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‘Seroquel’ (ICI 204,636)-Efficacy in treating the negative symptoms of schizophrenia
P.3 Psychoticdisorders andantipsychotics
S4-124
IP.3.064! negativesymptoms 'SER
Dose Mglday Up 10750 Up to 750
300
LS mean change in SANS at 042 from baseline (SE) -1.04 (0.61) 0.56 (O.W ) -1.65 (0.47) -0.14 (0.46) - 1.56 (0.51) -0.76 (0.51)
Actual N 51 51 51 56 49 50
P vs placebo 0.052" 0.004 0.005
This is significant p < 0.05 after the 3rd, 4th and 5th week of treatment
In studies 8 and 13. treatment with ICI 204,636 resulted in greater reductions in SANS score than did placebo, these differences being statistically significant (study 8 P =0.004; study 13p = 0.(05). Whilethe difference between ICI 204,636 and placebo after 42 days of treatment in study 6 approaches statistical significance (p = 0.052), a statistically greater reduction in SANS score was seen in the ICI 204.636 treated patients at the third,fourthand fifthweeksof treatment. In conclusion. ICI 204,636 demonstrates efficacy against negative symptoms of schizophrenia as evidenced by superiority over placebo. Thesedata provide additional support for the viewthat ICI 204.636 is an efficacious. well-tolerated. first-line antipsychotic withan atypical profile as indicated by an EPS and prolactin profile which is not different from placebo acrossthe dose range [1-3]. 'Seroquel ' is a trademark, the property of ZenecaLimited. References [1] Borison et a! (1996) Journal of Clinical Psychopharmacology 16:158-169 (in press) [2] Hirsch S. Arvanitis L. MiUer B. Smith A. Study Group (1994) European Neuropsycbopharmacology 4 (3. Spec Iss), 385-386 [3] Borison RL. Arvanitis LA and Miner BO (1996) Schizophrenia Research 18 (2,3 Spec Iss), 132
IP.3.06SI Twolong-term neuroleptic resistant patients
treated by 'SEROQUEL' (lei 204,636) an atypical neuroleptic
M. Avnon, V. Goldin, Y. Neissburg. Shaar Monashc, Government Hospital, Israel Case No.1 - DS 4601: She was born in Ukraine in 1965. the second of 8 children. Her father was a violent man and divorced in 1989. The family emigrated to Israel in 1983. D was educated in various religious institutions and was forced to marry a religious man when she was 21 years of age. She emigrated to the United States and gave birth to two daughters. Soon after her marriage her functional ability declined, she
beat her children and neglected herself. Her husband divorced her and her children wereunder protective care. He father returned her to Israel and she was hospitalised for over 1 year in a psychiatric hospital. She was discharged with little change in her mental status. despitereceiving several neuroleptic medications. She was admitted to Share Menashe Hospital on 1.4.94. On hospitalisation she expressed delusions of reference, persecution and control. She felt that "Satan" influenced her. She began treatment with Seroquel according to the clinical trial protocol. Her mental state improved and she was transferred to an "open" ward. She stillcomplained of hallucinations and of ideasof influence ("Satan") but when her dosage of Seroquel was increased to 600 mg/per day she became more cooperative and was then transferred to the rehabilitation programme at our hospital. She still complained of occasional auditory hallucinations but on receiving Seroquel 800 mg/per day, she became symptom free. She now works in the hospital kitchen, takes part in organised activities and visits her family at weekend. She is now a candidate for hostel accommodation. Apartfrom weightgain (10 kg) she has not suffered from side effects. She does not complain of psychotic symptoms. but her affectremains flat. Questionnaires: April 1994. DPRS-38, CGl-5. SANS-76 February 1996, BPRS-8, CGI-3, SANS-44 Present treatment: Seroquel 800 mg/perday. Diagnosis: Schizophrenic disorder, paranoid, chronic Case No. 2 - RP 4644: She was born in the former USSR in 1952. She emigrated to Israel with her motherand familyin 1960.Her parents divorced in 1954. According to her motherher father was mentally ill. her mother subsequently remarried. She had a normal childhood and completed army service. Her parents emigrated to the United States in 1974 butshe remained in Israel. She visited her parents severaI timesbut in 1983 she had a mental breakdown and was hospitalised twice in the US. She returned to Israel in 1987 and was continuously hospitalised at Goha hospital. She was admitted to our rehabilitation programme in 1990. On admission she was diagnosed as suffering from schizophrenia, disorganised typebut shefrequently suffered frompsychotic episodes and did notcomply withmedication. mainly due to sideeffects. In December 1994 she started Seroquel, according to the clinical trial protocol. She fully cooperated with drug medication but no significant change in her mental state was noted until she received Seroquel 700 mg/dayin April 1995. Since this time she has become organised, she is relaxed and cooperated withtaking her medication no sideeffects are evidentand she has no psychotic symptoms. She is nowaday patient, living in a training apartment. She works in the rehabilitation programme and will soon be transferred to a hostel. Questionnaires: December 1994, BPRS-38. CGI·5. SANS-81 March 1996, BPRS-IO.CGI-3. SANS-51 Present treatment: 700 mg Seroquellper day Diagnosis: Schizophrenia disorganised type. Conclusion: Seroquel (ICI 204,636) is useful in some long-term neuroleptic resistant schizophrenic patients, especially withits lowsideeffect profile. SEROQUEL'· is a trade mark, property of ZenecaPharmaceuticals.
IP.3.066] The atypical profile of 'Seroquel' (ICI204,636) Is supported by the lack of sustainedelevation of plasmaprolactIn in schizophrenic pIItients
W.W.Hong. L.A. Arvanitis. Central Nervous System Clinical Research, Zeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, Delaware 19850 USA Up to 60% of schizophrenic patients are untreated with antipsychotic medications and are therefore at increased risk for relapseand hospitalization. Many of these patients are noncompliant withstandard treatment because of side effects, such as extrapyramidal symptoms (BPS) and the gynecomastia, galactorrhea, amenorrhea, and impotence caused by chronic elevation of plasmaprolactin (PRL). 'Seroquel' (lCI 204,636) is an atypical dibenzothiazepine antipsychotic agent with a clozapinelike pharmacological profile that may improve compliance and outcome in patients with schizophrenia. Like clozapine, leI 204,636 is limbic selective and causes minimal dystonic liability
S4-124
IP.3.064! negativesymptoms 'SER
Dose Mglday Up 10750 Up to 750
300
LS mean change in SANS at 042 from baseline (SE) -1.04 (0.61) 0.56 (O.W ) -1.65 (0.47) -0.14 (0.46) - 1.56 (0.51) -0.76 (0.51)
Actual N 51 51 51 56 49 50
P vs placebo 0.052" 0.004 0.005
This is significant p < 0.05 after the 3rd, 4th and 5th week of treatment
In studies 8 and 13. treatment with ICI 204,636 resulted in greater reductions in SANS score than did placebo, these differences being statistically significant (study 8 P =0.004; study 13p = 0.(05). Whilethe difference between ICI 204,636 and placebo after 42 days of treatment in study 6 approaches statistical significance (p = 0.052), a statistically greater reduction in SANS score was seen in the ICI 204.636 treated patients at the third,fourthand fifthweeksof treatment. In conclusion. ICI 204,636 demonstrates efficacy against negative symptoms of schizophrenia as evidenced by superiority over placebo. Thesedata provide additional support for the viewthat ICI 204.636 is an efficacious. well-tolerated. first-line antipsychotic withan atypical profile as indicated by an EPS and prolactin profile which is not different from placebo acrossthe dose range [1-3]. 'Seroquel ' is a trademark, the property of ZenecaLimited. References [1] Borison et a! (1996) Journal of Clinical Psychopharmacology 16:158-169 (in press) [2] Hirsch S. Arvanitis L. MiUer B. Smith A. Study Group (1994) European Neuropsycbopharmacology 4 (3. Spec Iss), 385-386 [3] Borison RL. Arvanitis LA and Miner BO (1996) Schizophrenia Research 18 (2,3 Spec Iss), 132
IP.3.06SI Twolong-term neuroleptic resistant patients
treated by 'SEROQUEL' (lei 204,636) an atypical neuroleptic
M. Avnon, V. Goldin, Y. Neissburg. Shaar Monashc, Government Hospital, Israel Case No.1 - DS 4601: She was born in Ukraine in 1965. the second of 8 children. Her father was a violent man and divorced in 1989. The family emigrated to Israel in 1983. D was educated in various religious institutions and was forced to marry a religious man when she was 21 years of age. She emigrated to the United States and gave birth to two daughters. Soon after her marriage her functional ability declined, she
beat her children and neglected herself. Her husband divorced her and her children wereunder protective care. He father returned her to Israel and she was hospitalised for over 1 year in a psychiatric hospital. She was discharged with little change in her mental status. despitereceiving several neuroleptic medications. She was admitted to Share Menashe Hospital on 1.4.94. On hospitalisation she expressed delusions of reference, persecution and control. She felt that "Satan" influenced her. She began treatment with Seroquel according to the clinical trial protocol. Her mental state improved and she was transferred to an "open" ward. She stillcomplained of hallucinations and of ideasof influence ("Satan") but when her dosage of Seroquel was increased to 600 mg/per day she became more cooperative and was then transferred to the rehabilitation programme at our hospital. She still complained of occasional auditory hallucinations but on receiving Seroquel 800 mg/per day, she became symptom free. She now works in the hospital kitchen, takes part in organised activities and visits her family at weekend. She is now a candidate for hostel accommodation. Apartfrom weightgain (10 kg) she has not suffered from side effects. She does not complain of psychotic symptoms. but her affectremains flat. Questionnaires: April 1994. DPRS-38, CGl-5. SANS-76 February 1996, BPRS-8, CGI-3, SANS-44 Present treatment: Seroquel 800 mg/perday. Diagnosis: Schizophrenic disorder, paranoid, chronic Case No. 2 - RP 4644: She was born in the former USSR in 1952. She emigrated to Israel with her motherand familyin 1960.Her parents divorced in 1954. According to her motherher father was mentally ill. her mother subsequently remarried. She had a normal childhood and completed army service. Her parents emigrated to the United States in 1974 butshe remained in Israel. She visited her parents severaI timesbut in 1983 she had a mental breakdown and was hospitalised twice in the US. She returned to Israel in 1987 and was continuously hospitalised at Goha hospital. She was admitted to our rehabilitation programme in 1990. On admission she was diagnosed as suffering from schizophrenia, disorganised typebut shefrequently suffered frompsychotic episodes and did notcomply withmedication. mainly due to sideeffects. In December 1994 she started Seroquel, according to the clinical trial protocol. She fully cooperated with drug medication but no significant change in her mental state was noted until she received Seroquel 700 mg/dayin April 1995. Since this time she has become organised, she is relaxed and cooperated withtaking her medication no sideeffects are evidentand she has no psychotic symptoms. She is nowaday patient, living in a training apartment. She works in the rehabilitation programme and will soon be transferred to a hostel. Questionnaires: December 1994, BPRS-38. CGI·5. SANS-81 March 1996, BPRS-IO.CGI-3. SANS-51 Present treatment: 700 mg Seroquellper day Diagnosis: Schizophrenia disorganised type. Conclusion: Seroquel (ICI 204,636) is useful in some long-term neuroleptic resistant schizophrenic patients, especially withits lowsideeffect profile. SEROQUEL'· is a trade mark, property of ZenecaPharmaceuticals.
IP.3.066] The atypical profile of 'Seroquel' (ICI204,636) Is supported by the lack of sustainedelevation of plasmaprolactIn in schizophrenic pIItients
W.W.Hong. L.A. Arvanitis. Central Nervous System Clinical Research, Zeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, Delaware 19850 USA Up to 60% of schizophrenic patients are untreated with antipsychotic medications and are therefore at increased risk for relapseand hospitalization. Many of these patients are noncompliant withstandard treatment because of side effects, such as extrapyramidal symptoms (BPS) and the gynecomastia, galactorrhea, amenorrhea, and impotence caused by chronic elevation of plasmaprolactin (PRL). 'Seroquel' (lCI 204,636) is an atypical dibenzothiazepine antipsychotic agent with a clozapinelike pharmacological profile that may improve compliance and outcome in patients with schizophrenia. Like clozapine, leI 204,636 is limbic selective and causes minimal dystonic liability