BRITISH JOURNAL OF PSYCHIATRY (2006), 189, 433^440. doi: 10.1192/bjp.bp.105.019307 Comparative effectiveness of second-generation explained to them and who signed an informed consent statement were included. antipsychotics and haloperidol in acute Institutional review board approval was obtained for this study. {{ Pregnant or lactating women and schizophrenia patients with a medical condition in which pharmacotherapy would prove a significant ROBERT E. MCCCUE, RUBINA WAHEED, LEONEL URCUYO, clinical risk were excluded. Patients who GERALDINE ORENDAIN, MICHEL D. JOSEPH, RICHARD CHARLES had a clear history of response or lack and SYED M. HASAN of response to a particular antipsychotic drug and who, in the judgement of the treating psychiatrist, would best be Background ThereThereislittleinformation is little information Second-generation antipsychotic drugs have treated accordingly, were not entered into ononthe the comparative effectiveness of been heralded as a significant advance in the the study. Patients with a diagnosis of treatment of patients with schizophrenia. bipolar disorder, major depressive disorder second-generation antipsychotic agents. However, except for clozapine, none has or substance-induced psychotic disorder Aims Todetermine if any of five second- been conclusively shown to be superior in were also excluded. resolving the symptoms of schizophrenia. generation antipsychotics or haloperidolis Head-to-head studies are lacking. There is more effective in treating acutely ill little rational basis for selecting one over Study design patients with schizophrenia, another other than a patient’s history of Patients were admitted to one of the six schizoaffective disorder or response, lack of response or side-effects. general adult in-patient psychiatric units schizophreniform disorder. The purpose of this study was to determine based on bed availability, and this deter- if any of five second-generation antipsycho- mined the treating psychiatrist. All units MethodMethod Asampleof327newlyA sample of 327 newly tics was more effective in treating acutely ill have the same number of patients and staff- hospitalised patients with schizophrenia, ing, and are indistinguishable with respect admitted patients were randomised to schizoaffective disorder or schizophreni- to diagnoses and acuity of patients. Newly open-labeltreatment with aripiprazole, form disorder, and whether any of these admitted patients with a diagnosis of haloperidol, olanzapine, quetiapine, drugs had an advantage over haloperidol. schizophrenia, schizoaffective disorder or risperidone or ziprasidone for a minimum Two important features of this study were schizophreniform disorder were given in- of 3 weeks.Measures of effectiveness that it was designed to reflect clinical prac- formation about the study and asked to tice as a pragmatic clinical trial (March etet participate and provide informed consent. wereimprovementinwere improvementin mental status sothatso that alal, 2005) and that it was not supported by Consenting patients were randomly the patient no longer required acute in- pharmaceutical companies. assigned to treatment with one of six patientcare, and changesin Brief antipsychotics: aripiprazole, haloperidol, Psychiatric Rating Scale (BPRS) scores. olanzapine, quetiapine, risperidone and METHOD ziprasidone. A randomised medication ResultsResults By the first measure, assignment list was prepared before the SampleSample haloperidol (89%), olanzapine (92%) and study using the randomisation website The study examined patients 18 years and http://www.randomization.com. Hospital risperidone (88%) were significantlymoresignificantly more older of either gender, who were newly staff with no clinical responsibilities and effective than aripiprazole (64%), admitted to the hospital’s psychiatric in- no knowledge of the patients oversaw the quetiapine (64%) andziprasidoneand ziprasidone (64%). patient service between January 2004 and assignment procedure and assigned medica- Changes in BPRS ratings were not February 2005. The 135-bed psychiatric tions in sequential order, strictly following significant among treatments. in-patient service treats acutely ill adult the randomised list. The treating psy- patients and is part of a 413-bed general chiatrist did not have access to this list. Conclusions Haloperidol, olanzapine hospital which serves an impoverished Both the patient and the treating psy- and risperidone are superior to urban population. Approximately 70% of chiatrist were aware of the antipsychotic admissions are involuntary. being prescribed. The treating psychiatrists aripiprazole, quetiapine and ziprasidone All patients in the study were diagnosed followed standardised dosing guidelines for the acute treatmentof psychosisin with schizophrenia, schizoaffective disorder based on the manufacturers’ recommenda- hospitalised patients with schizophrenia, or schizophreniform disorder according to tions, with the objective of obtaining a schizoaffective disorder or DSM–IV criteria (American Psychiatric maximum recommended dosage within Association, 1994). Patients with a history 1–21–2weeks.weeks. Patients were given at least schizophreniform disorder. of substance misuse were included if the a 3-weeka3-weektrial of the antipsychotic to deter- Declaration of interest None.None. above diagnoses were present. Patients mine its effectiveness. As needed doses of were included regardless of whether they haloperidol, lorazepam and diphenhydra- had recently taken antipsychotics before mine for agitation were permitted. Following admission. Only patients who understood current practice at the facility, these medica- {{See editorial, pp. 391^392, thisissue. the nature of the study when it was fully tions are generally administered together and 433433 Downloaded from https://www.cambridge.org/core. 02 Oct 2021 at 15:09:14, subject to the Cambridge Core terms of use. McCUE ET AL intramuscularly for aggressive and threa- minimal involvement with managed-care variables were also examined with analyses tening behaviour. Oral doses of diphenhy- health insurance plans; as a result, decisions of variance. Categorical variables were ana- dramine were also administered, at the about discharge were made solely on lysed using a ww22 test. Logistic regression was patient’s request, for sleep. Benzatropine clinical grounds and not influenced by used to explore the effect of other indepen- could also be prescribed for extrapyramidal insurance arrangements. dent variables on the categorical outcome side-effects; it was the treating psychia- variable. All initial analyses used a two- trist’s decision whether to prescribe this Data collection tailedtailed aa level of 0.05. prophylactically or after side-effects devel- The two main measures of effectiveness oped. After the second week of treatment, used were the ability to discharge the RESULTSRESULTS an antidepressant, mood stabiliser or anxio- patient from acute in-patient care and the lytic could be added at the psychiatrist’s total score on the Brief Psychiatric Rating From January 2004 to February 2005 a discretion for significant mood symptoms Scale (BPRS; Overall & Gorham, 1988). total of 584 admissions to the psychiatric or impulsivity. These medications are often Ratings were made at baseline, weekly up in-patient service with the diagnoses of considered essential in the acute treatment to 3 weeks, and at end-point. The end-point schizophrenia, schizoaffective disorder or of schizophrenia (McCue et aletal, 2003).,2003). was when the antipsychotic was determined schizophreniform disorder were screened If the treating psychiatrist assessed the to be effective or ineffective. for entry into the study; 368 were ran- patient to be improving on the medication, A clinician masked to the patient’s anti- domised. This included some patients who it was continued until the patient was psychotic regimen administered the BPRS. had previously participated in the study well enough to be discharged. On the Before the study began, this clinician had and who were rehospitalised during its other hand, if the patient showed no sig- 6 h of training per week for 2 months with course and were randomised a second time nificant improvement after at least 3 weeks the study’s senior authors (R.E.M. and L.U.) if they consented. For the purpose of this of treatment with the randomly assigned in using the BPRS. At the end of the training study, only the first randomised entry of antipsychotic, the treating psychiatrist period there was a sufficiently high correla- those entered more than once (nn¼41) was41)was could discontinue the medication and the tion of BPRS ratings. At the study’s mid- used for data analysis. Of the 327 patients patient would be withdrawn from the point, a revalidation of the clinician’s randomised, 8 were withdrawn from the study. A period of 3 weeks was chosen BPRS ratings was performed with the study for reasons unrelated to antipsychotic because treatment guidelines (American study’s senior authors (R.E.M. and L.U.). treatment and were not included in the data Psychiatric Association, 2004) have recom- Side-effects were recorded concurrently analysis. A total of 319 patients were mended waiting 2–4 weeks before changing with BPRS ratings by a clinician masked included in the analysis: of these, 301 had antipsychotic pharmacotherapy, although to the patient’s antipsychotic regimen. at least a 3-week trial of the antipsychotic there is evidence that the lack of improve- Side-effect data were elicited by spon- and