Schizophrenia is a debilitating, often chronic, psychotic disorder with early onset and a lifetime prevalence of 7.2/1,000.¹ Onset is typically in early adulthood (between the ages of 15 and 25) but can occur at any age.

It is characterised by illogical thinking, abnormalities in speech and behaviour, delusions, hallucinations and negative symptoms, such as social withdrawal, self-neglect, loss of motivation and emotional blunting, see table 1.

It has a waxing-waning course, with each patient presenting with a varying and unique combination of signs and symptoms. Its long course is punctuated by times of great distress experienced by patients and their families, disability, significant treatment costs and stigmatisation.^2-4 Mortality is increased, partly as a result of higher frequency of suicide (about 10%) and violent death, and partly because of an increased risk of physical illness.⁵

The cause of schizophrenia remains largely unknown. Several biological, social and psychological factors are considered to be causative. Genetic association and linkage analysis studies have revealed that schizophrenia arises from the cumulative effect of several genes and follows a non-Mendelian pattern of inheritance. The risk of developing the disorder is increased in first-degree relatives of patients and in families with multiple affected members. The lifetime risk of developing schizophrenia for siblings of a diagnosed patient is 7-9% and 10-15% for the patient’s children.²²

Although no cure is available, effective treatment can be provided in primary and secondary care.

The longer the period without treatment, the worse the outcome.⁶ Even today in the UK, the mean duration of untreated psychosis is between one and two years.⁷

Diagnosis

There is no objective diagnostic test for schizophrenia, although there has been significant progress in establishing more consistent and reliable diagnostic criteria. The ICD-10, in the UK,⁸ and the DSM-5, in the USA,⁹ agree on the symptom clusters needed to confirm the diagnosis, see table 2. The ICD-10 requires the presence of symptoms together with deterioration or impaired functioning for a diagnosis of schizophrenia. The  DSM-5,  introduced last year, increases the symptom threshold, requiring a patient to have at least two of the specified symptoms for a diagnosis.

As patients’ predominant symptoms often change over time and because of other prevalent types of psychotic illness and isolated psychotic experiences in the general population,¹⁰ many clinicians in primary and secondary care are hesitant in making a confident diagnosis. This may hinder patients and their families receiving help early on. The new NICE guidelines for schizophrenia, published in February 2014,¹¹ recommend that all patients who are distressed and have a decline in social functioning accompanied by psychotic symptoms, or behaviour suggesting psychosis, should be comprehensively assessed by a specialist mental health service.

Assessment

Psychotic symptoms are frightening for the patient and stressful for their family. The wide spectrum of clinical presentations requires a thorough assessment by an expert. NICE recommends that the assessment should be carried out by a consultant psychiatrist or a specialist trained in the diagnosis of psychoses.¹¹ Additionally, early intervention by psychosis services should be accessible to all patients with a first presentation, irrespective of age or duration of symptoms, see table 3. To optimise access, referral to specialised services may come from health and social services, the patient or carer. NICE emphasises that professionals should work in collaboration with patients and carers.

Common comorbidities, such as depression, substance misuse and anxiety disorders, and recent traumatic events that may have led to PTSD and could be associated with the development of the psychotic episode should be evaluated.

This is important, as they can increase morbidity in patients with schizophrenia and are often overlooked because of a tendency to subsume such symptoms under the diagnosis of schizophrenia.¹²

After making the diagnosis, it is important to discuss it with the patient and carers. There is still a stigma associated with the term schizophrenia. Healthcare professionals need to provide an explanation for the patient’s symptoms and indicate the means of support, as well as explaining the negative consequences.¹³

Treatment

NICE recommends that a full range of pharmacological, psychological, social, occupational and educational interventions should be provided. Treatment can be broadly divided into the acute and the stabilisation-maintenance phase. Antipsychotic medication remains the cornerstone of treatment for both phases. Its superiority over placebo is well established, and the effectiveness of older and newer antipsychotics is similar.²¹  Newer antipsychotics have fewer extrapyramidal side effects, but are more likely to result in the metabolic syndrome than the older drugs.²²

The effectiveness of antipsychotics in treating negative symptoms of schizophrenia is limited.²¹

All patients experiencing a first episode should be offered an oral antipsychotic medication, initiated in secondary care, unless this is done by the GP after discussion with a consultant psychiatrist. Patients and their carers should be involved in choosing a suitable antipsychotic, taking into account the likely benefits, side-effect profile and the patient’s physical health. Patients should be informed about potential metabolic, cardiovascular, extrapyramidal, hormonal and other side effects, see table 3.

The trial of medication should be carried out for at least four to six weeks at optimum BNF dosage.¹¹

No more than one antipsychotic should be used except when changing medication. The use of antipsychotic medication for people at increased risk of developing psychosis is not supported by the evidence.¹¹

If after adequate use of two different antipsychotics (at least one of them should be second generation) the patient’s symptoms have not improved, clozapine should be offered. Clozapine is effective in 30-60% of treatment-resistant cases of schizophrenia.²⁰ However, careful monitoring is required because of its potential life-threatening haematological side effects.

After controlling acute symptoms, the maintenance phase will require continuation of an antipsychotic for a minimum of two years.

Patients should be informed that there is a high risk of relapse, if they stop medication.^{11, 14} Long-acting injectable antipsychotics remain a valuable part of the treatment for patients, who prefer this after an acute episode or when adherence to oral antipsychotics is poor.

Patients with recurrence should have a medication review, including assessment of adherence. For such patients, the rationale behind treatment is similar to that for a first episode of schizophrenia and the same guidelines apply.

The revised NICE guidelines emphasise the use of psychological, social, occupational and educational interventions early in treatment. Individual CBT or family therapy should be offered in conjunction with medication to patients with a first or subsequent episode of schizophrenia, even during the acute phase, if appropriate.

Clinicians should warn patients, and relatives, who prefer psychological interventions alone that these would be more effective when delivered in conjunction with antipsychotic medication. CBT can also be offered to patients at high risk of developing psychosis. This can be more important for patients with any comorbid anxiety disorders, depression, and emerging personality disorder or substance misuse. ¹¹

Social, occupational and educational interventions are emphasised in the new NICE guidelines, since the best predictor of poorer long-term functioning, particularly for unemployment, is poor functioning in the first three years following diagnosis.¹⁵

Supported employment programmes and occupational/educational activities may be very useful for patients without work, helping them to re-integrate into society and increase self-worth.²³ Peer support may help patients improve their experience of the health service, help alleviate distress from the disorder and improve their quality of life. Finally, self-management programmes for schizophrenia that follow a manual have proved an important part of the treatment, instilling hope and improving self-management and coping skills.¹²    

Monitoring mental health

Schizophrenia patients should be followed up by a multidisciplinary team with expertise in treating psychoses. Monitoring of mental and physical health should be carried out regularly and tailored to the individual needs of the patient and the carers. During the acute phase, daily contact from the early intervention, crisis or home treatment teams may be required to monitor mental state, adherence with medication, the development of side-effects and risk.

For patients in remission, the team will monitor early signs of relapse with the aim of avoiding admission. Mental health teams should also assess the patient’s level of functioning with respect to education, training and employment. If the diagnosis of schizophrenia is unclear, or the patient continues to have symptoms, impaired function or distress despite treatment, monitoring should continue for one to three years by the early intervention team using structured and validated assessment tools.¹¹ Patients’ carers should be involved in all phases of the follow-up.

Psycho-social treatments that could not be offered during the acute phase may be required later. During the maintenance-stability phase frequency of contacts may decrease, although mental health teams should be able to provide long-term follow-up, if needed. Any decision about discharge to primary care should be carefully discussed with all parties involved.

The decision to stop antipsychotics should be made jointly, undertaken gradually, and patients monitored for signs and symptoms of relapse for at least two years.⁹

Monitoring physical health

The association between schizophrenia and poor physical health is well established.16 Mortality rates in schizophrenia are high. Male and female patients die 20 and 15 years, respectively, earlier than the general population.¹⁷ The majority of premature deaths are accounted for by physical illnesses.18-20 These include cardiovascular disorders (coronary heart disease, peripheral vascular disease and stroke), diabetes mellitus, chronic obstructive pulmonary disease, certain cancers and infectious disorders (HIV, hepatitis C and tuberculosis).21 Although not generally responsible, chronic antipsychotic side effects contribute to the development of some of these physical problems. Consequently, regular health monitoring is paramount. The new NICE guidelines highlight this need and have increased  the number of recommended interventions related to patients’ physical health.11

Patients with schizophrenia should be offered an ECG before initiation of an antipsychotic, in the following situations:

• Evidence of cardiovascular risk e.g. high blood pressure

• A personal history of cardiovascular disease

• If specified by the drug manufacturer

Baseline checks should include weight, waist circumference and BMI, blood pressure, FBC, urea and electrolytes (including creatinine or eGFR), fasting plasma glucose and blood lipids (cholesterol and triglycerides), LFTs, CPK and prolactin. Table 3 summarises the NICE recommendations for physical health monitoring.¹¹

When patients are transferred from secondary to primary care, GPs should continue monitoring their physical health at least annually or more often, if there is an indication following the guidelines described above. Throughout follow-up, effective communication between primary and secondary care services is essential.

GPs should be provided with a care plan by mental health services early in the course of treatment. The mental health team should review the care plan yearly and ensure that patients receive physical healthcare from primary care.⁹

Follow-up

Primary care has a significant role to play in monitoring mental state and physical health. Patients with schizophrenia will return to primary care under shared care arrangements after 12 months under the care of the mental health team, provided that their mental state is stable.

GPs should be able to build a good therapeutic relationship, take account of patients’ and carers’ requests, to retain good engagement during the long course of the disorder.     

Monitoring patients’ mental state is crucial, and when relapse is threatened because of poor response to treatment, non-adherence to medication, intolerable side effects from medication, comorbid substance misuse, or if risk to self or others is suspected, GPs should refer the patient to the mental health team.

In addition, GPs should consider a re-referral for co-existing mental health disorders that may require expert pharmacological or psychological interventions.

GPs should provide a comprehensive health check yearly or more often, if there is an indication, see table 3, opposite. A copy of the results should be sent to the patient’s mental health team. When GPs identify problems related to the metabolic syndrome (obesity, abnormal lipid levels, and diabetes), high blood pressure or significant physical inactivity, they should treat them according to the relevant NICE guidelines.

Although healthy eating and physical activity programmes should be initiated early on in secondary care, this is often difficult and primary care should be able to offer this combined with smoking cessation/reduction treatments. Nicotine replacement therapy, bupropion or varenicline can be considered. If a patient decides to stop smoking, it is important to be vigilant for changes in plasma levels of specific antipsychotics (olanzapine, clozapine) and for potential side effects of bupropion and varenicline, including interaction effects (e.g. on seizure threshold), especially in the first 2-3 weeks.⁹