Depot & LAI good practice

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Introduction

NICE (CG178 Psychosis and schizophrenia in adults: prevention and management) recommends:

Consider offering depot/long-acting injectable antipsychotic medication to people with schizophrenia:

  • who would prefer such treatment after an acute episode
  • where avoiding covert non-adherence (either intentional or unintentional) to antipsychotic medication is a clinical priority within the treatment plan.’

There are disadvantages to depot use namely managing side effects that may be prolonged and patient perception.

Depot or long acting antipsychotic injection – an antipsychotic drug formulated in such a way as to allow the steady gradual release of a drug over a defined time period. There are a variety of formulations and delivery vehicles but all are administered by deep intra-muscular injection.

Dosage- first generation

First Generation

Depots are long acting and any adverse effects are likely to be long lived. Therefore, when using ‘first generation’ 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. 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 depot drug, the dose range per week and the usual dosage interval.

Drug

Test dose (mg)

Dose range (mg/wk)a

Dosing interval (wks)

Flupentixol decanoate

20

12.5 - 400

2 - 4

Haloperidol decanoate

25b

12.5 - 75

4

Zuclopenthixol decanoate

100

100 - 600

1 - 4

Notes

In older adults the dose should be quartered or halved.

a. Dose range is given as 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).

b. The SPC for haloperidol does not recommend a test dose therefore a test dose of 25mg is suggested. The use of haloperidol in combination with drugs known to prolong the QTc interval is contra-indicated. Such combinations should be avoided.

 

Dosage- second generation

Second Generation:

Risperdal Consta©:

  • Formulation and pharmacokinetics of preclude the use of a test dose.
  • Risperidone-naive patients should receive oral risperidone prior to initiating treatment to establish tolerability.
  • It is recommended that patients treated with higher doses of oral antipsychotics should be considered for a 37.5mg starting dose of Risperdal Consta.

Paliperidone palmitate:

  • Loading dose of 150mg on day 1 then 100mg on day 8.
  • Followed by monthly adjustments according to response.
  • The loading dose must be administered into the deltoid muscle.
  • Administered every calendar month not every 4 weeks.

Olanzapine embonate:

  • Complex starting dose depending on the oral dose of olanzapine taken.
  • Non-formulary and subject to IPTR3 process- contact PMG(MH) before prescribing.

 Aripiprazole:

  • Recommended initial dose is 400mg. 
  • Reduce as described in the SPC as necessary. 
  • Administered every calendar month not every 4 weeks.

Always refer to the SPC, BNF or pharmacy for the appropriate initial dosing.

Initiation

When initiating a depot, the following principles apply:

  • Give a test dose (first generation only) or the recommended loading or initial dose first.
  • Begin with the lowest therapeutic dose. Lower doses are likely to be better tolerated and are less expensive.
  • 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.
  • 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.

Drug

Time to steady state (weeks)

Flupentixol decanoate

6 - 12

Haloperidol decanoate

10 - 12

Zuclopenthixol decanoate

10 - 12

Aripiprazole

16

Olanzapine embonate

12

Paliperidone palmitate

9 - 21

Risperidone

6 - 8

Side effects

Like all drugs, depot antipsychotics may be associated with side effects. A full list of possible side effects can be found in the SPC for each drug. The following are some important points to remember:

  • Pain, erythema, swelling and nodules can occur at the injection site.
  • Depot antipsychotics do not produce extra-pyramidal side effects at the time of administration. They may occur after several hours or days.
  • 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 a depot be 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 be given in a healthcare facility and patients must remain there for 3 hours post dose.

Standardised tools or checklists e.g. GASS (Glasgow antipsychotic side-effect scale) should be used to monitor and assess side effects every 6 – 12 months minimum.

Prescribing

Depot antipsychotic injections must be prescribed on the prescription sheet (for inpatients only) and on a depot prescription card/sheet for all patients to standards described in GG&C guidance.

Depot prescription sheets should be reviewed every six months.

Licensed injection sites

The following table details the licensed site of administration for each long acting antipsychotic injection. The information has been taken from the current Summary of Product Characteristics for each drug.

Drug

Licensed site of administration

Flupentixol decanoate

Upper outer buttock or lateral thigh

Haloperidol decanoate

Gluteal

Zuclopenthixol decanoate

Upper outer buttock or lateral thigh

Aripiprazole

Deltoid or gluteal

Olanzapine embonate

Gluteal

Paliperidone palmitate

Deltoid or gluteal

Risperidone

Deltoid or gluteal

Administration and recording

Detailed guidance to support administration of depot antipsychotics can be found in full guidance.

 

Communication

When a patient is transferred between any settings the following details must be clearly communicated:

  • The depot preparation prescribed plus the dose and dosage interval.
  • Date last given and the next due date.

Good communication can be aided by transferring depot prescription & recording sheets with the patient as they move.

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

Staff within CMHTs are responsible for ensuring depot alerts on EMIS are up to date.

Medication related issues

A number of other important issues may impact on the use of depot antipsychotics

1. Concomitant medication

2. Changes to depot antipsychotic prescriptions

3. Drug Interactions

4. High Dose Antipsychotics

5. Extremes of weight

6. Consent to treatment

7. General Physical Monitoring

8. Storage and preparation requirements for Risperdal Consta

9. Audit

See Page 8 of full guideline for details.

Dose selection

The administration of depot antipsychotic drugs is a skilled procedure. Intra-muscular injections can be painful and this can be especially true of the depot injections. Pain can be minimised by using the smallest volume possible. Ideally, no more than 2ml should be given to one site if possible.

**Note** Under no circumstances should different strengths of depot preparation be mixed. The above advice is intended as a guide, if you require further advice contact pharmacy.

The following tables give guidance on product selection to minimise the volume of depot injection administered.

Flupenthixol Decanoate

Dose

Product

Volume

Method

10mg

Flupentixol 20mg/ml

0.5ml

Via 1ml syringe

20mg

Flupentixol 20mg/ml

1ml

Via 1ml syringe

30mg

Flupentixol 40mg/2ml

1.5ml

Via 2ml syringe

40mg

Flupentixol 40mg/2ml

2ml

Via 2ml syringe

50mg

Flupentixol 50mg/0.5ml

0.5ml

Via 1ml syringe

60mg

Flupentixol 100mg/ml

0.6ml

Via 1ml syringe

70mg

Flupentixol 100mg/ml

0.7ml

Via 1ml syringe

80mg

Flupentixol 100mg/ml

0.8ml

Via 1ml syringe

90mg

Flupentixol 100mg/ml

0.9ml

Via 1ml syringe

100mg

Flupentixol 100mg/ml

1ml

Via 1ml syringe

120mg

Flupentixol 200mg/ml

0.6ml

Via 1ml syringe

150mg

Flupentixol 200mg/ml

0.75ml

Via 1ml syringe

200mg

Flupentixol 200mg/ml

1ml

Via 1ml syringe

 

Zuclopenthixol decanoate - Clopixol

Dose

Product

Volume

Method

50mg

Zuclopenthixol 200mg/ml

0.25ml

Via 1ml syringe

100mg

Zuclopenthixol 200mg/ml

0.5ml

Via 1ml syringe

150mg

Zuclopenthixol 200mg/ml

0.75ml

Via 1ml syringe

200mg

Zuclopenthixol 200mg/ml

1ml

Via 1ml syringe

300mg

Zuclopenthixol 500mg/ml

0.6ml

Via 1ml syringe

400mg

Zuclopenthixol 500mg/ml

0.8ml

Via 1ml syringe

500mg

Zuclopenthixol 500mg/ml

1ml

Via 1ml syringe

600mg

Zuclopenthixol 500mg/ml

1.2ml

Via 2ml syringe

 

Fluphenazine decanoate

Dose

Product

Volume

Method

6.25mg

Fluphenazine 25mg/ml

0.25ml

Via 1ml syringe

12.5mg

Fluphenazine 25mg/ml

0.5ml

Via 1ml syringe

18.75mg

Fluphenazine 25mg/ml

0.75ml

Via 1ml syringe

25mg

Fluphenazine 25mg/ml

1ml

Via 1ml syringe

37.5mg

Fluphenazine 25mg/ml

1.5ml

Via 2ml syringe

50mg

Fluphenazine 50mg/0.5ml

0.5ml

Via 1ml syringe

62.5mg

Fluphenazine 25mg/ml

2.5ml

Via 2ml syringe*

75mg

Fluphenazine 100mg/ml

0.75ml

Via 1ml syringe

100mg

Fluphenazine 100mg/ml

1ml

Via 1ml syringe

 

Haloperidol decanoate - Haldol

Dose

Product

Volume

Method

50mg

Haloperidol 50mg/ml

1ml

Via 1ml syringe

100mg

Haloperidol 100mg/ml

1ml

Via 1ml syringe

150mg

Haloperidol 100mg/ml

1.5ml

Via 2ml syringe

200mg

Haloperidol 100mg/ml

2ml

Via 2ml syringe

250mg

Haloperidol 100mg/ml

2.5ml

Via 5ml syringe

 

Aripiprazole – Abilify Maintena

Dose

Product

Volume

Method

400mg

Aripiprazole 400mg

2ml

Via syringe provided

300mg

Aripiprazole 400mg

1.5ml

Via syringe provided

200mg*

Aripiprazole 400mg

1.0ml

Via syringe provided

160mg*

Aripiprazole 400mg

0.8ml

Via syringe provided

Flowchart for administration

 

 

Editorial Information

Last reviewed: 27 February 2020

Next review: 27 February 2023

Author(s): Safer Use of Medicines

Version: 2.2

Approved By: PMG-MH

Reviewer Name(s): Andrew Walker, Suzanne Burke