Evidence-Based Reviews

Long-acting injectable antipsychotics: What to do about missed doses

Current Psychiatry. 2018 July;17(7):10-12,14-19,56

Use a stepwise approach based on the unique properties of the specific medication.

References

1. Olfson M, Mechanic D, Hansell S, et al. Predicting medication noncompliance after hospital discharge among patients with schizophrenia. Psychiatr Serv. 2000;51(2):216-222.
2. Lehman AF, Lieberman JA, Dixon LB, et al; American Psychiatric Association; Steering Committee on Practice Guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(suppl 2):1-56.
3. Kane JM, Garcia-Ribera C. Clinical guideline recommendations for antipsychotic long-acting injections. Br J Psychiatry Suppl. 2009;195(52):S63-S67.
4. Velligan DI, Weiden PJ, Sajatovic M, et al. Strategies for addressing adherence problems in patients with serious and persistent mental illness: recommendations from the expert consensus guidelines. J Psychiatr Pract. 2010;16(5):306-324.
5. Kishimoto T, Robenzadeh A, Leucht C, et al. Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. Schizophr Bull. 2014;40(1):192-213.
6. Andreasen NC. Symptoms, signs, and diagnosis of schizophrenia. Lancet. 1995;346(8973):477-481.
7. de Sena EP, Santos-Jesus R, Miranda-Scippa Â, et al. Relapse in patients with schizophrenia: a comparison between risperidone and haloperidol. Rev Bras Psiquiatr. 2003;25(4):220-223.
8. Chue P. Long-acting risperidone injection: efficacy, safety, and cost-effectiveness of the first long-acting atypical antipsychotic. Neuropsychiatr Dis Treat. 2007;3(1):13-39.
9. Lafeuille MH, Frois C, Cloutier M, et al. Factors associated with adherence to the HEDIS Quality Measure in medicaid patients with schizophrenia. Am Health Drug Benefits. 2016;9(7):399-410.
10. Kishimoto T, Nitta M, Borenstein M, et al. Long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis of mirror-image studies. J Clin Psychiatry. 2013;74(10):957-965.
11. Marcus SC, Zummo J, Pettit AR, et al. Antipsychotic adherence and rehospitalization in schizophrenia patients receiving oral versus long-acting injectable antipsychotics following hospital discharge. J Manag Care Spec Pharm. 2015;21(9):754-768.
12. Haldol Decanoate injection [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; February 2017.
13. Magliozzi JR, Hollister LE, Arnold KV, et al. Relationship of serum haloperidol levels to clinical response in schizophrenic patients. Am J Psychiatry. 1981;138(3):365-367.
14. Mavroidis ML, Kanter DR, Hirschowitz J, et al. Clinical response and plasma haloperidol levels in schizophrenia. Psychopharmacology (Berl). 1983;81(4):354-356.
15. Reyntigens AJ, Heykants JJ, Woestenborghs RJ, et al. Pharmacokinetics of haloperidol decanoate. A 2-year follow-up. Int Pharmacopsychiatry. 1982;17(4):238-246.
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17. Chang WH, Lin SK, Juang DJ, et al. Prolonged haloperidol and reduced haloperidol plasma concentrations after decanoate withdrawal. Schizophr Res. 1993;9(1):35-40.
18. Ereshefsky L, Saklad SR, Jann MW. Future of depot neuroleptic therapy: pharmacokinetic and pharmacodynamic approaches. J Clin Psychiatry.1984;45(5 pt 2):50-58.
19. Marder SR, Hawes EM, Van Putten T, et al. Fluphenazine plasma levels in patients receiving low and conventional doses of fluphenazine decanoate. Psychopharmacology (Berl). 1986;88(4):480-483.
20. Marder SR, Hubbard JW, Van Putten T, et al. Pharmacokinetics of long-acting injectable neuroleptic drugs: clinical implications. Psychopharmacology (Berl). 1989;98(4):433-439.
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Antipsychotic agents are the mainstay of treatment for patients with schizophrenia,^1-3 and when taken regularly, they can greatly improve patient outcomes. Unfortunately, many studies have documented poor adherence to antipsychotic regimens in patients with schizophrenia, which often leads to an exacerbation of symptoms and preventable hospitalizations.^4-8 In order to improve adherence, many clinicians prescribe long-acting injectable antipsychotics (LAIAs).

LAIAs help improve adherence, but these benefits are seen only in patients who receive their injections within a specific time frame.^9-11 LAIAs administered outside of this time frame (missed doses) can lead to reoccurrence or exacerbation of symptoms. This article explains how to adequately manage missed LAIA doses.

First-generation long-acting injectable antipsychotics

Two first-generation antipsychotics are available as a long-acting injectable formulation: haloperidol decanoate and fluphenazine decanoate. Due to the increased risk of extrapyramidal symptoms, use of these agents have decreased, and they are often less preferred than second-generation LAIAs. Furthermore, unlike many of the newer second-generation LAIAs, first-generation LAIAs lack literature on how to manage missed doses. Therefore, clinicians should analyze the pharmacokinetic properties of these agents (Table 1^12-28), as well as the patient’s medical history and clinical presentation, in order to determine how best to address missed doses.

Haloperidol decanoate plasma concentrations peak approximately 6 days after the injection.¹² The medication has a half-life of 3 weeks. One study found that haloperidol plasma concentrations were detectable 13 weeks after the discontinuation of haloperidol decanoate.¹⁷ This same study also found that the change in plasma levels from 3 to 6 weeks after the last dose was minimal.¹⁷ Based on these findings, Figure 1 summarizes our recommendations for addressing missed haloperidol decanoate doses.

Fluphenazine decanoate levels peak 24 hours after the injection.¹⁸ An estimated therapeutic range for fluphenazine is 0.2 to 2 ng/mL.^21-25 One study that evaluated fluphenazine decanoate levels following discontinuation after reaching steady state found there was no significant difference in plasma levels 6 weeks after the last dose of fluphenazine, but a significant decrease in levels 8 to 12 weeks after the last dose.²⁶ Other studies found that fluphenazine levels were detectable 21 to 24 weeks following fluphenazine decanoate discontinuation.^27,28 Based on these findings, Figure 2 summarizes our recommendations for addressing missed fluphenazine decanoate doses.

Continue to: Second-generation LAIAs

Long-acting injectable antipsychotics: What to do about missed doses

References

First-generation long-acting injectable antipsychotics

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