When and how to use long-acting injectable antipsychotics
If antipsychotic polypharmacy is necessary, document your rationale.
In patients who are naïve to a specific LAI dosage form, ensure that the first dose does not exceed FDA and evidence-based guidelines for the initial dose (eg, 100 mg intramuscular [IM] for haloperidol decanoate).1
Consider a loading dose strategy to minimize the time a patient has to take an oral and LAI antipsychotic combination.14
Ensure that the total volume injected intramuscularly is not >3 ml per injection site per dose.
Use the recommended injection technique for the particular LAI (eg, Z-tract).1,15
Individualize the dose and dosing interval based on patient response, peak-related adverse effects (time to peak is approximately 5 half-lives for most drugs), and possible reduced symptom control at the end of the dosing interval.8
If your patient does not respond as expected, taking an antipsychotic plasma level to assess drug metabolism and other PK factors and characteristics may be useful.
LAI options
Fluphenazine decanoate is an older, inexpensive LAI with considerable interpatient variability in absorption rate and peak effects, and a relatively short duration of action. Dosing every 7 days may be necessary to avoid peak plasma level adverse effects or symptom recurrence. Variable PK make it difficult to accurately calculate an empiric conversion dose from oral to LAI; therefore, start at the low end (eg, 1.2 to 1.6 times the total daily oral dose) or 12.5 or 25 mg for the initial IM fluphenazine decanoate dose. A short overlap period—usually 1 to 2 weeks—may be necessary. Successful subcutaneous administration is possible.2
Haloperidol decanoate. A 28-day dosing interval is effective for most patients. It is possible to administer a loading dose so that no overlapping taper is required. My team has had good results using an initial loading dose 15 to 20 times the effective oral dose and a second dose 28 days later of 10 times the oral daily maintenance dose, with the same dose every month thereafter. If a patient is receiving his or her first haloperidol decanoate injection, the initial dose should not exceed 100 mg. The remainder of the loading dose may be administered 3 to 7 days later if no adverse effects occur. Similar to fluphenazine decanoate, haloperidol decanoate is relatively inexpensive. When considering giving a haloperidol decanoate loading dose >400 mg or a maintenance dose >200 mg every 28 days, carefully document the rationale (eg, rapid metabolism).16
Olanzapine pamoate. Clinicians who administer olanzapine pamoate must enroll in a national registry that documents the incidence of rare but serious ADEs, particularly hypotension, orthostatis, and post-injection delirium/sedation syndrome (0.1% incidence) at every injection, not just for drug-naïve patients. Patients should be observed for 3 hours after every dose and oral medication overlap may be necessary in some cases.10 Similar to clozapine, these monitoring difficulties and the expense may have inhibited olanzapine LAI use, even in patients who are likely to benefit.
Risperidone microspheres. This agent has been evolutionary, if not revolutionary, in schizophrenia treatment and data on its efficacy for BD will be available soon. Its 2-week dosing interval, necessity of oral overlap, and anecdotal reports of “dose dumping” possibly because of fragility of the microsphere formulation suggest the need for an improved version, which was addressed by the introduction of paliperidone palmitate.10,17,18
Paliperidone palmitate has a 28-day dosing interval. No overlapping oral taper is necessary. Details of a week-long, 2-dose loading dose strategy is provided in the package insert.11 It may be safe to use a more aggressive loading dose strategy.15,19
Related Resources
- Rothschild AJ. The evidence-based guide to antipsychotic medications. Arlington, VA: American Psychiatric Publishing, Inc.; 2010.
- Cañas F, Möller HJ. Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review. Expert Opin Drug Saf. 2010;9(5):683-697.
Drug Brand Names
- Aripiprazole • Abilify
- Fluphenazine deconoate • Prolixin Deconoate
- Haloperidol deconoate • Haldol Deconoate
- Iloperidone • Fanapt
- Olanzapine pamoate • Zyprexa Relprevv
- Paliperidone palmitate • Invega Sustenna
- Risperidone • Risperdal Consta
Disclosures
Dr. Kennedy receives grant or research support from Janssen and Johnson and Johnson.
