antipsychotic treatment lipids, glucose and BMI should be monitored within the first six months. ECG should be done at baseline and after dose increases to monitor QTc.¹²

Psychosocial interventions and engagement services

Cognitive behavioural therapy has been shown to improve positive and negative symptoms. CBT is most effective in medication-resistant psychosis, but NICE guidelines now suggest using it in the initial stages of the disease.¹⁰ Psychoeducation is important as there is often a high level of non-compliance with antipsychotic medication. Family education is also important as relapse rates are higher in families with high levels of expressed emotion which provide a more stressful environment for the patient.¹³

DETECT is an early intervention service for people who may be experiencing psychosis, and specific treatments for those who are experiencing psychosis for the first time, (www.detect.ie). Other services include Shine, a support service for people with mental health issues, including education, support groups for patients and their families and counselling services (www.shineonline.ie) and Hearing Voices, a support group where individuals meet with others and share experiences of hearing voices (www.voicesireland.com).

Schizophrenia is a lifelong psychiatric condition that is multifactorial in nature and affects social and occupational functioning, life expectancy and risk of physical health issues. Despite a better understanding of the natural course of this illness, there remains no consensus on treatment during the prodromal phase. 

With limited knowledge and exposure to schizophrenia in primary care and poor access to specialised tertiary care, improving patient outcomes remains difficult. Prognosis is poorer with delayed diagnosis but it can be difficult to detect early as most cases present insidiously. Where possible, early referral in suspected cases (even prior to onset of psychosis) is essential in improving patient outcomes. 

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References

1. Overview of psychosis. Michael D Jibson Uptodate.com (2013)
2. Perala J, Suvisaari j, Saarni SI, et al. Lifetime prevalence of pscyhotic and bipolar I disorders in  a general population. Arch Gen Psychiatry 2007, 65:19
3. Ho BC, Nopoulos P, Falum M et al. Two year outcome in first epidose schizophrenia: predictive value of symptoms for quality of life. AM J Psychiatry 1998; 155:1196
4. Schizophrenia: clinical manifestations, course, assessment and diagnosis. Berdnar A Fishcer, Rover W Buchana. Uptodate .com (2013)
5. Le Galudec M1, Stephan F, Mascret R, Bourgin J, Walter M. [Early diagnosis in schizophrenia: a mission for the general practitioners?]. Article in French. Presse Med. 2011 Jan;40(1 Pt 1):3-9 
6. Chang WC1, Tang JY, Hui CL, Lam MM, Wong GH, Chan SK, Chiu CP, Chung DW, Law CW, Tso S, Chan K, Hung SF, Chen EY. Duration of untreated psychosis: relationship with baseline characteristics and three-year outcome in first-episode psychosis. Psychiatry Res. 2012 Aug 15;198(3):360-5
7. Vilain J1, Galliot AM, Durand-Roger J, Leboyer M, Llorca PM, Schürhoff F, Szöke A. [Environmental risk factors for schizophrenia: a review]. Article in French. Encephale. 2013 Feb;39(1):19-28
8. Clinical manifestations, differential diagnosis, and initial management of psychosis in adults. Marler, M. Uptodate.com (2014). 
9. The Maudsley prescribing guidelines in psychiatry. Taylor, D., Paton, C., Kapur, S. Wiley-Blackwell 2011 (11th Ed). 
10. CATIE schizophrenia trial: results, impact, controversy. Manschreck, T.C., Boshes R.A. Harvard review of psychiatry, 2007 Sep-Oct;15(5):245-58. 
11. Psychosis and schizophrenia in adults: treatment and management. National Institute for Clinical Excellence UK (NICE) Guideline 178. Feb 2014. 
12. Pharmacotherapy for Schizophrenia: Acute and maintenance phase treatment. Stroup, S.T. UptoDate.com (2014)
13. Psychosocial interventions for schizophrenia. Bustillo, J., Weil., E. UptoDate.com (2014) 
14. Early Psychosis Intervention Program Standards. Ministry of Health and Long Term Care. Service Ontario March 2011. Accessed on http://www.health.gov.on.ca/english/providers/pub/mental/epi_program_standards.pdf