A current review of olanzapine's safety in the geriatric patient: from pre-clinical pharmacology to clinical data

Kennedy, J. S.; Bymaster, Frank P.; Schuh, Leslie M.; Calligaro, David O.; Nomikos, George G.; Felder, Christian C.; Bernauer, Mark; Kinon, Bruce J.; Baker, Robert W.; Hay, Donald P.; Roth, Heinz-Juergen; Dossenbach, M.; Kaiser, Christopher J.; Beasley, C.M.; Holcombe, John H.; Effron, Mark B.; Breier, Alan

doi:10.1002/1099-1166(200112)16:1+<::aid-gps571>3.0.co;2-5

Cited by 38 publications

(20 citation statements)

References 178 publications

(174 reference statements)

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“…The limited weight gain response in older adults applies also to other neuroleptics, such as olanzapine, 73,78 and to numerous other drugs, such as nortryptyline 79 and valproate. 80 Metabolic differences related to age have been postulated to partially 81 In this regard, it is of particular interest to note that whereas the risk of diabetes mellitus type II induced by neuroleptics is increased up to age 60, the relationship is no longer present above this age. 82,83 Youths appear to be particularly sensitive to other drugs that can cause weight gain, such as steroids, 84 valproate, 85 and insulin.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of Risperidone-Induced Weight Gain Across the Age Span

Safer

2004

Journal of Clinical Psychopharmacology

136

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A systematic and comprehensive literature search was performed to determine the extent of weight gain induced by risperidone (RIS) treatment across the age span. The review and pooled data analyses were based on double-blind, open trial, and case series studies containing findings on drug dose, age of subjects, weight gain, duration of treatment, and if available, baseline body weight, body mass index, and the percent of subjects experiencing a prominent RIS-induced weight gain. Drug-induced weight gain per month for youths was defined as recorded weight gain minus the age-expected weight gain. The major findings from pooled data were (1) preadolescent youths received a smaller average daily dose and lower mg/kg/d dose of RIS than adolescents, and adolescents in turn had lower mg/kg/d doses than middle-aged adults; (2) RIS-induced weight gain as a percentage of baseline body weight was most pronounced in the preadolescent years and decreased with advancing age; (3) adults over age 65 experienced little to no RIS-induced weight gain; and (4) RIS treatment led to consistently greater body mass index percentage increases for youths than for adults. Available data thus suggest that across the age span, youths are the most sensitive to weight gain induced by a commonly prescribed second-generation neuroleptic.

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Section: Discussionmentioning

confidence: 99%

A Comparison of Risperidone-Induced Weight Gain Across the Age Span

Safer

2004

Journal of Clinical Psychopharmacology

136

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“…Clozapine has also been found to reduce aggressive behavior and incidents requiring restraint in neuroleptic non-responsive patients (Rabinowitz et al 1996;Spivak et al 1998;Chalasani et al 2001). Olanzapine, which unlike clozapine is not associated with a risk of agranulocytosis, has also been found to reduce aggressive behavior in schizophrenics and geriatric patients (Bhana et al 2001;Kennedy et al 2001). However, many atypical antipsychotics also have effects on other neurotransmitter systems including serotonergic receptors.…”

Section: Pharmacological Manipulations Of Dopaminergic Systemsmentioning

confidence: 99%

Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin, dopamine and ?-aminobutyric acid systems

et al. 2002

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(1) The preclinical focus on the behavioral characteristics and determinants of intense aggression promises to be most relevant to the clinical distinction between the proposed impulsive-reactive-hostile-affective subtypes of human aggression and the controlled-proactive-instrumental-predatory subtypes of aggression. The neural circuits for many types of human and animal aggression critically involve serotonin, dopamine and gamma-aminobutyric acid (GABA) and specific receptor subtypes. (2) The dynamic changes in frontal cortical serotonin that are triggered by engaging in aggressive behavior imply that serotonergic drug effects are largely determined by the functional state of the receptors at the time of drug treatment. Of the numerous 5-HT receptors currently identified, the 5-HT(1B) receptors offer a promising target for reducing impulsive aggressive behavior, particularly if the action can be limited to sites in the central nervous system. (3) Aggressive confrontations are salient stressors, both for the aggressor as well as the victim of aggression, that are accompanied by activation of the mesocorticolimbic but not the striatal dopamine system. Dopaminergic manipulations, particularly targeting the D(2) receptor family, can influence aggressive behavior in animals and human patients, suggesting that mesocorticolimbic dopamine may have important enabling or permissive functions. (4) GABA is critical in the neurochemical control of aggressive behavior as evidenced by studies that directly modify GABAergic neurotransmission and neurochemical studies that correlate GABA measurements with aggressive behavioral responses in several animal species. The GABA(A) receptor complex is a mechanism through which certain benzodiazepines and alcohol enhance and inhibit aggressive behaviors. Social and pharmacological experiences decisively determine the effects of GABAergic positive modulators on aggression.

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“…Minimal anticholinergic side effects may be observed in geriatric patients. 20,21 Olanzapine, a newer antipsychotic and dopamine modifier, may induce or uncover extrapyramidal syndromes such as parkinsonism, akathisia, tardive dyskinesia, and neuroleptic malignant syndrome. The risk of the atypical antipsychotics for these adverse effects and cardiotoxicity is much lower than has been reported for the older typical medications including pimozide.…”

Section: Discussionmentioning

confidence: 99%