clozapine and Parkinson-Disease

The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood.. To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP.. We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. We estimated relative standardized mean differences (SMDs) for continuous outcomes and odds ratios (OR) for binary outcomes, with their respective 95% confidence intervals (CIs).. We included 19 unique studies evaluating AAPs in a total of 1,242 persons with PDP. Based on Clinical Global Impression Scale for Severity, pimavanserin (SMD, -4.81; 95% CI, -5.39, -4.24) and clozapine (SMD, -4.25; 95% CI, -5.24, -3.26) significantly improved symptoms compared with placebo. Also, compared to placebo, pimavanserin (OR, 1.16; 95% CI, 1.07, 1.24) significantly improved psychotic symptoms based on Scale for Assessment of Positive Symptoms for Parkinson's Disease Psychosis/Hallucinations and Delusions scores. In comparison to placebo, clozapine (SMD, -0.69; 95% CI, -1.35, -0.02), pimavanserin (SMD, -0.01; 95% CI, -0.56, 0.53), and quetiapine (SMD, 0.00; 95% CI, -0.68, 0.69) did not impair motor function per Unified Parkinson's Disease Rating scale. Based on Mini-Mental State Examination scale, quetiapine (SMD, 0.60; 95% CI, 0.07, 1.14) significantly impaired cognition compared to placebo.. In patients with PDP, pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. With quetiapine being associated with a significant decline in cognition and despite not impairing motor function, our findings suggest that it should be avoided in patients with PDP and reduced cognitive abilities.

Topics: Antipsychotic Agents; Clozapine; Humans; Network Meta-Analysis; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Over half of Parkinson's disease (PD) patients develop psychotic symptoms, and PD psychosis (PDP) is associated with significant distress to patients, caregiver burden, and impairs quality of life. Pharmacological therapy is limited to atypical antipsychotics.. This review will summarize efficacy but will focus on the safety of antipsychotics for treating PDP, and in particular the off-target safety issues including cognitive impairment, sleep disturbance, cardiovascular effects, and motor function.. Pimavanserin is the only medication approved in the US for treating PDP, however clozapine is also considered efficacious. Despite lack of substantial evidence for efficacy, quetiapine is commonly used to treat PDP. Despite the effectiveness of pimavanserin and clozapine for treating PDP, a need exists for additional pharmacological agents that are effective for PDP while providing an acceptable safety and tolerability profile. Medications to treat PDP should avoid worsening motor function, and also minimize sleep disturbances, cognitive impairment, cardiovascular effects, and other non-motor safety concerns. A neutral effect or reduction in mortality risk associated with PD and PDP would be ideal, and low rate of discontinuation due to AEs is desirable. Lastly, medications that can be used safely in combination with other pharmacological agents is essential.

Topics: Antipsychotic Agents; Clozapine; Delusions; Hallucinations; Humans; Parkinson Disease; Psychotic Disorders; Quality of Life

Clozapine is superior to other antipsychotics as a therapy for treatment-resistant schizophrenia and schizoaffective disorder with increased risk of suicidal behavior. This drug has also been used in the off-label treatment of bipolar disorder, major depressive disorder (MDD), and Parkinson's disease (PD). Although usually reserved for severe and treatment-refractory cases, it is interesting that electroconvulsive therapy (ECT) has also been used in the treatment of these psychiatric disorders, suggesting some common or related mechanisms. A literature review on the applications of clozapine and electroconvulsive therapy (ECT) to the disorders mentioned above was undertaken, and this narrative review was prepared. Although both treatments have multiple actions, evidence to date suggests that the ability to elicit epileptiform activity and alter EEG activity, to increase neuroplasticity and elevate brain levels of neurotrophic factors, to affect imbalances in the relationship between glutamate and γ-aminobutyric acid (GABA), and to reduce inflammation through effects on neuron-glia interactions are common underlying mechanisms of these two treatments. This evidence may explain why clozapine is effective in a range of neuropsychiatric disorders. Future increased investigations into epigenetic and connectomic changes produced by clozapine and ECT should provide valuable information about these two treatments and the disorders they are used to treat.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Depressive Disorder, Major; Electroconvulsive Therapy; Humans; Parkinson Disease; Schizophrenia

The development of delirium in patients with idiopathic Parkinson's disease (IPD) is a feared complication, which is often associated with sustained worsening of motor symptoms and psychopathological sequelae. Little is known regarding the prevalence and incidence rates, course and prognosis. Clinical studies from which recommendations for evidence-based management of delirium in IPD can be derived are lacking.. To summarize the state of the art regarding epidemiological and clinical features of delirium in IPD. Discussion of prevention strategies and non-pharmacological and pharmacological treatment options.. A literature search was carried out in PubMed.. The IPD is an independent risk factor for the development of delirium. Patients with IPD show poorer clinical outcome frequently with cognitive worsening and motor complications following development of delirium.. So far no validated rating scales for recognition and course evaluation of delirium in IPD are available. Preventive strategies and non-pharmacological measures should be consistently implemented to improve management. There are insufficient data concerning pharmacotherapy with quetiapine and clozapine, whereas other neuroleptics are contraindicated for delirium in IPD due to antidopaminergic side effects.

Topics: Antipsychotic Agents; Clozapine; Delirium; Humans; Parkinson Disease; Risk Factors

Psychosis is a common problem for people treated for Parkinson's disease. The syndrome is quite stereotypic, with hallucinations being the most common, followed by delusions. While the hallucinations are usually not very bothersome, the delusions are typically paranoid in nature. Treatment is often, but not always, required.. This article reviews the therapeutic approaches of this syndrome focusing on drug treatments used once contributory factors have been removed. This includes a review of the evidence supporting the use of clozapine and, most recently, pimavanserin, the first drug with antipsychotic efficacy that has no effect on dopamine. Treatment with second generation antipsychotic drugs and cholinesterase inhibitors are also reviewed.. Clozapine and pimavanserin have proven efficacy for Parkinson's disease psychosis (PDP), without impairing motor function. In clozapine's favor are its antipsychotic benefits seen within 1 week and its effectiveness in improving tremor in PD. However, this is counterbalanced by the need for blood monitoring, despite the extremely low doses used, and sedation. Pimanvanserin is well tolerated, without sedation or other significant side effects. Its onset of benefit, however takes 4-6 weeks. While quetiapine is also frequently used, its efficacy is not supported by double blinded, randomized trials.

Topics: Antipsychotic Agents; Clozapine; Dopamine; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea

The dopamine D

Topics: Animals; Drug Discovery; Humans; Ligands; Molecular Targeted Therapy; Neoplasms; Parkinson Disease; Receptors, Dopamine D4; Small Molecule Libraries; Substance-Related Disorders

To summarize and evaluate the existing literature regarding medications to treat Parkinson's disease (PD) psychosis.. MEDLINE (1946 to March 2017), EMBASE (1980 to March 2017), CINAHL (1982 to March 2017), and PsychInfo (1887 to March 2017) were searched using the following terms: Parkinson disease, Parkinson's disease, psychotic disorders, psychosis, delusions, and hallucinations.. The search was limited to randomized controlled trials (RCTs) reporting human outcomes. Data extracted included the following: study design, population, setting, intervention, control, outcomes related to psychosis and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool.. After assessment, 16 of 235 studies were included; 11 articles reported comparisons between active drug and placebo, whereas 5 compared clozapine and an active comparator. Placebo-controlled trials demonstrated benefit for clozapine (n = 2) and pimavanserin (n = 2), with no firm benefits observed for quetiapine (n = 4) or olanzapine (n = 3). Comparative studies demonstrated improved efficacy in symptom scores when clozapine or comparator agent (n = 2, quetiapine; n = 1, olanzapine; n = 1, risperidone; and n = 1, ziprasidone) was assessed alone. However, no comparator data suggest that one agent is better than another, and none are yet available for pimavanserin. Overall risk of bias across all studies was moderate to high.. Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Piperazines; Piperidines; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; Urea

Psychotic symptoms are present in up to 50% of patients with Parkinson's disease. These symptoms have detrimental effects on patients' and caregivers' quality of life and may predict mortality. The pathogenesis of psychotic symptoms in Parkinson's disease is complex, but the use of dopaminergic medications is one of the risk factors. The treatment of psychotic symptoms in Parkinson's disease is complicated due to the ability of antipsychotic medications to worsen motor symptoms. The efficacy of clozapine in the treatment of psychosis in patients with Parkinson's disease has been confirmed in several clinical trials; however, the adverse effects and the necessity of blood count monitoring are the reasons why the use of this drug is challenging. The studies on safety and efficacy of other antipsychotics conflicting results. The use of antipsychotics in these patients is also associated with increased mortality. Psychotic symptoms in Parkinson's disease per se are also proven predictors of mortality. Thus it is necessary to treat psychotic symptoms but the choice of an antipsychotic should be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic option with more favorable adverse effects profile is now available for this indication, but careful postmarketing monitoring is necessary to establish the true picture of this drug's long-term safety and efficacy.

Topics: Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Psychotic Disorders; Quality of Life; Risk Factors; Treatment Outcome

Psychosis in Parkinson's disease (PD) is one of the greatest determinants of nursing home placement and caregiver stress. Traditionally associated with medications with dopaminergic effect, it has now been linked to other medications and other stressors e.g. systemic illnesses. The development of hallucinations in a PD patient can herald the onset of dementia and usually predicts increased mortality risk. Medication reduction in PD psychosis usually reduces the symptoms; however, this comes at the cost of worsening motor function. If gradually decreasing the patient's medications does not resolve the psychosis, the treatment of choice is an atypical antipychotic. Though only clozapine has level A recommendation for this indication, other atypicals like quetiapine continue to get used for this purpose on account of the logistics involved with clozapine use. Cholinesterase inhibitors are also increasingly being used for PD psychosis on account of the association with dementia. The treatment of PD psychosis is an unmet need in PD management and search for suitable agents constitutes an active area of research in PD.

Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Humans; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate

Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT

Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Humans; Molecular Targeted Therapy; Neurotransmitter Agents; Parkinson Disease; Piperidines; Psychotic Disorders; Quetiapine Fumarate; Urea

Parkinson's disease (PD) affects 10 million people worldwide. Half will develop psychosis, the majority experiencing hallucinations rather than delusions. Emergence of psychosis increases the likelihood of institutionalization and mortality. Where pharmacological treatment is warranted, options are limited. Most currently licensed atypical antipsychotics are ineffective or worsen motor symptoms in people with PD. This review of provides an overview of the current landscape of treatments and the opportunities in emerging research. Clozapine is the only licensed antipsychotic with proven efficacy, although the associated side effects limit its use. With recent advances in understanding the role of serotonin, rational drug design approaches have delivered a novel pharmacological treatment with recently proven efficacy in clinical trials of people with PD and psychosis. Pimavanserin represents an important addition to treatment.

Topics: Animals; Antipsychotic Agents; Clozapine; Drug Design; Humans; Parkinson Disease; Psychotic Disorders; Serotonin

Psychosis, a frequent complication in Parkinson's disease (PD), contributes significantly to morbidity, mortality, nursing-home placement and quality of life. Medication side effects, issues of trial design and negative outcomes have limited clinical advances of new treatments for PD psychosis. Evidence-based medicine maintains clozapine as the most effective antipsychotic in PD without motor worsening, despite risk of agranulocytosis. Safe, effective treatments that improve psychosis without exacerbating parkinsonism are urgently needed.. This article reviews the: i) phenomenology of PD psychosis, ii) pharmacological rationale for antipsychotics in PD; iii) clinical trials of antipsychotics in PD; iv) novel research strategies such as neuroimaging, genetics and animal models; and v) associated challenges in studying and treating PD psychosis. Preparation of this review included an extensive literature search using PubMed.. Management of PD psychosis is complex. Challenges pertaining to study design, rating scales, subject recruitment and completion have limited PD psychosis treatment trials. Novel research strategies focus on nondopaminergic systems and incorporate neuroimaging, genetic associations and animal models. These strategies also have challenges but have the potential to enhance our understanding of PD psychosis and advance the development of agents that can ultimately be tested in well-designed, randomized, controlled trials.

Topics: Animals; Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Psychotic Disorders; Randomized Controlled Trials as Topic

Parkinson's disease (PD) patients often develop psychotic symptoms that severely affect quality of life and limit the use of medications to ameliorate motor symptoms. Psychotic symptoms are a major cause for nursing home placement. While these symptoms do not always require treatment, they often do but antipsychotic drugs all share the common pharmacological mechanism of blocking dopamine D2 receptors which may worsen motor problems in this very vulnerable population. Double blind, placebo controlled trials (DBPCT) have shown that clozapine is effective at controlling the psychotic symptoms at doses far below those used in schizophrenia, without worsening motor function, even improving tremor. DBPCT have demonstrated that olanzapine worsens motor function without improving psychosis. Quetiapine has been shown in DBPCT to be free of motor side effects in PD patients but not effective, whereas many open label studies have indicated that quetiapine is effective. The other atypical have been the subjects of conflicting open label reports. The effects of the atypicals in PD psychosis is reviewed.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack of agreement on the diagnosis of psychosis in PD, poor completion rates, mixed populations that included dementia, and other issues. Several reviews, guidelines, and consensus statements have sought to establish standards for treating these symptoms of PD. In 2006, the American Academy of Neurology (AAN) published a practice guideline (based on articles published up to 2004) for management of depression, psychosis, and dementia in patients with PD. Since then, a number of relevant studies have been published.. The purpose of this article was to review data that have appeared in the literature since publication of the AAN guideline regarding the management of hallucinations and psychosis in PD.. A literature search of the PubMed, CINAHL, and PsychInfo databases was conducted for human studies published in English from January 2004 to June 2010. All clinical studies were included except case reports and case series. Studies with <20 participants were also excluded. Search terms included psychosis, hallucinosis, hallucination, delusion, Parkinson, atypical antipsychotic, neuroleptic, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone.. Thirteen studies were included in the review: 3 studies of clozapine, 7 studies of quetiapine, 2 head-to-head trials comparing quetiapine and clozapine, and 1 noncomparative trial of clozapine or quetiapine interventions. Most of the studies included participants with a mean age in the early to mid 70s and a mean duration of PD typically >10 years.. Results of the identified studies suggested that patients with PD might benefit from long-term clozapine therapy. Results of the quetiapine studies were conflicting. However, no statistically significant difference in effectiveness was found between quetiapine and clozapine in comparative trials. The significance of the differences in treatment responses between patients with dementia and those without dementia remains unclear, and it was not possible to draw conclusions for or against other atypical antipsychotics because of insufficient evidence. Further studies are needed to address the methodologic issues in the current trials and to assess safety issues in larger cohorts.

Topics: Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Comorbidity; Delusions; Dementia; Depression; Dibenzothiazepines; Disease Progression; Guidelines as Topic; Hallucinations; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report; Risperidone

Clozapine was the first atypical 'broad spectrum' antipsychotic drug to be marketed and the first agent approved for the treatment of schizophrenia refractory to other medications. It is also effective for the treatment of aggressive behaviour in schizophrenic and demented patients and in the management of psychosis and aggression in Parkinson's disease and Lewy body dementia.. The aim of this review is to study the safety of clozapine for use in elderly patients.. An extensive Medline search was made. Some studies that were referenced in reports from our pharmacovigilance centre and from regulatory agencies such as the FDA, EMEA and WHO were included.. Clozapine treatment in the elderly requires a careful geriatric assessment. However, its use is strongly limited by the possibility of onset of severe adverse effects such as potentially fatal agranulocytosis, myocarditis and others such as seizures, weight gain and metabolic adverse effects.

Topics: Aged; Agranulocytosis; Antipsychotic Agents; Clozapine; Geriatric Assessment; Humans; Mental Disorders; Myocarditis; Parkinson Disease

Psychosis due to dopamimetic treatment is a difficult problem in patients with Parkinson's disease (PD). The aim of this structured review with meta-analysis was to evaluate which neuroleptic drugs can efficiently be used to treat drug-induced psychosis (DIP) in Parkinson's disease. Electronic databases were screened for the key words Parkinson's disease and psychosis. Only 7 trials with a satisfactory allocation concealment and data reporting were included into the study. Two trials compared low-dose clozapine versus placebo with a significantly better outcome for clozapine regarding efficacy and motor functioning. In one trial clozapine was compared against quetiapine showing equivalent efficacy and tolerability. However, in two placebo controlled trials quetiapine failed to show efficacy. In two further placebo controlled trials olanzapine did not improve psychotic symptoms and significantly caused more extrapyramidal side effects. Based on randomized trial-derived evidence which is currently available, only clozapine can be fully recommended for the treatment of DIP in PD. Olanzapine should not be used in this indication.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Data Interpretation, Statistical; Dibenzothiazepines; Dopamine; Dopamine Agents; Humans; Olanzapine; Parkinson Disease; Psychotic Disorders; Quality Assurance, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Psychosis may be seen with several movement disorders. As pharmacological treatments can sometimes worsen movement disorders, psychosis in these situations can be complex for clinicians to manage. This review covers the management of psychosis in three different movement disorders: Parkinson's disease, dementia with Lewy bodies and Huntington's disease.

Topics: Antipsychotic Agents; Clozapine; Haloperidol; Humans; Huntington Disease; Lewy Body Disease; Parkinson Disease; Patient Education as Topic; Psychotic Disorders; Risperidone

Lewy body dementia and Parkinson disease dementia are frequent causes of degenerative dementia: 20% of the dementias in patients older than 65 years are caused by the former and nearly 80% of patients with advanced Parkinson disease develop the latter. Symptoms of Lewy body dementia include fluctuations of cognitive performance, frontal and visuospatial impairment, visual hallucinations, and parkinsonism. Parkinson disease dementia could be differentiated in two subtypes: a "subcortical" subtype, characterized by frontal impairment with apathy and dullness and a "cortical" subtype with symptoms similar to those of Lewy body dementia. Mastery of potential iatrogenic factors is important: psychotropic drugs must be prescribed at the strict minimum, and L-dopa monotherapy at the minimal dose acceptable for correcting Parkinsonian motor symptoms should be the rule. Acetylcholinesterase inhibitors may be useful in both these types of dementia: rivastigmine is approved for treating Parkinson disease dementia and clozapine for reducing hallucinations.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Cholinesterase Inhibitors; Clozapine; Dementia; Diagnosis, Differential; Disease Progression; Dopamine Agents; Humans; Iatrogenic Disease; Levodopa; Lewy Body Disease; Neuroprotective Agents; Nootropic Agents; Parkinson Disease; Parkinsonian Disorders; Phenylcarbamates; Psychotropic Drugs; Rivastigmine; Serotonin Antagonists

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Aripiprazole; Cholinesterase Inhibitors; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Humans; Lewy Body Disease; Male; Parkinson Disease; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones

Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD.

Topics: Antipsychotic Agents; Anxiety Disorders; Cholinesterase Inhibitors; Clozapine; Dementia; Depressive Disorder; Humans; Mental Disorders; Parkinson Disease; Psychotic Disorders

The treatment of patients suffering from idiopathic Parkinson's disease has become more and more complex. From its beginning the treatment has to be tailored to the needs of each patient. Not only the individual symptomatology and its course have to be taken into consideration, but also the short- and longtime reaction to treatment.

Topics: Adult; Aged; Antidepressive Agents; Antiparkinson Agents; Antipsychotic Agents; Benserazide; Cholinesterase Inhibitors; Clozapine; Dementia; Depression; Diagnosis, Differential; Dopamine Agents; Dopamine Agonists; Drug Combinations; Humans; Levodopa; Parkinson Disease; Quality of Life; Sleep Wake Disorders; Time Factors

Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a neurodegenerative disorder now considered to be the second most common cause of dementia after Alzheimer's disease. Postmortem findings suggest that DLB accounts for 20% to 34% of all dementia cases and is often underdiagnosed. Salient features of DLB include fluctuations in cognition, perceptual abnormalities (e.g., visual hallucinations), and mild parkinsonism. Other symptoms include frequent falls, nighttime agitation, and depression. DLB symptomatology can be partly explained by the extensive destruction of dopaminergic and acetylcholinergic pathways caused by neurodegeneration. For this reason, DLB patients are especially vulnerable to the antidopaminergic and anticholinergic actions of most conventional antipsychotics, which makes treatment of the psychotic symptoms of DLB extremely difficult. Patients are particularly sensitive to developing extrapyramidal symptoms (EPS) and also to the potentially fatal complication of neuroleptic sensitivity, which affects approximately 50% of DLB patients. Therefore, a need exists for antipsychotic drugs with less propensity to induce EPS and reduced affinity for dopamine and acetylcholine receptors. Here we review studies evaluating the efficacy and tolerability of atypical antipsychotics for the treatment of psychoses associated with DLB. Olanzapine appears to be poorly tolerated, and risperidone has been associated with high risk of neuroleptic malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations of DLB without causing neuroleptic sensitivity or increasing EPS. Hence, quetiapine is an attractive candidate for the treatment of psychoses in DLB and other dementias.

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

Visual hallucinations (VHs) occur frequently in Parkinson's disease (PD). VHs occur more frequently in elderly patients with longer duration of illness, cognitive impairment, and sleep disturbances. The relationship between the use of antiparkinsonian drugs and VHs is complicated, but most drugs used to treat parkinsonian motor symptoms induce VHs and psychosis in some PD patients. The "continuum hypothesis" proposing that medication-induced psychiatric symptoms in PD begin with drug-induced sleep disturbances, followed by vivid dreams, with progression to hallucinatory and delusional experiences has been challenged. In some patients, VHs may represent intrusion of REM sleep-related imagery into wakefulness. Improving REM sleep abnormalities in PD (e.g., stimulants, anticholinesterase inhibitors) is one strategy now being tested to improve VHs in PD.

Topics: Antiparkinson Agents; Cholinesterase Inhibitors; Clozapine; Dopamine Agents; Dreams; Hallucinations; Humans; Parkinson Disease; Polysomnography; Psychotic Disorders; Sleep Deprivation; Sleep Disorders, Intrinsic; Sleep, REM

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome

Central criteria for the definition of atypical antipsychotics are antipsychotic efficacy and minimal or none extrapyramidal symptoms (EPS). This last criterium is of importance in the differentiation with the traditional antipsychotics. Of the four atypical antipsychotics which are discussed here, clozapine is the most atypical. The best proof is its good efficacy in the treatment of Parkinson psychosis with minimal adverse effects on motor function. Clozapine is the best choice for this indication. At this moment there is not enough evidence available concerning quetiapine. Risperidon and olanzapine give more Dopamine2-occupancy with higher doses and can evoke EPS, but this is still less compared to the traditional antipsychotics. All four atypical drugs cause less tardive dyskinesia. Atypical antipsychotics are not well studied in the treatment of elderly patients with functional psychosis. However the available information and the literature on the treatment of young adults makes it probable that the atypical antipsychotics are at least as effective in the elderly as the traditional antipsychotics. The median daily doses are lower for elderly than for younger patients. Risperidon has been proven effective in the treatment of agressive behaviour in dementia. Atypical antipsychotics have their 'own' adverse effects. Those which have the most impact in the elderly are discussed.

Topics: Aged; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Receptors, Dopamine D2; Treatment Outcome

Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders.. A comprehensive literature review.. Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer's disease.. There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

Topics: Aged; Alzheimer Disease; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder; Drug Administration Schedule; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Risperidone

Drug-induced iatrogenic hallucinations and psychosis occur in about 30% of Parkinson's disease (PD) patients and are the single most important precipitant for nursing home placement, which carries a grave prognosis. In addition, parkinsonism is a frequent accompaniment to the more common dementing syndromes, Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies (DLB). The five most recent antipsychotic drugs approved by the Food and Drug Administration in the United States have been marketed as "atypical" antipsychotics (AA) due to their relative freedom from extrapyramidal symptoms when used in schizophrenia patients. The use of these newer antipsychotic drugs in PD and other parkinson-sensitive populations represents the most stringent test to their freedom from motor side effects. To date, clozapine, risperidone, olanzapine, and quetiapine have been studied in parkinson-vulnerable populations. This article reviews the data and highlights the differences that these four drugs have on motor function. It also emphasizes the challenges in evaluating the available data on the motor effects of AA, especially on the non-PD elderly and cognitively impaired population. Suggestions are made for future research to improve the interpretability of these studies.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia, Vascular; Dibenzothiazepines; Hallucinations; Humans; Iatrogenic Disease; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Parkinson's disease is a neurodegenerative disorder that manifests clinically with variable degrees of tremor, muscle rigidity, bradykinesia and postural instability. Tremor-predominant Parkinson's disease is characterised by prominent tremor of one or more limbs with a relative lack of significant rigidity and bradykinesia. Despite the lack of other disabling motor symptoms, the tremor of tremor-predominant Parkinson's disease can be very disabling, especially if a postural and kinetic component exists. A wide variety of treatments for Parkinson's disease tremor are currently available and include use of oral medications, injections with botulinum toxin and neurosurgical procedures. Some of the first line medications (levodopa, dopamine agonists, anticholinergics) are very effective in controlling tremor. However, some patients with Parkinson's disease tremors are unresponsive to first line drugs and treatment with second line medications (clozapine, amantadine, clonazepam, propranolol, neurontin) should be attempted. In the small number of patients with disabling tremor that is refractory to all medications, neurosurgical intervention should be considered. Both thermocoagulation and deep brain stimulation at several different neuroanatomical sites (thalamus, globus pallidus, subthalamic nucleus) offer good to excellent tremor control with relatively low risk to the patient.

Topics: Acetates; Amantadine; Amines; Antiparkinson Agents; Botulinum Toxins; Cholinergic Antagonists; Clonazepam; Clozapine; Cyclohexanecarboxylic Acids; Dopamine Agonists; Electric Stimulation Therapy; Gabapentin; Gamma Rays; gamma-Aminobutyric Acid; Globus Pallidus; Humans; Neurosurgical Procedures; Parkinson Disease; Propranolol; Radiosurgery; Thalamus; Tremor

Levodopa is still the mainstay of the treatment of Parkinson's disease. Limitations of levodopa therapy have led to development of numerous therapeutic approaches at the level of levodopa/dopamine metabolism, dopamine receptors, dopamine transporter, and other neurotransmitter systems. New insights into the pathophysiology of Parkinson's disease have led to the promising concepts of neuroprotection and neurorestoration. In daily practice therapeutic management of Parkinson's disease is still symptomatic.

Topics: Amantadine; Antiparkinson Agents; Clozapine; Dopamine Agonists; Dopamine Antagonists; Female; History, 19th Century; History, 20th Century; Humans; Levodopa; Male; Parkinson Disease; Receptors, Dopamine; Substantia Nigra

Psychotic symptoms have become increasingly common in patients with idiopathic Parkinson's disease and other parkinsonian syndromes. This increased prevalence of psychoses is in part a reflection of the greater longevity of people with Parkinson's disease and, to a certain extent, is a consequence of our success in treating the motor symptoms of these syndromes. The psychotic symptoms associated with Parkinson's disease can be as varied as the motor symptoms. They stem from interactions between the underlying neuropathologies of the syndromes and the adverse effects associated with chronic antiparkinsonian drug administration. In patients with advanced Parkinson's disease, there is also a high prevalence of affective comorbidity. This increase in affective symptoms and the relatively high incidence of cognitive and affective side effects of the antiparkinsonian medications contribute to the increase in psychoses observed in these older patients. The most significant risk factors for developing psychosis in Parkinson's disease are (1) coexistence of dementia, (2) protracted sleep disturbances, and (3) nighttime use of long-acting dopaminomimetics. This article reviews the phenomenology, pathophysiology, and treatment of psychosis associated with parkinsonism and discusses how atypical antipsychotic medications have revolutionized the management of the symptoms and improved the quality of life of those affected.

Topics: Algorithms; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Comorbidity; Decision Trees; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Pirenzepine; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate

Clozapine, the only commercially available atypical neuroleptic, is approved for the treatment of schizophrenic patients who are unresponsive to or intolerant of typical neuroleptics. It has an unusual pharmacologic profile compared with standard neuroleptics, and it follows that clinical response to this drug is also different. It has shattered the notion that a drug must be capable of inducing or worsening parkinsonism to be a potent antipsychotic. Based on these findings, it is being used increasingly by neurologists for psychiatric and nonpsychiatric problems in patients with movement disorders. The most common use for clozapine among neurologists is in the management of drug-induced psychosis in Parkinson's disease (PD). This problem has been a source of increased morbidity and mortality in PD because of a lack of adequate therapeutic intervention. At this time, because of success in numerous open trials, with improvement of > 80% of patients, clozapine therapy for psychosis in PD is becoming the standard of care. It also appears to be of value in the management of some motor features of PD, including tremors and dyskinesia and possibly even sensory symptoms such as akathisia and pain. The literature also suggests that clozapine may be of potential benefit in hyperkinetic movement disorders including essential tremor, Huntington's disease, and tardive dyskinesia. We review the current data concerning the use of clozapine in patients with these movement disorders and others.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Dyskinesia, Drug-Induced; Humans; Huntington Disease; Movement Disorders; Parkinson Disease; Psychotic Disorders; Tremor

Topics: Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Psychotic Disorders

Psychotic symptoms such as visual hallucinations and delusions are a relatively common clinical problem in patients with Parkinson's disease (PD). A dilemma arises in the treatment of psychosis in these patients because traditional antipsychotics are dopaminergic antagonists that worsen the motor symptoms of PD. Clozapine, an atypical antipsychotic, has been successfully used in the treatment of psychosis in PD patients. The use of clozapine in these patients differs significantly, however, from its use in young, relatively healthy, treatment-resistant schizophrenic patients in the dosage required, side effects, and other aspects of management.

Topics: Antipsychotic Agents; Clozapine; Dementia; Humans; Parkinson Disease

The occurrence of psychosis is frequent during the evolution of Parkinson's disease. The reduction of therapeutics or the use of classical neuroleptics may improve the symptoms, but usually worsens parkinsonism. Clozapine is an atypical neuroleptic with only few extrapyramidal effects, which has been proposed at low dose in this indication since 1985. A review of the literature, about more than 200 patients shows good results in approximately 90% without worsening of extrapyramidal symptoms. Some patients even noted an improvement of their motor state while treated by clozapine alone or as dopatherapy was secondarily increased. More controversial results were obtained in demented or depressed patients. Sedation is one of the most frequently encountered side-effect but rarely necessitates the withdrawal of clozapine. Even if the risk of agranulocytosis is slight, regular blood cell counts must be done.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Humans; Parkinson Disease; Psychoses, Substance-Induced

Medical treatment of Parkinsonian syndromes is often complicated by psychiatric side effects such as confusional states, hallucinations and psychosis. Recent pilot studies report good clinical results with the atypical neuroleptic clozapine.. We report on 15 patients with Parkinsonian syndromes: 11 with idiopathic Parkinson's disease (IPD), 3 with multiple system atrophy (MSA) and 1 with postencephalitic Parkinsonism (SPP). The mean age was 68.8 +/- 10 years; the mean duration of Parkinsonian symptoms was 6.8 +/- 5.7 years. The Hoehn & Yahr grade was: 3.5 +/- 0.8. Eleven patients were suffering from psychotic episodes, 10 from hallucinations, 8 from confusional states. Clozpine was introduced at nighttime and dosage was modified until the appearance of clinical effect or intolerable side effects.. We report on an observed cumulative duration of clozapine treatment of 13 patient-years. The average treatment duration was 10.5 +/- 10.4 months. The mean daily dose was 33.3 +/- 30 mg (range: 6.2-100). There was at least transitory improvement of psychiatric symptoms in all patients. There was constant and complete improvement in 7 patients (46%) and satisfactory improvement in 5 patients (33.3%). The levodopa dosage was unchanged (mean dosage 563 +/- 232 mg), and the dosage of dopamine agonists was significantly increased. None of our patients experienced motor deterioration. Side effects comprised sialorrhoea, sedation, orthostatic hypotension, and delirium tremens and an epileptic seizure in one patient each. Two patients died suddenly at the 63rd and at the 86th day of treatment respectively, outside the hospital. These deaths seemed to be unrelated to the treatment. There was no agranulocytosis.. Clozapine is an efficient antipsychotic drug in Parkinsonian patients with no motor side effects in the dosages used. The effective dosage is very low in comparison to psychiatric patients. However various side effects may occur and close monitoring is required.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Female; Humans; Male; Mental Disorders; Middle Aged; Parkinson Disease

This article reviews the nature and prevalence of Lewy bodies (LBs) found during postmortem examination of demented individuals. Neuropathologic findings associated with diffuse Lewy body disease (DLBD) are contrasted with those of other causes of dementia (e.g., Pick's disease and Alzheimer's disease). A sufficiently specific clinical syndrome is suggested to enhance the antemortem diagnosis of DLBD. Current and speculative clinical management strategies of DLBD are discussed.

Topics: Alzheimer Disease; Antipsychotic Agents; Brain Stem; Clozapine; Dopamine Antagonists; Humans; Lewy Bodies; Neuropsychological Tests; Parkinson Disease; Risperidone

Clozapine is the first of a new generation of antipsychotic drugs which constitutes a major advance in the treatment of schizophrenia. Numerous theories have been proposed to explain the advantages of clozapine over typical neuroleptics. Most of these focus on its effects on dopaminergic and serotonergic neurotransmission. This article reviews the effects of clozapine and related antipsychotic drugs on dopamine (DA) D1, D2, and D4, and serotonin (5-HT) 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptors, as well as its ability to modulate DA and 5-HT release. Clozapine and other atypical antipsychotic drugs share the ability to cause fewer extrapyramidal symptoms at clinically effective doses. This may be related to their potent 5-HT2A and weak D2 receptor blocking properties, a profile shared by risperidone, melperone, olanzapine, amperozide, HP-873, seroquel, sertindole, and ziprasidone. The basis for the superior ability of clozapine to treat negative symptoms and enhance cognitive function compared to typical neuroleptic drugs in schizophrenic patients has not yet been ascertained, but there is evidence that its effect on 5-HT2A, D2, or D4 receptors may be important. Other aspects of the pharmacology of clozapine which may contribute to its actions include potent alpha 1-adrenergic, M1, M2, M3, and M5 receptor blocking properties, as well as M4 agonist effects.

Topics: Antipsychotic Agents; Clozapine; Dopamine; Humans; Parkinson Disease; Receptors, Dopamine D1; Schizophrenia; Serotonin

Topics: Clozapine; Frontal Lobe; HLA Antigens; Humans; Parkinson Disease; Schizophrenia

Drug-induced psychiatric states occur frequently in PD. In the prelevodopa era, depression and other psychiatric disorders were described in PD, but in untreated patients psychosis was rare. Since the development of levodopa and other pharmacological treatments for PD, however, psychotic symptoms have become much more common (10-50%). In some individuals these problems can be more disabling than the motor features of PD and, as a result, pose a serious threat to the patient's ability to maintain independence. The drug-induced psychoses consist of several distinct psychiatric syndromes that can be divided broadly into those occurring on a background of a clear sensorium and those which are accompanied by confusion and clouding of consciousness. Benign organic hallucinosis is the most common of these syndromes (30%). It usually occurs on a background of a clear sensorium and may not be a particularly troublesome problem if the patient is able to retain insight into the nature of these symptoms. More disabling syndromes usually include delusional thinking that is frequently paranoid, confusion and even frank delirium. Although all these psychotic syndromes can occur in isolation, there is a tendency for mild symptoms to progress to more disabling ones if adequate and timely treatment is not instituted. Abnormal dreaming and sleep disruption often precede these difficulties by weeks to months and may provide an important early clue to their onset. The mechanisms responsible for drug-induced psychotic symptoms in PD are unknown, but dopaminergic (especially mesolimbic) and serotoninergic systems are likely to be involved. The treatment of the drug-induced psychoses in PD should be undertaken in a stepwise manner. A detailed discussion of this approach, including the use of anti-PD medication adjustment, clozapine, and other medications (neuroleptic and nonneuroleptic) and ECT is provided (see Fig. 1). Although drug-induced psychoses are the most important of the drug-induced psychiatric states, mania, anxiety, and hypersexuality may also occur. Depression is also common in PD, but it is unlikely to occur as a side effect of antiparkinsonian medications.

Topics: Aged; Anxiety; Bipolar Disorder; Clozapine; Depression; Electroconvulsive Therapy; Humans; Levodopa; Lisuride; Male; Ondansetron; Parkinson Disease; Psychoses, Substance-Induced; Sexual Dysfunctions, Psychological

1. This article reviews the prevalence, diagnosis, pathophysiology and management of psychosis in Parkinson's disease. 2. Psychosis in Parkinson's disease has been associated with all antiparkinsonian medications. The most common symptoms are vivid disturbing dreams, visual hallucinations and paranoid delusions. 3. The emergence of psychosis reduces the patient's functional capacity and increases caregiver burden. It also poses a therapeutic dilemma because effective treatment of psychotic symptoms may result in worsening of motor symptoms and vice versa. 4. Increased physician awareness is essential for proper diagnosis and management. Withdrawal of anticholinergic medications and amantadine followed by levodopa dose adjustment is effective in many patients. 5. Atypical neuroleptics, in low doses, may be successful when other measures have failed. However, these agents are not approved for treating Parkinsonian psychosis and must be considered as investigational therapies.

Topics: Clozapine; Diagnosis, Differential; Humans; Parkinson Disease; Psychotic Disorders; Risperidone

Recent research on the role of clozapine in the treatment of Parkinson's disease and other movement disorders is discussed. Most clinical trials have shown resolution of or improvement in psychotic symptoms accompanying Parkinson's disease without worsening of parkinsonian symptoms. Adverse effects appear to be mild at dosages of < 100 mg/day; sedation is the most frequent problem. Most of these studies have serious limitations, however; until better studies have been completed, the decision to use clozapine for Parkinson's disease-related psychosis should be made on a case-by-case basis, with thorough evaluation of risks, benefits, and other therapeutic options. Some patients with Parkinson's disease have shown improvement in tremor and other abnormal movements when given clozapine. Clozapine cannot be recommended for treating tardive dyskinesia on the basis of the research done so far; some trials show dramatic resolution of symptoms, others no benefit. Anticholinergics or dopamine-reuptake inhibitors should be considered before clozapine is given to patients with tardive dyskinesia because of clozapine's potential for serious adverse effects. A few patients with Huntington's disease have responded to clozapine, but again no conclusions can be drawn. Clozapine appears to offer no real advantage over haloperidol for treating choreiform movements in Huntington's disease. The frequency of tics in Tourette's syndrome does not seem to be reduced by clozapine. Clozapine has shown some efficacy as a treatment for psychosis and abnormal movements in Parkinson's disease. Results have been less promising for other movement disorders. Further study in larger populations is needed before any definitive conclusions about clozapine's place in movement disorder therapy can be made.

Topics: Clinical Trials as Topic; Clozapine; Dyskinesia, Drug-Induced; Humans; Huntington Disease; Movement Disorders; Neurocognitive Disorders; Parkinson Disease; Tourette Syndrome

This article reviews new medical and surgical treatments for Parkinson's disease (PD). Catechol-O-methyl-transferase (COMT) inhibitors supplement the variety of antiparkinsonian drugs interacting with the dopaminergic system. Clinical studies show that COMT inhibitors prolong the action of levodopa in patients with the "wearing off" phenomenon. The atypical antipsychotic drug clozapine is the treatment of choice for the alleviation of levodopa-induced psychosis. Clozapine also has beneficial effects on tremor and levodopa-induced dyskinesias. Thus, COMT inhibitors and clozapine provide new opportunities for the treatment of patients with longstanding PD and fluctuating responses to levodopa. Experimental evidence in animals suggests that glutamate antagonists have symptomatic and neuroprotective actions in PD. At present, however, only weak antiglutamatergic drugs that have low specificity, such as memantine, amantadine, and budipine are available for clinical studies. Neurotrophic factors, in particular ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, are among the most promising new approaches for neuroprotection in PD. Problems of bioavailability, however, thus far preclude their use in patients. An improved understanding of the pathophysiology of parkinsonism has led to a renaissance of stereotaxic surgery. The subthalamic nucleus is a potential new target for surgical intervention. Ventroposterior pallidotomy has been shown to improve not only rigidity and tremor, but also akinesia. The techniques for thalamic interventions have been refined by introducing chronic thalamic stimulation. Future transplantation approaches to PD will focus on the use of genetically modified cells carrying genes for dopamine-synthesizing enzymes or neurotrophic factors. Animal studies show the feasibility of in vivo gene transfer for the treatment of PD.

Topics: Animals; Antiparkinson Agents; Brain Tissue Transplantation; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Clozapine; Corpus Striatum; Disease Models, Animal; Dopamine Agents; Electric Stimulation; Excitatory Amino Acid Antagonists; Humans; Levodopa; Parkinson Disease; Stereotaxic Techniques; Substantia Nigra; Thalamic Nuclei

The advent of clozapine has marked a major advance in the treatment of schizophrenia because of its low incidence of extrapyramidal side effects and superior efficacy. Because of a relatively high incidence of agranulocytosis, approved indications for use are limited to treatment-refractory or neuroleptic-intolerant patients with schizophrenia. However, an emerging body of literature suggests that clozapine may be preferable to typical neuroleptics for treating psychosis in certain neurologic disorders. In addition, clozapine may have a place in the treatment of movement disorders that are caused by or are a result of the pharmacologic treatment of some neurologic illnesses. In general, clozapine doses used in these settings are lower than that for treating psychosis in schizophrenia. This article reviews the experience with clozapine in selected neurologic disorders.

Topics: Clinical Trials as Topic; Clozapine; Drug Administration Schedule; Humans; Levodopa; Nervous System Diseases; Neurocognitive Disorders; Parkinson Disease; Tremor

At least five receptors for dopamine (D1-D5) have been recognised from molecular biological studies, and their pharmacological properties and brain localisations have been determined. The D1 and D2 subtypes are the principal subtypes in brain, and their cellular localisations in the caudate nucleus and putamen have been determined. With recent advances in the understanding of basal ganglia neuronal function, these localisation data enable insights into the mode of action of drugs used at present and in the future to treat Parkinson's disease.

Topics: Basal Ganglia; Basal Ganglia Diseases; Brain; Clozapine; Dopamine Agents; Dopamine D2 Receptor Antagonists; Female; Haloperidol; Humans; Levodopa; Male; Neostriatum; Neural Pathways; Parkinson Disease; Receptors, Dopamine D1; Receptors, Dopamine D2; Sulpiride

Although antipsychotic drugs originally helped to discover dopamine receptors, the five dopamine receptors presently identified and cloned are facilitating the search for and discovery of more selective antipsychotic and antiparkinson drugs. The D1-like dopamine receptors, D1 and D5, are sensitive to the same drugs as the D1 receptor in native tissues, but D5 is about 10 times more sensitive to dopamine than D1. The D2-like receptors, D2, D3, and D4, have approximately similar sensitivities to dopamine, but bromocriptine and raclopride are both about two orders of magnitude weaker at D4, whereas clozapine is one order more potent at D4, as compared with D2 and D3. The human dopamine D4 receptor has many variants. The sensitivities to clozapine of human variants D4.2, D4.4, and D4.7 are approximately similar, with dissociation constants between 5 and 24 nM, matching the spinal fluid concentration of clozapine under therapeutic conditions. Thus antipsychotic action may be effected through blockade of either dopamine D2 or D4 receptors.

Topics: Animals; Antiparkinson Agents; Antipsychotic Agents; Brain; Clozapine; Humans; Parkinson Disease; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Schizophrenia

Topics: Clozapine; Humans; Parkinson Disease; Psychotic Disorders; Tremor

Topics: AIDS Dementia Complex; Clozapine; HIV Infections; HIV-1; Humans; Mental Disorders; Neuroleptic Malignant Syndrome; Parkinson Disease

Topics: Animals; Clozapine; Dibenzazepines; Humans; Parkinson Disease; Psychoses, Substance-Induced

Topics: Antidepressive Agents; Clozapine; Depressive Disorder; Dopamine; Electroconvulsive Therapy; Female; Homovanillic Acid; Humans; Levodopa; Male; Mental Disorders; Nomifensine; Nortriptyline; Parkinson Disease; Personality; Psychotic Disorders; Serotonin; Tryptophan

To investigate the efficacy and safety of clozapine in the treatment of levodopa-induced dyskinesias (LID) in patients with severe Parkinson disease (PD).. Fifty patients were randomized to treatment in this 10-week, double-blind, parallel-group, placebo-controlled, multicenter trial. The principal measure of outcome was the diurnal change in the "on" time with LID assessed using a self-evaluation of the motor performance fluctuations performed every 2 weeks. An acute levodopa challenge was also performed at the beginning and end of the study.. A reduction in the duration of "on" periods with LID was noted in favor of the clozapine group at the end of the study (placebo group day 0: 4.54 +/- 0.53 hours, end: 5.28 +/- 0.70 hours; clozapine group day 0: 5.68 +/- 0.66 hours, end: 3.98 +/- 0.57 hours; p = 0.003). The mean clozapine dosage was 39.4 +/- 4.5 (SEM) mg/day. The maximal LID score at rest during the levodopa challenge was significantly decreased under clozapine treatment, with a variation from day 0 to day 70 in the placebo group of +0.15 +/- 1.01 and in the clozapine group of -2.22 +/- 0.52 (p < 0.05). Five patients receiving clozapine and seven receiving placebo discontinued on account of adverse events. Among them, three patients in the clozapine group developed eosinophilia, which rapidly resolved after withdrawal of the drug.. Clozapine is effective in the treatment of levodopa-induced dyskinesias in severe PD.

Topics: Aged; Antiparkinson Agents; Clozapine; Double-Blind Method; Dyskinesia, Drug-Induced; Humans; Levodopa; Middle Aged; Parkinson Disease; Serotonin Receptor Agonists; Treatment Outcome

To compare the efficacy and safety of clozapine in drug induced psychosis in Parkinson's disease (PD).. A four week, randomised, double blind, parallel comparison of clozapine and placebo, followed by a 12 week clozapine open period, plus a one month period after drug discontinuation, in 60 patients with PD. The primary efficacy outcome was the "clinical global impression scale" (CGI); the positive subscore of the "positive and negative syndrome scale" (PANSS) was used as the secondary efficacy parameter and the "unified Parkinson's disease rating scale" (UPDRS) and the "mini mental test examination" (MMSE) as safety outcomes.. The mean (SD) dosage of clozapine was 35.8 (12.5-50) mg at the end of the double blind period. The mean (SD) scores on the CGI improved by 1.8 (1.5) for the clozapine group compared with 0.6 (1.1) for the placebo group (p = 0.001). The mean (SD) positive subscore of PANSS improved by 5.6 (3.9) for the clozapine group (0.8 (2.8) for the placebo group; p < 0.0001). At the end of the open period, 25 patients had completely recovered from delusions and hallucinations, and 19 experienced a relapse within one month after the clozapine washout period. The UPDRS motor and MMSE mean scores did not change significantly in either group. Somnolence was more frequent with clozapine than with placebo.. Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function, and the effect wears off once the treatment stops.

Topics: Aged; Clozapine; Dose-Response Relationship, Drug; Double-Blind Method; Feasibility Studies; Female; Follow-Up Studies; GABA Antagonists; Humans; Levodopa; Male; Parkinson Disease; Prospective Studies; Psychoses, Substance-Induced

To examine the long-term outcome of PD patients with psychosis requiring antipsychotic therapy; to explore predictors of mortality, nursing home placement, dementia, and persistent psychosis; and to compare outcomes of those with persistent psychosis vs those whose psychosis resolved.. Baseline data available from 59 patients enrolled in the PSYCLOPS (PSychosis and CLOzapine in PD Study) trial included age, age at onset of PD, duration of PD and psychosis, character of psychosis, medications, living setting, and scores for Mini-Mental State Examination (MMSE), Unified Parkinson's Disease Rating Scale, Hoehn and Yahr Scale, and Clinical Global Impression Scale. Longitudinal data were collected 26 months later regarding four outcomes: death, nursing home placement, diagnosis of dementia, and persistence of psychosis. Logistic regression was used to explore whether any baseline characteristics were associated with an increased likelihood of one of these outcomes.. At baseline, 56% of patients had an MMSE score of <25, 12% were in a nursing home, 95% had hallucinations, and 60% had paranoia. On follow-up, 25% were dead, nursing home placement occurred in 42%, psychosis was persistent in 69%, and dementia was diagnosed in 68%. Select baseline characteristics predicted individual outcomes: Nursing home placement was associated with the presence of paranoia and older age; persistent psychosis was associated with younger age at onset of PD and longer disease duration; dementia was associated with older age at PD onset and lower initial MMSE score; no characteristics predicted death. Whether psychosis persisted or not had no significant effect on the development of the other three outcomes. The prevalence of hallucinations at follow-up was not different between groups currently receiving antipsychotics vs those on no treatment.. Psychosis in PD requiring antipsychotic therapy is frequently associated with death, nursing home placement, development and progression of dementia, and persistence of psychosis. Still, it appears the prognosis has improved with atypical antipsychotic therapy based on the finding that 28% of NH patients died within 2 years compared with 100% in a previous study done prior to availability of this treatment.

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Double-Blind Method; Female; Hallucinations; Humans; Longitudinal Studies; Male; Nursing Homes; Parkinson Disease; Psychotic Disorders; Treatment Outcome

This study investigated the efficacy and safety of quetiapine versus clozapine in parkinsonian patients with dopaminergic psychosis. All patients fulfilling the inclusion criteria were randomly assigned to receive either quetiapine or clozapine. The duration of the trial was 12 weeks. The severity of psychosis was assessed using the BPRS and the Clinical Global Impression Scale-Severity subscale (CGI-S). The UPDRS III was used to monitor the progression of PD during the study period. Twenty patients, 10 on clozapine, and 10 on quetiapine, completed the study. The psychopathological state, as assessed by the BPRS and by the CGI-S, improved significantly ( p<0.001) from baseline in both treatment groups. No differences were found between clozapine and quetiapine at each assessment time. The UPDRS score decreased significantly ( p<0.05) in the clozapine group, while was almost unchanged in the quetiapine group.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Disease Progression; Dopamine Agonists; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate

To report the results of the 12-week, prospective, open label extension of the 4-week, multicenter, placebo-controlled, double-blind PSYCLOPS (PSYchosis and CLOzapine in the treatment of Parkinsonism) trial. This extension examined the chronic safety and efficacy of clozapine in the treatment of drug-induced psychosis in Parkinson's disease (PD).. Psychosis is a serious late complication of PD and may be a harbinger to increased mortality. Clozapine, the first atypical antipsychotic, was shown in several small open label studies to improve psychosis without worsening of motor symptoms. This was recently confirmed in the double-blind PSYCLOPS trial.. The 53 patients who completed the double-blind portion of PSYCLOPS were evaluated on their original randomized treatment (clozapine or placebo), then had study medication stopped. All were started on clozapine. The patients from both treatment groups were evaluated every 4 weeks over a 12-week period using standardized measures for psychosis and PD.. The mean dose of clozapine was 28.78 mg/day. Those originally treated with placebo improved significantly in Brief Psychiatric Rating Scale and clinical global scores for psychosis to the same degree as the group originally randomized to clozapine in the double-blind study. Both groups maintained their response to week 16 (end of the combined double-blind and open label portions). There was no worsening of motor features as measured by the Unified Parkinson's disease rating scale. Eighteen patients were either hospitalized or died during the trial. The most common reasons were pulmonary.. Low-dose clozapine is effective in treating drug-induced psychosis without worsening motor features of PD, and the response is maintained for at least 4 months. Patients with psychosis and PD were previously described as a group with high risk for morbidity and mortality. The high risk continues despite antipsychotic therapy.

Topics: Antiparkinson Agents; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Double-Blind Method; Humans; Parkinson Disease; Prospective Studies; Psychoses, Substance-Induced; Treatment Outcome

The authors compared efficacy and safety of risperidone and clozapine for the treatment of psychosis in a double-blind trial with 10 subjects with Parkinson's disease (PD) and psychosis. Mean improvement in the Brief Psychiatric Rating Scale psychosis score was similar in the clozapine and the risperidone groups (P=0.23). Although the mean motor Unified Parkinson's Disease Rating Scale score worsened in the risperidone group and improved in the clozapine group, this difference did not reach statistical significance. One subject on clozapine developed neutropenia. In subjects with PD, risperidone may be considered as an alternative to clozapine because it is as effective for the treatment of psychoses without the hematologic, antimuscarinic, and seizure side effects. However, risperidone may worsen extrapyramidal symptoms more than clozapine and therefore must be used with caution.

Topics: Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Double-Blind Method; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Risperidone

To compare olanzapine and clozapine for safety and efficacy measures of psychosis and motor function in patients with PD and chronic hallucinations.. Hallucinations occur in approximately one third of patients with PD treated chronically with dopaminergic drugs. Although clozapine is known to be an effective antipsychotic agent that does not significantly exacerbate parkinsonism, its use requires frequent blood count assessment. Olanzapine is another novel antipsychotic that is not associated with blood dyscrasia, and if equally effective could become the preferred drug for treating hallucinations in subjects with PD.. A randomized, double-blind, parallel comparison of olanzapine and clozapine in patients with PD with chronic hallucinations was conducted. The primary outcome measure was the Scale for the Assessment of Positive Symptoms (SAPS) for psychotic symptoms. The Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale was used as a secondary outcome measure and as a safety monitoring tool.. After 15 patients had completed the study, safety stopping rules were invoked because of exacerbated parkinsonism in olanzapine-treated subjects. UPDRS motor impairment scores from baseline to study end significantly increased with olanzapine treatment, and change scores between the olanzapine and clozapine groups significantly differed. The primary clinical domains responsible for the motor decline were gait and bradykinesia. Even with a smaller patient number than originally anticipated, clozapine significantly improved hallucinations and overall behavioral assessment, whereas olanzapine had no effect.. At the doses studied, olanzapine aggravates parkinsonism in comparison with clozapine and should not be regularly used in the management of hallucinations in patients with PD.

Topics: Aged; Behavior; Benzodiazepines; Clozapine; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Movement; Olanzapine; Parkinson Disease; Pirenzepine

Drug-induced psychosis is a difficult problem to manage in patients with Parkinson's disease. Multiple open-label studies have reported that treatment with clozapine at low doses ameliorates psychosis without worsening parkinsonism.. We conducted a randomized, double-blind, placebo-controlled trial of low doses of clozapine (6.25 to 50 mg per day) in 60 patients at six sites over a period of 14 months. The patients (mean age, 72 years) had idiopathic Parkinson's disease and drug-induced psychosis of at least four weeks' duration. All the patients continued to receive fixed doses of antiparkinsonian drugs during the four weeks of the trial. Blood counts were monitored weekly in all the patients.. The mean dose of clozapine was 24.7 mg per day. The patients in the clozapine group had significantly more improvement than those in the placebo group in all three of the measures used to determine the severity of psychosis. The mean (+/-SE) scores on the Clinical Global Impression Scale improved by 1.6+/-0.3 points for the patients receiving clozapine, as compared with 0.5+/-0.2 point for those receiving placebo (P<0.001). The score on the Brief Psychiatric Rating Scale improved by 9.3+/-1.5 points for the patients receiving clozapine, as compared with 2.6+/-1.3 points for those receiving placebo (P=0.002). The score on the Scale for the Assessment of Positive Symptoms improved by 11.8+/-2.0 points for the patients receiving clozapine, as compared with 3.8+/-1.9 points for those receiving placebo (P=0.01). Seven patients treated with clozapine had an improvement of at least three on the seven-point Clinical Global Impression Scale, as compared with only one patient given placebo. Clozapine treatment improved tremor and had no deleterious effect on the severity of parkinsonism. In one patient, clozapine was discontinued because of leukopenia.. Clozapine, at daily doses of 50 mg or less, is safe and significantly improves drug-induced psychosis without worsening parkinsonism.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Double-Blind Method; Female; Humans; Male; Parkinson Disease; Psychoses, Substance-Induced; Treatment Outcome

Topics: Aged; Antipsychotic Agents; Clozapine; Double-Blind Method; Humans; Parkinson Disease; Psychoses, Substance-Induced

The aim of this study was to investigate the clinical efficacy of clozapine, an atypical neuroleptic, on L-dopa induced dyskinesias of Parkinson's disease.. In an open study, a group of 10 PD patients was treated with low dosage clozapine (mean 30 mg/day) for a 4-month period and L-dopa dyskinesias were evaluated in basal conditions and during clozapine treatment after the usual morning dose of clozapine. We utilized the AIMS for evaluation of dyskinesias and UPDRS for the assessment of motor performances.. Clozapine produced a significant (P<0.05) reduction of dyskinesias 1 week after the therapy onset. This effect was more pronounced at the end of the 2nd week and remained stable through the following months. We did not observe significant variations of motor performances.. A low dose of clozapine appears to be beneficial for patients with L-dopa induced dyskinesias that do not respond to other drugs and therapeutic measures.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Antiparkinson Agents; Clozapine; Dopamine Antagonists; Dyskinesia, Drug-Induced; Humans; Levodopa; Middle Aged; Parkinson Disease; Severity of Illness Index; Treatment Outcome

Four open-label studies have reported beneficial effects of clozapine on the tremor of idiopathic Parkinson's disease (PD). We performed a double-blind crossover trial with a 2-week washout, comparing low-dose clozapine to benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and 19 completed the study. Benztropine and clozapine were equally effective in improving tremor and the motor score of the United Parkinson's Disease Rating Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse events were experienced with each drug, but leukopenia was not encountered. We conclude that the atypical antipsychotic drug clozapine is helpful in the treatment of tremor in PD and should be considered when all other drug therapies fail.

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Benztropine; Clozapine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Parkinson Disease; Treatment Outcome; Tremor

The effects of the acute administration of clozapine on parkinsonian mixed tremor (i.e., resting and postural tremors) were evaluated to establish clozapine's predictive value for long-term response and to determine if there is a difference in the pharmacologic responses of the two tremors. We also investigated the correlation between reduction of tremor and induction of sedation after acute and chronic administration of clozapine. Clozapine (12.5 mg) or placebo were administered po in a double-blind manner to 17 PD patients with mixed L-dopa-resistant tremors. Two patients did not reach 50% improvement and were considered nonresponders. The remaining 15 patients reported moderate to marked reduction of tremor. Responsive patients in the acute test moved on to a long-term, open clozapine add-on study receiving an average daily dose +/- SD of 45 +/- 9.6 mg for a period of 15.5 +/- 8.3 months. A significant reduction of both resting (p < 0.05) and postural (p < 0.05) tremors was observed under clozapine from the first week of treatment through the entire period of the study. There was no statistically significantly difference between the degree of improvement for resting and postural tremors after either single or chronic clozapine administration. Sedation was the only side effect reported after clozapine; however, the time courses of sedation and tremor reduction did not coincide in the acute or in the chronic experimental paradigm, where it decreased considerably in a few weeks in all patients. During long-term clozapine treatment, neither systemic side effects nor worsening of motor disability scores were noted. Thus we wish to propose an acute test or a therapeutic attempt, or both, with clozapine before defining a case of mixed parkinsonian tremor as resistant tremor and therefore resorting to a neurosurgical approach.

Topics: Aged; Antipsychotic Agents; Clozapine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Parkinson Disease; Posture; Rest; Severity of Illness Index; Treatment Outcome; Tremor

The records of 49 patients with Parkinson's disease and psychosis who were treated with clozapine for up to 18 months were reviewed. Average starting dose of clozapine was 16 mg. Average maximum dose was 39 mg. The psychotic symptoms improved in 76% of the patients at 3 months, and response to clozapine within the first year ranged from 71% to 80%. This response allowed a maximization of levodopa dose. Improvements in scores on the Unified Parkinson's Disease Rating Scale and tremor subscale were seen in some patients but were not statistically significant. This study, the largest of its kind to date, suggests that clozapine is well tolerated and effective in treating psychosis in patients with Parkinson's disease.

Topics: Aged; Antipsychotic Agents; Clozapine; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Retrospective Studies

Twenty patients with Parkinson's disease (PD), who developed delusions and psychotic behavior, underwent electroencephalogram (EEG) recordings before and during treatment with low-dose clozapine. Resolution of the psychotic features was observed in all cases. The EEG was unaltered in 15, whereas five patients exhibited increased generalized or focal slowing when compared with the pretreatment tracings. These findings contrast with the high incidence of EEG abnormalities, including epileptiform activity, which are observed when larger doses of clozapine are used in schizophrenic patients, but they underscore that even in low doses, clozapine may cause EEG changes.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Electroencephalography; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders

The purpose of this study was to determine the plasma level of clozapine and its metabolite, N-desmethylclozapine, in Parkinson's disease patients with L-DOPA-induced psychosis responsive to clozapine. The psychotic symptoms of the three patients studied responded to low doses of clozapine with plasma levels of clozapine between 4.5 and 16.1 ng/ml and N-desmethylclozapine between 2.6 and 6.1 ng/ml, much below the plasma clozapine levels usually found in clozapine-treated refractory schizophrenia or affective disorders (range 100 to 687 ng/ml). Possible mechanisms that may account for clozapine's antipsychotic action in dopaminomimetic-induced psychosis in Parkinson's disease, including serotonin2A (5-HT2A) and dopamine D4 receptor blockade, at plasma levels that would be ineffective in refractory schizophrenia, are discussed. It is suggested that 5-HT2A receptor blockade is the most likely basis for the effectiveness of clozapine in L-DOPA psychosis.

Topics: Aged; Clozapine; Female; Humans; Levodopa; Male; Parkinson Disease; Psychoses, Substance-Induced

Delusions and other manifestations of psychotic behavior are common side effects in Parkinson's disease (PD) patients chronically treated with dopaminergic drugs. Clozapine, a dibenzodiazepine derivative, is an antipsychotic drug largely devoid of extrapyramidal side effects. We evaluated the effects of low doses of clozapine on the mental and motor functions in PD patients requiring antipsychotic treatment. Twenty-seven PD patients taking dopaminergic drugs and who had psychotic behavior received clozapine at 12.5 to 75 mg/d. Fifteen patients received clozapine for 1 to 11 months (mean, 6.8 months) and seven received it for 12 to 24 months (mean, 18 months). No patient exhibited motor deterioration, and the psychotic features disappeared immediately, allowing discontinuation of clozapine after several months in 10 patients. Fifteen patients are still receiving clozapine and are free of psychiatric symptoms. The clozapine treatment was discontinued after 5 days (25 mg/d) in two patients because of somnolence. No patient developed neutropenia. Clozapine in low doses is effective in the treatment of drug-induced delusions and hallucinations in PD.

Topics: Aged; Aged, 80 and over; Clozapine; Female; Humans; Levodopa; Male; Mental Disorders; Middle Aged; Parkinson Disease

We treated 17 patients with Parkinson's disease (PD) complicated by psychosis with the atypical antipsychotic drug, clozapine, for 6 to 24 months (mean, 15 months) in a prospective, open-label trial. At 3-month intervals we evaluated patients, using a simplified brief Psychiatric Rating Scale (PRS), the motor examination portion of the Unified Parkinson's Disease Rating Scale, and the Mini-Mental State Examination (MMSE). Mean PRS score was significantly improved when compared with baseline over 1 year (p < 0.01) and nonsignificantly improved for the second year. We maintained the levodopa dose at levels that were 17 to 68% higher than baseline, and the mean motor examination score improved by 11 to 22% in the first 15 months. Clozapine dosage utilized in the trial ranged from 6.25 mg every other day to 150 mg/d. Adverse effects, including sedation and confusion, were common. These results demonstrate that clozapine therapy can be effective in treating psychosis in PD patients over 1 to 2 years. The decline in efficacy in the second year was most likely related to an increase in daily levodopa dose, progression of dementia (illustrated by a decline in MMSE score), and an inability of PD patients to tolerate higher doses of clozapine.

Topics: Aged; Aged, 80 and over; Clozapine; Female; Humans; Male; Middle Aged; Parkinson Disease; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders

Clozapine has been shown not only to be effective in ameliorating dopaminomimetic psychosis but to improve parkinsonian symptomatology. Six parkinsonian patients with motor fluctuations under levodopa treatment and severe interdose "off" periods (believed to be mediated by an inhibitory effect of subthreshold levels of levodopa) underwent a trial of clozapine. The effects of this drug on levodopa response were measured by means of an acute levodopa test both before and after receiving clozapine. After 1 month of treatment, clozapine 25 mg/day reduced parkinsonian scores at all stages of the evaluation (pre-levodopa "off," "on," and interdose "off"). The effect was consistently more significant for the interdose "off." Clozapine could be exerting its beneficial effects through the inhibition of an inhibitory effect mediated by low-level dopaminergic stimulation, thus behaving as an apparent anti-parkinsonian drug.

Topics: Aged; Clozapine; Drug Interactions; Drug Therapy, Combination; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Receptors, Dopamine; Severity of Illness Index

Topics: Adult; Aged; Clozapine; Female; Humans; Male; Mental Status Schedule; Middle Aged; Parkinson Disease; Psychomotor Performance; Psychotic Disorders

Clozapine has gained acceptance as an antipsychotic in treatment-resistant schizophrenia. Its low propensity to induce extrapyramidal side effects makes clozapine an attractive treatment for patients with Parkinson's disease and dopaminomimetic psychosis. Recent evidence demonstrates that Parkinson's patients are exquisitely sensitive to both the antipsychotic and the potential extrapyramidal effects of clozapine. The uncontrolled studies suggest that low-dose clozapine may be efficacious in this population. The dose range, side effect profiles, and length of treatment varied in these reports.. We report our experience with five patients with Parkinson's disease and psychosis who were treated with clozapine in an open trial.. Three patients were successfully treated with clozapine (25-100 mg/day, mean = 66.7 mg) without worsening their parkinsonism. Adverse effects unrelated to the motor disability required discontinuation of clozapine in the other two patients. At 1- to 2-year follow-up, each patient had required increased dosages of clozapine (75-150 mg/day, mean = 125 mg) for continued management of their psychosis and parkinsonism. The higher dose range was well tolerated.. These results suggest that clozapine may effectively treat psychosis in Parkinson's disease.

Topics: Aged; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Male; Middle Aged; Neurocognitive Disorders; Parkinson Disease; Psychoses, Substance-Induced

In a double-blind placebo-controlled study, we evaluated the effects of clozapine (75 to 250 mg/day, mean 170.8) on dopaminomimetic psychosis and parkinsonian disability. Clozapine prevented deterioration of psychosis during the increase of dopaminomimetics in the 3 patients who completed the study. Worsening of parkinsonism occurred in 3 of the 6 patients. In the dosage used, clozapine's usefulness was limited by its propensity to produce sedation, confusion, and increased parkinsonism.

Topics: Aged; Aged, 80 and over; Clozapine; Dibenzazepines; Dopamine Agents; Double-Blind Method; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Randomized Controlled Trials as Topic; Sleep

After preliminary observations on 5 psychotic and 7 nonpsychotic parkinsonian patients had shown unexpected impressive beneficial effects of the atypical neuroleptic clozapine on tremor, an open clinical study including 12 patients was started. Under a dosage-range approximately 25-50 mg/day significant reduction of tremor intensity and tremor related functional disability (CURS, Sweet's scale) was achieved. Akinesia was not deteriorated, initial fatigue disappeared spontaneously. Pharmacological mode of action of clozapine's antitremor effect remains unclear. Its broad receptor binding spectrum with strong antiserotonergic properties might here play a major role.

Topics: Aged; Aged, 80 and over; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Parkinson Disease; Tremor

In an open trial 25 tremor patients were treated with clozapine in small doses (18-75 mg per day). The effect was measured with a new movement analyzer. Nine of 12 essential tremor patients were greatly improved. In six of nine patients with Parkinson tremor and in two combined essential tremor/Parkinson tremor patients tremor almost disappeared. Sedation is a major side effect, but decreases in most patients with time. The risk of agranulocytosis makes blood control necessary.

Topics: Alcoholism; Clinical Trials as Topic; Clozapine; Dibenzazepines; Double-Blind Method; Humans; Parkinson Disease; Tremor

1. Human neuroleptogenic EPMS-disturbances are reversed by clozapine in animal experiments and in clinical use. This is consistent with the central anticholinergic efficacy of clozapine. 2. Clozapine seems to be a favourable concomitant medication when high dosage therapy of neuroleptics is applied--or at the incidence of dyskinesia.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Clozapine; Dibenzazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Parkinson Disease; Placebos

Pimavanserin is the only approved drug for Parkinson's disease psychosis (PDP) and is an increasingly used therapy where available. Clozapine has proven efficacy for PDP but is much less commonly used secondary to frequent blood tests to monitor for agranulocytopenia. We identified 27 patients with PDP (72 ± 7.3 years, 11 (41%) female), with an inadequate response to pimavanserin, who subsequently started clozapine. The final mean daily dose of clozapine was 49.5 mg [range 25-100] at night, and mean duration of follow-up was 17 months [range: 2-50 months]. Patients reported clozapine to be markedly effective in 11 (41%), moderately effective in 6 (22%), somewhat effective in 5 (18%). No patient reported that it was ineffective, but 5 (19%) had inadequate follow-up. Clozapine should be considered in pimavanserin refractory psychosis.

Topics: Antipsychotic Agents; Clozapine; Female; Humans; Male; Parkinson Disease; Psychotic Disorders

The use of antipsychotics in persons with Parkinson's disease (PD) is common, although their use may aggravate the symptoms of PD. Clozapine and quetiapine are the only antipsychotics recommended in PD treatment guidelines. Information on factors associated with initiation of antipsychotics is needed. We investigated whether recent hospitalization is associated with initiation of antipsychotics in persons with PD, and whether discharge diagnoses differ between those who had antipsychotics initiated and those who did not.. Nested case-control study in the nationwide register-based Finnish Study on Parkinson's disease (FINPARK).. The FINPARK study includes 22,189 persons who received an incident, clinically verified PD diagnosed during 1996-2015 and were community-dwelling at the time of diagnosis. The cases were 5088 persons who had antipsychotics initiated after PD diagnosis, identified with 1-year washout. The controls were 5088 age-, sex-, and time from PD diagnosis-matched persons who did not use antipsychotics on the matching date (antipsychotic purchase date). Recent hospitalization was defined as discharge in the 2-week period preceding the matching date.. Associations were investigated with conditional logistic regression.. Quetiapine was the most commonly initiated antipsychotic (72.0% of cases), followed by risperidone (15.0%). Clozapine was initiated rarely (1.1%). Recent hospitalization associated strongly with antipsychotic initiation [61.2% of cases and 14.9% of controls, odds ratio (OR) 9.42, 95% CI 8.33-10.65], and longer hospitalizations were more common among cases. PD was the most common discharge diagnosis category (51.2% of hospitalized cases and 33.0% controls), followed by mental and behavioral disorders (9.3%) and dementia (9.0%) among cases. Antidementia and other psychotropic medication use were more common among cases.. These results suggest that antipsychotics were initiated because of neuropsychiatric symptoms or aggravation of those symptoms. Antipsychotics should be prescribed after careful consideration to avoid adverse effects in persons with Parkinson's disease.

Topics: Antipsychotic Agents; Case-Control Studies; Clozapine; Hospitalization; Humans; Parkinson Disease; Quetiapine Fumarate

Topics: Clozapine; Humans; Neurodegenerative Diseases; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; United States

Dopamine receptor blocking atypical antipsychotic (DRB-AAP) use has previously been associated with increased adverse effects and mortality risk among persons with Parkinson disease (PD). Pimavanserin, the only AAP indicated for PD psychosis in the U.S., is a serotonin receptor inverse agonist/antagonist with no known DRB activity. Early observational data have reported inconsistent findings regarding mortality risk associated with pimavanserin. The objective of this study was to estimate all-cause mortality risks of pimavanserin as compared to DRB-AAPs.. We conducted a retrospective cohort study using a large U.S. commercial insurance database. Cox proportional hazards models were used to compare all-cause mortality risks between propensity score-matched groups of PD patients who were new users of pimavanserin or a DRB-AAP, further dividing DRB-AAPs into preferred (quetiapine, clozapine) and non-preferred (other remaining AAPs).. We identified 775, 4,563, and 1,297 individuals on pimavanserin, preferred, and non-preferred DRB-AAPs, respectively. There was no difference in mortality risk for pimavanserin vs. preferred DRB-AAPs [adjusted hazard ratio (aHR) 0.99, 95% CI: 0.81-1.20], or pimavanserin vs. non-preferred DRB-AAPs (aHR 0.98, 95% CI: 0.79-1.22) in intention-to-treat analyses.. Mortality risk among PD patients using AAPs did not differ by antipsychotic drug categorization based on mechanism of action. Research on the comparative efficacy and morbidity of AAPs, and the mortality associated with psychosis itself is needed to guide clinical decision-making in the PD population.

Topics: Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Serotonin; Retrospective Studies

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Case-Control Studies; Clozapine; Female; Humans; Longitudinal Studies; Male; Odds Ratio; Parkinson Disease; Pneumonia; Risk Factors; Taiwan

Topics: Antipsychotic Agents; Clozapine; COVID-19; Humans; Pandemics; Parkinson Disease; Psychotic Disorders; SARS-CoV-2

Coexistence of idiopathic Parkinson's disease (iPD) and schizophrenia can pose great diagnostic and therapeutic challenges because of their pathophysiology. Our case highlights such challenges in management. We present a case of 73-year-old man who had parkinsonism for last several years and was also diagnosed with schizophrenia. Due to lack of collateral information about the onset of symptoms and clinical course, it was difficult to distinguish iPD from neuroleptic-induced parkinsonism. Even though, certain clinical findings may help to differentiate between the two conditions, single positron emission computerized tomography/DatScan was used to confirm the diagnosis of iPD. Treatment of coexisting iPD and schizophrenia can be challenging, and a delicate pharmacologic balance must be maintained to ensure adequate symptomatic control. Current evidence suggests that clozapine is a better choice for managing psychosis in these patients due to its unique receptor profile and better safety data.

Topics: Aged; Clozapine; Humans; Male; Parkinson Disease; Parkinson Disease, Secondary; Positron-Emission Tomography; Schizophrenia

Topics: Agammaglobulinemia; Antipsychotic Agents; Betacoronavirus; Clozapine; Contraindications, Drug; Coronavirus Infections; COVID-19; Drug Monitoring; Drug Prescriptions; Humans; Pandemics; Parkinson Disease; Pneumonia, Aspiration; Pneumonia, Viral; Psychotic Disorders; SARS-CoV-2; Schizophrenia; Sialorrhea

Parkinson's disease (PD), classically defined as a progressive motor disorder accompanied with dopaminergic neuron loss and presence of Lewy bodies, is the second most common neurodegenerative disease. PD also has various non-classical symptoms, including cognitive impairments. In addition, inflammation and astrogliosis are recognized as an integral part of PD pathology. The hippocampus (Hipp) is a brain region involved in cognition and memory, and the neuropeptide orexin has been shown to enhance learning and memory. Previous studies show impairments in Hipp-dependent memory in a transgenic mouse model of Parkinson's disease (A53T mice), and we hypothesized that increasing orexin tone will reverse this. To test this, we subjected 3, 5, and 7-month old A53T mice to a Barnes maze and a contextual object recognition test to determine Hipp dependent memory. Inflammation and astrogliosis markers in the Hipp were assessed by immuno-fluorescence densitometry. The data show that early cognitive impairment is coupled with an increase in expression of inflammatory and astrogliosis markers. Next, in two separate experiments, mice were given intra-hippocampal injections of orexin or chemogenetic viral injections of an orexin neuron specific Designer Receptor Exclusively Activated by Designer Drug (DREADD). For the pharmacological approach mice were intracranially treated with orexin A, whereas the chemogenetic approach utilized clozapine N-oxide (CNO). Both pharmacological orexin A intervention as well as chemogenetic activation of orexin neurons ameliorated Hipp-dependent early memory impairment observed in A53T mice. This study implicates orexin in PD-associated cognitive impairment and suggests that exogenous orexin treatment and/or manipulation of endogenous orexin levels may be a potential strategy for addressing early cognitive loss in PD.

Topics: Animals; Calcium-Binding Proteins; Cell Count; Clozapine; Disease Models, Animal; Glial Fibrillary Acidic Protein; Gliosis; Hippocampus; Inflammation; Injections; Male; Maze Learning; Memory Disorders; Mice, Inbred C57BL; Mice, Transgenic; Microfilament Proteins; Orexins; Parkinson Disease; Reproducibility of Results

Parkinson's disease is a chronic multi-system disease that can cause motor and non-motor symptoms, cognitive changes and variably effective medications. Optimal management of the condition requires a multi-disciplinary team of healthcare professionals to work closely with the patient and their carers. The National Institute for Health and Care Excellence published updated guidelines on managing Parkinson's disease in adults in 2017. Here we discuss the implications of this guidance to current healthcare professionals involved in the care of people with Parkinson's disease. The guidance highlights the importance of clear communication with people with Parkinson's disease. We discuss examples of this, including providing a point of contact with specialist services for people with Parkinson's disease and ensuring information about the risks of impulse control disorders are given to people on dopaminergic therapy. The breadth of services required by people with Parkinson's disease is also described, including the need for access to physiotherapy, occupational therapy and speech and language therapy as well as treatment monitoring services for Clozapine. In addition, we emphasise the continued importance of ensuring people with Parkinson's disease receive their medications on time when in hospital or a care home.

Topics: Antiparkinson Agents; Clozapine; Hallucinations; Humans; Levodopa; Parkinson Disease; Patient Care Team; Patient Education as Topic; Practice Guidelines as Topic

Psychotic disorders in Parkinson's disease (PDPD) are common and significantly influence the quality of life and disability level. The pathogenesis of PDPD is complex and not yet fully understood. Taking into consideration the features of the Parkinson's disease (usually older patients with a risk of cognitive decline), and the pharmacodynamics of the antiparkinsonian and traditional antipsychotic drugs, the management of PDPD is a challenging issue of clinical neurology and psychiatry. In this systematic review, scientific publications for the period 2014-2016 were analyzed within two bibliographic databases: MEDLINE/PubMed and eLIBRARY.RU. Additionally, the guidelines of the International Parkinson and Movement Disorders Society, American Academy of Neurology and European Academy of Neurology were included in the analysis. Clozapine is recommended to use in the treatment of PDPD, quetiapine is possible to use, pimavanserin will probably become a remedy of choice. Nonpharmacological approaches have positive effects on the general condition of the patients with PDPD, however the efficacy of such approaches to treat psychosis is unclear.. Психотические расстройства при болезни Паркинсона (ПРБП) отмечаются у большого числа пациентов. Они оказывают значительное влияние на качество жизни и уровень инвалидизации. Патогенез ПРБП является сложным и до конца не изученным. Принимая во внимание специфику БП (как правило, пациенты пожилого возраста с риском появления когнитивных нарушений), а также фармакодинамические особенности антипаркинсонических и классических антипсихотических средств, лечение ПРБП требует особого внимания неврологов и психиатров. Представлен систематический обзор, в котором обобщены результаты научных публикаций за период 2014-2016 гг. в двух библиографических базах данных: MEDLINE/PubMed и eLIBRARY.RU, а также клинических рекомендаций Международного общества болезни Паркинсона и нарушений движения, Американской и Европейской академий неврологии. Из антипсихотических средств клозапин является препаратом, рекомендованным к применению, кветиапин - препарат, который признается возможным к применению, пимавансерин, вероятно, станет одним из препаратов выбора в терапии ПРБП. Нефармакологические методы лечения оказывают положительный эффект в плане улучшения общего состояния пациентов с ПРБП, однако их эффективность по лечению собственно ПРБП остается неясной.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Piperidines; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Urea

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Female; Humans; Male; Neutropenia; Parkinson Disease; Psychotic Disorders

Transplantation of human pluripotent stem cell (hPSC)-derived neurons is a promising avenue for treating disorders including Parkinson's disease (PD). Precise control over engrafted cell activity is highly desired, as cells do not always integrate properly into host circuitry and can cause suboptimal graft function or undesired outcomes. Here, we show tunable rescue of motor function in a mouse model of PD, following transplantation of human midbrain dopaminergic (mDA) neurons differentiated from hPSCs engineered to express DREADDs (designer receptors exclusively activated by designer drug). Administering clozapine-N-oxide (CNO) enabled precise DREADD-dependent stimulation or inhibition of engrafted neurons, revealing D1 receptor-dependent regulation of host neuronal circuitry by engrafted cells. Transplanted cells rescued motor defects, which could be reversed or enhanced by CNO-based control of graft function, and activating engrafted cells drives behavioral changes in transplanted mice. These results highlight the ability to exogenously and noninvasively control and refine therapeutic outcomes following cell transplantation.

Topics: Animals; Cell Differentiation; Cell Line; Clozapine; Disease Models, Animal; Dopaminergic Neurons; Drug Design; Excitatory Postsynaptic Potentials; gamma-Aminobutyric Acid; Glutamates; Human Embryonic Stem Cells; Humans; Mesencephalon; Mice; Motor Activity; Neostriatum; Neurons; Parkinson Disease; Pluripotent Stem Cells; Receptors, Dopamine D1; Stem Cell Transplantation

Topics: Aged; Clozapine; GABA Antagonists; Humans; Intracranial Thrombosis; Male; Parkinson Disease

Capgras delusion is a delusional misidentification syndrome, in which the patient is convinced that someone that is well known to them, usually a close relative, has been replaced by an impostor or double. Although it has been frequently described in psychotic syndromes, including paranoid schizophrenia, over a third of the documented cases of Capgras delusion are observed in patients with organic brain lesions or neurodegenerative disease, including Parkinson's Disease. Variants of Capgras involving animals or inanimate objects have also been described. The etiology of Capgras in Parkinson's remains unclear, but may arise from a combination of factors, such as frontal lobe dysfunction and dopaminergic medication.. We present the case of a 53-year old right-handed female with Parkinson's disease who developed Capgras delusion during treatment with dopamine agonists and Levodopa/Carbidopa. She became convinced that her pet dogs and the plants in her garden had been substituted by identically looking ones. Our patient was initially treated with Quetiapine, with no improvement, and subsequently treated with Clozapine, which lead to partial regression of her symptoms. Neuropsychological Evaluation showed Mild Cognitive Impairment in Executive Functions.. Given the clinical history, onset and evolution of symptoms we believe our patient's delusion resulted from the overlap of dopaminergic medication and Mild Cognitive Impairment in executive functions. Zoocentric Capgras, the variant we describe, has been rarely described in scientific literature, and we believe it is of interest due to its unusual characteristics.

Topics: Animals; Antiparkinson Agents; Antipsychotic Agents; Capgras Syndrome; Carbidopa; Clozapine; Cognitive Dysfunction; Delusions; Dibenzothiazepines; Dogs; Dopamine Agonists; Drug Therapy, Combination; Female; Humans; Levodopa; Parkinson Disease; Pets; Plants; Quetiapine Fumarate

The comorbidity of schizophrenia and idiopathic Parkinson's disease (IPD) is illustrated by a case description of a schizophrenic patient who develops motor symptoms finally diagnosed and treated as comorbid IPD. Several aspects of the clinical challenges of this comorbidity are discussed and an overview of earlier reported cases is presented. IPD must be distinguished from neuroleptic-induced parkinsonism by clinical course and characteristics. A SPECT scan is helpful for diagnosis. We recommend antiparkinsonian treatment to be prescribed only with the protection of antipsychotic agents, of which clozapine and quetiapine are the best choices.

Topics: Antiparkinson Agents; Antipsychotic Agents; Brain; Carbidopa; Catechols; Clozapine; Diagnosis, Differential; Fluphenazine; Follow-Up Studies; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease; Schizophrenia; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Topics: Aged, 80 and over; Antipsychotic Agents; Clozapine; Fatal Outcome; Female; Humans; Neuroleptic Malignant Syndrome; Parkinson Disease

To examine our eight year clinic-based experience in a Parkinson's disease expert clinical care center using clozapine as a treatment for refractory psychosis in Parkinson's disease (PD).. The study was a retrospective chart review which covered eight years of clozapine registry use. Statistical T-tests, chi-square, correlations and regression analysis were used to analyze treatment response for potential associations of age, disease duration, and Hoehn & Yahr (H&Y) score, and degree of response to clozapine therapy.. There were 36 participants included in the analysis (32 PD, 4 parkinsonism-plus). The characteristics included 30.6% female, age 45-87 years (mean 68.3±10.15), disease duration of 17-240 months (mean 108.14±51.13) and H&Y score of 2 to 4 (mean 2.51±0.51). The overall retention rate on clozapine was 41% and the most common reasons for discontinuation were frequent blood testing (28%), nursing home (NH) placement (11%) and leucopenia (8%). Responses to clozapine across the cohort were: complete (33%), partial (33%), absent (16%), and unknown (16%). Age (r = -0.36, p<0.01) and H&Y score (r = -0.41, p<0.01) were shown to be related to response to clozapine therapy, but disease duration was not an associated factor (r = 0.21, p>0.05).. This single-center experience highlights the challenges associated with clozapine therapy in PD psychosis. Frequent blood testing remains a significant barrier for clozapine, even in patients with therapeutic benefit. Surprisingly, all patients admitted to a NH discontinued clozapine due to logistical issues of administration and monitoring within that setting. Consideration of the barriers to clozapine therapy will be important to its use and to its continued success in an outpatient setting.

Topics: Age Factors; Aged; Aged, 80 and over; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Female; Hematologic Tests; Humans; Levodopa; Male; Medication Adherence; Middle Aged; Nursing Homes; Parkinson Disease; Psychotic Disorders; Retrospective Studies

To explore the pattern of clozapine use in persons with severe mental illness and in persons with Parkinson's disease and the characteristics associated with early discontinuation in naturalistic conditions.. A historical fixed cohort study of persons newly treated with clozapine was performed on a representative community-based sample of persons affiliated to the French health insurance system (n = 611,393). Treatment for Parkinson's disease was used as a proxy for this condition and lack of such treatment as a proxy for severe mental illness (SMI).. The prevalences of antipsychotic and clozapine use were 4.4% and <0.1% respectively. Of the 237 persons with a new outpatient prescription of clozapine, 25% were prescribed an antiparkinsonian treatment. In persons with SMI, the median duration of the index episode of clozapine treatment was 4.9 months (Interquartile range 1.0-20.5). Longer duration was independently associated with coprescription of anxiolytics or antidepressant. Few new additions of antipsychotics were observed during the clozapine episode.. Efforts have to be made to optimize clozapine treatment in real-world conditions. Considering the high frequency of persons with Parkinson's disease among clozapine users, further studies have to be performed in this population.

Topics: Adult; Affective Disorders, Psychotic; Aged; Anti-Anxiety Agents; Antidepressive Agents; Antiparkinson Agents; Antipsychotic Agents; Bipolar Disorder; Case-Control Studies; Clozapine; Cohort Studies; Female; France; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders; Schizophrenia

Psychotic symptoms in Parkinson's disease (PD) caused by dopamimetic treatment are a relevant clinical problem. As clozapine does not cause extrapyramidal side effects, it is suitable for treatment of dopamimetic psychosis. The main aim of the present study was (1) to establish an indication-specific recommendation for therapeutic reference range of clozapine among patients with dopamimetic psychosis in PD and related disorders. Secondary goals were (2) to test whether clozapine therapy is safe and calculable despite pharmacokinetic changes expected in the study population and (3) to assess influencing variables on clozapine serum levels.. We carried out a retrospective chart review of patients suffering from dopamimetic psychosis as well as Lewy body dementia treated with clozapine. We extracted demographic and clinical data as well as results from therapeutic drug monitoring that was carried out via high-performance liquid chromatography in order to analyse clozapine and norclozapine serum concentrations.. n = 35 patients could be identified and were included in the study. Mean age was 72.4 years. Clozapine treatment for patients with dopamimetic psychosis in PD and related disorders seems to be safe and calculable. Mean clozapine serum concentration was 77.9 ng/ml (SD 63.4 ng/ml). Clozapine dose is significantly correlated with serum clozapine concentration (r = 0.35; R (2) = 0.122). Women showed lower clozapine serum concentrations although they received higher weight-corrected clozapine doses.. We suggest an orienting indication-specific therapeutic reference range of 15-141 ng/ml among PD patients with dopamimetic psychosis. Therapeutic drug monitoring is recommended and might help to minimize the risk of adverse events by screening for unexpectedly high serum concentrations of clozapine.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders

Visual hallucinations (VH) are sometimes difficult to treat in patients with Lewy body dementia (LBD). We describe the concurrent use of clozapine and levodopa for the treatment of persistent VH and parkinsonism in a patient with LBD and severely increased sensitivity to antipsychotics.

Topics: Aged; Antipsychotic Agents; Brain; Clozapine; Comorbidity; Hallucinations; Humans; Levodopa; Lewy Body Disease; Male; Parkinson Disease; Treatment Outcome

There have been emerging cases of medication refractory obsessions, impulsivity, compulsivity, and/or punding in Parkinson's disease. These cases have proven difficult to treat, even for the experienced clinician. We report several medication refractory cases with a positive response to treatment with clozapine.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Compulsive Behavior; Humans; Impulsive Behavior; Male; Middle Aged; Parkinson Disease; Treatment Outcome

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease, but can lead to adverse effects including psychiatric disturbance. Little is known about the risk factors and treatment options for such effects. Here, we describe a patient who reproducibly developed stimulation-induced hypomania when using ventrally located electrodes and responded well to pharmacological intervention while leaving the stimulation parameters unchanged to preserve motor benefits. In spite of clinical remission, [¹⁵O]-positron-emission-tomography (PET) demonstrated activation patterns similar to those reported during mania. This case, therefore, highlights an important treatment option of adverse effects of DBS, but also points toward the need for investigations of its risk factors and their underlying neurobiological mechanisms.

Topics: Antimanic Agents; Bipolar Disorder; Clozapine; Deep Brain Stimulation; Humans; Male; Middle Aged; Parkinson Disease; Treatment Outcome; Valproic Acid

Topics: Aged; Bipolar Disorder; Carbamazepine; Clozapine; Deep Brain Stimulation; Female; Humans; Male; Middle Aged; Parkinson Disease

Topics: Adult; Antiparkinson Agents; Benzothiazoles; Cabergoline; Clozapine; Ergolines; Female; Gambling; Humans; Male; Middle Aged; Parkinson Disease; Pramipexole; Selegiline; Serotonin Antagonists

Topics: Catatonia; Clozapine; Family Health; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders; Substance Withdrawal Syndrome

Delusional jealousy or Othello syndrome (OS) is a well-described psychiatric disorder with paranoid features reported in both organic and functional psychoses. In organic psychoses, the disorder occurs more frequently among chronic male alcoholics and in demented patients. To date, only 2 anecdotal cases of OS have been reported in Parkinson disease (PD) during dopaminergic treatment.. To investigate the presence of OS in PD patients and to study the relationship between dopaminergic treatment, avoiding the possible influence of dementia.. Five hundred sixty-three PD patients without dementia encountered in our movement disorders practice were included in the study. All patients who developed OS were studied. Relationships between clinical and familial history and dopaminergic therapy and OS were assessed.. Six patients with OS were identified. They were all male, with a relatively recent diagnosis of PD characterized by mild-moderate motor deficit. Dopaminergic treatment had been prescribed at low dosages. Neither confusional states (including agitated confusion) nor delirium were associated with OS. The disorder became manifest mainly at time of introduction/increment of antiparkinson treatment. Invariably, OS decreased or receded after reduction/suspension of the antiparkinson drug and prescription of an atypical neuroleptic, usually clozapine or quetiapine.. We hypothesize that nondemented PD patients affected by OS do not necessarily present with severe motor complications and may well have a biologic predisposition for psychiatric disorders. In our opinion this paranoid delusion is rarely considered in PD.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Delusions; Dementia; Dibenzothiazepines; Humans; Jealousy; Male; Middle Aged; Parkinson Disease; Quetiapine Fumarate; Retrospective Studies; Schizophrenia, Paranoid

Myocarditis is a rare but life threatening adverse effect of clozapine. Some symptoms of myocarditis--elevated temperature, tachycardia and fatigue--appear commonly during the onset of treatment with clozapine and during the dose titration. We present a case of a patient with concurrent schizoaffective disorder and Parkinson's disease, who twice developed clozapine-induced myocarditis. All symptoms disappeared after the discontinuation of the drug. Early diagnosis, discontinuation of clozapine and supportive therapy of myocarditis lower the risk of a fatal outcome.

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Myocarditis; Parkinson Disease; Periodicity; Psychotic Disorders; Recurrence

Atypical antipsychotics (AA) are generally associated with weight gain. We determined body mass index (BMI) change in Parkinson's disease (PD) before and after taking AA and compared against PD controls and Alzheimer's disease (AD) patients on AA. In 66 consecutive PD subjects started on AA who had accurate weights for more than 6 months before and after initiation of AA, we compared weight change before and after AA use, against a control group of sixty-one sex-matched PD subjects, and against twenty-eight AD subjects taking AA. A linear regression model was created to compare weight changes. Fifty-nine PD subjects had complete data, quetiapine (n=53) and clozapine (n=6). The mean BMI change in the period before starting AA was 0.00 kg/m(2)/month over 1.95+/-1.41 years. After starting AA, subjects lost 0.03 kg/m(2)/month (95% CI 0.62-1.21, P<0.0001), comparing PD before AA to the same PD patients after AA. In 61 PD controls, the mean BMI loss was 0.01 kg/m(2)/month (95% CI 0.15-0.94, P=0.007) comparing PD on AA vs. PD controls. The BMI for 28 AD subjects on AA increased 0.01 kg/m(2)/month (95% CI 0.26-0.83, P<0.0001), comparing PD on AA vs. AD on AA. The weight loss seen in the PD/AA group, compared to AD, suggest uniquely altered weight homeostasis in PD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Body Mass Index; Body Weight; Case-Control Studies; Clozapine; Confidence Intervals; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Odds Ratio; Parkinson Disease; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Male; Middle Aged; Parkinson Disease

Clozapine has been used as an attempt to manage levodopa complications in advanced Parkinson's disease (PD). To investigate the use of clozapine in this context in a Brazilian sample, a retrospective chart review was carried out at the Movement Disorders Clinic from the Federal University of Minas Gerais. This study enrolled 43 PD patients who used or were in use of clozapine. Patients had a mean age of 64 years and a mean UPDRS score of 55. Clozapine was indicated for dyskinesias in 17 patients, for psychosis in 15 and for both reasons in 11. The average maximum dose was 70 mg/day. Twenty six patients used it for a mean of 3.5 years. Twenty nine presented an improvement of their condition, 9 remained clinically stable. Twenty subjects interrupted the use of clozapine, being 9 due to adverse effects. Clozapine may play a role in the management of motor and psychiatric complications in PD, but it is associated with low tolerability.

Topics: Adult; Aged; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Retrospective Studies

The authors report an improvement in delusions and hallucinations after antidepressant treatment (Clomipramine) in a parkinsonian patient with psychosis and comorbid depression. Their findings, which support a previous case treated with Citalopram, highlight the possible effectiveness of antidepressant therapy on psychotic symptoms in parkinsonian patients.

Topics: Affect; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antiparkinson Agents; Antipsychotic Agents; Clomipramine; Clozapine; Delusions; Depressive Disorder; Hallucinations; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Pergolide; Psychiatric Status Rating Scales; Psychotic Disorders

"Atypical anti-psychotics" are substances of choice in treating drug-induced psychosis (DP) in Parkinson's disease (PD). We report on four patients with DP who received treatment with ziprasidone after previously applied clozapine and quetiapine had failed. Three patients showed a significant improvement of DP, without deterioration of motor function. In one case, ziprasidone considerably increased decline in off-periods. Two patients developed pathological laughing as a possible side-effect of ziprasidone. Ziprasidone may serve as an additional "atypical anti-psychotic" for the treatment of DP in PD but can also induce deterioration of motor function.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Laughter; Levodopa; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Parkinson Disease, Secondary; Piperazines; Psychoses, Substance-Induced; Quetiapine Fumarate; Thiazoles

To determine whether psychiatrically stable patients with a history of drug-induced psychosis could be successfully weaned off their antipsychotic drug, we offered consecutive Parkinson disease (PD) patients on quetiapine or clozapine, who were free of any on-going psychosis, to be slowly weaned off their antipsychotic drug. Before the study was aborted 6 PD patients (mean age, 78 years) with an average antipsychotic exposure of 20 months (5 on quetiapine, 1 on clozapine) were enrolled. After the antipsychotic agent was discontinued, psychosis recurred in 5 of 6 patients. In 3 patients the "rebound psychosis" was worse than the original psychotic episode and required subsequent higher antipsychotic medication doses.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Parkinson Disease; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Recurrence; Time Factors

Topics: Antipsychotic Agents; Clozapine; Dibenzothiazepines; Humans; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate

Motor complications arising after long-term treatment with levodopa remain one of the main challenges in the treatment of patients with Parkinson's disease (PD). Monotherapy with dopamine agonists may delay the onset of motor complications or reduce their severity when added to levodopa treatment. Here, we retrospectively analyzed data from 62 patients with advanced PD who presented with moderate to severe response fluctuations in whom we increased the dose of oral treatment with pergolide beyond 4.5mg daily. Patients had been treated with levodopa for 10.7+/-4.8 years. Pergolide was increased to 8.2+/-4.3 mg per day over a median titration period of 13.5 weeks. Mean daily dose of levodopa prior to pergolide high-dose treatment was 733+/-468 mg and decreased to 348+/-186 mg after pergolide titration. The duration of OFF times decreased from 7.3+/-3.8 to 1.7+/-0.9 h per day (p < 0.001) measured by patients' diaries. Dyskinesias, present for 5.0+/-3.3 h per day at baseline, were reduced to 1.4+/-0.8 h per day (p < 0.001) and the total daily duration of motor fluctuations (off-time duration plus dyskinesia duration) decreased from 10.5+/-7.0 to 2.8+/-2.2 h (p < 0.001). There was a significant improvement in parkinsonian symptoms (baseline to endpoint reduction of UPDRS III from a median of 36 to 8; p < 0.001). To reduce gastrointestinal side effects 23 patients required concomitant treatment with domperidone. Seven patients developed hallucinations during the titration period, six patients required treatment with clozapine. Our data indicate that increasing the dose of pergolide above 5mg per day can dramatically reduce the need for levodopa, motor fluctuations and severity of clinical symptoms. Controlled trials are needed to further substantiate the efficacy and safety of this treatment strategy.

Topics: Adult; Aged; Amantadine; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Dyskinesias; Endpoint Determination; Female; Germany; Humans; Male; Middle Aged; Movement Disorders; Parkinson Disease; Pergolide; Psychotic Disorders; Retrospective Studies

A retrospective analysis was carried out on 39 parkinsonian patients on clozapine treatment >/=24 months for psychosis. The cohort had a mean age of 76 years and an average clozapine dose of 47 mg/day over 60 months of clozapine use. Of 39 patients, 13 (33%) patients were eventually admitted to nursing homes, 6 (46%) of whom died over a period of 5 years. The overall 5-year mortality rate in this cohort was 44% (17/39). Of 39 patients, 33 (85%) had continued partial/good response and 5 (13%) had complete resolution of psychosis. None discontinued clozapine due to motor worsening. Among patients who responded early on, the long-term efficacy of clozapine for psychosis was sustained. The risk of nursing home placement and mortality among parkinsonian patients treated with clozapine for psychosis in this geriatric cohort was better than that reported previously. Our data are more consistent with recently published long-term outcome data suggesting an improvement in the prognosis of parkinsonian patients with psychosis with the use of atypical antipsychotic agents such as clozapine.

Topics: Aged; Antipsychotic Agents; Clozapine; Cohort Studies; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Retrospective Studies; Time

Stroke-induced hemiballismus (HB) has been reported to improve motor function in people with Parkinson's disease (PD). We report on a patient who developed HB from a parietal infarct. The HB was improved by very low-dose clozapine but the HB did not improve the parkinsonism. This suggests that HB itself, whether from a lesion in the subthalamic nucleus or elsewhere, is not what improves motor function in PD; instead, the physiological function of the damaged structure is the determining factor.

Topics: Aged; Antipsychotic Agents; Clozapine; Dyskinesias; Humans; Infarction, Anterior Cerebral Artery; Magnetic Resonance Imaging; Male; Parkinson Disease; Stroke

Clozapine is the gold standard treatment for Parkinson's disease (PD) psychosis based on double blinded, placebo controlled trials, and has also been shown to alleviate tremor and dyskinesia. There is accumulating data suggesting that clozapine may be associated with increased frequency of diabetes mellitus (DM) compared to conventional neuroleptic drugs in treating schizophrenia. Forty-four predominantly geriatric parkinsonian subjects on clozapine for psychosis, tremor or dyskinesia, on an average dose of 50.6 mg/d for a mean duration of 41 months were reviewed. The prevalence of DM in this cohort was 18.1% (8/44). This rate was similar to that reported in the aged-matched general population (prevalence = 19.3% for ages > or = 60 years). In this small study, parkinsonian patients on long-term, low dose clozapine were not at increased risk for developing DM. Larger controlled prospective studies are needed to confirm this.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Cohort Studies; Dementia; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Parkinson Disease

Topics: Adult; Antipsychotic Agents; Clozapine; Epilepsy; Humans; Male; Parkinson Disease

Three patients with Parkinson's disease developed psychosis. None of the three showed any other somatic cause for the psychosis except the Parkinson's disease. The first patient, a 73-year-old male, was initially treated with olanzapine and rivastigmine, without any effect. While treating the second patient, a 75-year-old male who had been suffering from Parkinson's disease for years, the Parkinson medication was first reduced and later on olanzapine and rivastigmine were prescribed, without a lasting effect on the psychotic symptoms. In the third patient, an 85-year-old male, medication reduction was unsuccessful. Finally, all three were treated effectively with clozapine. Psychosis in Parkinson's disease is a serious disorder that is often difficult to treat. In most cases, antipsychotic medication is needed. The atypical antipsychotic clozapine is effective without aggravation of the motor symptoms. Despite the side effects, such as the risk of agranulocytosis, drowsiness and weight gain, clozapine should be considered as a possible treatment.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Humans; Male; Neuroprotective Agents; Olanzapine; Parkinson Disease; Phenylcarbamates; Psychotic Disorders; Rivastigmine; Treatment Outcome

Topics: Anemia, Aplastic; Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders

To examine the possible association of neuropsychiatric symptoms and pallidal surgery for Parkinson disease (PD).. Parkinson disease may be accompanied by a variety of psychiatric symptoms. It is important to distinguish these from psychiatric syndromes that are associated with the treatment of PD.. Case description of a patient with PD and a history of right pallidotomy who developed a psychiatric syndrome, including prominent hypersexuality, after surgical implantation of a deep brain stimulator electrode in the left globus pallidus.. This case demonstrates that patients receiving antiparkinson medication may be at risk for the development of psychiatric sequelae after pallidal surgery.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Electric Stimulation Therapy; Electrodes, Implanted; Globus Pallidus; Humans; Male; Middle Aged; Neuropsychological Tests; Neurosurgical Procedures; Parkinson Disease; Sexual Dysfunction, Physiological; Tomography, X-Ray Computed

Abrupt clozapine withdrawal can cause rebound psychosis and severe somatic symptoms in psychiatric patients. We report on the case of an advanced Parkinson's disease patient who developed myoclonus, tremor, rigidity, hyperreflexia, and stupor after abrupt clozapine withdrawal. The patient's symptoms resolved with treatment with cyproheptadine. This clinical picture suggests serotonergic rebound as an explanation for the patient's symptoms, although other pharmacological mechanisms are possible. Clozapine should be gradually withdrawn over a period of 1 to 2 weeks when possible, and abruptly discontinued only when necessary.

Topics: Aged; Antipsychotic Agents; Carbidopa; Clozapine; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Drug Therapy, Combination; Hallucinations; Humans; Levodopa; Male; Neurologic Examination; Parkinson Disease; Parkinson Disease, Secondary; Substance Withdrawal Syndrome

(1) Psychotic disorders occurring in patients with Parkinson's disease are usually linked to antiparkinsonian treatments. Tapering the dose of dopaminergic or anticholinergic drugs does not always yield a satisfactory balance between the psychotic and motor disorders. Most neuroleptics tend to worsen extrapyramidal manifestations and are contraindicated in combination with dopaminergic agents. Their assessment in patients with Parkinson's disease has been limited. (2) Clozapine, a neuroleptic, is now indicated in this type of patient. (3) The evidence comes from two double-blind placebo-controlled trials, each involving 60 patients. In these trials, 40% of patients lost all their psychotic disorders on low-dose clozapine, usually with no worsening of parkinsonian manifestations. (4) In clinical trials of clozapine in Parkinson's disease, the incidence of neutropenia was between 2 and 3%, and that of agranulocytosis 0.3%. The risks of myocarditis, dilated myocardiopathy and malignant neuroleptic syndrome associated with clozapine call for strict pharmacovigilance. (5) In practice, when adjusting antiparkinsonian treatment fails to strike a balance between psychotic and parkinsonism disorders, clozapine is the standard neuroleptic. It should be used with care, however, because of its adverse effects.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clinical Trials as Topic; Clozapine; Dopamine Agents; Drug Approval; France; Humans; Parkinson Disease; Psychoses, Substance-Induced; Treatment Outcome

Psychosis is a common complication of the drug treatment of Parkinson's disease (PD). Treatment of this complication is difficult as most antipsychotic drugs worsen motor symptoms of PD. Only the atypical antipsychotic clozapine improves psychosis without worsening of parkinsonism. The aim of the present study was to assess the rate of initiation of antipsychotic treatment in patients with PD compared with controls. The quality of pharmacotherapy was determined by assessing which antipsychotic drugs were initiated.. Data came from the PHARMO database, which includes drug-dispensing information for all residents of six Dutch cities. Selected were all persons aged 55 years and older who used levodopa for at least 180 days and who started antiparkinsonian drugs at least 180 days after entry into PHARMO. These patients were matched to at most three controls for age, gender, pharmacy and time of use. The association between rate of initiation of antipsychotic drug treatment and PD was determined using the Cox proportional hazards model.. The study included 271 patients with PD and 748 controls. During follow-up, 38 patients and 25 controls started taking an antipsychotic drug; relative risk was 3.9 (95% confidence interval 2.3, 6.4). Six patients with PD received an atypical agent (16%). Clozapine was given to five patients with PD. No control used clozapine. Haloperidol was most frequently prescribed to the patients (29%) and the controls (36%).. Patients with PD began taking antipsychotic drugs almost four times more frequently than controls. The quality of pharmacotherapy can be improved by prescribing atypical antipsychotic drugs to patients with PD.

Topics: Aged; Antipsychotic Agents; Case-Control Studies; Clozapine; Female; Humans; Male; Middle Aged; Netherlands; Parkinson Disease; Pharmacoepidemiology; Psychoses, Substance-Induced

Topics: Clozapine; Dibenzothiazepines; Dopamine Agonists; Dyskinesias; Hallucinations; Humans; Levodopa; Parkinson Disease; Practice Guidelines as Topic; United States

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Hallucinations; Humans; Male; Olanzapine; Parkinson Disease; Pirenzepine

Topics: Antipsychotic Agents; Benzodiazepines; Bias; Clozapine; Hallucinations; Humans; Olanzapine; Parkinson Disease; Pirenzepine

Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins were previously implicated in the pathophysiology and treatment of mood and other neuropsychiatric disorders. Recently we showed that untreated patients with schizophrenia have a significantly elevated dopamine-induced Gs protein function which is correlated with the severity of the psychotic symptoms. In contrast, an inverse picture with reduction in the function and the immunoreactivity of Gs protein was detected in patients with Parkinson's disease. The present study aims at investigating the effect of antipsychotic medications on dopamine-induced Gs protein hyperfunction in schizophrenia comparing the classical antipsychotic haloperidol and the newer antipsychotic clozapine, which is devoid of extrapyramidal side effects, on G protein measures.. G protein functional measurements coupled to beta-adrenergic, muscarinic, and dopamine receptors were undertaken through bacterial toxin sensitive, agonist enhanced [3H]-Gpp(NH)p binding capacity, substantiated by quantitative measures of Gs alpha, Gi alpha, and G beta subunit proteins through immunoblot analysis in mononuclear leukocytes obtained from patients with schizophrenia under haloperidol, or clozapine treatments in comparison with untreated patients with schizophrenia and healthy volunteers.. Dopamine-induced Gs hyperfunction characteristic of untreated patients with schizophrenia was not detected under antipsychotic treatment with either haloperidol or clozapine. Haloperidol caused a significant decrease in Gs function and immunoreactivity below normal levels. The extend of reduction in Gs function was found to be correlated with the intensity of extrapyramidal side effects. The pattern of G protein subunits levels in patients with schizophrenia under haloperidol treatment resembles the one obtained in patients with Parkinson's disease.. In the present study it is shown that G protein measurements in patients with schizophrenia under antipsychotic treatments can be used to biochemically monitor effects of antipsychotic medications in living patients. Moreover, these measurements may be used also for monitoring parkinsonian side effects induced by antipsychotic medications.

Topics: Adult; Antipsychotic Agents; Binding, Competitive; Brain Chemistry; Clozapine; Dopamine; Dopamine Agonists; Female; GTP-Binding Proteins; Haloperidol; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Parkinson Disease; Receptors, Adrenergic, beta; Receptors, Dopamine; Receptors, Muscarinic; Schizophrenia; Up-Regulation

Topics: Adult; Aged; Antipsychotic Agents; Cardiomyopathies; Clozapine; Death, Sudden, Cardiac; Drug Hypersensitivity; Female; Humans; Male; Myocarditis; Parkinson Disease; Schizophrenia

Topics: Aged; Clozapine; Dibenzothiazepines; Humans; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Quetiapine Fumarate; Retrospective Studies

Four patients affected by severe Parkinson's disease developed leucopenia (900-1200 WBC) during treatment of psychosis (3) or untreatable insomnia (1) with clozapine (37.5-75 mg/day). Clozapine withdrawal was followed by recovery of leucopenia (4000-6000 WBC) in two weeks with no need for the administration of leucokines. After 1-6 months olanzapine was administered (increasing the dose from 2.5 to 10 mg/day) to treat persisting disturbances, but the drug induced severe worsening of parkinsonism and also this drug had to be withdrawn.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Leukopenia; Male; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Sexual Dysfunctions, Psychological; Sleep Initiation and Maintenance Disorders

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Humans; Parkinson Disease; Psychoses, Substance-Induced; Serotonin Antagonists

P450 enzymes in the CYP2D subfamily have been suggested to contribute to the susceptibility of individuals in developing Parkinson's disease. We have used specific anti-peptide antisera and peroxidase immunohistochemistry to investigate the expression of CYP2D enzymes in the rat brain and some possible factors that may affect their regulation. In male Wistar rats, CYP2D1 was not detected in the basal ganglia or in any other brain region. CYP2D2 was weakly expressed within neurones of the subthalamic nucleus, substantia nigra and interpeduncular nucleus as well as in the hippocampus, dentate gyrus, red nucleus and pontine nucleus. CYP2D3 and CYP2D4 were absent from the basal ganglia, although moderate amounts of CYP2D3 were detected within fibres of the oculomotor root, and very low levels of CYP2D4 were present in white matter tracts. In contrast, CYP2D5 was extensively expressed in the basal ganglia, including neurones in the subthalamic nucleus, substantia nigra and interpeduncular nucleus, as well as other areas of the brain, including the ventral tegmental area, piriform cortex, hippocampus, dentate gyrus, medial habenular nucleus, thalamic nucleus and pontine nucleus. Lesioning of the nigro-striatal tract to cause almost a complete loss of tyrosine hydroxylase containing neurones in the substantia nigra, also reduced the number of neurones expressing CYP2D5 by 50%, indicating that CYP2D5 is expressed in dopaminergic neurones. Castration of pre-pubertal or adult Wistar rats had no effect on the number of CYP2D5-positive neurones in the substantia nigra. Although Dark Agouti rats lack hepatic CYP2D2, expression in the midbrain was similar to that of Wistar rats; furthermore, there was no difference in expression or distribution between male and female rats. In contrast to naive rats, extensive expression of CYP2D4 was found throughout the basal ganglia and in other brain nuclei in Wistar rats treated with not only clozapine, but also saline, suggesting that CYP2D4 may be induced as a result of mild stress. The function of CYP2D enzymes in the brain remains unknown, but their selective localisation suggests a physiological role in neuronal activity and in adaptation to abnormal situations.

Topics: Animals; Antibody Specificity; Basal Ganglia; Brain Chemistry; Clozapine; Cytochrome P-450 Enzyme System; Dopamine; Enzyme-Linked Immunosorbent Assay; Female; GABA Antagonists; Isoenzymes; Liver; Male; Microsomes; Nerve Degeneration; Orchiectomy; Oxidopamine; Parkinson Disease; Rats; Rats, Wistar; Substantia Nigra; Sympathomimetics

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Humans; Neuroleptic Malignant Syndrome; Parkinson Disease; Psychoses, Substance-Induced

There are many difficulties associated with the late stages of Parkinson's disease (PD), but psychosis and agitation may be the most disturbing for both patients and care givers, and often precipitate the pivotal decision for long-term nursing home placement. While the addition of antipsychotic drugs or the withdrawal of antiparkinsonian drugs may improve the behavioral problem, these strategies usually worsen the motor difficulties. Clozapine has been studied in PD for over a decade, and while it appears to be effective, there are safety and tolerability concerns associated with it. In addition, in New Jersey, Medicaid no longer pays for the home blood draws that are required for home-bound patients. This led to a situation in which we had patients who needed to stop clozapine and begin an alternative therapy. Because quetiapine seems particularly well suited to patients with PD based on in vitro and in vivo studies we have begun to try this medication in PD patients who need to stop clozapine. This article reports three case histories of patients with PD, confusion and dopamimetic psychosis who had been previously managed with clozapine and who were successfully switched to quetiapine. At doses from 12.5 to 150 mg/day quetiapine was well tolerated, resulting in behavioral improvement and no real increase in parkinsonism. These case histories raise the possibility that quetiapine may represent a viable alternative to clozapine in PD patients with dopamimetic psychosis and behavioral disturbances.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Confusion; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome

The atypical antipsychotic drug olanzapine has been proposed for treatment of dopaminergic psychosis in Parkinson's disease (PD). We report on a 68-year-old patient who developed a severe akinetic-rigid extrapyramidal syndrome, accompanied by additional paranoid symptoms, following olanzapine treatment of optic hallucinosis in PD. Olanzapine may also induce clinically relevant extrapyramidal side effects in PD patients.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Drug Therapy, Combination; Hallucinations; Humans; Levodopa; Male; Olanzapine; Paranoid Disorders; Parkinson Disease; Piperidines; Pirenzepine; Selegiline; Severity of Illness Index

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Hallucinations; Humans; Male; Parkinson Disease; Seizures

The delusional misidentification syndrome (DMS) has been associated with a range of neurological conditions. Three cases of DMS in patients with Parkinson's disease and dementia, treated with dopaminergic medications, are presented. It is postulated that DMS associated with parkinsonism results from a combination of dopaminergic psychosis and cognitive dysfunction involving the frontal lobe in particular. DMS in the setting of parkinsonism may be more frequent than commonly supposed.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Capgras Syndrome; Clozapine; Delusions; Female; Hallucinations; Humans; Male; Parkinson Disease

We conducted a multicentered, retrospective review of clozapine's (CZP) effects on a range of psychiatric, sleep, cognitive, motor, and sensory disorders in Parkinson's disease (PD). Therapeutic outcomes and adverse events were compared with varying prescribing practices at participating sites. The medical records of 172 consecutive PD patients treated with CZP at four movement disorder clinics were reviewed. Low-dose CZP improved psychiatric symptoms of psychosis, anxiety, depression, hypersexuality, sleep disturbance, and akathisia. Tremor, torticollis, limb dystonia, and pain showed modest rates of improvement. Twenty-three percent of patients withdrew as a result of adverse events or treatment failure. Inpatient CZP initiation did not improve therapeutic efficacy, or reduce adverse events or the withdrawal rate. Low-dose CZP in the outpatient setting is generally an effective and well-tolerated treatment for many of the psychiatric, sleep, motor, and sensory disturbances common to late-stage PD.

Topics: Aged; Ambulatory Care; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Levodopa; Male; Middle Aged; Neurocognitive Disorders; Neurologic Examination; Neuropsychological Tests; Parkinson Disease; Patient Admission; Retrospective Studies; Treatment Outcome

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Carbidopa; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Paraphilic Disorders; Parkinson Disease; Pergolide

The severity of parkinsonian motor disability and dyskinesias was evaluated in seven levodopa-responsive patients with Parkinson's disease after an acute challenge with the mixed dopamine agonist apomorphine, before and after low-dose clozapine (50 mg) for 18 +/- 2 days. There was a significant 59% improvement (p < 0.05) of apomorphine-induced dyskinesias without aggravation of parkinsonian motor disability following clozapine treatment. The results suggest that low-dose clozapine, already shown to improve psychotic symptoms, may help to reduce severe levodopa-induced dyskinesias in parkinsonian patients.

Topics: Aged; Antipsychotic Agents; Clozapine; Humans; Middle Aged; Movement Disorders; Parkinson Disease; Pilot Projects; Treatment Outcome

Topics: Antipsychotic Agents; Australia; Clozapine; Drug Approval; Humans; Parkinson Disease

Levodopa-induced psychosis can complicate the treatment of Parkinson's disease (PD). In this retrospective, uncontrolled report, we describe our experience treating PD-related psychosis with clozapine, emphasizing those patients treated for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1 year. Most patients showed a rapid improvement from baseline within 1 month using the Clinical Global Impression and Global Psychosis Rating Scores. Five patients discontinued the drug due to side effects, but only two patients reported side effects after 6 months of treatment. Clozapine appears to be effective in treating PD related psychotic symptoms while not interfering with motor function.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Female; Humans; Levodopa; Long-Term Care; Male; Parkinson Disease; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Retrospective Studies; Treatment Outcome

Dopaminergic psychosis frequently complicates the pharmacological treatment of Parkinson's disease. Dose reduction of dopaminomimetic therapy or treatment with conventional neuroleptics improves psychosis but worsens parkinsonism. In an open-label 12-month trial, the clinical antipsychotic efficacy of the atypical neuroleptic clozapine was investigated in 36 parkinsonian patients (age range 46-85 years) with symptoms of dopaminergic psychosis including delusions, vivid dreams, hallucinations, frank paranoid delirium, and hypersexuality. Clozapine, given orally at bedtime, was started at a dose of 6.25 mg and titrated upward to the minimal effective dose. In all patients, psychosis responded to very low clozapine doses (mean 10.59 +/- 6.48 mg/day). Clozapine doses correlated with the severity of psychosis. During clozapine treatment, parkinsonian disabilities and levodopa dosage remained statistically unchanged. During the 12-month study, no patient had clozapine-induced agranulocytosis or other severe side effects. These findings indicate that even at low doses, clozapine effectively controls dopaminergic psychosis in Parkinson's disease patients without compromising motor function.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Delusions; Dopamine; Female; Hallucinations; Humans; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced

Topics: Aged; Clozapine; Female; Hallucinations; Humans; Levodopa; Parkinson Disease; Pergolide

In patients with Parkinson' disease and dopaminergic psychosis, clozapine treatment is recommended as the drug is free from extrapyramidal side effects and does not worsen motor symptoms of the underlying disease. The use of clozapine, however, is limited due to its hematotoxic side effects. For treatment of clozapine-induced agranulocytosis, granulocyte colony-stimulating factors (G-CSF) are recommended. We report the case of a 72-years-old male patient with clozapine-induced agranulocytosis and thrombopenia. Neutropenia was successfully treated with G-CSF, but thrombopenia persisted and resolved spontaneously after 14 days. Bone marrow toxicity of clozapine is not restricted to white cell maturation, but may also impair thrombocytopoesis.

Topics: Aged; Agranulocytosis; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Dopamine Agents; Humans; Leukocyte Count; Male; Parkinson Disease; Platelet Count; Psychoses, Substance-Induced; Thrombocytopenia

Drug-induced psychosis is a serious late complication of Parkinson's disease (PD) that requires aggressive treatment. Recent studies have found clozapine a highly effective and ECT a possibly useful intervention. Two cases are presented that illustrate a possible treatment role for ECT. The cases demonstrate that ECT has significant but short-lived antipsychotic effects when used alone. However, patients who do not respond to clozapine monotherapy can be given adjunctive treatment with ECT. The combination therapy resulted in abrupt alleviation of psychotic symptoms in one of the cases, and maintenance with low-dose clozapine allowed for long-term efficacy. On the basis of these findings, a therapeutic approach to patients with drug-induced psychosis in PD is suggested.

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Combined Modality Therapy; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced

Topics: Carbidopa; Clozapine; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Psychotic Disorders

Topics: Agranulocytosis; Clozapine; Ethnicity; Humans; Neutropenia; Parkinson Disease; Tremor

Topics: Clozapine; Humans; Parkinson Disease

Topics: Apomorphine; Clozapine; Drug Approval; Humans; Parkinson Disease; United Kingdom

We report six cases of psychosis in patients with akinetic-rigid syndromes who were treated with risperidone.. Five of the six patients experienced intolerable exacerbation of parkinsonism. Four subsequently did well on clozapine therapy. One patient required nursing home placement and a feeding gastrostomy as a result of the worsening parkinsonism during risperidone treatment, but was able to return home and have the gastrostomy removed after switching from risperidone to clozapine. Two of the five patients who worsened motorically also developed encephalopathy during risperidone treatment; the encephalopathy resolved when the patients were switched to clozapine treatment. Only one patient, the youngest, did well on risperidone therapy.. We believe that risperidone is not a substitute for clozapine in treating psychosis in parkinsonian patients and should be used with caution.

Topics: Aged; Antiparkinson Agents; Clozapine; Dyskinesia, Drug-Induced; Humans; Male; Parkinson Disease; Parkinson Disease, Secondary; Psychoses, Substance-Induced; Risperidone

In a prospective, open-label study, 12 patients manifesting psychosis associated with Parkinson's disease were treated with clozapine. Cognitive functioning and type of psychotic symptoms were measured prior to treatment, and changes in psychiatric and behavioral symptoms were studied by using the Behave-AD Scale. Significant resolution in psychotic symptoms was found and improvement in global behavioral status observed in all cases, with 10 patients maintaining improvement at follow-up. Careful initiation and titration of the drug resulted in few side effects, and dementia was not found to be a contraindication to such treatment.

Topics: Aged; Antipsychotic Agents; Clozapine; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurocognitive Disorders; Neuropsychological Tests; Parkinson Disease; Prospective Studies; Social Behavior

Topics: Aged; Aged, 80 and over; Clozapine; Dementia; Drug Synergism; Drug Therapy, Combination; Female; Glaucoma; Humans; Leukocyte Count; Methazolamide; Neutropenia; Parkinson Disease

Topics: Aged; Clozapine; Humans; Male; Parkinson Disease

Topics: Aged; Aged, 80 and over; Clozapine; Female; Humans; Parkinson Disease; Psychoses, Substance-Induced

Dyskinesias commonly appear during L-dihydroxyphenylalanine (L-DOPA) therapy of advanced Parkinson's disease (PD) and can occur in both dose-related and dose-independent patterns. Clozapine exerts a dose-related suppression of L-DOPA-induced dyskinesias by shifting the i.v. L-DOPA dose-response curve for production of dyskinesias without altering relief of parkinsonism. We report our outpatient experience with 13 patients on daily clozapine therapy (maximum dose 400 mg/day), followed for 3-21 months (median 10). Beneficial effects of clozapine, determined from twice-weekly diaries, included increased "on time" and decreased "off time" and time "on with dyskinesia." Improvements were statistically apparent by 75 mg/day and remained so through 200 mg/day. Sedation was a common problem, reflected by increased time "asleep" which was significant by 50 mg/day. Sedation was dose limiting in most patients. Orthostatic hypotension and sialorrhea were variably present. No patients had seizures, bone marrow toxicity, or detectable loss of efficacy of clozapine with chronic use. We conclude that clozapine is an effective agent for suppression of dyskinesias in PD with an effective daily dose for most patients of 100-200 mg/day.

Topics: Aged; Clozapine; Disability Evaluation; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Long-Term Care; Male; Middle Aged; Neurologic Examination; Parkinson Disease

Tremor at rest is a classic symptom of Parkinson's disease that causes significant disability and distress for the patient and is generally only weakly responsive to conventional treatment, like anticholinergic and dopaminergic medication. This study describes the treatment with Clozapine in patients with Parkinson's disease, who despite optimal antiparkinson medical therapy still have a major disabling tremor at rest. Clozapine is an "atypical" neuroleptic agent, producing fewer extra pyramidal side effects common to conventional antipsychotic drugs. Clozapine, however, has as its most serious complication agranulocytosis, and hence all patients taking Clozapine must undergo blood tests at least several times a month. Under these frequent blood monitoring conditions, in this study Clozapine produced a substantial alleviation of parkinsonian tremor in 17 of 23 patients (73%). The beneficial response was reached with a relative low dose of Clozapine (18 mg./day), while previous antiparkinson medication was kept unchanged. The improvement of tremor at rest was noticeable generally within 2 weeks of beginning Clozapine therapy. No tolerance to the antitremor efficacy of Clozapine was seen during study-period of at least 6 months. Leucopenia developed in one patient, other major adverse events were hypersalivation and day-time drowsiness. These findings confirm the substantial antitremor efficacy of Clozapine in Parkinson's disease.

Topics: Aged; Aged, 80 and over; Clozapine; Disability Evaluation; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Tremor

Two patients with long-standing idiopathic Parkinson's disease (PD), without individual or family histories of affective disorders, developed bipolar mood disorders. Both were treated with lithium and clozapine, and one responded favorably. These may be the first reported cases in which mania was treated with clozapine in PD patients.

Topics: Bipolar Disorder; Clozapine; Drug Therapy, Combination; Female; Humans; Levodopa; Lithium Carbonate; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Recurrence

Topics: Aged; Antiparkinson Agents; Clozapine; Drug Administration Schedule; Humans; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced

Topics: Aged; Clozapine; Humans; Male; Parkinson Disease; Psychotic Disorders

Topics: Clozapine; Dose-Response Relationship, Drug; Humans; Levodopa; Movement Disorders; Parkinson Disease

We gave increasing daily doses of clozapine to six patients with advanced Parkinson's disease (PD) and levodopa-induced dyskinesias. Clozapine reduced the daily dyskinesia time five-fold, increased "on" time eight-fold, and doubled the serum [DOPA] producing half-maximal dyskinesia. Parkinsonism scores after overnight DOPA withdrawal improved with increasing daily clozapine intake, and there was no clozapine dose-related shift in levodopa dose response for relief of parkinsonism. Patients experienced sedation, sialorrhea, and orthostatic hypotension. Clozapine appears to be an effective agent for suppression of levodopa-induced dyskinesias in PD.

Topics: Aged; Clozapine; Dihydroxyphenylalanine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease

Seven patients with idiopathic Parkinson's disease, aged 62 to 76 years, average duration of the disease approximately eleven years, suffering from severe hallucinosis and paranoid delusions of different degree, in whom conventional therapeutic strategies (administration of benzodiazepines and mild neuroleptics) had no antipsychotic effect, received clozapine, a non-classical highly potent neuroleptic, while blood count was strictly monitored. Paranoid ideas disappeared in all seven patients after a maximum of four days administration of 25-125 mg/day. No deterioration of parkinsonian symptoms, quantified according to UPDRS was seen. Given the protection of clozapine, we could increase the L-dopa dose in two cases, thereby improving the patients' motor function. Blood count showed no abnormalities in any of the patients during an average observation period of seventeen months. Our results support the assumption that clozapine has a potent antipsychotic effect in the treatment of psychotic decompensation in advanced Parkinson's disease in carefully selected patients. We saw no negative influence of the neuroleptic on extrapyramidal symptoms.

Topics: Aged; Benserazide; Blood Cell Count; Clozapine; Female; Hallucinations; Humans; Levodopa; Male; Middle Aged; Paranoid Disorders; Parkinson Disease; Psychotic Disorders

Topics: Aged; Antiparkinson Agents; Carbidopa; Clozapine; Dementia; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Levodopa; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Psychoses, Substance-Induced

We present the results obtained using low doses of clozapine (mean dose 26.4 mg at bedtime) in the treatment of nocturnal akathisia in nine patients with Parkinson's disease for a mean period of 12.5 months. The results were excellent in all the patients. Furthermore, three patients experienced a remarkable improvement in rest tremor and in five patients the confusional state that accompanied the akathisia also disappeared. No serious side-effects were observed. We believe that clozapine is a very useful drug for the relief of nocturnal akathisia in parkinsonian subjects.

Topics: Adult; Aged; Aged, 80 and over; Benserazide; Carbidopa; Circadian Rhythm; Clozapine; Confusion; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Psychomotor Agitation; Sleep Wake Disorders

Diffuse Lewy body disease, a severely disabling neuropsychiatric disease, presents with progressive dementia, psychotic symptoms, depression, and parkinsonian symptoms. The authors report a case illustrating that clozapine, a novel neuroleptic drug, has special efficacy in treating psychotic symptoms in these patients.

Topics: Clozapine; Female; Humans; Middle Aged; Parkinson Disease

Topics: Clozapine; Humans; Leukocytosis; Male; Middle Aged; Monocytes; Parkinson Disease; Time Factors

Psychosis secondary to dopaminergic therapy can limit the ability to manage motor symptoms of advanced Parkinson's disease (PD). We report the results of an open label 3-month trial that evaluated the antipsychotic effects of clozapine in eight PD patients with drug-induced psychosis. Response was quantified using a simplified brief psychiatric rating scale and two PD scales. Clozapine significantly improved psychiatric scores at low doses. The use of every other day regimens (not previously utilized) led to good control of symptoms and minimized side effects. Clozapine also had a positive sleep effect in four patients and improved dyskinesia in one. Finally, this treatment prevented recurrence of psychosis while levodopa doses were significantly increased and while other antiparkinsonian medications were added. Motor disability related to PD improved as a result of these treatment adjustments. We conclude that clozapine is effective in treating drug-induced psychosis in PD and allows for safe optimization of antiparkinsonian therapy.

Topics: Activities of Daily Living; Aged; Antiparkinson Agents; Clozapine; Dopamine Agents; Dose-Response Relationship, Drug; Female; Humans; Levodopa; Male; Middle Aged; Neurologic Examination; Parkinson Disease; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Sleep Stages

Topics: Aged; Bromocriptine; Clozapine; Drug Therapy, Combination; Humans; Levodopa; Male; Parkinson Disease; Psychoses, Substance-Induced

Topics: Antiparkinson Agents; Carbidopa; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Levodopa; Male; Middle Aged; Paranoid Disorders; Parkinson Disease; Psychoses, Substance-Induced

Topics: Clozapine; Depressive Disorder; Female; Humans; Middle Aged; Neurocognitive Disorders; Parkinson Disease

Topics: Aged; Clozapine; Female; Hallucinations; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders

Topics: Clozapine; Humans; Parkinson Disease; Product Surveillance, Postmarketing; United States

Clozapine is an atypical neuroleptic medication that is free of parkinsonian side effects and that has been reported to ameliorate the tremor of Parkinson's disease. We report (with videotape illustration) the dramatic improvement of severe yet classic rest tremors in one elderly nonpsychotic patient with Parkinson's disease and significant improvement in four others. We believe that clozapine, in low doses, may be a useful medication for the treatment of rest tremor in Parkinson's disease, even in cases without mental abnormalities.

Topics: Aged; Clozapine; Dibenzazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Parkinson Disease

The clinical efficacy of clozapine, an atypical antipsychotic, in treating levodopa-induced hallucinations was investigated in five patients with Parkinson's disease under open label conditions. Two patients could not tolerate clozapine, even in doses as low as 12.5-25 mg daily, because of extreme sedation. Three patients could tolerate clozapine and experienced improvement or elimination of their hallucinations at doses below 100 mg daily. Despite a significant risk of adverse effects, cautious use of clozapine in low doses may be beneficial for patients with levodopa-induced psychosis who do not respond to more conservative measures.

Topics: Aged; Clozapine; Dibenzazepines; Dose-Response Relationship, Drug; Hallucinations; Humans; Levodopa; Male; Parkinson Disease

Topics: Clozapine; Dibenzazepines; Humans; Parkinson Disease

Treating psychosis in patients with Parkinson's disease (PD) is one of the more difficult problems in clinical psychiatry. In this case report, a patient with PD and psychosis was treated with the novel neuroleptic clozapine and sustained improvement in both behavior and PD symptoms.

Topics: Clozapine; Female; Humans; Middle Aged; Neurocognitive Disorders; Neurologic Examination; Neuropsychological Tests; Parkinson Disease; Psychomotor Performance

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.

Topics: Aged; Antiparkinson Agents; Clozapine; Dibenzazepines; Female; Humans; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced

Topics: Aged; Clozapine; Dibenzazepines; Humans; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced

Topics: Adult; Carbidopa; Clozapine; Dibenzazepines; Drug Administration Schedule; Drug Therapy, Combination; Humans; Levodopa; Male; Parkinson Disease; Schizophrenia

A total of 13 patients with drug-induced psychosis in Parkinson's disease were treated with two non-classical neuroleptics-clozapine and fluperlapine. Patients mainly complained about severe hallucinatory symptoms and different degrees of paranoid delusions. Complete relief was observed in 8 patients, moderate improvement in 3 and no effects in 2. Parkinsonian disability did not increase under neuroleptic medication with clozapine and fluperlapine, but could be ameliorated by additional L-dopa or bromocriptine medication. The non-classical neuroleptics employed are dopamine D2 blocking agents with a preferential binding to mesolimbic, mesocortical and hippocampal D2 receptors and no substantial binding to striatal dopamine receptors. Restricted use of these two neuroleptics is necessitated because of the danger of agranulocytosis.

Topics: Aged; Antipsychotic Agents; Benserazide; Bromocriptine; Clozapine; Delusions; Dibenzazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hallucinations; Humans; Hydrazines; Levodopa; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Tryptophan

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Haloperidol; Humans; Parkinson Disease; Parkinson Disease, Secondary; Receptors, Cholinergic; Sleep