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Best Clinical Practice With Ziprasidone IM: Update After 2 Years of Experience

  • Dan L. Zimbroff, Michael H. Allen (a1), John Battaglia (a2), Leslie Citrome (a3), Avrim Fishkind (a4), Andrew Francis (a5), Daniel L. Herr (a6), Douglas Hughes (a7), Marc Martel (a8), Horacio Preval (a9) and Ruth Ross (a10)...

Abstract

Acute agitation is a common psychiatric emergency often treated with intramuscular (IM) medication when rapid control is necessary or the patient refuses to take an oral agent. Conventional IM antipsychotics are associated with side effects, particularly movement disorders, that may alarm patients and render them unreceptive to taking these medications again. Ziprasidone (Geodon®) is the first second-generation, or atypical, antipsychotic to become available in an IM formulation. Ziprasidone IM was approved by the Food and Drug Administration in 2002 for the treatment of agitation in patients with schizophrenia. In October 2004, a roundtable panel of physicians with extensive experience in the management of acutely agitated patients met to review the first 2 years of experience with this agent. This monograph, a product of that meeting, discusses clinical experience to date with ziprasidone IM and offers recommendations on its use in various settings.

In clinical trials, patients treated with ziprasidone IM demonstrated significant and rapid (within 15-30 minutes) reduction in agitation and improvement in psychotic symptoms, agitation, and hostility to an extent greater than or equal to that attained with haloperidol IM. Tolerability of ziprasidone IM was superior to that of haloperidol IM, with a lower burden of movement disorders. Clinical trials have also shown that ziprasidone IM can be administered with benzodiazepines without adverse consequences. Transition from IM to oral ziprasidone has been well tolerated, with maintenance of symptom control. The most common adverse events associated with ziprasidone IM were insomnia, headache, and dizziness in fixed-dose trials and insomnia and hypertension in flexible-dose trials. No consistent pattern of escalating incidence of adverse events with escalating ziprasidone doses has been observed. Changes in QTc interval associated with ziprasidone at peak serum concentrations are modest and comparable to those seen with haloperidol IM. Results of randomized clinical trials of ziprasidone IM have been corroborated in studies in real-world treatment settings involving patients with extreme agitation or a recent history of alcohol or substance abuse. In these circumstances, clinically significant improvement was seen within 30 minutes of ziprasidone IM administration, without regard to the suspected underlying etiology of agitation. Agents with a good safety/tolerability profile, such as ziprasidone IM, may be more cost effective long term than older agents, due to reduced incidence of acute adverse effects (eg, acute dystonia) that often require extended periods of observation. Additional trials of ziprasidone IM in agitated patients in a variety of clinical settings are warranted to generate comparative risk/benefit data with conventional agents and other second-generation antipsychotics.

Copyright

Corresponding author

Dan L. Zimbroff, MD, Pacific Clinical Research Medical Group, 1317 West Foothill Blvd, Ste. 200, Upland, CA 91786. E-mail: dan.zimbroff@pcrmg.com.

References

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1.Allen, MH, Currier, GW. Use of restraints and pharmacotherapy in academic psychiatric emergency services. Gen Hosp Psychiatry. 2004;26:4249.
2.Fisher, WA. Restraint and seclusion: A review of the literature. Am J Psychiatry. 1994;151:15841591.
3.Sundram, CJ, Stack, EW, Benjamin, WP. Restraint and Seclusion Practices in New York State Psychiatric Facilities. Albany, NY: New York State Commission on Quality of Care for the Mentally Disabled; 1994.
4.Currier, GW, Allen, MH. American Association for Emergency Psychiatry survey, I: Psychiatric Emergency Service Structure and Function. Presented at: the 51st American Psychiatric Association Institute on Psychiatric Services; October 29-November 2, 1999; New Orleans, LA.
5.Medical Directors Council of the National Association of State Mental Health Program Directors. Reducing the Use of Seclusion and Restraint: Findings, Strategies, and Recommendations. Alexandria, VA: National Association of State Mental Health Program Directors; 1999.
6.Altimari, D, Blint, DF, Weiss, EM, et al.Deadly restraint. Hartford Courant. October 1998. Summary available at: http://www.nami.org/update/990324.html.
7.Allen, MH, Currier, GW, Hughes, DH, Reyes-Harde, M, Docherty, JP. Expert Consensus Panel for Behavioral Emergencies. The Expert Consensus Guideline Series. Treatment of behavioral emergencies. Postgrad Med. 2001;(spec no):188.
8.Allen, MH, Carpenter, D, Sheets, JL, et al.What do consumers say they want and need during a psychiatric emergency? J Psychiatr Pract. 2003;9:3958.
9.National Collaborating Centre for Mental Health, National Institute for Clinical Excellence (NICE). Schizophrenia: Full National Clinical Guideline on Core Interventions in Primary and Secondary Care. London, England: The Royal College of Psychiatrists: Gaskell Books; 2003.
10.Casey, DE. Motor and mental aspects of acute extrapyramidal syndromes. Acta Psychiatr Scand Suppl. 1994;89(suppl 380):1420.
11.King, DJ, Burke, M, Lucas, RA. Antipsychotic drug-induced dysphoria. Br J Psychiatry. 1995;167:480482.
12.Glassman, AH, Bigger, JT Jr.Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry. 2001;158(11):17741782.
13.Hassaballa, HA, Balk, RA. Torsade de pointes associated with the administration of intravenous haloperidol: A review of the literature and practical guidelines for use. Expert Opin Drug Saf. 2003;2:543547.
14.Allen, MH. Managing the agitated psychotic patient: a reappraisal of the evidence. J Clin Psychiatry. 2000;61(suppl 14):1120.
15.Battaglia, J. Pharmacological management of acute agitation. Drugs. 2005;65:12071222.
16.Battaglia, J, Moss, S, Rush, J, et al.Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Am J Emerg Med. 1997;15:335340.
17.Awad, AG, Voruganti, LNP, Heslegrave, RJ. Assessment of the patient's subjective experiences in acute neuroleptic treatment: implications for compliance and outcome. Int Clin Psychopharmacol. 1996;11(Suppl 2):5560.
18.Voruganti, L, Cortese, L, Oyewumi, L, Cernovsky, Z, Zirul, S, Awad, A. Comparative evaluation of conventional and novel antipsychotic drugs with reference to their subjective tolerability, side-effect profile and impact on quality of life. Schizophr Res. 2000;43:135145.
19.Geodon (ziprasidone mesylate) for Injection. [Package insert]. New York, NY: Pfizer, Inc: August, 2004.
20.FDA Psychopharmacological Drugs Advisory Committee. Briefing document for ziprasidone mesylate for intramuscular injection. February 15, 2001. Available at: http://www.fda.gov/ohrms/dockets/ac/01/briefing/3685b2_01_pfizer.pdf. accessed January 24, 2005.
21.Lesem, MD, Zajecka, JM, Swift, RH, et al.Intramuscular ziprasidone, 2 mg versus 10 mg, in the short-term management of agitated psychotic patients. J Clin Psychiatry. 2001;62:1218.
22.Daniel, DG, Potkin, SG, Reeves, KR, et al.Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: A double-blind, randomized trial. Psychopharmacology (Berl). 2001;155:128134.
23.Preskorn, SH. Pharmacokinetics and therapeutics of intramuscular ziprasidone. Clin Pharmacokinetics. 2005. In press.
24.Swift, RH, Harrigan, EP, Cappelleri, JC, et al.Validation of the behavioural activity rating scale (BARS): a novel measure of activity in agitated patients. J Psychiatr Res. 2002;36:8795.
25.Brook, S, Lucey, JV, Gunn, KP. Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group. J Clin Psychiatry. 2000;61:933941.
26.Overall, JE, Gorham, DR. The Brief Psychiatric Rating Scale (BPRS): Recent developments in ascertainment and scaling. Psychopharmacol Bull. 1988;24:9799.
27.Brook, S, Walden, J, Benattia, I, Siu, CO, Romano, SJ. Ziprasidone and haloperidol in the treatment of acute exacerbation of schizophrenia and schizoaffective disorder: comparison of intramuscular and oral formulations in a 6-week, randomized, blinded-assessment study. Psychopharmacology (Berl). 2005;178:514523.
28.Daniel, D, Zimbroff, DL, Swift, RH, Harrigan, EP. The tolerability of intramuscular ziprasidone and haloperidol treatment and the transition to oral therapy. Int Clin Psychopharmacol. 2004;19:915.
29.Citrome, L, Brook, S, Loebel, A, Mandel, FS, Weissman, A. Ziprasidone versus haloperidol for the treatment of agitation. Neuropsychopharmacology. 2004;29(Suppl 1):S111.
30.Gueorgguieva, R, Krystal, JH. Move over ANOVA. Arch Gen Psychiatry. 2004;61:310317.
31.Rabinowitz, J, Avnon, M, Rosenberg, V. Effect of clozapine on physical and verbal aggression. Schizophr Res. 1996;22(3):249255.
32.Volavka, J, Citrome, L. Atypical antipsychotics in the treatment of the persistently aggressive psychotic patient: methodological concerns. Schizophr Res. 1999;35(Suppl):S2333.
33.Schillerstrom, TL, Schillerstrom, JE, Taylor, SE. Laboratory findings in emergently medicated psychiatry patients. Gen Hosp Psychiatry. 2004;26:411414.
34.Beedham, C, Miceli, JJ, Obach, RS. Ziprasidone metabolism, aldehyde oxidase, and clinical implications. J Clin Psychopharmacol. 2003;23:229232.
35.Prakash, C, Kamel, A, Cui, D, et al.Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions. Br J Clin Pharmacol. 2000;49(suppl 1):35S42S.
36.Miceli, JJ, Anziano, RJ, Robarge, L, et al.The effect of carbamazepine on the steady-state pharmacokinetics of ziprasidone in healthy volunteers. Br J Clin Pharmacol. 2000;49(suppl 1):65S70S.
37.Miceli, JJ, Smith, M, Robarge, L, Morse, T, Laurent, A. The effects of ketoconazole on ziprasidone pharmacokinetics – a placebo-controlled crossover study in healthy volunteers. Br J Clin Pharmacol. 2000b;49(suppl 1):71S76S.
38.Daniel, D, Brook, S, Benattia, I. Efficacy of intramuscular ziprasidone without adjunctive benzodiazepines. Poster presented at: the 16th Congress of the European College of Neuropsychopharmacology; September 20-24, 2003; Prague, Czech Republic.
39.ZYPREXA® Olanzapine Tablets, ZYPREXA® ZYDIS® Olanzapine Orally Disintegrating Tablets, ZYPREXA® IntraMuscular Olanzapine for Injection [Package Insert]. Indianapolis, IN; Eli Lilly and Company; 2005. Available at: www.ZYPREXA.com. Accessed July 13, 2005.
40.Miceli, JJ, Anziano, MS, Swift, RH, et al.IM ziprasidone and IM haloperidol show comparable QTc effects at Cmax. Poster presented at: 156th Annual Meeting of the American Psychiatric Assciation; May 17-22, 2003; San Francisco, CA.
41.Shale, JH, Shale, CM, Mastin, WD. A review of the safety and efficacy of droperidol for the rapid sedation of severely agitated and violent patients. J Clin Psychiatry. 2003;64(5):500505.
42.Heinrich, TW, Biblo, LA, Schneider, J. Torsades de pointes associated with ziprasidone. Psychosomatics. 2005. In press.
43.FDA Psychopharmacological Drugs Advisory Committee. Briefing document for Zeldox® capsules (Ziprasidone HCl). July 19, 2000. Available at: http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3619b1a.pdf. Accessed January 24, 2005.
44.Freeman, J, Platt, R. Erythromycin prolongs the QTc interval among patients with pneumonia. Pharmacoepidemiol Drug Saf. 1997;6:1319.
45.Harrigan, EP, Miceli, JJ, Anziano, R, et al.A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol. 2004;24(1):6269.
46.Burton, S, Heslop, K, Harrison, K, Barnes, M. Ziprasidone overdose. Am J Psychiatry. 2000;157:835.
47.House, M. Overdose of ziprasidone. Am J Psychiatry. 2002;159:10611062.
48.Bryant, SM, Zilberstein, J, Cumpston, KL, Magdziarz, DD, Costerisan, DD. A case series of ziprasidone overdoses. Vet Hum Toxicol. 2003;45:8182
49.Preval, H, Klotz, SG, Southard, R, Francis, A. Rapid-acting IM ziprasidone in the psychiatric emergency service: a naturalistic study. Gen Hosp Psychiatry. 2005;27:140144.
50.Hick, JL, Smith, SW, Lynch, MT. Metabolic acidosis in restraint-associated cardiac arrest: a case series. Acad Emerg Med. 1999;6(3):239243.
51.Miner, JR, McCoy, C. Use of a standardized sedation scale in intoxicated patients in the emergency department. Acad Emerg Med. 2002;9:536.
52.Miner, JR, McCoy, C, Biros, MA. Standardized intoxication scale vs breath ethanol level as a predictor of observation time in the emergency department. Academic Emer Med. 2003;10:520.
53.Ely, EW, Shintani, A, Truman, B, et al.Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004a;291:17531762.
54.Milbrandt, EB, Deppen, S, Harrison, PL, et al.Costs associated with delirium in mechanically ventilated patients. Crit Care Med. 2004;32(4):955962.
55.Jacobi, J, Fraser, GL, Coursin, DB, et al.Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002;30:119141.
56.Ely, EW, Stephens, RK, Jackson, JC, et al.Current opinions regarding the importance, diagnosis, and management of delirium in the intensive care unit: a survey of 912 healthcare professionals. Crit Care Med. 2004b;32:106112.
57.Data on file. Pfizer Inc; New York, NY.
58.Keck, PE Jr, Versiani, M, Potkin, S, West, SA, Giller, E, Ice, K. Ziprasidone in Mania Study Group. Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry. 2003;160:741748.
59.Russell, JM, Mackel, JA, Leaderer, MC. Economic model of IM ziprasidone and haloperidol in acute agitation. Poster presented at: the American Psychiatric Association 55th Institute on Psychiatric Services; October 29–November 2, 2003; Boston, Massachusetts.
60.Ely, EW, Truman, B, Shintani, A, et al.Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003;289(22):29832991.
61.Ely, EW, Margolin, R, Francis, J, et al.Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001;29:13701379.

Best Clinical Practice With Ziprasidone IM: Update After 2 Years of Experience

  • Dan L. Zimbroff, Michael H. Allen (a1), John Battaglia (a2), Leslie Citrome (a3), Avrim Fishkind (a4), Andrew Francis (a5), Daniel L. Herr (a6), Douglas Hughes (a7), Marc Martel (a8), Horacio Preval (a9) and Ruth Ross (a10)...

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