Effectiveness of second-generation antipsychotics: a naturalistic, randomized comparison of olanzapine, quetiapine, risperidone, and ziprasidone

Abstract

Background: No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes.

Methods: Patients >or= 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years.

Results: A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups.

Conclusions: Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis.

Trial registration: ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

Figure 1

Flow of patients through the study. Not meeting inclusion criteria = Score below 4 on all the items Delusions, Hallucinatory behaviour, Grandiosity, Suspiciousness/persecution, or Unusual thought content in the Positive and Negative Syndrome Scale (PANSS); Uncoop. = the patient was not able or willing to cooperate with testing and assessments; Organic braindis. = Organic brain disorder, principally dementia; Randomization not acceptable = patient or treating clinician not willing to change existing antipsychotic medication; Administrative causes = principally patient discharged before assessments could be made. ¹ Enrolment started March 2003 until 2008, week 26. Full details on enrolment were only registered from 2006, week 31 until 2008, week 26. Consequently only percentages are displayed for patients assessed for eligibility and excluded patients. ² Before discharge/6 weeks. ³ One patient in the risperidone and olanzapine groups missed the first follow-up visit, but was retested on later visits.

Figure 2

Survival functions. Time to discontinuation = Time (days) until discontinuation of first antipsychotic drug since index admission.

Figure 3

Survival functions. Time to discharge from index admission = Time (days) until hospital discharge after index hospital admission.

Figure 4

Survival functions. Time to rehospitalisation = Time (days) until rehospitalisation after discharge from index admission.

Figure 5

Reduction of PANSS total score. Linear mixed effects model curves. Linear slopes for the randomization groups generated based on linear mixed effects models PANSS total score output as displayed in Additional file 2 for risperidone, olanzapine, quetiapine, and ziprasidone, respectively. The curves are confined to the first 300 days because the major bulk of data is obtained before 300 days.

Figure 6

Change of PANSS subscores, CDSS, GAF-F, and CGI-S scores. The curves are generated based on drug-specific linear mixed effects slopes as displayed in Additional file 2 for risperidone, olanzapine, quetiapine, and ziprasidone, respectively. PANSS = the Positive and Negative Syndrome Scale; CDSS = the Calgary Depression Scale for Schizophrenia; GAF-F = the Global Assessment of Functioning scale - Split Version, Functions scale; CGI-S = the Clinical Global Impression - Severity of Illness Scale. The curves are confined to the first 300 days because the major bulk of data is obtained before 300 days.