- Email: [email protected]
Switching from conventional antipsychotics to ziprasidone: An interim analysis of a 6-week study
S264
P2 Psychotic disorders and antipsychotics
Because weight gain can have a negative impact on quality of life, clinicians should consider the potential for weight gain when prescribing antipsychotic medications and assist patients in adopting wellness haloperidol.i’!europsychophannaco~o~ 1996;14: 111-123. [Z] Gupta S, DroneyT, Al-SamarraiS, KellerP, BradfordE Olanzapine-induced behaviors to maintain weight. weight gain. Annuls of ClinicalP+c/ziaq 1998;10 (1): 39.
References
[l] Beasley Jr. CM, Tollefson G, Pierre T, et al. Olanzapineversus placebo and
References 111 . Wirshine DA. Soellbere BJ. Erhart SM. Marder SR. Wirshine WC. Novel antipsyciotics id ncw&sei diabetes. L&r Psychiahy 1998; G(8): 778-83. [2] Fleischhacker WW, Meise U, Gunther V, Kurt M. Compliance with antipsychotic drug treatment: influence of side effects. Acta Psy&iaMcn Stand 1994; 89(832): 11-15. 1
-1
A 28.week comparison of riprasidone and haiooeridoi in outpatients with stable schizophrenia
S. Hirsch, A. Power. Department of Psychiatry, Imperial School of Medicine, London, UK
IP.2.031I h;H'd'rug interactions with ziprasidone: an
randomized, double-blind study was undertaken to compare flexible-dose oral ziprasidone 80-160 mg/day (n = 148) with haloperidol 5-15 mg/day (n = 153) over 28 weeks in outpatients with stable chronic or subchronic schizophrenia. Patients with a baseline PANSS negative subscale score 2 10 and a GAF score > 30 were assessed using the PANSS, CGI-S, MADRS, Simpson-Angus, Barnes Akathisia, and AIMS scales. Modal doses at endpoint were 80 mg/day and 5 mg/day for ziprasidone and haloperidol, respectively. Robust improvements in all efficacy variables with both ziprasidone and haloperidol were observed. The percentage of patients classified as PANSS negative symptom responders at endpoint (220% reduction) was significantly greater with ziprasidone compared with haloperidol(48% vs 32%; P < 0.05). A trend for greater efficacy in improving depressive symptoms was also observed with ziprasidone. Ziprasidone was associated with fewer adverse events and discontinuations than haloperidol. Ziprasidone had clear advantages over haloperidol in all evaluations of movement disorders. Changes in body weight were negligible with both treatments. Ziprasidone and haloperidol were both effective in reducing overall psychopathology. Ziprasidone was superior in the treatment of negative symptoms and was better tolerated than haloperidol. Thus, ziprasidone appears to offer a superior alternative to haloperidol in the medium-term treatment of stable outpatients. This
References [I] Tandon R, Harrigan E, Zom S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. JSerotonin Res 1997; 4 (3): 159-177. [Z] Risch SC. Pathophysiology of schizophrenia and the role of newer antipsychotics. Pharmacothempy 1996; 16: 11%14s
J. Miceli, T. Tensfeldt, C. Folger, K. Wilner. Central Research Diuision, Pfier Inc, Groton, CT, USA Objective: To characterize the drug interaction profile of the novel antipsychotic ziprasidone. Methods: The potential for drug interactions with ziprasidone was extensively studied in vitro and in healthy subjects using model substrates and inhibitors for cytocbrome P-450 (CUP) isofonns. Results: In vitro studies which examined the effects of ziprasidone using human liver microsomes suggest that ziprasidone does not inhibit CYPlA2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 at clinically relevant doses. In vitro inhibition of CYP3A4 and CYP2D6 only occurs at a free drug concentration at least 1500-fold higher than that achievable with clinically effective doses. In healthy subjects, ziprasidone did not inhibit the metabolism of dextromethorphan (a CYP2D6 substrate) or the metabolism of ethinylestradiol (a CYP3A4 subs&ate). Ziprasidone is metabolized by CYP3A4. However, there was only a modest increase in ziprasidone steady-state AUCO-cc (33%) when ziprasidone was administered with ketoconazole (a potent CYP3A4 inhibitor) and a similar reduction in AUCO-I2 (36%) when administered with carbamazepine (a CYP3A4 inducer). No clinically significant interactions have been reported with lithium, combined oral contraceptives, combined aluminium and magnesium hydroxide antacid (Maalox@), or cimetidine. Conclusions: Ziprasidone has a very low potential for drug interactions. Metabolic pathways, in addition to metabolism by CYP3A4, have a role in the elimination of ziprasidone and, therefore, clinically significant interactions between ziprasidone and inhibitors or substrates of this isoform are unlikely. References
[p.2.030/
The impact of weight gain on quality of life among individuals with schizophrenia
D. Allison, J. Mackell. StLuke WRooseueltHospital, Columbia University College of Physicians & Sueeons,
New York, USA
Substantial weight gains have been linked to treatment with antipsychotic medications (Amdisen, 1964; Leadbetter et al., 1992). This research examines the impact of weight gain on life quality and psychological well-being as self-reported by individuals with schizophrenia. Two national mental health organizations were surveyed in June, 1998. The 304 individuals with schizophrenia who provided relevant information were classified into four weight gain groups. Quality of life was measured using a one-item global evaluation and a lo-item scale, assessing satisfaction within life domains such as housing and social activities. Psychological status was assessed with the Psychological WellBeing Index. The results of these surveys showed that, within the previous year, 113 respondents (37%) reported no weight gain, 68 (22%) gained l-10 lbs., 60 (20%) gained 1l-20 Ibs., and 63 (21%) gained more than 20 lbs. Analysis of covariance controlling for gender demonstrated that higher weight gain was related to lower life quality using single item (P < .06) and scale (P < .04) measures. No linkage to psychological well-being was found.
[l] Tandon R, Harrigan E, Zom S. Ziprasidone: a novel antipsychotic with unique Dharmacoloev and theraueutic ootential. JSemtonin Res 1997: 4 (3): 159-177. [2] ‘Meyer MC~Baldessari& RJ, ‘Gaff DC, Centorrino E Clinically’ significant interactions of psychotropic agents with antipsychotic drugs. Drug Safety1996; 15 (5): 333-346.
l-1
Switching from conventional antipsychotics to riprasldone: an interim analysis of a 6-week study
F! Weiden, G. Simpson, T. Kramer, P. Harvey. The Switch Study Group; St Luke WRooseueltHospital, Columbia University College of Physicians & Surgeons, New York, USA The aim of this study was to investigate the course of switching outpatients with schizophrenia who have efficacy problems or unacceptable side effects from their conventional antipsychotics to ziprasidone. This was an interim analysis of a 6-week, randomized, blinded-rater study in which stable outpatients (n = 68) were switched from their maintenance conventional antipsychotic medication to ziprasidone 4& 160 mg/day. At week 6, 65% of patients were rated as improved on the 0X-I. Meat PANSS total, positive, negative, and cognitive subscales and CGIseverity scores decreased significantly (P < 0.05) from baseline. There
S265
f?2 Psychotic disorders and antipsychotics
were reductions in mean EPS movement disorder scores and a substantial decrease in the percentage of patients requiting anticholinergic medication. Significant improvements in cognitive function tests related to motor skill, planning, and to verbal learning and recall were also observed. The most frequent adverse events with ziprasidone included nausea, headache, somnolence and insomnia. Baseline prolactin levels decreased and body weight change was negligible. The significant improvements in psychopathology and reductions in EPS without any additional weight gain were observed after 6 weeks of ziprasidone therapy. This study suggest that ziprasidone will be helpful for many “stable” outpatients who have persistent symptoms or EPS side effects on their current conventional antipsychotic.
[ 1] Tandon R, Harrigan E, Zom S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. JSerotonin Res 1997; 4 (3): 159-177. [2] W&den PJ, Aquila R, Dalheim L, Standard JM. Switching antipsychotic medications, J C/in Psychiatry 1997; 58 (suppl 10): 63-72.
lP.2.0331 Switching from risperidone to ziprasidone:
an
interim analysis of a B-week study G. Simpson, S. Potkin. The Switch Study Group; Department of Psychiatry; LAC + USC Medical Center, Los Angeles, USA
The objective of this study was to investigate stable outpatients with schizophrenia, primarily seeking enhanced efficacy, who were switched from risperidone to ziprasidone. This was an interim analysis of a 6-week, randomized, blindedrater study in which stable outpatients (n = 23) were switched from risperidone to ziprasidone 40-160 mgday. Assessments included the PANSS, CGI, and a battery of cognitive tests, as well as standard safety and tolerability monitoring. Statistically significant improvements were seen in the PANSS total score and the negative, positive, and cognitive subscales. The majority of patients (64%) were rated as improved on the CGI and only one discontinued due to inadequate efficacy. Also notable were the significant improvements in assessments of cognitive function, specifically: a computerized Continuous Performance Test, the Rey Verbal Learning Test, verbal fluency, Digit Span Distraction, and the Wisconsin Card Sorting Task. Ziprasidone was well tolerated. In addition, prolactin and triglyceride levels decreased substantially (63% and 15%, respectively). The significant improvements in psychopathology and cognitive function in these patients switched from risperidone to ziprasidone are encouraging. Improvements in attention, vigilance, verbal learning and recall, and executive function indicated by these results, suggest that ziprasidone has a beneficial effect on cognitive function in patients with schizophrenia. References
[ 1]
Taudon R, Harrigau E, Zom S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. JSemtonin Res 1997; 4 (3): 159-177. [2] Meltzer HY, The Collaborative Working Group on Clinical Trial Evaluations. Evaluating the effects of antipsychotics on cognition in schizophrenia. J Chin Psychiafry 1998; 59 (suppl 12): 35110.
Im p rovement [p.2.0341
in markers of health status 6 weeks after switching from olanzapine to ziprasldone
D. Daniel, J. Liebennan, R. Bimbaum. Clinical Studies Limited, Falls Church, Virginia, USA
This study was undertaken to evaluate changes in key markers of health status in stable outpatients with schizophrenia who were switched from olanzapine to ziprasidone. This was an interim analysis of a randomized, blinded-rater study in which stable outpatients (n = 58) discontinued olanzapine and received ziprasidone 40-160 mg/day for 6 weeks. Standard laboratory tests and
medical examinations were conducted at screening, baseline, and during the study. At baseline 49% of patients had a BMI of 130. After 6 weeks of treatment, there was a reduction in mean body weight in men (1.4 kg) and a significant reduction in women (2.3 kg; P < 0.05). Median decreases between baseline and endpoint in plasma cholesterol (11%) and triglycerides (28%) were also recorded. The percentage of patients with elevated triglycerides (1.2XULN) decreased from 35% at baseline to 9% at endpoint. Declines in SGOT, SGPT, LDH, and alkaline phosphatase were also observed. Psychopathology, as measured by standard rating scales, improved and ziprasidone was well tolerated. These analyses indicate that the incidence of obesity and elevations in cholesterol and triglycerides and LFTs associated with olanzapine may be reduced when patients are switched to ziprasidone. These meaningful improvements in several key indicators of health status were observed after just 6 weeks. The implications of these findings warrant consideration in treatment selection for patients with schizophrenia and the long-term medical consequences require further study. References [1] Tandon R, Harrigan E, Zom S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. JSer~tonin Res 1997; 4 (3): 159-177. [2] Meltzer HY, The Collaborative Working Group on Clinical Trial Evaluation. Adverse effects of the atypical antipsychotics, J Chin Psychiahy 1998; 59 (suppl 12): 17-22.
lP.2.0351 Switching from olanzapine to ziprasidone:
an
interim analysis of a g-week study
D. Daniel, R. Stem, T. Kramer. The Switch Study Group; Clinical Studies Limited, Falls Church, Virginia, USA The objective of this study was to investigate switching patients with schizophrenia, who required a change in medication due to inadequate efficacy or unacceptable side effects, from olanzapine to ziprasidone. This was an interim analysis of a randomized, blinded-rater study in which stable outpatients (n = 58) discontinued olanzapine and received ziprasidone 40-160 mg/day for 6 weeks. Standard psychopathology rating scales and a cognitive battery were administered as part of the clinical assessment. After 6 weeks of treatment, there were significant reductions in PANSS total, and the PANSS positive and negative subscale scores as well as the CGI-severity score (P < 0.05). Almost half the patients were rated as improved on the CGI and only 5% discontinued due to insufficient response. Significant improvements were seen in verbal learning and memory Mean baseline movement disorder assessment scales scores and anticholinergic use were very low and remained so on ziprasidone treatment. Treatment-emergent extrapyramidal side-effects were very rare. Mean body weight decreased significantly, and median cholesterol and triglyceride levels decreased. Patients who may require a change from olanzapine therapy appear to benefit from switching to ziprasidone. Symptoms improved in many patients and ziprasidone was well tolerated. The significant improvement in verbal learning and memory, a key domain of cognitive function, on ziprasidone is noteworthy as this may be linked with functional outcome. Beneficial changes in markers of health status after just 6 weeks of ziprasidone therapy are also noteworthy. References
[11Tandon
R, Harrigau E, Zom S. Ziprasidone: a novel a&psychotic with unique pharmacology and therapeutic potential. JSemtonin Res 1997; 4 (3): 159-177. [2] Weiden PJ, Aquila R, Dalheim L, Standard JM. Switching antipsychotic medications. J C/in Psychiahy 1997; 58 (suppl 10): 63-72.
P2 Psychotic disorders and antipsychotics
Because weight gain can have a negative impact on quality of life, clinicians should consider the potential for weight gain when prescribing antipsychotic medications and assist patients in adopting wellness haloperidol.i’!europsychophannaco~o~ 1996;14: 111-123. [Z] Gupta S, DroneyT, Al-SamarraiS, KellerP, BradfordE Olanzapine-induced behaviors to maintain weight. weight gain. Annuls of ClinicalP+c/ziaq 1998;10 (1): 39.
References
[l] Beasley Jr. CM, Tollefson G, Pierre T, et al. Olanzapineversus placebo and
References 111 . Wirshine DA. Soellbere BJ. Erhart SM. Marder SR. Wirshine WC. Novel antipsyciotics id ncw&sei diabetes. L&r Psychiahy 1998; G(8): 778-83. [2] Fleischhacker WW, Meise U, Gunther V, Kurt M. Compliance with antipsychotic drug treatment: influence of side effects. Acta Psy&iaMcn Stand 1994; 89(832): 11-15. 1
-1
A 28.week comparison of riprasidone and haiooeridoi in outpatients with stable schizophrenia
S. Hirsch, A. Power. Department of Psychiatry, Imperial School of Medicine, London, UK
IP.2.031I h;H'd'rug interactions with ziprasidone: an
randomized, double-blind study was undertaken to compare flexible-dose oral ziprasidone 80-160 mg/day (n = 148) with haloperidol 5-15 mg/day (n = 153) over 28 weeks in outpatients with stable chronic or subchronic schizophrenia. Patients with a baseline PANSS negative subscale score 2 10 and a GAF score > 30 were assessed using the PANSS, CGI-S, MADRS, Simpson-Angus, Barnes Akathisia, and AIMS scales. Modal doses at endpoint were 80 mg/day and 5 mg/day for ziprasidone and haloperidol, respectively. Robust improvements in all efficacy variables with both ziprasidone and haloperidol were observed. The percentage of patients classified as PANSS negative symptom responders at endpoint (220% reduction) was significantly greater with ziprasidone compared with haloperidol(48% vs 32%; P < 0.05). A trend for greater efficacy in improving depressive symptoms was also observed with ziprasidone. Ziprasidone was associated with fewer adverse events and discontinuations than haloperidol. Ziprasidone had clear advantages over haloperidol in all evaluations of movement disorders. Changes in body weight were negligible with both treatments. Ziprasidone and haloperidol were both effective in reducing overall psychopathology. Ziprasidone was superior in the treatment of negative symptoms and was better tolerated than haloperidol. Thus, ziprasidone appears to offer a superior alternative to haloperidol in the medium-term treatment of stable outpatients. This
References [I] Tandon R, Harrigan E, Zom S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. JSerotonin Res 1997; 4 (3): 159-177. [Z] Risch SC. Pathophysiology of schizophrenia and the role of newer antipsychotics. Pharmacothempy 1996; 16: 11%14s
J. Miceli, T. Tensfeldt, C. Folger, K. Wilner. Central Research Diuision, Pfier Inc, Groton, CT, USA Objective: To characterize the drug interaction profile of the novel antipsychotic ziprasidone. Methods: The potential for drug interactions with ziprasidone was extensively studied in vitro and in healthy subjects using model substrates and inhibitors for cytocbrome P-450 (CUP) isofonns. Results: In vitro studies which examined the effects of ziprasidone using human liver microsomes suggest that ziprasidone does not inhibit CYPlA2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 at clinically relevant doses. In vitro inhibition of CYP3A4 and CYP2D6 only occurs at a free drug concentration at least 1500-fold higher than that achievable with clinically effective doses. In healthy subjects, ziprasidone did not inhibit the metabolism of dextromethorphan (a CYP2D6 substrate) or the metabolism of ethinylestradiol (a CYP3A4 subs&ate). Ziprasidone is metabolized by CYP3A4. However, there was only a modest increase in ziprasidone steady-state AUCO-cc (33%) when ziprasidone was administered with ketoconazole (a potent CYP3A4 inhibitor) and a similar reduction in AUCO-I2 (36%) when administered with carbamazepine (a CYP3A4 inducer). No clinically significant interactions have been reported with lithium, combined oral contraceptives, combined aluminium and magnesium hydroxide antacid (Maalox@), or cimetidine. Conclusions: Ziprasidone has a very low potential for drug interactions. Metabolic pathways, in addition to metabolism by CYP3A4, have a role in the elimination of ziprasidone and, therefore, clinically significant interactions between ziprasidone and inhibitors or substrates of this isoform are unlikely. References
[p.2.030/
The impact of weight gain on quality of life among individuals with schizophrenia
D. Allison, J. Mackell. StLuke WRooseueltHospital, Columbia University College of Physicians & Sueeons,
New York, USA
Substantial weight gains have been linked to treatment with antipsychotic medications (Amdisen, 1964; Leadbetter et al., 1992). This research examines the impact of weight gain on life quality and psychological well-being as self-reported by individuals with schizophrenia. Two national mental health organizations were surveyed in June, 1998. The 304 individuals with schizophrenia who provided relevant information were classified into four weight gain groups. Quality of life was measured using a one-item global evaluation and a lo-item scale, assessing satisfaction within life domains such as housing and social activities. Psychological status was assessed with the Psychological WellBeing Index. The results of these surveys showed that, within the previous year, 113 respondents (37%) reported no weight gain, 68 (22%) gained l-10 lbs., 60 (20%) gained 1l-20 Ibs., and 63 (21%) gained more than 20 lbs. Analysis of covariance controlling for gender demonstrated that higher weight gain was related to lower life quality using single item (P < .06) and scale (P < .04) measures. No linkage to psychological well-being was found.
[l] Tandon R, Harrigan E, Zom S. Ziprasidone: a novel antipsychotic with unique Dharmacoloev and theraueutic ootential. JSemtonin Res 1997: 4 (3): 159-177. [2] ‘Meyer MC~Baldessari& RJ, ‘Gaff DC, Centorrino E Clinically’ significant interactions of psychotropic agents with antipsychotic drugs. Drug Safety1996; 15 (5): 333-346.
l-1
Switching from conventional antipsychotics to riprasldone: an interim analysis of a 6-week study
F! Weiden, G. Simpson, T. Kramer, P. Harvey. The Switch Study Group; St Luke WRooseueltHospital, Columbia University College of Physicians & Surgeons, New York, USA The aim of this study was to investigate the course of switching outpatients with schizophrenia who have efficacy problems or unacceptable side effects from their conventional antipsychotics to ziprasidone. This was an interim analysis of a 6-week, randomized, blinded-rater study in which stable outpatients (n = 68) were switched from their maintenance conventional antipsychotic medication to ziprasidone 4& 160 mg/day. At week 6, 65% of patients were rated as improved on the 0X-I. Meat PANSS total, positive, negative, and cognitive subscales and CGIseverity scores decreased significantly (P < 0.05) from baseline. There
S265
f?2 Psychotic disorders and antipsychotics
were reductions in mean EPS movement disorder scores and a substantial decrease in the percentage of patients requiting anticholinergic medication. Significant improvements in cognitive function tests related to motor skill, planning, and to verbal learning and recall were also observed. The most frequent adverse events with ziprasidone included nausea, headache, somnolence and insomnia. Baseline prolactin levels decreased and body weight change was negligible. The significant improvements in psychopathology and reductions in EPS without any additional weight gain were observed after 6 weeks of ziprasidone therapy. This study suggest that ziprasidone will be helpful for many “stable” outpatients who have persistent symptoms or EPS side effects on their current conventional antipsychotic.
[ 1] Tandon R, Harrigan E, Zom S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. JSerotonin Res 1997; 4 (3): 159-177. [2] W&den PJ, Aquila R, Dalheim L, Standard JM. Switching antipsychotic medications, J C/in Psychiatry 1997; 58 (suppl 10): 63-72.
lP.2.0331 Switching from risperidone to ziprasidone:
an
interim analysis of a B-week study G. Simpson, S. Potkin. The Switch Study Group; Department of Psychiatry; LAC + USC Medical Center, Los Angeles, USA
The objective of this study was to investigate stable outpatients with schizophrenia, primarily seeking enhanced efficacy, who were switched from risperidone to ziprasidone. This was an interim analysis of a 6-week, randomized, blindedrater study in which stable outpatients (n = 23) were switched from risperidone to ziprasidone 40-160 mgday. Assessments included the PANSS, CGI, and a battery of cognitive tests, as well as standard safety and tolerability monitoring. Statistically significant improvements were seen in the PANSS total score and the negative, positive, and cognitive subscales. The majority of patients (64%) were rated as improved on the CGI and only one discontinued due to inadequate efficacy. Also notable were the significant improvements in assessments of cognitive function, specifically: a computerized Continuous Performance Test, the Rey Verbal Learning Test, verbal fluency, Digit Span Distraction, and the Wisconsin Card Sorting Task. Ziprasidone was well tolerated. In addition, prolactin and triglyceride levels decreased substantially (63% and 15%, respectively). The significant improvements in psychopathology and cognitive function in these patients switched from risperidone to ziprasidone are encouraging. Improvements in attention, vigilance, verbal learning and recall, and executive function indicated by these results, suggest that ziprasidone has a beneficial effect on cognitive function in patients with schizophrenia. References
[ 1]
Taudon R, Harrigau E, Zom S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. JSemtonin Res 1997; 4 (3): 159-177. [2] Meltzer HY, The Collaborative Working Group on Clinical Trial Evaluations. Evaluating the effects of antipsychotics on cognition in schizophrenia. J Chin Psychiafry 1998; 59 (suppl 12): 35110.
Im p rovement [p.2.0341
in markers of health status 6 weeks after switching from olanzapine to ziprasldone
D. Daniel, J. Liebennan, R. Bimbaum. Clinical Studies Limited, Falls Church, Virginia, USA
This study was undertaken to evaluate changes in key markers of health status in stable outpatients with schizophrenia who were switched from olanzapine to ziprasidone. This was an interim analysis of a randomized, blinded-rater study in which stable outpatients (n = 58) discontinued olanzapine and received ziprasidone 40-160 mg/day for 6 weeks. Standard laboratory tests and
medical examinations were conducted at screening, baseline, and during the study. At baseline 49% of patients had a BMI of 130. After 6 weeks of treatment, there was a reduction in mean body weight in men (1.4 kg) and a significant reduction in women (2.3 kg; P < 0.05). Median decreases between baseline and endpoint in plasma cholesterol (11%) and triglycerides (28%) were also recorded. The percentage of patients with elevated triglycerides (1.2XULN) decreased from 35% at baseline to 9% at endpoint. Declines in SGOT, SGPT, LDH, and alkaline phosphatase were also observed. Psychopathology, as measured by standard rating scales, improved and ziprasidone was well tolerated. These analyses indicate that the incidence of obesity and elevations in cholesterol and triglycerides and LFTs associated with olanzapine may be reduced when patients are switched to ziprasidone. These meaningful improvements in several key indicators of health status were observed after just 6 weeks. The implications of these findings warrant consideration in treatment selection for patients with schizophrenia and the long-term medical consequences require further study. References [1] Tandon R, Harrigan E, Zom S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. JSer~tonin Res 1997; 4 (3): 159-177. [2] Meltzer HY, The Collaborative Working Group on Clinical Trial Evaluation. Adverse effects of the atypical antipsychotics, J Chin Psychiahy 1998; 59 (suppl 12): 17-22.
lP.2.0351 Switching from olanzapine to ziprasidone:
an
interim analysis of a g-week study
D. Daniel, R. Stem, T. Kramer. The Switch Study Group; Clinical Studies Limited, Falls Church, Virginia, USA The objective of this study was to investigate switching patients with schizophrenia, who required a change in medication due to inadequate efficacy or unacceptable side effects, from olanzapine to ziprasidone. This was an interim analysis of a randomized, blinded-rater study in which stable outpatients (n = 58) discontinued olanzapine and received ziprasidone 40-160 mg/day for 6 weeks. Standard psychopathology rating scales and a cognitive battery were administered as part of the clinical assessment. After 6 weeks of treatment, there were significant reductions in PANSS total, and the PANSS positive and negative subscale scores as well as the CGI-severity score (P < 0.05). Almost half the patients were rated as improved on the CGI and only 5% discontinued due to insufficient response. Significant improvements were seen in verbal learning and memory Mean baseline movement disorder assessment scales scores and anticholinergic use were very low and remained so on ziprasidone treatment. Treatment-emergent extrapyramidal side-effects were very rare. Mean body weight decreased significantly, and median cholesterol and triglyceride levels decreased. Patients who may require a change from olanzapine therapy appear to benefit from switching to ziprasidone. Symptoms improved in many patients and ziprasidone was well tolerated. The significant improvement in verbal learning and memory, a key domain of cognitive function, on ziprasidone is noteworthy as this may be linked with functional outcome. Beneficial changes in markers of health status after just 6 weeks of ziprasidone therapy are also noteworthy. References
[11Tandon
R, Harrigau E, Zom S. Ziprasidone: a novel a&psychotic with unique pharmacology and therapeutic potential. JSemtonin Res 1997; 4 (3): 159-177. [2] Weiden PJ, Aquila R, Dalheim L, Standard JM. Switching antipsychotic medications. J C/in Psychiahy 1997; 58 (suppl 10): 63-72.