Question

Schizophrenia patients treated with antipsychotic medications can develop dyskinesia as an adverse reaction. Psychiatrists typically switch dyskinetic patients from their initial medication to another antipsychotic medication in order to mitigate the dyskinesia. Conventionally, dyskinetic patients who get switched to clozapine tend to improve quite well. Startup company NoDyskin seeks to develop SCH23390 as an alternative to clozapine for dyskinesia patients. The researchers used three different antipsychotic drugs (APD) – APD1, APD2, and APD3 – to induce dyskinesia so that they could address the question of whether the anticipated benefit of SCH23390 would depend on the type of antipsychotic medication patients were already taking before the switch. In the study, 72 rats were randomly divided into 3 cohorts of 24 each, and each cohort was respectively administered one of three chronic APDs (switching from) treatments: APD1, APD2, and APD3. These chronic treatments were continued for 6 weeks in order to mimic the human therapy process that precipitates dyskinesia. Afterwards, the animals were used in experiments to measure catalepsy – a rat behavioral response that is used as an experimental model of dyskinesia. To test if SCH23390 would be as good as clozapine in inducing low catalepsy or as bad as spiperone in inducing high catalepsy after chronic antipsychotic treatment, 6 rats from each chronic treatment group were randomly selected and administered a fixed dose of one of the acute test (switching to) agents: clozapine, SCH23390, or spiperone. Analyze the catalepsy data in the table below and address the following questions: Can we, on the basis of these data, conclude that treatment with different APDs for 6 weeks results in differences in mean catalepsy response? Do the acute test agents produce different mean levels of catalepsy? If there is an interaction between chronic treatment agent and acute test agent, what does that mean? Based on these results, would you recommend to NoDyskin to push ahead with efforts to develop SCH23390 as an alternative to clozapine? (Hint: in order for SCH23390 to make it in the market as an alternative to clozapine, SCH23390 must be as good as clozapine or, at the very least, it must be significantly better than spiperone). Chronic Antipsychotic (Switching From) Treatment Acute Test (Switching To) Agent Clozapine SCH23390 Spiperone APD1 4 35 69 8 36 77 8 40 86 12 44 95 17 44 95 20 54 103 APD2 10 41 77 11 55 85 16 61 108 18 61 125 24 61 138 25 71 150 APD3 5 41 123 6 50 125 13 60 135 15 68 143 17 71 169 22 75 178

          Schizophrenia patients treated with antipsychotic medications can develop dyskinesia as an adverse reaction. Psychiatrists typically switch dyskinetic patients from their initial medication to another antipsychotic medication in order to mitigate the dyskinesia. Conventionally, dyskinetic patients who get switched to clozapine tend to improve quite well. Startup company NoDyskin seeks to develop SCH23390 as an alternative to clozapine for dyskinesia patients. The researchers used three different antipsychotic drugs (APD) – APD1, APD2, and APD3 – to induce dyskinesia so that they could address the question of whether the anticipated benefit of SCH23390 would depend on the type of antipsychotic medication patients were already taking before the switch. In the study, 72 rats were randomly divided into 3 cohorts of 24 each, and each cohort was respectively administered one of three chronic APDs (switching from) treatments: APD1, APD2, and APD3. These chronic treatments were continued for 6 weeks in order to mimic the human therapy process that precipitates dyskinesia. Afterwards, the animals were used in experiments to measure catalepsy – a rat behavioral response that is used as an experimental model of dyskinesia. To test if SCH23390 would be as good as clozapine in inducing low catalepsy or as bad as spiperone in inducing high catalepsy after chronic antipsychotic treatment, 6 rats from each chronic treatment group were randomly selected and administered a fixed dose of one of the acute test (switching to) agents: clozapine, SCH23390, or spiperone. Analyze the catalepsy data in the table below and address the following questions:
Can we, on the basis of these data, conclude that treatment with different APDs for 6 weeks results in differences in mean catalepsy response?
Do the acute test agents produce different mean levels of catalepsy?
If there is an interaction between chronic treatment agent and acute test agent, what does that mean?
Based on these results, would you recommend to NoDyskin to push ahead with efforts to develop SCH23390 as an alternative to clozapine? (Hint: in order for SCH23390 to make it in the market as an alternative to clozapine, SCH23390 must be as good as clozapine or, at the very least, it must be significantly better than spiperone).

Chronic Antipsychotic (Switching From) Treatment
Acute Test (Switching To) Agent
Clozapine
SCH23390
Spiperone
APD1
4
35
69
8
36
77
8
40
86
12
44
95
17
44
95
20
54
103
APD2
10
41
77
11
55
85
16
61
108
18
61
125
24
61
138
25
71
150
APD3
5
41
123
6
50
125
13
60
135
15
68
143
17
71
169
22
75
178

Added by Joanne J.

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