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.
BACKGROUND
Conventional intramuscular (IM) antipsychotics used in managing acute exacerbation of schizophrenia are associated with side effects such as acute dystonia.


OBJECTIVE
To compare the efficacy and tolerability of sequential IM/oral ziprasidone with haloperidol in acute exacerbation of schizophrenia or schizoaffective disorder.


METHODS
In a 6-week, multicenter, parallel-group, flexibly dosed study, patients were randomized to ziprasidone (IM up to 3 days, then oral 40-80 mg, b.i.d.) or haloperidol (IM up to 3 days, then oral 5-20 mg/day). Assessments were rater-blinded.


RESULTS
At the end of IM treatment, patients receiving ziprasidone (n=427) showed significantly improved Brief Psychiatric Rating Scale Total (BPRS total) scores compared with those receiving haloperidol (n=138) [least-squares (LS) mean change -6.14 for ziprasidone versus -4.13 for haloperidol, P<0.0018]. At endpoint, there were no significant between-group differences in BPRS total scores. There was a significantly greater improvement in BPRS negative subscale scores in ziprasidone-treated patients, both at the end of IM treatment (LS mean change -1.15 for ziprasidone and -0.28 for haloperidol, P<0.0001) and at study endpoint (LS mean change -2.94 for ziprasidone and -2.24 for haloperidol, P<0.0001). Haloperidol-treated patients exhibited significantly greater increases in Extrapyramidal Symptom Rating Scale at end of IM treatment and at endpoint (P<0.0001). They also had significantly higher ratings on the Barnes Akathisia Scale (P<0.0001) and the Movement Disorder Burden Score (P<0.005), as well as higher incidences of movement disorder-related adverse events.


CONCLUSIONS
Sequential IM and oral ziprasidone offers important efficacy and tolerability advantages over haloperidol in acute schizophrenia.
Brook
Shlomo
S
Department of Psychiatry, Sterkfontein Hospital, P.O. Box 2368, Krugersdorp, South Africa, 1740. brook@global.co.za
Walden
Jeorg
J
Benattia
Isma
I
Siu
Cynthia O
CO
Romano
Steven J
SJ
D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D000341:Affective Disorders, Psychotic / Q000175:diagnosis / Q000188:drug therapy*; D010054:Brief Psychiatric Rating Scale; D003710:Demography; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008347:Manifest Anxiety Scale / Q000706:statistics & numerical data; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment / Q000706:statistics & numerical data
D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone; D006220:Haloperidol