CAFE TRIAL Ron Beasley, PharmD Candidate Preceptor: Soheyla Mahdavian, PharmD 1

CAFE TRIAL Comparison of Atypicals in First Episode of psychosis The study, Comparison of Atypicals for First-Episode Psychosis (CAFE), involved 26 centers in the U.S. and Canada, and it recruited patients who were experiencing their first psychotic episode. CAFE was funded by AstraZeneca, the maker of Seroquel. Published in the American Journal of Psychiatry in

Objectives To determine whether there were any advantages among the atypical antipsychotic agents for first- episode This was a 52-week randomized, double-blind, flexible- dose, multicenter study 3

Methods Compared quetiapine (Seroquel®), risperidone (Risperdal®), and olanzapine (Zyprexa®) in these patients. There were 134 patients in the quetiapine (Seroquel®) group and 133 each in the olanzapine and risperidone (Risperdal®) groups. 4

Criteria Inclusion 16 to 40 years old, had a diagnosis of first-episode schizophrenia, and had psychotic symptoms for one month to five years, Scores greater than 4 on the Positive and Negative Symptoms Score (PANSS) psychosis subscale. Exclusion The patients could not have had a previous psychotic episode from which they recovered; nor could they have a lifetime history of more than 16 weeks of antipsychotic treatment. 5

Positive and Negative Syndrome Scale The PANSS or the Positive and Negative Syndrome Scale is a medical scale used for measuring symptom severity of patients with schizophrenia. 1-Absent 2-Minimal 3-Mild 4-Moderate 5-Moderate severe 6-Severe 7-Extreme 6

Positive Scale 7 Items, (minimum score = 7, maximum score = 49) Delusions Conceptual disorganization Hallucinations Hyperactivity Grandiosity Suspiciousness/persecution Hostility 7

Negative Scale 7 Items, (minimum score = 7, maximum score = 49) Blunted Affect Emotional withdrawal Poor rapport Passive/apathetic Difficulty in abstract thinking Lack of spontaneity and flow of conversation Stereotyped thinking 8

General Psychopathology Scale 16 Items, (minimum score = 16, maximum score = 112) Somatic concern Anxiety Guilt feelings Tension Mannerisms and posturing Depression Motor retardation Uncooperativeness Unusual thought content Disorientation Poor attention Lack of judgment and insight Disturbance of volition Poor impulse control Preoccupation Active social avoidance 9

PANSS Total Score Minimum = 30 Maximum = 210 The PANSS is a relatively brief interview, requiring 45 to 50 minutes to administer. 10

Primary Outcome Measurment Discontinuation of treatment could be due to an Inadequate effect Adverse effects Patient decision Failure to keep appointments, Desire to stop medication for personal reasons Patient-specific reasons for stopping treatment. 11

Results There was no difference among the drugs in terms of the all- cause discontinuation rate After one year of treatment, all three of the medications had a pretty high rate of discontinuation, about 70% in all of them. There was no difference in subcategories of reasons for discontinuation, whether it was patient decision or inadequate effect The analysis of the improvement of positive symptoms showed that patients on olanzapine improved more than those on quetiapine 12

Results Cont. Of those treated with olanzapine, 80% gained 7% or more over their baseline weight compared with 57.6% of those receiving risperidone and 50% of those receiving quetiapine. 13

Critique Pros The three testing groups were not significantly different giving more accurate results They tested for multiple secondary outcomes making this trial more clinically useful Cons They allowed patients who had some prior antipsychotic treatment to participate CAFE was funded by AstraZeneca, the maker of Seroquel. 14

References 1. Gaebel W, Moller HJ, Buchkremer G, Ohmann C, Riesbeck M, Wolwer W, Von Wilmsdorff M, Bottlender R, Klingberg S: Phar- macological long-term treatment strategies in first episode schizophrenia: study design and preliminary results of an on- going RCT within the German Research Network on Schizo- phrenia. Eur Arch Psychiatry Clin Neurosci 2004; 254:129– Good KP, Kiss I, Buiteman C, Woodley H, Rui Q, Whitehorn D, Kopala L: Improvement in cognitive functioning in patients with first-episode psychosis during treatment with quetiapine: an interim analysis. Br J Psychiatry 2002; 43(suppl):S45–S49 3. Malla AK, Norman RM, Scholten DJ, Zirul S, Kotteda V: A com- parison of long-term outcome in first-episode schizophrenia following treatment with risperidone or a typical antipsychotic. J Clin Psychiatry 2001; 62:179–184 15