Psychomotor and Memory Effects of Haloperidol, Olanzapine, and Paroxetine in Healthy Subjects After Short-Term Administration

Morrens, Manuel; Wezenberg, E.; Verkes, Robbert‐Jan; Hulstijn, Wouter; Ruigt, G.S.F.; Sabbe, Bernard

doi:10.1097/jcp.0b013e31802dfff0

Cited by 38 publications

(29 citation statements)

References 47 publications

(59 reference statements)

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“…Finally, although antipsychotics have been associated with modest improvement in cognition in some studies of patients with schizophrenia [28][29][30], they have also been associated with adverse cognitive effects across a wide range of doses [31][32][33]. Such adverse effects are particularly relevant in older adults considering that patients with schizophrenia demonstrate persistent or worsening cognitive deficits with age [34].…”

Section: Adverse Effectsmentioning

confidence: 93%

Sensitivity to Antipsychotic Drugs in Older Adults

Leon

Gerretsen

Uchida

et al. 2010

Curr Psychiatry Rep

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Antipsychotic medications are widely used to manage psychotic and behavioral disorders in older adults, including primary psychotic disorders such as schizophrenia, and psychosis and behavioral disturbances associated with dementia. These two broad diagnostic indications are associated with contrasting recommended treatment durations, with the former requiring indefinite treatment across the life span. Antipsychotic drug dosing for schizophrenia is based primarily on studies of younger patients and thus may not apply to older adults. It is critically important to address the effects of aging on antipsychotic dosing given the recent emergence of data that suggest a critical role for age-related sensitivity to these drugs. Antipsychotic drugs are not only associated with somatic and neurological adverse effects but also increased all-cause mortality and sudden cardiac death in this vulnerable population. This review focuses on the sensitivity of older adults to adverse effects from antipsychotic medications and the current pharmacokinetic and pharmacodynamic explanatory models of susceptibility. Implications of recent research findings for individualized pharmacotherapy are discussed.

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Section: Adverse Effectsmentioning

confidence: 93%

Sensitivity to Antipsychotic Drugs in Older Adults

Leon

Gerretsen

Uchida

et al. 2010

Curr Psychiatry Rep

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“…12,14 The difference is thought to stem from the magnitude of histamine H1-receptor antagonism. 2 However, both drugs are used in the treatment of aggressive patients 29 when some sedation is preferred.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 In healthy subjects, 2.5 mg risperidone caused no motor side effects but induced negative symptoms, 12 whereas single administration of 10 mg olanzapine led to sedation and reduced motor activity. 13,14 Stride length is altered in schizophrenia with most prominent disturbances in patients treated with conventional antipsychotics in contrast to atypical drugs or drug-naive patients. 15 Analysis of fast diadochokinetic movements revealed higher velocity in patients on olanzapine as compared with conventional antipsychotics.…”

mentioning

confidence: 99%

Higher Motor Activity in Schizophrenia Patients Treated With Olanzapine Versus Risperidone

Walther

Horn

Razavi

et al. 2010

Journal of Clinical Psychopharmacology

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There are indications that atypical antipsychotics differ in the probability of causing motor retardation. Whereas olanzapine seems to exert sedation, risperidone might slow patients because of parkinsonism or increased negative symptoms. Objective data on gross motor activity are not available. We present actigraphic data of 16 schizophrenia patients treated with olanzapine (mean dose, 21.1 mg/d) and 23 with risperidone (mean dose, 4.7 mg/d) to investigate possible differences in their effects on motor activity. Participants wore actigraphs continuously for 24 hours at the nondominant arm. Groups did not differ in age, Positive and Negative Syndrome Scale scores, duration of illness, and number of episodes. Patients treated with olanzapine had higher activity levels than those treated with risperidone (P = 0.024); this effect was robust and also present after covarying for chlorpromazine equivalents and Positive and Negative Syndrome Scale scores. Movement index (proportion of active episodes) and the average duration of immobility, however, failed to show any difference between groups. The results indicate that patients on olanzapine are more active during the day than patients on risperidone. It remains unclear whether this difference is due to subthreshold parkinsonism with risperidone or stronger beneficial effects of olanzapine on psychomotor slowing. Because the average duration of immobility remained unaffected, sedation is not likely to be the cause for the observed differences.

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“…It should be noted that the dose of greater than 3.0 mg/d is still partially within the recommended dose range. Negative effects of antipsychotics on cognition have been found not only with higher doses [65], but also with lower therapeutic doses (eg, risperidone, 2 mg; olanzapine, 10 mg) [66,67]. Furthermore, Minzenberg et al [68] investigated the effects of psychotropic medications on cognitive functions in patients with schizophrenia and found that doses within the range of routine practice may have negative effects on complex attention and memory.…”

Section: Evidence-based Suggestions On Dosing In Older Patients With mentioning

confidence: 96%

A Tipping Point in Drug Dosing in Late-Life Schizophrenia

Tsuboi

Suzuki

Uchida

2011

Curr Psychiatry Rep

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Minimally effective doses of antipsychotics are likely influenced by several clinical and demographic characteristics of patients, with age being one of the most important elements. In light of age-related physiologic changes as well as interindividual differences in pharmacokinetic and pharmacodynamic systems, individualized dosing with regard to age will be critically important for safer drug treatment for older patients with schizophrenia. In the present review, we propose the following cautious psychopharmacologic interventions for this population: 1) simple regimen (avoid polypharmacy), 2) be aware of the presence of patients who are very sensitive to drugs, 3) gradual dose titration, and 4) timely and thorough assessments of therapeutic and side effects. The age-related antipsychotic sensitivity highlights the importance of finding the lowest possible effective dose of antipsychotic drugs as patients with schizophrenia age to maximize therapeutic effects and minimize side effects.

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Psychomotor and Memory Effects of Haloperidol, Olanzapine, and Paroxetine in Healthy Subjects After Short-Term Administration

Abstract: Short-term administration of olanzapine, and not of haloperidol, impedes several aspects of psychomotor function and verbal memory in healthy volunteers.

Cited by 38 publications

References 47 publications

Sensitivity to Antipsychotic Drugs in Older Adults

Sensitivity to Antipsychotic Drugs in Older Adults

Higher Motor Activity in Schizophrenia Patients Treated With Olanzapine Versus Risperidone

A Tipping Point in Drug Dosing in Late-Life Schizophrenia

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