Safety and tolerability: How do second-generation atypical antipsychotics compare?

Tandon, Rajiv; Jibson, Michael D.

doi:10.1007/bf02629434

Cited by 38 publications

(60 citation statements)

References 21 publications

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“…While relative adherence to treatment has been reported to be better with SGAs as compared with FGAs (Tandon, 2002), as seen in the CATIE study, the majority of schizophrenic patients eventually discontinue treatment early . In addition, among SGAs, varying degrees of treatment-associated weight gain and related consequences still represent a significant concern (Tarricone et al, 2006).…”

Section: Introductionmentioning

confidence: 83%

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Wallingford

Sinnayah

Bymaster

et al. 2008

Neuropsychopharmacol

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Olanzapine (OLZ), one of the second-generation atypical antipsychotics (SGAs), has shown relative advantages in patient adherence and outcomes. However, OLZ has also been associated with a higher incidence of weight gain than most other SGAs. Excessive weight gain may in turn contribute to long-term health concerns for some individuals. Zonisamide (ZNS), a medication approved in the United States as an adjunct in the management of epilepsy, has a diverse pharmacological profile, including sodium channel blockade, monoamine enhancement, and inhibition of carbonic anhydrase. ZNS has also been reported to cause weight loss in both humans and rodents. We hypothesized that this profile might be beneficial when co-administered with OLZ. To test this hypothesis, we evaluated the effects of OLZ on body weight, as well as the pathways known to regulate feeding behavior and arousal in the Sprague-Dawley rat. As indicated via c-Fos expression, we found an OLZ-induced activation in the nucleus accumbens and orexin neurons in the lateral hypothalamus. An OLZ-associated development of hyperphagia, weight gain and elevated blood glucose in the rat was also found. These outcomes were attenuated and reversed in the presence of concomitant ZNS. These results suggest the hypothesis that ZNS may effectively treat or prevent weight gain or metabolic changes associated with the SGAs. Future studies of this combination in patients through appropriately designed human clinical studies are encouraged.

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Section: Introductionmentioning

confidence: 83%

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Wallingford

Sinnayah

Bymaster

et al. 2008

Neuropsychopharmacol

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“…Indeed, several earlier studies have shown that schizophrenia patients treated with typical antipsychotic medication exhibited significantly less P50 suppression than did patients receiving atypical antipsychotics Becker et al, 2004;Adler et al, 2004). Specifically, patients receiving clozapine (Tandon and Jibson, 2003;Adler et al, 2004) or olanzapine (Berg and Balaban, 1999) had superior suppression levels relative to those treated with typical antipsychotic medication. Moreover, Nagamoto et al (1996) reported that schizophrenia patients, who therapeutically responded to clozapine after 1 month of treatment also showed enhanced P50 suppression levels.…”

Section: P50 Suppressionmentioning

confidence: 98%

Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels

Csomor

Stadler

Feldon

et al. 2007

Neuropsychopharmacol

101

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Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D 2 -like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebocontrolled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D 2 -like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance.

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“…This leads us to believe that this is a robust finding. Heart rate increases have often been reported with risperidone and other atypical antipsychotics (Tandon, 2002;Stigler, Potenza, & McDougle (2001)). Consistent with the RUPP report and many other investigations (Aman et al, 2005;Martin et al, 2004), we observed significant increases in weight with risperidone.…”

Section: Physical Measuresmentioning

confidence: 99%

Effects of risperidone on cognitive-motor performance and motor movements in chronically medicated children

Aman

Hollway

Leone

et al. 2009

Research in Developmental Disabilities

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This study was designed to explore the placebo-controlled effects of risperidone on cognitive-motor processes, dyskinetic movements, and behavior in children receiving maintenance risperidone therapy. Sixteen children aged 4-14 years with disruptive behavior were randomly assigned to drug order in a crossover study of risperidone and placebo for 2 weeks each. Dependent measures included tests of sustained attention, memory, visual matching, tremor, seat activity, abnormal movements, and parent behavior ratings. Results were compared by repeated measures ANOVA Fourteen boys and 2 girls with disruptive behavior and IQ ≤ 84 all completed the protocol. Risperidone was superior to placebo on response time (p = 0.01, η P 2 = 0.43) and seat movement (p < 0.05, η P 2 = 0.29) on a short-term memory task, and on a measure of static tremor (p = 0.05, η P 2 = 0.28). There was not a significant difference between treatment conditions on the Abnormal Involuntary Movement scale. Risperidone was superior to placebo on three subscales of the Nisonger Child Behavior Rating Form [Overly Sensitive (p < 0.01, η P 2 = 0.44), Conduct Problem (p = 0.02, η P 2 = 0.36), Hyperactivity (p = 0.03, η P 2 = 0.32)] and on the Hyperactivity/Noncompliance subscale of the Aberrant Behavior Checklist (p = 0.01, η P 2 = 0.41). Significant increases in heart rate (p = 0.05, η P 2 = 0.27) and weight (p = 0.02, η P 2 = 0.36) occurred in the risperidone condition. The findings suggest a beneficial effect of risperidone after several months of treatment on efficiency of responding, activity level, static tremor, and aspects of behavior.

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Safety and tolerability: How do second-generation atypical antipsychotics compare?

Cited by 38 publications

References 21 publications

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels

Effects of risperidone on cognitive-motor performance and motor movements in chronically medicated children

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