High dose antipsychotic therapy guidelines

1. See appendix I, Identification of Patients on High-Dose Antipsychotic Therapy.
2. Consider alternative approaches including certain antipsychotics which are considered more effective, namely haloperidol, amisulpride, risperidone and olanzapine. Adjuvant and newer antipsychotics should also be considered.
3. A depot antipsychotic preparation should be considered if adherence to oral antipsychotic medication is a concern.
4. Clozapine should be considered in established treatment resistant schizophrenia following failed treatment from two adequate trials of antpsychotics, at least one of which was a second generation antipsychotic.
5. The responsibility to exceed the licensed dose of a single antipsychotic or a combination of more than one lies with the patient’s consultant psychiatrist. The decision should be discussed with the multidisciplinary team, the patient and/or carer and valid consent obtained. For detained patients, ensure compliance with the Mental Health (Care and Treatment) (Scotland) Act 2003. The details of the decision- making process should be recorded in the patient’s case notes including the clinical indication for use of HDAT. That the patient was informed of the HDAT, or the reason why they have not been informed, should be documented in the notes.
6. HDAT may be prescribed in an emergency for acute symptoms. This must be discussed with a Consultant Psychiatrist before it is prescribed. If this is not possible the reason should be documented and the prescription reviewed at the next opportunity by the Consultant or deputy.
7. Only the Consultant or deputy should make the decision to use HDAT regularly. The decision should be documented in the patient's notes.
   
   
8. Action
   • Indicate on the medicine chart that the patient is receiving high-dose antipsychotics by filling out “high dose monitoring applicable” section.
   • A High-Dose Antipsychotic Monitoring Sheet (Appendix III) should be completed for the patient and filed in notes under investigations.
     
     (a)  Consider risk factors such as:
     
     
   • Cardiac history (particularly MI, arrhythmias, abnormal ECG)
   • Hepatic / renal impairment
   • Alcoholism / smoking
   • Old age
   • Obesity
     
     (b)  Consider potential drug interactions e.g.
     
     
   • Drugs which are known to prolong QTc interval including anti-arrythmics
   • For an up-to-date list of drugs known to prolong QTc interval, see online reference www.crediblemeds.org and follow link for QT drugs list, selecting option: 
     ‘To view QT-prolonging drugs grouped by risk of Torsades, possible risk of Torsades and conditional risk of Torsades’
     
     
   • Pharmacokinetic interactions i.e. drugs that increase antipsychotic plasma levels.(NB smoking can decrease plasma levels of antipsychotics, therefore, smoking cessation will increase plasma levels.)
   • Diuretics which can cause electrolyte abnormalities e.g. hypokalaemia, hypocalcaemia, hypomagnesaemia.
     
     (c)    Obtain a pre-high-dose antipsychotic baseline ECG. If a prolonged QT interval is recorded (QTc >440ms-1), review treatment. Consider cardiology assessment. If it is decided to continue treatment, record reasons for doing so in patient’s case notes. All patients on HDAT should have regular ECGs (baseline, when steady-state serum levels have been reached after each dosage increment, and then every 6-12 months). Additional biochemical/ECG monitoring is advised if drugs that are known to cause electrolyte disturbances or QTc prolongation are subsequently co-prescribed.
     
     (d)   Serum urea and electrolytes and liver function should be checked before prescribing. Biochemical monitoring should be undertaken every 6 months and if drugs that are known to cause electrolyte disturbances of QTc prolongation are subsequently co-prescribed.
     
     
9. Where possible increase the dose slowly ideally over intervals of at least one week.
10. Review progress at least once every 3 months, reducing dose to within the licensed range if no significant progress is observed and consider alternative approaches, e.g. adjuvant therapy and newer or 2nd generation antipsychotics such as Clozapine. Continued use of high-dose therapy where there is no clinical response should be justified in the case notes. Consultants should consider seeking a second opinion from a colleague. The review should be documented in the patients’ notes.
11. The Royal College of Psychiatrists Consensus Statement recommends monitoring of psychotic symptoms. Improvement in psychotic symptoms and side effects should be regularly assessed. Rating scales may be useful, for example CGI (Clinical Global Impression) & HoNoS (health of nation outcome scales) to assess progress and, GASS (Glasgow Antipsychotic Side effect scale) & LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) to assess side effects. These would be performed at weeks 0, 6 and 12, then at least annually.

Medical Staff Responsibilities

• Identify that a patient is on high-dose antipsychotics on the medicine chart and alert nursing team.
• On the High Dose Antipsychotic Monitoring Form (appendix III) complete the following:
  • Patient details
  • High dose details and %
  • Interacting medicines section
  • Risk factors

• Inform key worker and medical staff of high-dose status
• Arrange ECGs at recommended intervals
• Check FBC, U&Es and LFTs at recommended intervals and if change in hepatic function suspected
• Document reason for high-dose in clinical notes
• Inform patient and document consent in notes
• Ensure HDAT is authorised on Form T2 / T3, if applicable
• Ensure on patients’ discharge that GP and other relevant community mental health personnel are informed of HDAT status and required checks
• Ensure that other medical prescribers (GPs and Psychiatrists) with a responsibility for the patient are informed of prescribing which generates HDAT
• Ensure a system by which the required tests and reviews will be conducted and is agreed with the relevant community mental health personnel & / or GP
• Ensure policy is followed for HDAT

Initiation of high-dose antipsychotic therapy is the responsibility of the consultant. Pharmacists will support monitoring by identifying patients on high dose therapy.

Nursing Staff Responsibilities – document initially, after dose changes and three monthly on the high dose monitoring chart

• Temperature Blood pressure and pulse checks at recommended intervals
• Document “high dose” status in Nursing Notes / Care Record
• Check that monitoring form is being completed and forms uploaded to EMIS after each completion and bring to medical staff attention if monitoring not in place
• Ensure that high-dose status is discussed at MDT reviews

References

Barnes et al. Evidence based guidelines for the pharmacological treatment of schizophrenia: updated recommendations from the British Association of Psychopharmacology. British Association of Psychopharmacology. 2019

Huhn, M et al (2019). Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet., 394: 939-951.

Harrington et al, (2002) The results of a multi-centre audit of the prescribing of antipsychotic drugs for in-patients in the UK. Psychiatric Bulletin, 26, 414-418.

Royal College of Psychiatry. Consensus statement on the risks and benefits of high-dose antipsychotic medication. College Report CR190 2014 (Revised January 2023)

The Maudsley Prescribing Guidelines in Psychiatry, 14th Edition, 2021.

High dose antipsychotic prescribing may be achieved in TWO ways:

A. Single antipsychotic drug prescribed at a daily dose above the BNF upper recommended limit (High Dose single drug).

B. More than one antipsychotic prescribed concurrently (High Dose through the prescribing of multiple drugs). In defining what constitutes a high-dose of antipsychotics for patients receiving more than one antipsychotic at doses within the normal BNF ranges, use the percentage method for calculating high dose status. When expressed as a percentage of their respective recommended maximum dose and added together, a cumulative dose of greater than 100% is considered ‘high dose’

Use of “Discretionary” (PRN or ’as required’) antipsychotic medication should also be taken into account.

** Subject to annual ECG irrespective of dosage.

WPOMH: Prescribing Observatory for Mental Health, Royal College of Psychiatrists

More than one antipsychotic drug should only be given concurrently as part of a considered treatment plan.

• There is no evidence to support combinations of first and second generation antipsychotics having fewer neurological side effects than first generation medicines alone
• Polypharmacy regimes are more complex, potentially confusing and error prone.
• Polypharmacy with antipsychotics does not allow an accurate assessment of the effectiveness of each drug nor the effect of dose titration of any given drug accurately.
• There are few good RCTs of antipsychotic polypharmacy (there are some RCTs of clozapine augmentation). Although this does not mean that some combinations are not effective in some individuals, more robustly evidence-based approaches should be considered before resorting to non-evidence based and higher-risk treatments.
• “High dose” can inadvertently occur with combinations. PRN antipsychotics are particularly problematic in this respect.
• Subtle drug interactions can occur with combinations through P450 and other enzyme systems.

Before combination antipsychotics are used, check:

• The diagnosis is correct
• Plasma levels (if appropriate) are therapeutic and drug compliance assured.
• Treatment duration has been fully adequate.
• Delayed onset of action
• Adverse social and psychological factors are minimised.
• Alternative adjunctive drug therapies have been tried.
• An objective measure of effectiveness of drug therapy on symptomatology is used.

If a combination will result in exceeding 100% BNF maximum dose the High-dose antipsychotic policy should be adhered to.

Appropriate indications for use of combination therapy include:

√    Failure to respond to Clozapine

√    Failure to tolerate Clozapine

√    Where Clozapine had produced a partial response, as augmentation.

√    During the switch from one antipsychotic to another

√    As a temporary measure during an acute exacerbation of illness.

Inappropriate indications would include:

x   Utilising drug for sedative rather than antipsychotic effect.

x   Initiation before adequate length of trial of first drug (at least 6 weeks).

x   As a substitute for planning, communicating and completing a change to alternative antipsychotic therapy. x     Where clinical improvement occurs before a switch is completed. An improvement seen during the switch may indicate a trial of the combination if appropriate.

x   Where inadequate resources and/or modifiable environment factors are associated with higher medication dosages

If multiple antipsychotics are to be used:

• The patient should be informed and consent obtained and documented, using relevant legislation as needed (this is to cover t2/3). 
• The rationale for use should be documented in the patients’ clinical notes.
• The clinical indication for use should be documented in the patients’ clinical notes.
• The use of multiple antipsychotic therapies should be reviewed regularly (at least every 3 months) with regard to the clinical indication and the result of this review documented.
• If no improvement is seen at review, discontinuation of multiple antipsychotic therapies should be considered and decision documented.
• More than two regular antipsychotics would indicate the need for further medication review with pharmacy support; a second medical opinion should be considered.

High Dose Therapy Patients Form

Audit Criteria