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Effects of risperidone on the schedule-induced polydipsia in rats
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P.6 Other topics Zaleplon provides safe long-term treatment of insomnia In the elderly
J. Hedner, R. Mangano. Srmnlab Lungdivisionen Kvinnokliniken, AVD
70, 4th Floor, Sahlgrenska Sjukhuset, Bldstrdket 6, 41345, Grteborg, Sweden Wyeth-Ayerst Research, 145 King of Prussia Road, Radnor, PA, 19087, USA Objectives: Residual effects caused by hypnotics previously used to alleviate insonmia can present concerns relating to patient safety. A hypnotic that is both effective and safe would be ideal for use in this population. Zaleplon has been shown to effectively reduce sleep latency in 14-day double-blind studies in both nonelderly adults (18 to 65 years o f age) [1] and elderly adults (65 years of age or older) with primary insomnia [2]. In the present study, long-term safety and tolerability of zaleplon for up to 12 months in elderly outpatient insomniacs was evaluated. The occurrence of rebound phenomena after treatment discontinuation was also assessed. Methods: Elderly patients who had successfully completed randomized, double-blind, placebo-controlled, 14-day studies of zaleplon efficacy [2], were eligible for enrollment in open-label followup studies. Patients received zaleplon 5 mg for the first 7 to 14 days o f the openlabel studies, followed by 5 or 10 mg for up to 6 to 12 months total treatment. Sleep was measured using questionnaires in which patients recorded time to sleep onset (TSO), total time slept (TTS), number of awakenings (NAW), and sleep quality. Rebound insomnia was evaluated in one study at 6 months by comparing group medians ofTSO, TTS, and NAW at open-label baseline with the first night o f the placebo ran-out phase. Open-label baseline values were based on data from the 5 nights before initiation of this treatment phase. Results: No evidence o f significant rebound insomnia for TSO, TTS, or NAW was documented with either zaleplon dose after 6 months of open-label zaleplon use. Efficacy of zaleplon 5 or 10 mg was maintained in both studies compared with open-label baseline throughout the openlabel extension. In one study, median TSO fell to under 30 minutes in the second month of zaleplon use and remained fairly constant throughout the remainder of the 12-month treatment in the study for which the evaluation was done. Conclusions: Zaleplon was safe and well tolerated throughout these open-label investigations in elderly insomniacs. Data from sleep questionnaires demonstrate that compared with baseline values, shorter median time to sleep onset and longer median sleep duration endured throughout the open-label period of both studies. The continuing effects on sleep latency suggest the absence of pharmacologic tolerance to zaleplon. Zaleplon 5 and 10 mg can be used safely and effectively for 6 to 12 months in the treatment of elderly insomniacs.
References [1] Walsh JK, Fry J, Erwin CW, Scharf M, Roth T, Vogel GW. Efficacy and tolerability of 14-day administration of zaleplon 5 mg and 10 mg for the treatment of primary insomnia. Clin Drag Invest 1998; 16 (5): 347-354. [2] Whitaker T, Mangano R, Entsuah IL et al. Zaleplon safely improves sleep in elderly patients with insomnia. Presentation at the 51 st Annual Meeting of the Gerontological Society of America. Philadelphia, PA; 1998 Nov 20-24.
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Effects of risperidone on the schedule-induced polydipsla in rats
G.C. Lee, J.H. Lee, H.K. Jeong, T.S. Kim, D.J. Yoon. Inje Unioersity, Sanggye Paik Hospital, Department of Psychiatry, Seoul, Korea
Object: We evaluated the effects of risperidone on the schedule-induced polydipsia, an animal model of obsessive-compulsive disorder in rat. Methods: Spraque-Dawley rats weighing 200-250 grn were individually housed and allowed free access to water for 1 week. Rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90 mg pellets on a fixed-time 60 seconds (FT 60 s) feeding schedule over 150 minute
test session per day. The 5 groups of polydipsie rats were administered risperidone 0.1 mg/kg, i.p.), risperidone (0.5 mg/kg, i.p.), fluoxetine (5 mg/kg, i.p.), haloperidol (0.1 mg/kg, i.p.), and vehicle (1 cc/kg, i.p.), for 3 weeks. The schedule induced polydipsie behavior and body weight of rats were tested once a week. The water consumption of nonpolydipsic food deprived rats were checked with given a single bolus (14.5 gin) of food per day for 4 weeks. We compared the amount of water consumption and body weight of non-polydipsic food deprived rats with experimental group. Effects of experimental drugs on polydipsic behavior were analyzed with repeated analysis of variance and Scheffe test as a post-hoc comparison. Results: 1. After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks, At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2. Within each drug treatment group, the fluoxetine group showed significant decrease in the amount of water intake at 1st, 2nd, and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The risperidone 0.1 mg group and the risperidone 0.5 mg group showed significant decrease in the amount of water intake at the 3rd weeks of drug treatment as compared with their baseline of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their baseline of polydipsie water intakes. 3. Among each drug treatment group, the fluoxetine group (22.50 -410.3 5 ml) showed significantly lower amounts of water intake than haloperidol group (41.25 ± 7.06 ml) at 2nd weeks of drug treatment. And also the fluoxetine group (18.75 ± 3.54 ml) showed significantly lower amounts of water intake than the haloperidol group (35.00 ± 11.65 ml) and the vehicle control (34.38 ± 6.78 ml) at 3rd weeks of drug treatment. The risperidone 0.1 mg group and the risperidone 0.5 mg group showed significantly lower amounts of water intake than the haloperidol group (35.00 ± 11.65 ml) and the vehicle control (34.38 4- 6.78 ml) at 3rd weeks of drug treatment. Conclusion: We identified that chronic treatment with risperidone revealed antipolydipsic effect as effective as fluoxetine on the scheduleinduced polydipsic behaviour but the onset of effect was later than that of fluoxetine.
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Suicidal behavlour associated with substance abuse
J. Irurita, M. Irurita, J. Larrache, E Betancor, E Saavedra. El Pino-
Sabinal Hospital, Las Palmas de Gran Canaria University, Las Palmas, Spain Substance abuse induces a myriad of physiological, behavioural and cognitive symptoms. Additional major psychiatric disorders are common in abusers and may present associated with recurrent maladaptive patterns, impulsivity and suicidal behaviour. Substance abuse magnifies the individual instantaneous vulnerability based on the interplay of personality traits, stressful conditions, endurance and family backgrounds. To determine the importance of substance abuse in suicidal behaviour we studied prospectively a series of 105 random suicide attempts related to substance use within the 12 hours previous to the attempt. Semistructured patient and family interviews focusing on quality of life, Psychological Stress Rating Scales, and a self administered Social Adjustment Rating Scale (SASS), provided a total of 75 parameters to analyse statistically. The mean age of the series was 31 + 6 years, 89% were male. Both personal and family stressors influenced quality of life. Weak family or social attachments were found in 91% of the patients. Low academic status and a high incidence of unemployment depicted the social profile of substance abusers. In spite of chronic suicidal ideation, the attempts appeared scarcely planned, and in 71% of the cases suicidal decisions were triggered by interpersonal conflicts. Life threatening overdose, particularly combinations of benzodiazepines
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P.6 Other topics Zaleplon provides safe long-term treatment of insomnia In the elderly
J. Hedner, R. Mangano. Srmnlab Lungdivisionen Kvinnokliniken, AVD
70, 4th Floor, Sahlgrenska Sjukhuset, Bldstrdket 6, 41345, Grteborg, Sweden Wyeth-Ayerst Research, 145 King of Prussia Road, Radnor, PA, 19087, USA Objectives: Residual effects caused by hypnotics previously used to alleviate insonmia can present concerns relating to patient safety. A hypnotic that is both effective and safe would be ideal for use in this population. Zaleplon has been shown to effectively reduce sleep latency in 14-day double-blind studies in both nonelderly adults (18 to 65 years o f age) [1] and elderly adults (65 years of age or older) with primary insomnia [2]. In the present study, long-term safety and tolerability of zaleplon for up to 12 months in elderly outpatient insomniacs was evaluated. The occurrence of rebound phenomena after treatment discontinuation was also assessed. Methods: Elderly patients who had successfully completed randomized, double-blind, placebo-controlled, 14-day studies of zaleplon efficacy [2], were eligible for enrollment in open-label followup studies. Patients received zaleplon 5 mg for the first 7 to 14 days o f the openlabel studies, followed by 5 or 10 mg for up to 6 to 12 months total treatment. Sleep was measured using questionnaires in which patients recorded time to sleep onset (TSO), total time slept (TTS), number of awakenings (NAW), and sleep quality. Rebound insomnia was evaluated in one study at 6 months by comparing group medians ofTSO, TTS, and NAW at open-label baseline with the first night o f the placebo ran-out phase. Open-label baseline values were based on data from the 5 nights before initiation of this treatment phase. Results: No evidence o f significant rebound insomnia for TSO, TTS, or NAW was documented with either zaleplon dose after 6 months of open-label zaleplon use. Efficacy of zaleplon 5 or 10 mg was maintained in both studies compared with open-label baseline throughout the openlabel extension. In one study, median TSO fell to under 30 minutes in the second month of zaleplon use and remained fairly constant throughout the remainder of the 12-month treatment in the study for which the evaluation was done. Conclusions: Zaleplon was safe and well tolerated throughout these open-label investigations in elderly insomniacs. Data from sleep questionnaires demonstrate that compared with baseline values, shorter median time to sleep onset and longer median sleep duration endured throughout the open-label period of both studies. The continuing effects on sleep latency suggest the absence of pharmacologic tolerance to zaleplon. Zaleplon 5 and 10 mg can be used safely and effectively for 6 to 12 months in the treatment of elderly insomniacs.
References [1] Walsh JK, Fry J, Erwin CW, Scharf M, Roth T, Vogel GW. Efficacy and tolerability of 14-day administration of zaleplon 5 mg and 10 mg for the treatment of primary insomnia. Clin Drag Invest 1998; 16 (5): 347-354. [2] Whitaker T, Mangano R, Entsuah IL et al. Zaleplon safely improves sleep in elderly patients with insomnia. Presentation at the 51 st Annual Meeting of the Gerontological Society of America. Philadelphia, PA; 1998 Nov 20-24.
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Effects of risperidone on the schedule-induced polydipsla in rats
G.C. Lee, J.H. Lee, H.K. Jeong, T.S. Kim, D.J. Yoon. Inje Unioersity, Sanggye Paik Hospital, Department of Psychiatry, Seoul, Korea
Object: We evaluated the effects of risperidone on the schedule-induced polydipsia, an animal model of obsessive-compulsive disorder in rat. Methods: Spraque-Dawley rats weighing 200-250 grn were individually housed and allowed free access to water for 1 week. Rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90 mg pellets on a fixed-time 60 seconds (FT 60 s) feeding schedule over 150 minute
test session per day. The 5 groups of polydipsie rats were administered risperidone 0.1 mg/kg, i.p.), risperidone (0.5 mg/kg, i.p.), fluoxetine (5 mg/kg, i.p.), haloperidol (0.1 mg/kg, i.p.), and vehicle (1 cc/kg, i.p.), for 3 weeks. The schedule induced polydipsie behavior and body weight of rats were tested once a week. The water consumption of nonpolydipsic food deprived rats were checked with given a single bolus (14.5 gin) of food per day for 4 weeks. We compared the amount of water consumption and body weight of non-polydipsic food deprived rats with experimental group. Effects of experimental drugs on polydipsic behavior were analyzed with repeated analysis of variance and Scheffe test as a post-hoc comparison. Results: 1. After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks, At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2. Within each drug treatment group, the fluoxetine group showed significant decrease in the amount of water intake at 1st, 2nd, and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The risperidone 0.1 mg group and the risperidone 0.5 mg group showed significant decrease in the amount of water intake at the 3rd weeks of drug treatment as compared with their baseline of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their baseline of polydipsie water intakes. 3. Among each drug treatment group, the fluoxetine group (22.50 -410.3 5 ml) showed significantly lower amounts of water intake than haloperidol group (41.25 ± 7.06 ml) at 2nd weeks of drug treatment. And also the fluoxetine group (18.75 ± 3.54 ml) showed significantly lower amounts of water intake than the haloperidol group (35.00 ± 11.65 ml) and the vehicle control (34.38 ± 6.78 ml) at 3rd weeks of drug treatment. The risperidone 0.1 mg group and the risperidone 0.5 mg group showed significantly lower amounts of water intake than the haloperidol group (35.00 ± 11.65 ml) and the vehicle control (34.38 4- 6.78 ml) at 3rd weeks of drug treatment. Conclusion: We identified that chronic treatment with risperidone revealed antipolydipsic effect as effective as fluoxetine on the scheduleinduced polydipsic behaviour but the onset of effect was later than that of fluoxetine.
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Suicidal behavlour associated with substance abuse
J. Irurita, M. Irurita, J. Larrache, E Betancor, E Saavedra. El Pino-
Sabinal Hospital, Las Palmas de Gran Canaria University, Las Palmas, Spain Substance abuse induces a myriad of physiological, behavioural and cognitive symptoms. Additional major psychiatric disorders are common in abusers and may present associated with recurrent maladaptive patterns, impulsivity and suicidal behaviour. Substance abuse magnifies the individual instantaneous vulnerability based on the interplay of personality traits, stressful conditions, endurance and family backgrounds. To determine the importance of substance abuse in suicidal behaviour we studied prospectively a series of 105 random suicide attempts related to substance use within the 12 hours previous to the attempt. Semistructured patient and family interviews focusing on quality of life, Psychological Stress Rating Scales, and a self administered Social Adjustment Rating Scale (SASS), provided a total of 75 parameters to analyse statistically. The mean age of the series was 31 + 6 years, 89% were male. Both personal and family stressors influenced quality of life. Weak family or social attachments were found in 91% of the patients. Low academic status and a high incidence of unemployment depicted the social profile of substance abusers. In spite of chronic suicidal ideation, the attempts appeared scarcely planned, and in 71% of the cases suicidal decisions were triggered by interpersonal conflicts. Life threatening overdose, particularly combinations of benzodiazepines