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Lack of drug interactions with ziprasidone: An overview
P..2 Psychotic disorders and antipsychotics
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References [1] Beasley Jr. CM, Tollefson G, Pierre T, et al. Olanzapine versus placebo and haloperidol. Neuropsychopharmacology 1996; 14:111-123. [2] Gupta S, Droney T, Al-Samarrai S, Keller P, Bradford E Olanzapine-induced weight gain. Annals of Clinical Psychiatry 1998; 10 (1): 39.
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 behaviors to maintain weight.
References JP.2.0)91 A 28-week comparison of zlprasidone and haloperidol in outpatients with stable schizophrenia
[1] Wirshing DA, Spellberg BJ, Erhart SM, Marder SR, Wirshing WC. Novel antipsyehotics and new onset diabetes. Biol Psychiatry 1998; 44 (8): 778-83. [2] Fleisehhacker WW, Meise U, Gunther V, Kurz M. Compliance with antipsychotie drug treatment: influenceof side effects. Acta PsychiatricaScand 1994; 89(832): 11-15.
S. Hirsch, A. Power. Department of Psychiatry, Imperial School of
Medicine, London, UK This 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 > 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 (>20% 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.
References [1] Tandon R, Harrigan E, Zorn S. Ziprasidone: a novel antipsychoticwith unique pharmacology and therapeutic potential. JSerotonin Res 1997; 4 (3): 159--177. [2] Risch SC. Pathophysiologyof schizophrenia and the role of newer anfipsyehotics. Pharmacotherapy 1996; 16: 11S-14S
•
ofa drug Interactions Loverview c kwith zlprasldone:
an
J. Miceli, T. Tensfeldt, C. Folger, K. Wilner. Central Research Division,
Pfizer 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 cytochrome P-450 (CYP) isoforms. Results: In vitro studies which examined the effects of ziprasidone using human liver microsomes suggest that ziprasidone does not inhibit CYP1A2, CYP2C9, CYP2CI9, 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 substrate). Ziprasidone is metabolized by CYP3A4. However, there was only a modest increase in ziprasidone steady-state AUC0-oo (33%) when ziprasidone was administered with ketoconazole (a potent CYP3A4 inhibitor) and a similar reduction in AUC0-12 (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 ~ T h e
Impact of weight gain on quality of life among Individuals with schizophrenia
D. Allison, J. Mackell. St Luke 's/Roosevelt Hospital, Columbia University
College of Physicians & Surgeons, New York, USA Substantial weight gains have been linked to treatment with antipsyehotic 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 10-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 1-10 lbs., 60 (20%) gained 11-20 lbs., 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.
[1] Tandon R, Harrigan E, Zorn S. Ziprasidone:a novel antipsychoticwith unique pharmacology and therapeutic potential. J Serotonin Res 1997; 4 (3): 159-177. [2] Meyer MC, Baldessarini ILl, Goff DC, Centorrino E Clinically significant interactionsofpsychotropic agents with antipsychoticdrugs. DrugSafety 1996; 15 (5): 333-346.
•
Switching from conventional antipsychotics to ziprasldone: an interim analysis of a 6-week study
P. Weiden, G. Simpson, T. Kramer, P. Harvey. The Switch Study Group; St Luke 's/Roosevelt Hospital, 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 40160 rag/day. At week 6, 65% of patients were rated as improved on the CGI-I. Meat PANSS total, positive, negative, and cognitive subscales and CGIseverity scores decreased significantly (P < 0.05) from baseline. There
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References [1] Beasley Jr. CM, Tollefson G, Pierre T, et al. Olanzapine versus placebo and haloperidol. Neuropsychopharmacology 1996; 14:111-123. [2] Gupta S, Droney T, Al-Samarrai S, Keller P, Bradford E Olanzapine-induced weight gain. Annals of Clinical Psychiatry 1998; 10 (1): 39.
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 behaviors to maintain weight.
References JP.2.0)91 A 28-week comparison of zlprasidone and haloperidol in outpatients with stable schizophrenia
[1] Wirshing DA, Spellberg BJ, Erhart SM, Marder SR, Wirshing WC. Novel antipsyehotics and new onset diabetes. Biol Psychiatry 1998; 44 (8): 778-83. [2] Fleisehhacker WW, Meise U, Gunther V, Kurz M. Compliance with antipsychotie drug treatment: influenceof side effects. Acta PsychiatricaScand 1994; 89(832): 11-15.
S. Hirsch, A. Power. Department of Psychiatry, Imperial School of
Medicine, London, UK This 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 > 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 (>20% 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.
References [1] Tandon R, Harrigan E, Zorn S. Ziprasidone: a novel antipsychoticwith unique pharmacology and therapeutic potential. JSerotonin Res 1997; 4 (3): 159--177. [2] Risch SC. Pathophysiologyof schizophrenia and the role of newer anfipsyehotics. Pharmacotherapy 1996; 16: 11S-14S
•
ofa drug Interactions Loverview c kwith zlprasldone:
an
J. Miceli, T. Tensfeldt, C. Folger, K. Wilner. Central Research Division,
Pfizer 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 cytochrome P-450 (CYP) isoforms. Results: In vitro studies which examined the effects of ziprasidone using human liver microsomes suggest that ziprasidone does not inhibit CYP1A2, CYP2C9, CYP2CI9, 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 substrate). Ziprasidone is metabolized by CYP3A4. However, there was only a modest increase in ziprasidone steady-state AUC0-oo (33%) when ziprasidone was administered with ketoconazole (a potent CYP3A4 inhibitor) and a similar reduction in AUC0-12 (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 ~ T h e
Impact of weight gain on quality of life among Individuals with schizophrenia
D. Allison, J. Mackell. St Luke 's/Roosevelt Hospital, Columbia University
College of Physicians & Surgeons, New York, USA Substantial weight gains have been linked to treatment with antipsyehotic 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 10-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 1-10 lbs., 60 (20%) gained 11-20 lbs., 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.
[1] Tandon R, Harrigan E, Zorn S. Ziprasidone:a novel antipsychoticwith unique pharmacology and therapeutic potential. J Serotonin Res 1997; 4 (3): 159-177. [2] Meyer MC, Baldessarini ILl, Goff DC, Centorrino E Clinically significant interactionsofpsychotropic agents with antipsychoticdrugs. DrugSafety 1996; 15 (5): 333-346.
•
Switching from conventional antipsychotics to ziprasldone: an interim analysis of a 6-week study
P. Weiden, G. Simpson, T. Kramer, P. Harvey. The Switch Study Group; St Luke 's/Roosevelt Hospital, 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 40160 rag/day. At week 6, 65% of patients were rated as improved on the CGI-I. Meat PANSS total, positive, negative, and cognitive subscales and CGIseverity scores decreased significantly (P < 0.05) from baseline. There