title: Best clinical practice with ziprasidone IM: update after 2 years of experience.
abstract: Acute agitation is a common psychiatric emergency often treated with intramuscular (i.m.) medication when rapid control is necessary or the patient refuses to take an oral agent. Conventional i.m. 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 i.m. 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 i.m. 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 i.m. 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 setting are warranted to generate comparative risk/benefit data with conventional agents and other second-generation antipsychotics.
authors.affiliation: Pacific Clinical Research Medical Group, Upland, California 91786, USA. dan.zimbroff@pcrmg.com
authors.forename: Dan L
authors.initials: DL
authors.lastname: Zimbroff
authors.forename: Michael H
authors.initials: MH
authors.lastname: Allen
authors.forename: John
authors.initials: J
authors.lastname: Battaglia
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.forename: Avrim
authors.initials: A
authors.lastname: Fishkind
authors.forename: Andrew
authors.initials: A
authors.lastname: Francis
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Herr
authors.forename: Douglas
authors.initials: D
authors.lastname: Hughes
authors.forename: Marc
authors.initials: M
authors.lastname: Martel
authors.forename: Horacio
authors.initials: H
authors.lastname: Preval
authors.forename: Ruth
authors.initials: R
authors.lastname: Ross
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003422:Critical Care; D004632:Emergency Medical Services; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D011595:Psychomotor Agitation / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D012720:Severity of Illness Index; D013844:Thiazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone