Evidence-Based Reviews

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

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

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.
16. Jann MW, Ereshefsky L, Saklad SR. Clinical pharmacokinetics of the depot antipsychotics. Clin Pharmacokinet. 1985;10(4):315-333.
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.
21. Mavroidis ML, Kanter DR, Hirschowitz J, et al. Fluphenazine plasma levels and clinical response. J Clin Psychiatry. 1984;45(9):370-373.
22. Balant-Gorgia AE, Balant LP, Andreoli A. Pharmacokinetic optimisation of the treatment of psychosis. Clin Pharmacokinet. 1993;25(3):217-236.
23. Van Putten T, Marder SR, Wirshing WC, et al. Neuroleptic plasma levels. Schizophr Bull. 1991;17(2):197-216.
24. Dahl SG. Plasma level monitoring of antipsychotic drugs. Clinical utility. Clin Pharmacokinet. 1986;11(1):36-61.
25. Miller RS, Peterson GM, McLean S, et al. Monitoring plasma levels of fluphenazine during chronic therapy with fluphenazine decanoate. J Clin Pharm Ther. 1995;20(2):55-62.
26. Gitlin MJ, Midha KK, Fogelson D, et al. Persistence of fluphenazine in plasma after decanoate withdrawal. J Clin Psychopharmacol. 1988;8(1):53-56.
27. Wistedt B, Wiles D, Kolakowska T. Slow decline of plasma drug and prolactin levels after discontinuation of chronic treatment with depot neuroleptics. Lancet. 1981;1(8230):1163.
28. Wistedt B, Jørgensen A, Wiles D. A depot neuroleptic withdrawal study. Plasma concentration of fluphenazine and flupenthixol and relapse frequency. Psychopharmacology (Berl). 1982;78(4):301-304.
29. Risperdal Consta [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; February 2017.
30. Marder SR, Conley R, Ereshefsky L, et al. Clinical guidelines: dosing and switching strategies for long-acting risperidone. J Clin Psychiatry. 2003;64(suppl 16):41-46.
31. Invega Sustenna [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; February 2017.
32. Invega Trinza [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; February 2017.
33. Abilify Maintena [package insert]. Rockville, MD: Otsuka America Pharmaceutical, Inc.; December 2016.
34. Artistada [package insert]. Waltham, MA: Alkermes, Inc.; June 2017.
35. Zyprexa Relprevv [package insert]. Indianapolis; IN: Eli Lilly and Co.; February 2017.
36. Heres S, Kraemer S, Bergstrom RF, et al. Pharmacokinetics of olanzapine long-acting injection: the clinical perspective. Int Clin Psychopharmacol. 2014;29(6):299-312.
37. Detke HC, Zhao F, Garhyan P, et al. Dose correspondence between olanzapine long-acting injection and oral olanzapine: recommendations for switching. Int Clin Psychopharmacol. 2011;26(1):35-42.

Maintenance phase. During the maintenance phase, PP1M can be administered 7 days before or after the monthly due date. If the patient has missed a maintenance injection and it has been <6 weeks since the last dose, the maintenance injection can be given as soon as possible (Figure 5).³¹ If it has been 6 weeks to 6 months since the last injection, the patient should receive their prescribed maintenance dose as soon as possible and the same dose 1 week later, with both injections in the deltoid muscle. Following the second dose, the patient can resume their regular monthly maintenance schedule, in either the deltoid or gluteal muscle. For example, if the patient was maintained on 117 mg of PP1M and it had been 8 weeks since the last injection, the patient should receive 117 mg immediately, then 117 mg 1 week later, then 117 mg 1 month later. An exception to this is if a patient’s maintenance dose is 234 mg monthly. In this case, the patient should receive 156 mg of PP1M immediately, then 156 mg 1 week later, and then 234 mg 1 month later.³¹If it has been >6 months since the last dose, the patient should start the initiation schedule as if he or she were receiving a new medication.³¹

Paliperidone palmitate 3-month long-acting injection (PP3M) should be administered every 3 months. This injection can be given 2 weeks before or after the date of the scheduled dose.³²

If the patient missed an injection and it has been <4 months since the last dose, the next scheduled dose should be given as soon as possible.³² If it has been 4 to 9 months since the last dose, the patient must return to PP1M for 2 booster injections 1 week apart. The dose of these PP1M booster injections depends on the dose of PP3M that the patient had been stabilized on:

78 mg if stabilized on 273 mg
117 mg if stabilized on 410 mg
156 mg if stabilized on 546 mg or 819 mg.³²

After the second booster dose, PP3M can be restarted 1 month later.³² If it has been >9 months since the last PP3M dose, the patient should be restarted on PP1M. PP3M can be reconsidered once the patient has been stabilized on PP1M for ≥4 months (Figure 6).³²