Recommendations
Urgent
Risk assess the situation to ensure the safety of the patient and yourself.[60]
If there are concerns about the patient’s risk of self-harm or harm to others:
If you are concerned that the patient is at risk and may leave without further assessment or treatment, carefully document a physical description that can be used to find the patient if they do so.[107]
If the patient wants to leave before further assessment and treatment, consider assessing their mental capacity to make this decision. Always assume the patient has capacity, unless there is evidence to suggest an assessment is required.[63][64] Seek help from a senior colleague if needed.
Apply the principles of the Mental Capacity Act 2005 and its Code of Practice.[63] Mental Capacity Act 2005: Code of Practice Opens in new window
In Scotland, the Adults with Incapacity Act 2000 is used. Adults with Incapacity Act Opens in new window In Northern Ireland, the Mental Capacity Act (Northern Ireland) 2016 is used. Mental Capacity Act Code of Practice (Northern Ireland) Opens in new window
Give the patient the opportunity to make informed decisions about their care and treatment and take into account their needs and preferences.[65]
Always ensure there is appropriate follow-up in place if the patient leaves.
If a patient is severely agitated or distressed use de-escalation techniques as first-line.[60][108]
If a patient becomes aggressive or violent, involve a senior colleague and seek advice from the mental health team.
Parenteral medication (rapid tranquillisation) may be used if de-escalation techniques have failed and only if absolutely necessary after weighing up the risks and benefits.[111] Physical restraint may be used if there is potential for harm to the patient or other people.[60] The decision to use rapid tranquilisation and/or physical restraint should be made by a senior clinician with mental health team input. Patients at high risk of sedation may be transferred to a setting where ventilatory support is available.
Key Recommendations
Discuss all patients with a mental health professional to determine whether they need a specialist assessment.
An antipsychotic should be started by a specialist after discussion and agreement about the choice of antipsychotic with the patient and/or carer.[1][2][111]
[ 
]
[ ]
Check baseline bloods before starting an antipsychotic including fasting blood glucose, HbA1c, cholesterol, triglycerides, and prolactin, as well as body mass index, pulse, and blood pressure.[1][2][112]
Check your local protocol to decide whether to perform an ECG before starting an antipsychotic because guidance varies.
If treatment with an antipsychotic is not effective the patient may be switched to an alternative antipsychotic.
Clozapine is used if the patient has treatment-resistant schizophrenia.[1][2][68][111][113][114]
Monitor the patient’s response to treatment as well as for any side effects and their overall physical health.
A rare but serious side effect of antipsychotics is neuroleptic malignant syndrome.[111] See Neuroleptic malignant syndrome.
It is important to identify and manage any risk factors for cardiovascular disease and diabetes early (even if the patient isn’t taking an antipsychotic) as these are commonly missed and can cause significant morbidity and mortality if left untreated.[1][87][112][115]
The mean life expectancy of a patient with schizophrenia is 14.5 years shorter compared with the general population.[116] This is mostly due to physical health causes; treatment with antipsychotics can cause significant and rapid weight gain. However, schizophrenia itself increases mortality, especially if untreated, and can also interfere with the patient’s ability to communicate their needs and access care.[14][87][112]
Ensure all patients have access to psychosocial therapies. The National Institute for Health and Care Excellence (NICE) recommends to offer all patients cognitive behavioural therapy for psychosis (CBTp).[1]
[ ]
[ ]
However, a Cochrane review notes there is no clear and convincing advantage for CBT over other psychosocial therapies.[117] Family interventions may also be used if the patient lives with or is in close contact with family.[1][118]
Manage the safety of the patient
Risk assess the situation to ensure the safety of the patient and yourself.[60]
If there are concerns about the patient’s risk of self-harm or harm to others:
If you are concerned that the patient is at risk and may leave without further assessment or treatment, carefully document a physical description that can be used to find the patient if they do so.[107]
If the patient wants to leave before further assessment and treatment, consider assessing their mental capacity to make this decision. Always assume the patient has capacity, unless there is evidence to suggest an assessment is required.[63][64] Seek help from a senior colleague if needed.
Apply the principles of the Mental Capacity Act 2005 and its Code of Practice.[63] Mental Capacity Act 2005: Code of Practice Opens in new window
In Scotland, the Adults with Incapacity Act 2000 is used. Adults with Incapacity Act Opens in new windowIn Northern Ireland, the Mental Capacity Act (Northern Ireland) 2016 is used. Mental Capacity Act (Northern Ireland) 2016 Opens in new window
Give the patient the opportunity to make informed decisions about their care and treatment and take into account their needs and preferences.[65]
Always ensure there is appropriate follow-up in place if the patient leaves.
Manage agitation and distress
Sometimes, patients may understandably become very agitated or distressed by psychosis. They may use aggression as a defence against perceived persecutors, which can increase the risk of harm to themselves and others.
If the patient is severely agitated or distressed use appropriate psychological and behavioural de-escalation techniques as first-line.[60][108]
If the patient becomes aggressive or violent, involve a senior colleague and seek advice from the mental health team.
Use appropriate psychological and behavioural de-escalation techniques as first-line. Parenteral medication (rapid tranquillisation) may be used if de-escalation techniques and oral medication have failed and only if absolutely necessary after weighing up the risks and benefits.[111] Physical restraint may be used if there is potential for harm to the patient or other people.[60] The decision to use rapid tranquillisation and/or physical restraint should be made by a senior clinician with mental health team input. Patients at high risk of sedation may be transferred to a setting where ventilatory support is available.
Consider intramuscular treatment (e.g., lorazepam, promethazine plus haloperidol) if oral medication is not possible or appropriate and urgent sedation with medication is needed.[60] The UK National Institute for Health and Care Excellence (NICE) recommends either intramuscular lorazepam alone, or intramuscular haloperidol combined with intramuscular promethazine, for rapid tranquillisation in adults.[60] Adding promethazine to the antipsychotic reduces the risk of extrapyramidal side effects.
Always inform the patient that medication is going to be administered and give them the opportunity to accept oral medication voluntarily.
NICE recommends against the use of intramuscular haloperidol combined with intramuscular promethazine if the patient has any evidence of cardiovascular disease (including a prolonged QT interval) or if no ECG has been carried out. Intramuscular lorazepam can be used in this patient group instead.[60]
NICE recommends monitoring side effects, pulse, blood pressure, respiratory rate, temperature, level of hydration, and level of consciousness at least every hour until there are no further concerns. Consider monitoring oxygen saturation using pulse oximetry; check your local protocol. Monitor the patient every 15 minutes if the maximum dose has been exceeded or they:[60]
Appear to be asleep or sedated
Have taken illicit drugs or alcohol
Have a pre-existing medical condition
Have experienced harm as a result of a restrictive intervention.
Practical tip
Use caution when giving benzodiazepines to the very young or older people and those with pre-existing brain damage or impulse-control problems as disinhibition reactions are more likely.[119]
Determine a treatment setting
Discuss all patients with a mental health professional to determine whether they need a specialist assessment.
In practice, many patients may have acute treatment in the community. This should be considered, with support from the crisis resolution and home treatment teams if necessary, before admission to an inpatient unit.[1]
Admission may be considered if the patient is at significant risk of self-neglect or harming themselves or others.
Practical tip
If the patient needs to be admitted they may agree to this voluntarily, or it may be necessary to use legal procedures to admit the patient involuntarily. The Mental Health Act 1983 is used in England and Wales.[69] Mental Health Act 1983: Code of Practice Opens in new window In Scotland, the Mental Health (Scotland) Act 2015 is used.[70] Mental Health (Scotland) Act 2015 Opens in new window In Northern Ireland, the Mental Capacity Act (Northern Ireland) 2016 is used.[71] Mental Capacity Act Code of Practice (Northern Ireland) Opens in new window
Start or review antipsychotic treatment
Always check whether the patient could be pregnant. Pregnancy is not covered in this topic; discuss pregnant patients with a senior colleague.
First episode of psychosis
An antipsychotic should be started by a specialist.[1][2][5][68][111]
[ ]
[ ]
The patient and/or carer should be involved as much as possible when choosing an antipsychotic. The benefits and possible side effects of each drug should be discussed with them, including:[1][2][68]
Metabolic (including weight gain and diabetes)
Extrapyramidal (including akathisia, dystonia, and dyskinesia)
Cardiovascular (including prolonging the QT interval)
Hormonal (including increasing plasma prolactin)
Other (including unpleasant subjective experiences).
Aim to check the following before starting an antipsychotic:
ECG if indicated; check your local protocol because guidance varies.
NICE recommends an ECG before starting an antipsychotic if any of the following are present:[1]
It is specified in the summary of product characteristics/prescribing information
A physical examination has identified specific cardiovascular risk (such as a diagnosis of high blood pressure)
There is a personal history of cardiovascular disease
The patient is being admitted as an inpatient.
If the ECG is abnormal, repeat it. If in doubt or the ECG remains abnormal, discuss this with a cardiologist.
Baseline bloods including fasting blood glucose, HbA1c, cholesterol, triglycerides, and prolactin.[1]
Assessment of any movement disorders.[1]
Practical tip
There is little difference between the efficacy of non-clozapine antipsychotics.[9] Choice of antipsychotic should be determined by patient preference wherever possible as well as taking into account the patient’s medication history and individual patient factors such as risk of extrapyramidal side effects, weight gain, impaired glucose tolerance, or QT-interval prolongation, or the presence of negative symptoms.[68][120] Be aware that patients with schizophrenia are at significant risk of cardiovascular disease and diabetes from side effects of antipsychotics but also from schizophrenia itself, which can also interfere with their ability to communicate their needs and access care.[14][87][112] In the acute setting, consider giving a sedative antipsychotic, or sedative in addition to an antipsychotic, to help with sleep disturbance.[121] See Insomnia.
Relapse of known schizophrenia
Review the patient’s current antipsychotic; a switch to an alternative antipsychotic may be considered but this should only be done by a specialist.
[ ]
[ ]
Consider the possibility of non-adherence with prescribed medication.[90]
Practical tip
Check adherence with antipsychotic treatment through pharmacy records because non-adherence with antipsychotics is common. This is frequently due to adverse effects of an antipsychotic; consider assessing adverse effects using a validated tool (e.g., the Glasgow Antipsychotic Side-effect Scale).[68][122][123] Glasgow Antipsychotic Side-effect Scale Opens in new window
Assess antipsychotic efficacy and adherence
The antipsychotic should be trialled for 4-6 weeks at optimum dosage.[113] Consider using a formal assessment tool such as the Clinical Global Impression (CGI) Scale to monitor response to treatment.[124] Clinical Global Impression Scale Opens in new window
A reduction of 1 point on the CGI scale indicates a significant response to an antipsychotic.[68]
The patient should be reassessed following this trial.[113]
The antipsychotic should be continued at the current dose established if effective.
If the antipsychotic is not effective, identify any underlying reasons for this (e.g., poor adherence). A switch to an alternative antipsychotic may be considered but this should only be done by a specialist. [
]
[ ]
A long-acting injectable antipsychotic should be considered if the patient is concerned about taking medication reliably.[1] However, in practice, a long-acting injectable formulation should only be started after a trial of the same oral medication to make sure the patient tolerates the medication. The starting dose of the long-acting injectable formulation depends on the patient’s previous oral dose, and the oral formulation may need to be continued for a short time after the first dose of the long-acting injectable formulation. Consult a drug formulary or pharmacist for further information on starting these formulations.
Practical tip
Check adherence with antipsychotic treatment through pharmacy records because non-adherence with antipsychotics is common. This is frequently due to adverse effects of an antipsychotic; consider assessing adverse effects using a validated tool (e.g., the Glasgow Antipsychotic Side-effect Scale).[68][122][123] Glasgow Antipsychotic Side-effect Scale Opens in new window
Continue antipsychotic long-term
Continue antipsychotic treatment for 1-2 years if this is effective.[2]
[ ]
Longer-term maintenance treatment may be considered for patients who have ongoing symptoms, or frequent relapses that are associated with high risk to themselves or others.[125]
Continue to monitor the patient’s adherence to the antipsychotic and for adverse effects.[1]
Explore and address reasons for non-adherence (e.g., adverse effects of the antipsychotic, practical problems with access to prescriptions).
Psychological therapy and social interventions
The National Institute for Health and Care Excellence (NICE) recommends to offer all patients cognitive behavioural therapy for psychosis (CBTp).[1]
[ ]
[ ]
However, a Cochrane review notes there is no clear and convincing advantage for CBT over other psychosocial therapies.[117] Family interventions may also be used if the patient lives with or is in close contact with family.[1][118]
Ensure patients have follow-up depending on their needs and that long-term social support is in place. Offer support with finances, accommodation, and access to supported employment programmes if the patient is out of work and wanting to find work.[1][126]
[ ]
Offer support for any carers involved with the patient, including an assessment of their own needs.[1]
Manage physical health
Monitor patients taking an antipsychotic for:[1]
Side effects of treatment and impact on functioning. Use a formal rating scale such as the Glasgow Antipsychotic Side-effect Scale.[122] Glasgow Antipsychotic Side-effect Scale Opens in new window
Signs of extrapyramidal movement disorders with antipsychotic medications (EPSE).
Use a formal rating scale such as the Abnormal Involuntary Movement Scale. Abnormal Involuntary Movement Scale Opens in new window For information on managing EPSE, see Complications.
Weight: weekly for the first 6 weeks, then at 12 weeks, at 1 year, and then annually (plotted on a chart).
Waist circumference, annually.
Pulse and blood pressure at 12 weeks, at 1 year, and then annually.
Fasting blood glucose, HbA1c, and blood lipid levels at 12 weeks, at 1 year, and then annually.
Prolactin, as clinically indicated.[2]
ECG, as clinically indicated.[2]
Overall physical health, including smoking, exercise, and diet.
A rare but serious side effect of antipsychotics is neuroleptic malignant syndrome. Assess the patient urgently if this is suspected; consider urgent transfer to hospital.[111] See Neuroleptic malignant syndrome.
Practical tip
Recognise and manage risk factors for cardiovascular disease and diabetes early as they can cause significant morbidity and mortality if left untreated.[1][87][112][115]
In general, this is performed poorly in patients with schizophrenia; the mean life expectancy of a patient with schizophrenia is 14.5 years shorter compared with the general population.[116] This is mostly due to physical health causes; treatment with antipsychotics can cause significant and rapid weight gain. However, schizophrenia itself increases mortality, especially if untreated, and can also interfere with the patient’s ability to communicate their needs and access care.[14][87][112]
Address alcohol and substance misuse and encourage smoking cessation.[1][87]
Smoking is a major contributor to increased mortality in individuals with serious mental illness.[9][127][128] People with schizophrenia are more likely to smoke than the general population but are less likely to be offered support to quit.[87][129]
There appears to be an increased risk of blood-borne viruses in patients with serious mental illness, including schizophrenia.[130][131] One Swedish population-based study found that, after accounting for sociodemographic factors, the odds of HIV were 2.57 times higher in people with serious mental illness than in the general population; the odds of hepatitis B virus were 2.29 times higher; and the odds of hepatitis C virus were 6.18 times higher. Substance use was found to contribute most to this increased risk, indicating a need to identify comorbid substance use in patients with serious mental illness, as well as to identify interventions to prevent infection with blood-borne viruses.[132]
Monitor for signs of relapse
Ensure patients, carers, and key-workers are aware of the early signs of relapse and how to access help.[133]
[ ]
Identify and aim to modify risk factors that increase the chance of relapse. These are:[5][68][134]
Clozapine should be considered for patients who have not had an adequate response to a trial of two different antipsychotics; this should only be started by a specialist.[2][68][114]
Review existing medication, blood tests, general health, and smoking status before clozapine is started, particularly for drug interactions and concurrent side effects.[120]
Check full blood count prior to starting clozapine and at set intervals thereafter.[120]
Consider seeking specialist advice if the patient has a history of heart disease or cardiac abnormalities are found.
Monitor for adverse effects of clozapine including constipation, weight gain (and associated metabolic syndrome), postural hypotension, dry mouth/hypersalivation, neutropenia, agranulocytosis, myocarditis, and cardiomyopathy.[120]
Advise the patient to immediately report symptoms of infection.[120]
Monitor clozapine levels according to local protocols; there is no consensus on a defined monitoring schedule.
Practical tip
Adverse effects of clozapine tend to be more common and severe at the start of treatment. Monitor for these closely; the clozapine dose should be titrated accordingly.[9]
If treatment with clozapine has been omitted for more than 48 hours it must be stopped and retitrated from the starting dose. Seek advice from a senior colleague or pharmacist.
Practical tip
Be aware that patients who stop smoking while they are taking clozapine can have a doubling of their blood clozapine levels. This can lead to serious adverse effects including seizures.[137]
Drug safety alert: MHRA/CHM advice on the potentially fatal risk of intestinal peristalsis in patients taking clozapine
In October 2017, the Medicines and Healthcare products Regulatory Agency (MHRA)/Commision on Human Medicines (CHM) issued a reminder that clozapine has been associated with varying degrees of impairment of intestinal peristalsis, including intestinal obstruction, faecal impaction, and paralytic ileus. Patients and their carers should be advised to seek immediate medical advice before taking the next dose of clozapine if constipation develops.[138]
If clozapine is ineffective or partially effective, augmentation strategies should be considered.[1][2] However, these are highly specialist and should be used with caution.
[ ]
Evidence: Electroconvulsive therapy
In people with treatment-resistant schizophrenia, the evidence for electroconvulsive therapy (ECT) is very limited and recommendations vary.
[ ]
[Evidence C]
The National Institute for Health and Care Excellence does not recommend the use of ECT in people with schizophrenia. This is based on its technology appraisal (last updated 2009, last reviewed April 2014), which concludes: “The current state of the evidence does not allow the general use of electroconvulsive therapy in the management of schizophrenia to be recommended.”[139]
The Scottish Intercollegiate Guidelines Network (SIGN) 2013 guideline based its recommendation that ECT should only be used as an adjunct to antipsychotic medication in people with treatment-resistant schizophrenia on a 2005 Cochrane review.[2][140]
The Cochrane review identified one small trial relevant to SIGN.[141] People with treatment-resistant schizophrenia who responded to an open trial of ECT and flupenthixol were randomised to:
Continuation ECT (CECT - weekly bilateral ECT for 1 month then bimonthly for 5 months, total 14 treatments, n=16)
CECT plus flupenthixol (n=17), or
Flupenthixol alone (n=18).
Global improvement (measured by Global Assessment of Functioning Scale) was greater with ECT plus antipsychotics compared with medication alone (n=30, weighted mean difference 19.1, 95% CI 9.7 to 28.5).
Adding CECT to antipsychotics also reduced the risk of relapse (40% compared with 93% in each of the other groups; risk ratio [RR] 0.43, 95% CI 0.23 to 0.81; number needed to treat 2, 95% CI 1.5 to 2.5).
A non-significant trend favoured antipsychotic alone compared with CECT plus antipsychotic for cognitive impairment at the end of treatment (measured by Mini Mental State Exam); however, this appeared to be transient.
Since the publication of the SIGN guideline a new Cochrane review was published in 2015 and updated in 2019.[142]
The review authors included 15 studies (1285 people) with treatment-resistant schizophrenia.
Treatment duration ranged from 2 weeks to 24 weeks.
The review authors determined that 14/15 studies were at high risk of bias due to issues related to blinding.
Overall the review authors concluded that when ECT plus standard care (defined as the treatment the participants received alongside the trial intervention as part of their ongoing care for their illness) was compared with standard care, moderate-quality evidence (assessed by GRADE) indicated that ECT improved medium-term clinical response for people with treatment-resistant schizophrenia (nine studies; n=819; RR 2.06, 95% CI 1.75 to 2.42).
There was also some medium-term improvement for mental state (Brief Psychiatric Rating Scale; two studies; n=345; mean deviation [MD] -11.18, 95% CI -12.61 to -9.76; GRADE low) and general functioning (Global Assessment of Functioning; two studies; n=97; MD 10.66, 95% CI 6.98 to 14.34; GRADE very low).
However, adding ECT to standard care may increase the risk of short-term memory deterioration (one study; n=72; RR 27.00, 95% CI 1.67 to 437.68; GRADE very low).
There was no clear difference for adding ECT to standard care for satisfaction and acceptability of treatment.
There was a lack of evidence comparing ECT alone versus antipsychotics (flupenthixol) alone.
There was insufficient evidence regarding the long‐term effects or safety parameters of ECT.
The review authors concluded that more good-quality evidence is needed to inform the role ECT may play in the management of people with treatment-resistant schizophrenia.
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