Managing Long-acting Antipsychotic Depots During COVID-19

Long acting antipsychotic depots (depots) or Long-acting Injections (LAIs) are used commonly in both inpatient and outpatient settings and have frequently been shown to improve adherence and reduce relapse rates leading to fewer readmissions. They are administered at frequencies between weekly and monthly.

Patients may attend clinics for their injection, or have it administered in their own homes and injections may be administered by nurses from Community Mental Health Teams or via their GP.

Antipsychotics and COVID-19

Whilst there is little information on whether antipsychotics create any specific concerns in the context of COVID-19, there is evidence that the use of antipsychotics can increase the risk of developing pneumonia therefore patients who have symptomatic COVID-19 should be closely monitored.

This document was written to support patients currently receiving depots within NELFT services however the principles may be used to support patients who receive depots elsewhere. Additionally, local Mental Health Pharmacy staff can provide advice on managing patient-specific queries e.g. managing missed doses or altering depot injection frequencies.

Where patients who are not currently under MH services are receiving a depot antipsychotic from their GP this provision should continue during this pandemic and MH staff would not be expected to take on a stable patient purely to administer a depot injection.

Options for improving capacity of depot clinics

As capacity to administer depots may be reduced during the pandemic, consideration should be given to options which may reduce the amount of depot administrations required by increasing the interval between injections. See the table on the next page.

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Depot / LAI Depot Maximum Maximum Potential options half-life* interval dose per injection Flupentixol 3-7 days 4 weeks 400mg For patients on more frequent dosing Decanoate consider increasing the interval between doses and adjusting the dose. Haloperidol 3- 4 weeks 4 weeks 300mg For patients on more frequent dosing Decanoate consider increasing the interval between doses and adjusting the dose. Zuclopenthixol 19 days 4 weeks 600mg For patients on more frequent dosing Decanoate consider increasing the interval between doses and adjusting the dose. Aripiprazole LAI 5-6 weeks Monthly 400mg Aripiprazole can be given at an interval of up to 6 weeks in stable patients and due to its long half-life, this is likely to have minimal impact. Paliperidone LAI 4 – 7 Monthly 150mg Licensed to be given every 6 weeks in (Xeplion®) weeks stable patients and due to its long half- life, this is likely to have minimal impact. Consider the 3 monthly Paliperidone formulation (Trevicta®) as an alternative for patients who are stable and have had at least 4 months of monthly Paliperidone LAI. Risperidone LAI 3-4 weeks 2 weeks 50mg Consider paliperidone as an alternative Olanzapine 4 weeks 4 weeks 405mg Monitoring requirements may be Pamoate difficult to facilitate. To obtain maximum doses (equivalent to 20mg oral) 300mg fortnightly is required. * Depot half-life gives an estimate of how long a depot will remain in the body should it be delayed or stopped. The longer the half-life the longer the depot will remain in the body after a medicine is stopped.

Approval may be required before switching to monthly or 3 monthly Paliperidone injections however local arrangements may be altered due to the pandemic.

Examples where changes in frequency of a depot may be considered: • Patient has Zuclopenthixol Decanoate 300mg weekly, consider 600mg every two weeks. • Patient on Haloperidol Decanoate 100mg every 2 weeks, consider 200mg every 4 weeks.

Examples where changes in frequency may not be appropriate: • Patient is on Zuclopenthixol Decanoate 400mg weekly, equivalent dose of 800mg every 2 weeks is above the licensed maximum dose for a single injection, unlicensed use could be considered. • Patient starts to deteriorate around the time that depots are due, increasing the dose interval may exacerbate this effect as a bigger single dose will be given at one time. • Patient has tried higher doses before but this lead to side effects.

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Whilst the above switches are generally well tolerated, it is important to review the patient after the change to ensure that they have tolerated the switch. This could be done over the phone.

Switching from Risperidone LAI to Paliperidone LAI

Patients who have a GFR less than 50ml/min should not be switched to Paliperidone

When switching patients from Risperidone long acting injection, initiate Paliperidone therapy in place of the next scheduled injection. Paliperidone should then be continued at monthly intervals. The one- week initiation dosing (or “loading”) regimen is not required for this switch. Patients previously stabilised on different doses of Risperidone LAI can attain similar Paliperidone steady-state exposure during maintenance treatment with Paliperidone monthly doses according to the following:

Doses of Risperidone long acting injection and Xeplion® needed to attain similar paliperidone exposure at steady-state Previous Risperidone LAI fortnightly dose Paliperidone monthly LAI 25 mg every 2 weeks 50 mg monthly 37.5 mg every 2 weeks 75 mg monthly 50 mg every 2 weeks 100 mg monthly

Switching from Paliperidone 1monthly injection (Xeplion®) to Paliperidone 3 monthly injection (Trevicta®)

Patients who are adequately treated with 1-monthly Paliperidone injection for a minimum of 4 months and do not require dose adjustment, may be switched to 3-monthly (Trevicta®) Paliperidone injection. Trevicta® should be initiated in place of the next scheduled dose of 1-monthly Paliperidone Palmitate injectable (± 7 days). The Trevicta® dose should be based on the previous 1-monthly Paliperidone dose using a 3.5-fold higher dose shown in the following table:

TREVICTA doses for patients adequately treated with 1-monthly paliperidone palmitate injectable Last dose of 1-monthly Paliperidone LAI Initiate 3-monthly Paliperidone LAI (Trevicta®) at: (Xeplion®): 50 mg 175 mg 75 mg 263 mg 100 mg 350 mg 150 mg 525 mg

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Switching from a depot to oral antipsychotic

In some cases, it may be appropriate to switch a patient from a depot antipsychotic to an oral equivalent however it is important to consider the risk of relapse due to destabilisation or if the patient were to be non-adherent to the oral antipsychotic.

Risks associated with depot/LAI to oral antipsychotic switches:

• Relapse or destabilisation, should the dose of oral medication be too low or if the patient has reduced adherence to the oral medicine. • Exacerbation of condition due to stress and anxiety from the switch. • Potential medication errors during the cross over. • Difficulties in working out equivalent doses requiring periods of dose adjustments and more frequent contact. • Combined adverse drug reactions (ADRs) during the period of crossover or ADRs due to the oral dose equivalent being too high.

Consideration should be given to the above factors and to individual patient risks before determining whether a switch from a depot/LAI to an oral antipsychotic is appropriate.

How to switch from a depot antipsychotic to the equivalent oral antipsychotic

Depot/LAI Frequency How to switch to oral Flupentixol Decanoate Weekly, Fortnightly Stop depot. Start oral on the day the next depot is or Zuclopenthixol due at 50% of the equivalent dose for one week Decanoate and then the full equivalent dose. 4 weekly Stop depot. Start oral dose on the day the next depot is due at the full equivalent dose. Haloperidol Decanoate Fortnightly Stop depot. Start oral dose on the day the next depot is due at 25% of the equivalent for a week then 50% for two weeks and then the full equivalent dose. 4 weekly Stop depot. Start oral dose on the day the next depot is due at 50% of the equivalent for a week then and then the full equivalent dose. Aripiprazole LAI Monthly Stop depot. Start oral at 5-10mg daily when the next depot would be due then increase after 7 days as necessary. Risperidone LAI Fortnightly Stop depot. Start oral risperidone at 1-2mg and increase weekly until equivalent dose is reached. Note that medication continues to be released until about 6 weeks after the final injection. Paliperidone LAI Monthly Stop depot. Start oral Risperidone at 1-2mg daily but increase slowly as the depot takes a long time to be eliminated. Reference – Psychotropic Drug Directory 2018

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Antipsychotic equivalent doses

The following table gives examples of equivalent oral to depot doses for the main antipsychotic depots. Note that for each antipsychotic there is a range of equivalent doses in the literature. The wider that range is, the less certainty in the equivalent doses and therefore caution should be advised. The patient should be closely monitored where any switching is undertaken.

Extra care should be taken when calculating equivalents at either the top or bottom of the dosage range.

Each patient should be considered individually, bearing in mind any adverse effects, physical frailty, other medication, and the patient’s risk of becoming unwell before deciding on an equivalent dose. The pharmacy team can help advise on individual antipsychotic switches.

Antipsychotic Daily Oral Dose Range per day Depot/LAI dose Depot/LAI Range Flupentixol 2.5 mg 2-3mg 10mg / week 8-20mg / week Haloperidol 2.5 mg 1-5mg 15mg / week 5-25mg / week Zuclopenthixol 25mg 25-60mg 100mg / week 40-100mg / week Aripiprazole 15mg 10-20mg 400mg / month Risperidone 2mg 0.5-3mg 25mg / 2 weeks Paliperidone 2mg 0.5-3mg 50mg / month References – SmPC, Psychotropic Drug Directory 2018, The Maudsley prescribing guidelines in psychiatry 13th Edition

Managing the closure of a depot clinic

In the event of a depot clinic no longer being operational, the team should arrange for patients to attend other clinics or attend a patient’s home to administer the depot. Pharmacy staff will assist clinics in relocating where necessary.

Monitoring switches

Where patients are switched they should be reviewed at least one week after a switch has taken place to monitor for any problems that may be occurring. Weekly reviews should be carried out during any period of cross titration for oral medicines, and at the next administration for depot switches. Patients should also be advised to contact their team should any problems occur in between reviews.

Patients should be checked for any adverse effects, any signs of emerging symptoms or relapse, and any problems they may have with adherence to their new regimen (particularly for switches to oral medicines). Doses may need adjusting during this period.

Reviews can be carried out over the phone where appropriate.

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Administration of Depots/LAIs to patients who are isolated or have suspected COVID-19

Where a patient is isolated or has confirmed COVID-19 staff may attend to administer the depot/LAI at a patient’s home using full PPE in line with the Trust’s infection control policy. In some a clinical decision may be made to delay administration, particularly if the patient is physically unwell. Where a patient has missed or been delayed receiving a depot/LAI pharmacy staff can provide advice on how to continue the depot/LAI.

Guidance on missed doses of Depots/LAIs

Please see below guidance for missed dose of Aripiprazole, Paliperidone or Risperidone. Whilst some guidance suggests giving an increased dose following a missed dose, in most cases it would be appropriate to continue at the previous dose and interval for Flupentixol Decanoate, Zuclopenthixol Decanoate and Haloperidol Decanoate. The Pharmacy Team can provide specific information on individual switches if required.

Aripiprazole LAI (Abilify Maintena®)

Missed 2nd or 3rd dose and time since last injection is:

Administer the LAI as soon as possible then resume monthly injection > 4 weeks but < 5 weeks schedule.

Concomitant oral Aripiprazole should be restarted for 14 days with next > 5 weeks administered injection and then resume monthly injection schedule.

Missed 4th or subsequent dose missed (i.e. at steady state) and time since last injection is:

Administer the LAI as soon as possible then resume monthly injection > 4 weeks but < 6 weeks schedule.

Concomitant oral aripiprazole should be restarted for 14 days with next > 6 weeks administered injection and then resume monthly injection schedule.

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Paliperidone 1-monthly LAI (Xeplion®)

Missed 2nd initiation dose (100mg) and time since last injection is:

100mg should be injected into the deltoid muscle as soon as possible. A third paliperidone injection of 75 mg (deltoid or gluteal) should be administered 5 weeks after the first injection (regardless of the timing < 4 weeks of the second injection). The normal monthly cycle of injections in either the deltoid or gluteal muscle of 50 mg to 150 mg based on individual patient tolerability and/or efficacy should be followed thereafter.

Day 1 – 100mg deltoid injection ASAP Day 8 – 100mg deltoid injection > 4 weeks but < 7 weeks Day 36 - Resume the normal monthly cycle of injections (deltoid or gluteal) based on individual patient tolerability and/or efficacy.

Day 1 – 150mg deltoid injection ASAP Day 8 – 100mg deltoid injection > 7 weeks Day 36 – Resume the normal monthly cycle of injections (deltoid or gluteal) based on individual patient tolerability and/or efficacy.

Monthly maintenance dose and time since last injection is: < 6 weeks Administer depot as soon as possible

50mg – 100mg: Day 1 – Deltoid injection at same dose patient was previously stabilised on asap Day 8 – another Deltoid injection (same dose) Day 36 – Resume the normal monthly cycle of injections (deltoid or > 6 weeks and < 6months gluteal) based on individual patient tolerability and/or efficacy. 150mg: Day 1 – 100mg deltoid injection asap Day 8 – 100mg deltoid injection Day 36 - Resume the normal monthly cycle of injections (deltoid or gluteal) based on individual patient tolerability and/or efficacy.

Day 1 – 150mg deltoid injection asap Day 8 – 100mg deltoid injection > 6 months Day 36 – Resume the normal monthly cycle of injections (deltoid or gluteal) based on individual patient tolerability and/or efficacy.

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Paliperidone 3-monthly LAI (Trevicta®) Missed doses

If scheduled dose is missed and the time since last injection is: > 3½ The injection should be administered as soon as possible and then resume the 3-monthly injection months schedule. up to 4 months

4 Recommended re-initiation regimen after missing 4 months to 9 months of TREVICTA months Administer 1-monthly paliperidone palmitate injectable, two Then administer TREVICTA (into deltoid or to 9 doses one week apart (into deltoid muscle) gluteal muscle) Last dose was months Day 1 Day 8 1 month after day 8

175 mg 50 mg 50 mg 175 mg 263 mg 75 mg 75 mg 263 mg 350 mg 100 mg 100 mg 350 mg 525 mg 100 mg 100 mg 525 mg

> 9 Re-initiate treatment with 1-monthly paliperidone palmitate injectable as described in the prescribing months information for that product. Trevicta® can then be resumed after the patient has been adequately treated with 1-monthly paliperidone palmitate injectable preferably for four months or more.

Risperidone LAI (Risperidone Consta®)

Time since last What happens to Plan injection risperidone plasma levels? 2-6 weeks Therapeutic risperidone plasma levels Administer LAI as soon as possible and consider remain supplementation with oral risperidone if indicated. >6 weeks but Risperidone plasma level starts to decrease Administer LAI as usual but monitor mental < 7 weeks and may become subtherapeutic after a state closely and consider supplementation further 1-3 weeks with oral risperidone if indicated. >8-9 weeks All risperidone will have been eliminated Administer LAI as soon as possible and give oral from the body risperidone for at least 3 weeks until plasma level is therapeutic.

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