Long-acting injections

What it is

A long-acting injection, also called a depot, is an antipsychotic given into a muscle. The medicine is released slowly over weeks or months, so it replaces daily tablets. Older antipsychotics such as haloperidol and zuclopenthixol come in this form.^1,2 So do several newer ones: risperidone, paliperidone, aripiprazole and olanzapine.^3,4

NICE recommends considering a long-acting injection for people who would prefer it after an acute episode, and where making sure doses are not missed without anyone knowing is a priority in the treatment plan.⁵

How it works

The medicine is made in a form that dissolves slowly from the muscle. Haloperidol decanoate, for example, takes on average three weeks to fall to half its level in the body, against about a day for haloperidol tablets.¹ The result is a steady level of medicine in the blood, which lowers the risk of relapse.⁶ A missed injection is also noticed, where a missed tablet may not be.⁵

History

In the Netherlands, zuclopenthixol decanoate was registered in 1976 and haloperidol decanoate in 1981.^2,1 When newer antipsychotics arrived as tablets, confidence in long-acting injections declined.⁷ A long-acting form of risperidone was registered in the Netherlands in 2002.³ Injections of paliperidone, aripiprazole and olanzapine followed, and paliperidone can now be given every 3 or every 6 months.^8,9

How well it works

Across 137 studies with almost 400,000 people, long-acting injections went with a lower risk of hospital admission or relapse than tablets. In randomised trials, the risk was about 12 per cent lower. In studies that compared the same people before and after switching to an injection, it was more than halved.¹⁰

In a Swedish study of all 29,823 people aged 16 to 64 with schizophrenia in the country, the risk of being readmitted to hospital was about a fifth lower on long-acting injections than on the same medicines as tablets.¹¹

In trials comparing antipsychotics for preventing relapse, no medicine was clearly better than the others, whether given as tablets or as injections. The choice depends mainly on side effects.¹² Newer long-acting injections also reduced symptoms in people who were acutely unwell.⁴

Longer intervals worked about as well. Over a year, 7.5 in 100 people relapsed on paliperidone every 6 months, against 4.9 in 100 on paliperidone every 3 months, a difference within the trial’s margin for “no worse”.⁹

Side effects

The side effects are mostly those of the medicine itself: see, for example, olanzapine (opens in a new tab) and aripiprazole (opens in a new tab). Some may be less marked with the injection than with tablets, though this still needs confirming in direct comparisons.⁴ In addition:

• Where the injection is given. Pain, swelling or a lump can occur. In a trial of the olanzapine injection, 3 in 100 people had a reaction at the injection site.¹³ With risperidone injections, rare serious reactions such as abscesses and tissue damage have been reported, in a single case needing surgery.³
• The olanzapine injection. After about 7 in 10,000 injections, affecting 1.4 in 100 people, too much olanzapine entered the blood at once. This caused heavy sleepiness or confusion, as in an overdose. Symptoms began from straight away to 5 hours after the injection, and everyone recovered within 3 days. People are therefore watched for a while after each injection.¹⁴
• Side effects last longer. Because the medicine stays in the body for weeks, an unwanted effect cannot be stopped quickly. Psychiatrists in an Italian survey named this as a barrier to using injections.¹⁵

Side effects can be reported to Lareb, the Dutch side-effects centre, to the FAMHP in Belgium, or to the manufacturer.

Administration

A nurse or doctor gives the injection into a muscle of the buttock or upper arm.³ How often depends on the medicine:

• every 2 weeks: risperidone³
• every 1 to 4 weeks: zuclopenthixol²
• usually every 4 weeks: haloperidol¹
• every 2 or 4 weeks: olanzapine¹³
• every month, or every 2 months: aripiprazole^16,17
• every month, every 3 months or every 6 months: paliperidone^8,9

An injection is usually started once the same medicine has worked as tablets. Haloperidol decanoate, for example, is for people who are stable on haloperidol tablets.¹ After the first risperidone injection, the person keeps taking an antipsychotic by mouth for three weeks, until the injection starts to work.³

NICE advises taking into account how the person feels about regular injections, and practical arrangements such as home visits and where the clinic is.⁵ Psychiatrists report that some people turn injections down because the medicine stays in the body for a long time, or because injections make them feel controlled.¹⁵

Contraindications and cautions

The cautions for each medicine apply to its injection too. Haloperidol decanoate is dissolved in sesame oil, which can rarely cause severe allergic reactions.¹ After an olanzapine injection, people are watched before going home.¹⁴

Check the patient leaflet, and ask the prescriber about your own situation.

Stopping

Because the medicine is released slowly, its level falls gradually over weeks after the last injection.¹ Across 30 trials with 4,249 people, 24 in 100 people who stayed on an antipsychotic relapsed within 7 to 12 months, against 61 in 100 who switched to placebo.¹⁸ Changes are best planned with the prescriber.

Alternatives

The same medicines are available as tablets, among them olanzapine (opens in a new tab) and aripiprazole (opens in a new tab). Clozapine (opens in a new tab) is not available as a long-acting injection. Family intervention (opens in a new tab) also lowers the risk of relapse and helps people keep taking their medicine.¹⁹

What we don’t know yet

• Whether starting a long-acting injection soon after a first episode improves the long-term course.
• Which interval suits whom.
• Why the benefit looks larger in everyday care than in randomised trials.