Clozapine in the treatment of psychosis in Parkinson's disease

Friedman, Joseph H.; Lannon, Margaret C.

doi:10.1212/wnl.39.9.1219

Cited by 142 publications

(57 citation statements)

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“…98 The average dose for clozapine is 55 mg day −1 (for 51 patients), [93][94][95][96][97] while that for remoxipride is 150 mg day −1 , 98 much lower than that used in schizophrenia for either drug ( Figure 1). These lower doses follow directly from the wellknown fact that 90-99% of the brain dopamine has been depleted in Parkinson's disease.…”

Section: Does the Present Analysis For Clozapine Extend To Other New mentioning

confidence: 99%

“…The psychosis caused by L-DOPA or bromocriptine in Parkinson's Disease can be readily treated by low doses of either clozapine 49,[93][94][95][96][97] or remoxipride. 98 The average dose for clozapine is 55 mg day −1 (for 51 patients), [93][94][95][96][97] while that for remoxipride is 150 mg day −1 , 98 much lower than that used in schizophrenia for either drug ( Figure 1).…”

Section: Does the Present Analysis For Clozapine Extend To Other New mentioning

confidence: 99%

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Antipsychotic drugs which elicit little or no Parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors

1998

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This review addresses two questions. First, why does clozapine apparently occupy low levels of dopamine D2 receptors in patients, in contrast to all other antipsychotic drugs which occupy 70-80% of brain dopamine D2 receptors? Second, what is the receptor basis of action of antipsychotic drugs which elicit low levels of Parkinsonism?Antipsychotic doses of clozapine occupy between 0% and 50% of D2 receptors, as measured in patients by a variety of radioligands. It has recently been found, however, that the percent occupancy of a receptor by a drug depends on the radioligand used to measure that receptor. Based on this new finding, this review concludes that clozapine clinically occupies high levels of D2 receptors in the absence of any radioligand. This occupancy is estimated to be of the order of 70-80% in the dopamine-rich region of the human striatum, and even higher in the limbic D2-containing regions which are low in endogenous synaptic dopamine. This conclusion arises from two different approaches. One approach is to relate the reported clozapine occupancies in the human striatum with the dissociation constants of the various radioligands at the D2 receptor. This relation extrapolates to approximately 70-80% occupancy by clozapine when clozapine competes with endogenous dopamine at the D2 receptor. The second approach is to calculate the D2 occupancy of each antipsychotic drug, using the average spinal fluid concentration and the correct dissociation constant of the antipsychotic, thereby revealing that all antipsychotic drugs, including clozapine, occupy approximately 70-80% of dopamine D2 receptors in the human striatum, and possibly higher in the limbic regions.As determined by the new dissociation constants, antipsychotic drugs which elicit Parkinsonism (trifluperazine, chlorpromazine, raclopride, haloperidol, fluphenazine, risperidone) bind more tightly than dopamine to D2, while those antipsychotic drugs which elicit little or no Parkinsonism (melperone, seroquel, perlapine, clozapine, remoxipride, molindone, sulpiride, olanzapine, sertindole) bind more loosely than dopamine to D2 receptors. Compared to the tightly bound antipsychotic drugs, the more loosely bound antipsychotics generally require higher clinical doses, require fewer days for clinical adjustment, but may dissociate from the D2 receptor more rapidly and could lead to clinical relapse somewhat earlier than that found with the traditional tightly bound antipsychotic drugs.

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Section: Does the Present Analysis For Clozapine Extend To Other New mentioning

confidence: 99%

Section: Does the Present Analysis For Clozapine Extend To Other New mentioning

confidence: 99%

Antipsychotic drugs which elicit little or no Parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors

1998

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“…However, in clinical practice, both clozapine and risperidone cause unacceptable worsening of parkinsonian state in most cases. Despite clozapine's association with blood dyscrasias, it possibly remains the best therapy for levodopa-induced psychosis when other measures have failed [21,22].…”

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confidence: 99%

Achieving 24-Hour Control of Parkinson’s Disease Symptoms: Use of Objective Measures to Improve Nocturnal Disability

Chaudhuri¹,

Pal

Bridgman

et al. 2001

Eur Neurol

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Sleep-related problems are common in Parkinson’s disease (PD) and may occur due to the disease process, alteration in sleep architecture or nocturnal motor problems such as akinesia and dystonia. Neuropsychiatric problems and nocturia can also cause significant sleep disruption in PD. Poor sleep may lead to daytime consequences such as excessive daytime sleepiness or fatigue. As there are no PD-specific sleep scales, we have devised a simple visual analogue scale – the Parkinson’s disease sleep scale (PDSS) which is aimed at formal quantification of various aspects of nocturnal sleep disturbance in PD. In this paper, we discuss the development of this scale, its clinical use and how the scale could be used to devise targeted treatment strategies for nocturnal problems in PD.

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“…In addition to the neurochemical profile of negative schizophrenia, which overlaps with that of Parkinsonism, the co-occurrence of both disorders in the same patient suggests that they are interrelated (Crow et al, 1976;Friedman & Lannon, 1989). In addition, the unusually high degree of basal ganglia involvement in diseases which resemble schizophrenia, supports the association of Parkinsonism with schizophrenia (Bowman & Lewis, 1980).…”

Section: Negative Schizophrenia Of Parkinsonismmentioning

confidence: 94%

“…More recently, Friedman and Lannon (1989) described five patients with Parkinsonism who, during the course of the disease, suffered a severe psychotic illness that responded to clozapine. Attenuation of psychotic symptoms with clozapine (Scholz & Dichgans, 1985) is in fact associated with improvement in Parkinsonism (Pakkenbergy & Pakkenberg, 1986;Friedman & Lannon, 1989), underscoring the possibility that both conditions are interrelated.…”

Section: Negative Schizophrenia Of Parkinsonismmentioning

confidence: 99%

Is negative schizophrenia a variant of parkinsonism?

Sandyk

Kay

1990

International Journal of Neuroscience

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Clozapine in the treatment of psychosis in Parkinson's disease

Abstract: Clozapine is an antipsychotic medication that is virtually free of extrapyramidal side effects. We report our successful treatment of 6 patients with idiopathic Parkinson's disease and various psychoses using clozapine on a chronic basis along with carbidopa/L-dopa.

Cited by 142 publications

References 0 publications

Antipsychotic drugs which elicit little or no Parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors

Antipsychotic drugs which elicit little or no Parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors

Achieving 24-Hour Control of Parkinson’s Disease Symptoms: Use of Objective Measures to Improve Nocturnal Disability

Is negative schizophrenia a variant of parkinsonism?

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