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

• Published in: Psychopharmacologia Vol. 178; no. 4; pp. 514 - 523
• Main Authors: BROOK, Shlomo, WALDEN, Jeorg, BENATTIA, Isma, SIU, Cynthia O, ROMANO, Steven J
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.04.2005; Springer Nature B.V
• Subjects: Acute Disease; Administration, Oral; Adult; Affective Disorders, Psychotic - diagnosis; Affective Disorders, Psychotic - drug therapy; Biological and medical sciences; Brief Psychiatric Rating Scale; Demography; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Haloperidol - administration & dosage; Haloperidol - adverse effects; Haloperidol - therapeutic use; Humans; Injections, Intramuscular; Male; Manifest Anxiety Scale - statistics & numerical data; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - therapeutic use; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Schizophrenia - diagnosis; Schizophrenia - drug therapy; Severity of Illness Index; Thiazoles - administration & dosage; Thiazoles - adverse effects; Thiazoles - therapeutic use; Time Factors; Treatment Outcome; Withholding Treatment - statistics & numerical data; Human; Schizoaffective psychosis; Atypical antipsychotic; Neuroleptic; Psychotropic; Ziprasidone; Dopamine antagonist; Acute; Oral administration; Schizophrenia; Acute schizophrenia; Butyrophenone derivatives; Haloperidol; Intramuscular administration; 5-HT2 Serotonine receptor; Antipsychotics; Chemotherapy; Randomization; D2 Dopamine receptor; Treatment; Sequential intramuscular/ oral; Formulation; Dosage form; Comparative study
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-004-2082-5

Conventional intramuscular (IM) antipsychotics used in managing acute exacerbation of schizophrenia are associated with side effects such as acute dystonia. To compare the efficacy and tolerability of sequential IM/oral ziprasidone with haloperidol in acute exacerbation of schizophrenia or schizoaffective disorder. 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. 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. Sequential IM and oral ziprasidone offers important efficacy and tolerability advantages over haloperidol in acute schizophrenia.