Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis

A randomized, double-blind trial of olanzapine versus haloperidol

Jeffrey A. Lieberman, Gary Tollefson, Mauricio Tohen, Alan I. Green, Raquel E. Gur, Rene Kahn, Joseph McEvoy, Diana Perkins, Tonmoy Sharma, Robert Zipursky, Hank Wei, Robert M. Hamer

Research output: Contribution to journalArticle

327 Citations (Scopus)

Abstract

Objective: Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. Method: Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. Results: Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Åsberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%). Conclusions: As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.

Original languageEnglish (US)
Pages (from-to)1396-1404
Number of pages9
JournalAmerican Journal of Psychiatry
Volume160
Issue number8
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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olanzapine
Haloperidol
Psychotic Disorders
Antipsychotic Agents
Safety
Schizophrenia
Therapeutics
Psychomotor Agitation
Controlled Clinical Trials
Parkinsonian Disorders
Psychopathology

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis : A randomized, double-blind trial of olanzapine versus haloperidol. / Lieberman, Jeffrey A.; Tollefson, Gary; Tohen, Mauricio; Green, Alan I.; Gur, Raquel E.; Kahn, Rene; McEvoy, Joseph; Perkins, Diana; Sharma, Tonmoy; Zipursky, Robert; Wei, Hank; Hamer, Robert M.

In: American Journal of Psychiatry, Vol. 160, No. 8, 01.08.2003, p. 1396-1404.

Research output: Contribution to journalArticle

Lieberman, Jeffrey A. ; Tollefson, Gary ; Tohen, Mauricio ; Green, Alan I. ; Gur, Raquel E. ; Kahn, Rene ; McEvoy, Joseph ; Perkins, Diana ; Sharma, Tonmoy ; Zipursky, Robert ; Wei, Hank ; Hamer, Robert M. / Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis : A randomized, double-blind trial of olanzapine versus haloperidol. In: American Journal of Psychiatry. 2003 ; Vol. 160, No. 8. pp. 1396-1404.
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abstract = "Objective: Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. Method: Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. Results: Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-{\AA}sberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67{\%} versus 54{\%}). Conclusions: As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.",
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AU - Tohen, Mauricio

AU - Green, Alan I.

AU - Gur, Raquel E.

AU - Kahn, Rene

AU - McEvoy, Joseph

AU - Perkins, Diana

AU - Sharma, Tonmoy

AU - Zipursky, Robert

AU - Wei, Hank

AU - Hamer, Robert M.

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N2 - Objective: Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. Method: Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. Results: Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Åsberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%). Conclusions: As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.

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