Use of antipsychotic depot and long acting injections

The antipsychotics currently available as depot preparations are: First Generation:

• Flupentixol Decanoate (Depixol, Psytixol)
• Haloperidol Decanoate (Haldol Decanoate)
• Zuclopenthixol Decanoate (Clopixol Decanoate)

Second Generation:

• Aripiprazole (prefilled syringes and prolonged-release suspension for injection vials)
• Risperidone (Risperdal Consta, Okedi) (not on current Formulary)
• Paliperidone Palmitate (paliperidone generic, Trevicta, Byannli)
• Olanzapine Pamoate (Zypadhera) (not on current Formulary)

They are indicated for the maintenance of schizophrenia and other psychoses.

When initiating an antipsychotic depot, the following principles apply:

1. Give a test dose (first generation only) or the recommended loading or initial dose first.
2. Begin with the lowest therapeutic dose. Lower doses are likely to be better tolerated and are less expensive.
3. Administer at the longest possible licensed interval. Follow the recommended licensed dosing interval, there is no evidence to suggest that shortening the dosing interval will improve efficacy.
4. Allow an adequate assessment period before adjusting doses. Peak plasma levels, therapeutic effect and steady state plasma levels are delayed with depot injections. Adequate time must be allowed for these to occur before increasing doses. Therefore, it would be prudent to wait until these have been achieved before considering increasing the dose. The following table gives the approximate time to steady state for these drugs.

First Generation Antipsychotic Depot:

Depots are long acting and any adverse effects are likely to be prolonged. Therefore, when using first generation antipsychotic depots, a small test dose is always given to identify if patients are likely to be susceptible to side effects or will suffer a severe reaction to the drug or delivery vehicle. Once a test dose has been given it is necessary to wait at least 4-10 days before initiating any titration to maintenance dose (always refer to the summary of product characteristics (SPC) for individual products). Adverse reactions may occur at any time during this period and the patient must be closely monitored.

The following table summarises the test doses for each first generation antipsychotic depot, the dose range per week and the usual dosage interval.

Second Generation Antipsychotic Depots:

Risperidone (Risperdal Consta): This preparation is non formulary. Please contact pharmacy to discuss before prescribing. The formulation and pharmacokinetics of Risperdal Consta preclude the use of a test dose. For Risperidone naïve patients it is recommended to establish tolerability with oral Risperidone prior to initiating treatment with Risperdal Consta. It is recommended that patients treated with higher doses of oral antipsychotics (risperidone or other) should be considered for 37.5mg starting dose of Risperdal Consta. Sufficient antipsychotic coverage with oral risperidone or other previous antipsychotic is necessary during the three-week lag period following the first risperidone depot administration. This depot requires to be reconstituted prior to use. Staff should be familiar with and deemed competent to prepare this drug. Once reconstituted the product must be used within 6 hours.

Paliperidone : With Paliperidone Palmitate a loading dose of 150mg on day 1 then 100mg on day 8 is given followed by monthly adjustments according to response. The loading dose must be administered into the deltoid muscle. Please note that Paliperidone LAI is administered every calendar month, not every 4 weeks. A three monthly formulation is available for patients established on monthly paliperidone depot injections.

Olanzapine (Zypadhera): This preparation is non formulary and must follow the Non-Formulary Process. Please contact pharmacy to discuss before prescribing. Olanzapine Pamoate has a complex starting dose depending on the oral dose of Olanzapine the patient was taking.

Aripiprazole: Oral aripiprazole 10mg/day for 14 days is recommended initially to establish tolerability and response. One of two recommended regimens may be followed for administering the starting dose of aripiprazole LAI –

1. One-injection start – on day of initiation administer one 400mg aripiprazole LAI and continue 10-20mg oral aripiprazole per day for 14 days.
2. Two-injection start – on day of initiation administer two separate injections of 400mg aripiprazole LAI at separate injection sites in two different muscles along with one 20mg dose of oral aripiprazole. This depot should be administered every calendar month not every 4 weeks.

1. Dose range is given is mg/week for illustrative purposes only. Avoid using shorter dose intervals than those recommended (last column) except where the dose required necessitates an unacceptably high injection volume (>2.5ml of injection).

Like all drugs, antipsychotic depots are associated with side effects. A full list of possible side effects can be found in the SPC for each drug found at  https://www.medicines.org.uk/emc/. The following are some important points to remember:

1. Pain, erythema, swelling and nodules can occur at the injection site.
2. Antipsychotic depots do not produce extra pyramidal side effects at the time of administration. They may occur after several hours or days.
3. Rarer adverse effects such as rashes and agranulocytosis are well documented with antipsychotics, anaphylaxis is not. However, it is recommended that the first dose of an antipsychotic depot is administered in a clinical base with access to emergency equipment (disposable ambubag, airways, Laerdal pocket mask and supportive medicines). Thereafter there should be no need for nursing staff to carry adrenaline in case of anaphylaxis. Olanzapine LAI must always begiven in a healthcare facility and patients must remain there for 3 hours post dose.
4. Standardised tools or checklists e.g. Borders Modified LUNSERS scale should be used to monitor and assess side effects every 6-12 months.

Antipsychotic depot injections must be prescribed. This prescription should be reviewed every 6 months. The prescription must be legibly written and signed by a medical practitioner or a suitably qualified non-medical prescriber. Verbal prescriptions for depot injections are not permitted.

On initiation and also at any change of medication, dose or frequency, the date the injection is due must be clearly annotated. Prescriptions should not be post dated.

The prescription must contain:

1. The patient’s name, address and CHI number
2. Any known allergies or “no known allergies” recorded on the prescription
3. Special notes of relevance to administration of the depot
4. The drug name, dosage, strength and frequency of administration
5. A review date
6. Prescribers signature

The following table details the licensed site of administration for each antipsychotic LAI. The
information has been taken from the current SPC for each drug.

Detailed guidance to support administration of antipsychotic depots is outlined in Appendix 5. The following provides summary guidance.

1. Antipsychotic depots may only be administered against a valid prescription.
2. Before administering any new antipsychotic depot check:
   • A test dose has been given, if appropriate, and no adverse reactions occurred.
   • The patient has received an adequate explanation of the treatment and has received any appropriate written information.
   • The patient consents to the treatment or if detained under Mental Health Legislation that the appropriate documentation is in place.
3. Patients' identity is confirmed. If the patient is unknown to the CPN, confirm the patient’s name and date of birth.
4. Once the above criteria are satisfied appropriately trained staff or student nurses under supervision may administer antipsychotic depots. All staff must meet the competencies required for administering depot injections.
5. Select the appropriate strength of antipsychotic depot preparation to administer the required dose in the lowest possible volume (Appendix 2).
6. Observe good practice guidelines for hand washing and ‘no touch’ technique when preparing the dose for administration.
7. Administer the antipsychotic depot by deep intramuscular injection.
8. Dispose of all materials used as indicated by local policy.
9. Undertake hand hygiene as per local policy.

Accurate record keeping is essential to patient safety, medication incidents have occurred because of poor record keeping. For example:

• Doses being given before or after the next due date in error.
• Wrong medication or dose being dispensed or administered.
• Doses missed completely

The following table lists the details that must be recorded:

Local areas should devise a system for tracking the next due dates for all patients prescribed depot antipsychotics.

If the patient did not attend the appointment the CPN should discuss with the RMO and devise a plan for further administration attempts.

Depot antipsychotics prescribed in NHS Borders are ordered directly from the BGH Pharmacy Department by Community Mental Health Teams. Orders are placed by email to the Mental Health Pharmacy Team, who then process the order and send a supply fo the requested products to a location specified by the CMHT for storage.

Depot ordering for Community Mental Health Teams

Individual CMHTs must have a robust process for managing their stock of depot antipsychotics. The CMHTs are responsible for ordering the products they need and checking the stock they have stored in their specified location for expiries.

Depot antipsychotics must be prescribed on prescription, as detailed above, and this includes community Kardexes completed by a prescriber, with details of administration documented by the CPN giving the depot to the patient.

Orders can be audited via the Mental Health Pharmacy Team, and the CMHTs can advise on when they wish to change their stock of products which will depend on the number of patients they are treating with depot medication and the products they are routinely using.

Where there is a defined long-term shortage of a depot, the Mental Health services, in discussion with the Mental Health Pharmacy Team, will review and change patients where appropriate.

It is essential to good patient care that communication between patient settings regarding antipsychotic depot prescriptions is robust. This may be between community teams and mental health in-patient settings, between community teams and acute medical in-patient settings. When a patient is transferred between any of these settings the following details must be clearly communicated:

1. The antipsychotic depot preparation prescribed, the dose and dosage interval
2. Date last given and date next due

It is the responsibility of ward staff in mental health or acute settings to administer antipsychotic depots when patients are in hospital. In no circumstances should community staff administer antipsychotic depots to patients in hospitals.

Staff within community mental health teams are responsible for ensuring antipsychotic depot alerts on IT medical note system (e.g. EMIS) are up to date.

A number of other important issues may impact the use of antipsychotic depots:

Concomitant medication: Patients may be prescribed or be taking a variety of other medications. It is important to be aware of these when prescribing/advising antipsychotic depots. It is especially important when a psychiatrist is responsible for prescribing the antipsychotic depot and the GP prescribes everything else.

Changes to antipsychotic depot prescriptions: It is essential that all changes to an antipsychotic depot prescription are quickly and clearly communicated to all relevant staff.  

Drug interactions: It is important that all health professionals involved in the use of antipsychotic depots are aware of the clinically significant interactions between antipsychotic depots and other medicines. Staff should refer to the current edition of the BNF or contact pharmacy for advice.

High dose antipsychotics: The Royal College of Psychiatrists has issued revised guidance to the use of high dose antipsychotics (January 2023). It is possible that a patient could be prescribed regular or as required oral antipsychotics whilst on an antipsychotic depot. This may result in them reaching high dose status. Refer to available guidelines on high dose antipsychotics.

Consent to treatment: If a patient is detained under the Mental Health Act and/or subject to a CTO, or is being treated under Adults with Incapacity legislation, treatment with an antipsychotic depot must comply with any relevant treatment plan in place. All staff involved with the patient must be aware of the contents of any treatment plan. Staff must have access to a copy of the treatment plan with the antipsychotic depot prescription sheet at the point of administration.

General physical monitoring: The regular interaction between community staff and patients prescribed antipsychotic depots may provide an ideal opportunity to monitor relevant physical parameters. This is especially true for those patients who don't or won't attend their GP. Some of the parameters for monitoring include blood pressure, pulse, ECG, weight and adverse effects.

Storage and preparation of Risperdal Consta: Unlike the other antipsychotic depots, this preparation requires refrigeration prior to use. Accordingly, it is subject to cold chain transportation. If the cold chain is broken at any point the depot should be stored at room temperature and used within 7 days. Appendix 1: Preparing to administer an antipsychotic depot injection.

Appendix 1:  Preparing to administer an antipsychotic depot injection, Preparation and equipment, Criteria for selection of injection site, Injection techniques

Appendix 2: Dose selection for antipsychotic depot injection

Appendix 3: Equipment checklist

Appendix 4: Preparation for administering depot antipsychotic injections

Appendix 5: Administering depot antipsychotic injections