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CUtLASS TRIAL

Ron Beasley, PharmD Candidate

Preceptor: Soheyla Mahdavian, PharmD

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CUtLASS TRIALCost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study

Tested at Fourteen community psychiatric services in the English National Health Service.

Published in Archives of General Psychiatry in 2006

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ObjectivesTo test the hypothesis that in people with

schizophrenia SGAs improve quality of life across 1 year compared with FGAs.

Multisite, randomized controlled trial of antipsychotic drug classes, with

Blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis.

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Methods227 people aged 18 to 65 years with DSM-IV

schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects.

Following randomization, the referring psychiatrists would choose a medication from the assigned class to administer for up to 1 year's duration.

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Methods Cont. The FGAs were

Chlorpromazine hydrochloride, Flupenthixol * Haloperidol Loxapine Methotrimeprazine* Sulpiride* Trifluoperazine hydrochloride Zuclopenthixol* Depot Preperations

Fluphenazine decanoate, Flupentixol decanoate * Haloperidol decanoate Pipothiazine palmitate * Zuclopenthixol decanoate *

*Not in the USA

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Methods Cont.SGAs were

RisperidoneOlanzapineAmisulpride*Zotepine*Quetiapine

*Not in the USA

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CriteriaInclusion

DSM-IV schizophrenia, schizoaffective disorder, or delusional disorder

Age 18 to 65 years At least 1 month since

the first onset of positive psychotic symptoms

Psychiatrist electing to change the current FGA or SGA treatment because of inadequate clinical response or in- tolerance.

Exclusion

Substance misuse or a medical disorder considered clinically to be the major cause of positive psychotic symptoms and a history of neuroleptic malignant syndrome.

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Outcome MeasurementsThe primary outcome measure was total score

on the Quality of Life Scale (QLS), assessed blindly at baseline and at Weeks 12, 26, and 52 of the study.

Secondary outcome measures included:Positive and Negative Syndrome Scale (PANSS)Calgary Depression ScaleVarious scales looking at adverse medication

effectsParticipant satisfaction

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ResultsSGAs did not show superiority in improvement in

the QLS. In fact, there was a numerical trend toward greater improvement with the FGA cohort.

Healthcare costs were similar in both groups with psychiatric inpatient hospitalization responsible for the majority of the expense.

Although SGAs were more expensive than FGAs, total antipsychotic medication cost was a relatively small proportion of total expenses (2.1% and 3.8% for FGAs and SGAs, respectively).

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Results cont.There was no measurable difference between

the 2 cohorts in:Positive or negative symptomsDepressive symptomsAdverse effects

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Critique (Pros)It is consistent with several other recent studies

showing minimal to no clinical or cost-savings advantage of SGAs over FGAs

It is a practical, blinded, well-designed trial that contains discussion about why the original premise (SGA superior to FGA) could not be proven

Effect size, sample size, statistical power, utility of the QLS all were assed for bias

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Critique (Cons)This study fails to answer key questions:

Are second-generation antipsychotic medications overrated?

Do SGA’s really provide patients with an advantage over first-generation antipsychotics?

Limited sample size and statistical power

Psychiatrists may have been less ready to change from SGAs compared with FGAs in treating the patients skewing results.

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References1. Voruganti L, Cortese L, Oyewumi L, Cernovsky Z,

Awad A. Comparative evalu- ation of conventional and novel antipsychotic drugs with reference to their sub- jective tolerability, side-effect profile and impact on quality of life. Schizophr Res. 2000;43:135-145.

2. National Collaborating Centre for Mental Health. Guidance on the Use of Newer (Atypical) Antipsychotic Drugs for the Treatment of Schizophrenia. London, En- gland: National Institute for Clinical Excellence; 2002.

3. Davis JM, Chen N, Glick ID. A meta-analysis of the efficacy of second- generation antipsychotics. Arch Gen Psychiatry. 2003;60:553-564.