Knowing how to use IM risperidone—and other long-acting atypicals that are likely to be approved—will enable you to help your patients benefit from reliable antipsychotic dosing. Long-acting antipsychotics address the challenge that makes schizophrenia particularly difficult to treat: medication nonadherence because of psychotic illness’ effect on insight, reality testing, and motivation.1,2
Too few schizophrenia patients in the United States—perhaps <5% of appropriate candidates—receive depot antipsychotics.1 We believe these agents provide the best delivery system to our patients and welcome IM risperidone’s approval3
This article shares what we have learned from research and clinical practice about using injectable antipsychotics, with a focus on how to effectively use long-acting IM risperidone.
CONVENTIONAL ANTIPSYCHOTICS
Once seen as an improvement over oral conventional antipsychotics, IM agents were relegated over time to a means of coercion (as in, “If you don’t take your medicine orally, we’ll force you to take a shot.”). Oral atypical antipsychotics, with improved side-effect profiles and possibly reduced relapse risk, also discouraged psychiatrists from using long-acting conventional antipsychotics as first-line medication.4
Available agents. Fluphenazine and haloperidol—the two long-acting conventional antipsychotics available in the United States (Table 1)—are esterified to a fatty acid (oil) to create an IM injectable prodrug. They can be given in gluteal or deltoid injection, although doses >2 cc should be given in the gluteus.
Hydrolysis releases the active drug, usually within 3 days. This interval allows loading doses to reach therapeutic blood levels rapidly when the goal is to stabilize patients in the hospital or during a short-term crisis stay. Disadvantages include:
- pain and lasting reactions at the injection site
- risk of extrapyramidal symptoms (EPS), neuroleptic malignant syndrome, and tardive dyskinesia.5
Table 1
Administering long-acting injectable antipsychotics
| Name | Preparation | Dose range | Interval | Injection site | Comment |
|---|---|---|---|---|---|
| Fluphenazine | 25 mg/mL | 5 to 75 mg each injection | Every 1 to 2 weeks | Deltoid or gluteal | Site reaction common |
| Haloperidol | 50 or 100 mg/mL | 25 to 200 mg each injection | Every 2 to 4 weeks | Deltoid or gluteal | Site reaction common |
| Risperidone | 25, 37.5, or 50 mg in prefilled bottles | 25 to 50 mg each injection | Every 2 weeks | Gluteal only | Requires reconstitution, proprietary kit |
Depot administration. Fluphenazine depot is commonly given every 2 weeks, starting with 25 mg, but a weekly or monthly interval is not rare. The dose range is broad because the drug can be given in fine gradations from as low as 2.5 mg (0.1 cc) to 75 mg (3 cc). Thus, you can individually titrate it by varying the dose and/or interval.
Because haloperidol is usually given monthly and thus requires less-frequent dosing, it tends to be used more often than fluphenazine. Haloperidol can be given in shorter intervals but is rarely used at intervals >4 weeks. Usual dosing is 50 to 100 mg per shot but can range from small amounts to hundreds of milligrams.
Transition from oral to IM. Switching from an oral antipsychotic to a long-acting medication is straightforward. As long as test doses or history predetermine that patients have no untoward effects from fluphenazine or haloperidol, the first injection can be given and the oral agent maintained for 3 to 5 days.
Monitor for dystonias and other emergent EPS. Some practitioners pretreat with anticholinergics to avoid these neurologic side effects. If you can monitor the patient over the first week, you can often avoid pretreatment and add side-effect medication as needed.
LONG-ACTING IM RISPERIDONE
For technical and approval reasons, it took nearly a decade for a long-acting atypical to be developed and approved. Because risperidone could not easily be attached to an oil, the solution to making risperidone long-acting was to use microspheres.6
Microspheres are best conceptualized as a solid sphere of dissolvable suture-like material (glycolide-lactide polymers) embedded with risperidone bits. The microspheres are packaged dry and reconstituted at the clinic with aqueous diluent at the time of medication. Once reconstituted, it forms a suspension of microspheres in water.
‘Snow in a snow globe.’ Reconstituted long-acting risperidone appears like snow in a snow globe. With shaking, the microspheres become suspended but quickly settle in the bottle or syringe. Shake to resuspend the microspheres if you are giving an injection more than 2 minutes after the initial reconstitution. Reconstituted microspheres can be given up to 6 hours after hydration.
Transfer the medication to the syringe via the proprietary exchange system, and use the specialized needle to inject the medication into the gluteal region. Once injected, the microspheres swell with water from local muscle, then break down.
Delayed action. The microspheres begin releasing risperidone in 3 to 4 weeks. Therapeutic levels last approximately 2 weeks until the microspheres gradually convert to carbon dioxide and water. This delayed action requires coverage with oral or other depot medication. Coverage is no longer needed after the medication reaches a steady state (Figure).