Managing Long acting Antipsychotic Depots During COVID-19

Long acting antipsychotic depots (Depots) 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.

Patients either attend clinics for a depot or have them administered in their own homes. Depots are administered at frequencies between weekly and monthly. In NELFT the majority of staff administering depots are nurses from community mental health teams. A small number of patients may have their depot administered via their GP.

Antipsychotics and COVID-19

Whilst there is little information on whether antipsychotics have any specific concerns with 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.

Requests for patients outside of NELFT

This document is written to support patients currently receiving depots within NELFT services however the principles may be used to support patients who receive depots elsewhere and NELFT staff can help provide advice on how to manage individual patients queries for example how to manage missed doses or reducing depot frequencies.

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

Options for improving capacity of depot clinics

As it is envisaged that capacity to administer depots may be reduced consideration should be given to options which may reduce the amount of depot administrations that are required. This could be done by increasing the interval between depots

Depot Depot half Maximum Maximum dose Potential options life* interval per injection Flupentixol 3-7 days 4 weeks 400mg For patients on more frequent dosing consider increasing the interval between doses and adjusting the dose Haloperidol 3- 4 weeks 4 weeks 300mg For patients on more frequent dosing consider increasing the interval between doses and adjusting the dose Zuclopenthixol 7 days 4 weeks 600mg For patients on more frequent dosing consider increasing the interval between doses and adjusting the dose Aripiprazole 4-7 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

Guidance produced by Nicola Greenhalgh Lead clinical pharmacist MHS, March 2020 V1.2

Paliperidone 4 – 7 weeks Monthly 150mg Is licensed to be given 6 weeks apart at (Xeplion®) the same dose in stable patients and due to long half-life this is likely to have minimal impact Consider Paliperidone 3 monthly (Trevicta® ) as an alternative for patients who are stable and have had 6 months of paliperidone Risperidone 3-4 weeks 2 weeks 50mg Consider paliperidone as an alternative * 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.

Initiation forms would normally be required to be approved before switching to paliperidone 1 monthly or 3 monthly injections however these would not require to be completed.

Examples where changes in frequency of a depot may be considered

• Patient has zuclopenthixol 300mg weekly, consider 600mg every two weeks • Patient on haloperidol 100mg every 2 weeks, consider 200mg every 4 weeks

Examples where changes in frequency may not be appropriate

• Patient is on zuclopenthixol 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

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 long acting injection to Paliperidone

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 regimen including the intramuscular injections (day 1 and 8, respectively) is not required. Patients previously stabilised on different doses of risperidone long acting injection 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 long acting injection dose Paliperidone injection 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

Guidance produced by Nicola Greenhalgh Lead clinical pharmacist MHS, March 2020 V1.2

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

Patients who are adequately treated with 1-monthly paliperidone injection for at least 6 months and do not require dose adjustment may be switched to 3-monthly 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 If the last dose of 1-monthly paliperidone palmitate Initiate TREVICTA at the following dose injectable is 50 mg 175 mg 75 mg 263 mg 100 mg 350 mg 150 mg 525 mg

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 what the risks are should the patient become non- adherent to the oral antipsychotic.

Risks Associated with depot 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

Considerations should be given to the above factors and the risks of individual patients before determining whether a switch from a depot to an oral antipsychotic is appropriate

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

Depot Frequency How to switch to oral Fupentixol or zuclopenthixol Weekly, 2 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 4 weekly Stop depot, Start oral dose on the day the next depot is due at the full equivalent dose

Guidance produced by Nicola Greenhalgh Lead clinical pharmacist MHS, March 2020 V1.2

haloperidol 2 weekly 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 Monthly Stop depot, start oral at 5-10mg daily when the next depot would be due then increase after 7 days as necessary Risperidone 2 weekly Stop depot Levels continue to release until about 6 weeks after the final injection, start oral risperidone at 1-2mg and increase to weekly until equivalent dose is reached Paliperidone Monthly Stop depot Start oral Risperidone at 1-2mg daily but increase slowly as the depot takes a long time to be completely removed from the system Reference – Psychotropic Drug Directory 2018

Antipsychotic equivalent doses (wider range - less uncertainty)

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 indicates that there is less certainty in the equivalent doses and therefore caution should be advised and the patient should be closely monitored.

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

Guidance produced by Nicola Greenhalgh Lead clinical pharmacist MHS, March 2020 V1.2

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. Further reviews should be carried out weekly 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.

Administration of long acting antipsychotic depots to patients who are isolated or have suspected COVID-19

Where a patient is isolated or has confirmed COVID-19 staff can attend to administer the depot at a patient’s home using full PPE in line with the Trust’s infection control policy. Due to the long acting nature of depot antipsychotics in some cases a clinical decision may be made to delay the depot, particularly if the patient is physically unwell. Where patient’s have missed or delayed a depot pharmacy staff can assist in providing advice on how to continue the depot.

Guidance on missed doses of long acting injections (depots)

Please see below guidance for missed dose of aripiprazole, paliperidone or risperidone. For flupentixol, zuclopenthixol and haloperidol, 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. Contact pharmacy if you need specific information on individual switches.

Aripiprazole LAI (Abilify Maintena®)

If 2nd or 3rd dose is missed and time since Action last injection is: > 4 weeks and < 5 weeks The injection should be administered as soon as possible and then resume monthly injection schedule. > 5 weeks Concomitant oral aripiprazole should be restarted for 14 days with next administered injection and then resume monthly injection schedule. If 4th or subsequent doses are missed Action (i.e., after attainment of steady state) and time since last injection is:

Guidance produced by Nicola Greenhalgh Lead clinical pharmacist MHS, March 2020 V1.2

> 4 weeks and < 6 weeks The injection should be administered as soon as possible and then resume monthly injection schedule.

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

Paliperidone 1-monthly LAI (Xeplion®)

2nd initiation dose (100mg) and Action time since last injection is: < 4 weeks 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 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. > 4 weeks and < 7 weeks 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. > 7 weeks Day 1 – 150mg 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. Monthly maintenance dose and Action time since last injection is: < 6 weeks Administer depot as soon as possible > 6 weeks and < 6months 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 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. > 6 months Day 1 – 150mg 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.

Guidance produced by Nicola Greenhalgh Lead clinical pharmacist MHS, March 2020 V1.2

Paliperidone 3-monthly LAI (Trevicta®) Missed doses

If scheduled dose is missed and the Action time since last injection is > 3½ months up to 4 months The injection should be administered as soon as possible and then resume the 3-monthly injection schedule. 4 months to 9 months Use the recommended re-initiation regimen shown in the table below. > 9 months Re-initiate treatment with 1-monthly paliperidone palmitate injectable as described in the prescribing 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 depot asap remain >6 weeks but Risperidone plasma level starts to decrease Administer depot as usual but monitor mental < 7 weeks and may become subtherapeutic after a state closely and, if necessary, give oral further 1-3 weeks risperidone >8-9 weeks All risperidone will have been eliminated Administer depot asap and give oral risperidone from the body for at least 3 weeks until plasma level becomes therapeutic again

Guidance produced by Nicola Greenhalgh Lead clinical pharmacist MHS, March 2020 V1.2