Depot & LAI good practice

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.

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.

Second Generation:

Risperdal Consta©:

• Formulation and pharmacokinetics 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.
• Oral risperidone should be continued during the three-week lag period following the first RISPERDAL CONSTA injection.

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.

Paliperidone 3 monthly injection (Trevicta):

• Offers the convenience of reduced numbers of annual injections.
• Patients who have responded well to and tolerated monthly paliperidone, who are clinically stable on treatment for at least 4 months may be switched to 3 monthly injections if clinically appropriate. (See table below for equivalent doses)

Paliperidone 6 monthly injection (Byannli)

• Of use in the following patients:
  • Adequately treated with 1-monthly paliperidone palmitate injection at doses of 100 mg or 150 mg (preferably for four months or more) or
  • 3-monthly paliperidone palmitate injection at doses of 350 mg or 525 mg (for at least one injection cycle) and do not require dose adjustment (See table below for equivalent doses)

Paliperidone equivalent doses

Full prescribing details may be found in the SPC for each product.

Olanzapine embonate:

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

Aripiprazole:

• Recommended initial dose is 400mg. 
• Reduce as described in the SPC as necessary. 
  • If a dose other than 400mg is to be given this can be achieved via adjustment of the injection volume only by using Abilify Maintena powder and solvent for prolonged-release suspension for injection, the pre-filled syringe should NOT be used.
• Administered every calendar month not every 4 weeks.
• There are 2 initiation regimes for aripiprazole:
  • One injection start: On the day of initiation, administer one injection of 400 mg Abilify Maintena and continue treatment with 10 mg to 20 mg oral aripiprazole per day for 14 consecutive days to maintain therapeutic aripiprazole concentrations during initiation of therapy.
  • Two injection start: On the day of initiation, administer two separate injections of 400 mg Abilify Maintena at separate injection sites, along with one 20 mg dose of oral aripiprazole.

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

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.

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.

Depot antipsychotic injections must be prescribed on HEPMA (for inpatients only) and on a depot prescription card/sheet for all patients.

Depot prescription sheets should be reviewed every six months.

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.

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

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.

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.

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.