Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychotic disorders in the elderly are frequent, of multiple etiologies, and little researched. With the advent of "atypical" neuroleptics, their role in treating elderly psychiatric patients needs to be investigated. Clozapine is widely used; however, its use is common in the elderly whose psychosis is a feature of neurological morbidity (Parkinson's disease, dementia, etc.), making it difficult to ascertain the safety, tolerability, and efficacy in psychiatric disorders in late life. The aim of the present review is to evaluate clozapine's effect in elderly psychiatric patients with no neurological comorbidity. A computerized literature search (MedLine 1966 to 1997) revealed 133 patients fulfilling said criteria. Fifteen patients had side effects and/or adverse events during treatment; nine of these were receiving a dosage greater than 100 mg clozapine daily. In 19 patients, treatment was discontinued, three due to noncompliance and 16 due to side effects. In seven patients, leukopenia/agranulocytosis was reported. The majority of side effects (27 of 34) and treatment discontinuations were within the first 90 days of treatment. Although efficacy is difficult to compare across studies because of differing methods of evaluation, the great majority of patients showed moderate to marked improvement of psychotic features. The reported effectiveness in patients able to continue treatment for extended periods is significant. Thus, clozapine at a relatively low mean dose (134 mg daily) seems to be safe, tolerated, and effective in elderly psychiatric patients. Agranulocytosis is more frequent than in younger adults and should be monitored carefully.
 ...
PMID:Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy. 1042 93

Clozapine is the current treatment of choice for drug-induced psychosis (DIP) occurring in Parkinson's disease. However, alternative medications have been sought because of the small but significant risk of agranulocytosis and the need for frequent blood testing. The new "atypical" antipsychotic olanzapine (OLZ) has recently been proposed as a safe and effective option for treating psychosis in this setting. To investigate this, we retrospectively evaluated all 12 of our patients treated with OLZ for DIP. Symptoms of psychosis were improved in nine of 12 patients, but nine of 12 patients also experienced worsening of motor functioning while on OLZ. The worsening was considered dramatic in six of these patients. Overall, there was no significant increase in levodopa doses on OLZ. Only one patient remained on OLZ at the time of the analysis. Nine patients were switched to alternative treatment for DIP. We conclude that although OLZ may improve symptoms of psychosis in parkinsonian patients, it can also worsen motor functioning. In some patients, the degree of motor worsening may be intolerable.
 ...
PMID:Worsening of motor features of parkinsonism with olanzapine. 1058 79

Drug-induced psychosis is one of the most disabling complications of advancing Parkinson's disease. It has also been one of the most difficult to treat. Clozapine was the first medication shown to be safe and effective in this setting, and it remains the standard by which newer atypical antipsychotics are measured. However, due to the small but significant risk of agranulocytosis and the need for frequent blood testing, alternatives have been sought. Risperidone, olanzapine, and quetiapine are new atypical antipsychotics that have each been proposed as an alternative to clozapine, but the literature concerning their use in Parkinson's disease is conflicted and confusing. Although quetiapine appears to be the best current choice, none of these medications have equaled clozapine's ability to safely treat drug-induced psychosis without the risk of worsening parkinsonism.
 ...
PMID:Parkinson's disease: the treatment of drug-induced hallucinations and psychosis. 1189 37

(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.
 ...
PMID:Clozapine: new preparation. A last resort for parkinsonian patients with psychosis. 1198 66

Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much more commonly, psychosis is induced by drug therapy for Parkinson's disease and is the strongest known risk factor for nursing home placement. Delusions are less frequent than hallucinations, but are more concerning as they are often paranoid in nature. Treatment begins with a search for correctable infectious, toxic, and metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications are slowly reduced. However, withdrawal of these drugs usually worsens parkinsonism and is often not tolerated. Certain atypical antipsychotics can be used to treat psychosis without compromising motor function. The choice of atypical antipsychotic is largely based on ease of use and adverse effect profile as most have comparable efficacy in improving psychosis. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not been reported in Parkinson's disease. The most common adverse effects of clozapine in Parkinson's disease are sedation, orthostatic hypotension and sialorrhoea. Sedation is generally helpful since these patients are frequently awake at night and tend to have worse behavioural problems then. Clozapine does not induce deterioration of motor function, but it has the potential to cause agranulocytosis, which is idiosyncratic and not dose-related. In risperidone-treated Parkinson's disease patients, reported adverse effects include somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium, fatigue, leg cramps, depression, urinary incontinence and hypotension. Although in some Parkinson's disease studies, risperidone has been well tolerated, others have shown that many patients are unable to tolerate the drug due to deterioration of motor function. While an initial study of olanzapine in Parkinson's disease psychosis showed the drug to be effective without deterioration of motor function, succeeding reports demonstrated a deleterious effect of the drug on motor functioning. The most common adverse effects of quetiapine in Parkinson's disease patients are sedation and orthostatic hypotension. There is a lack of double-blind trials; however, cumulative reports involving >200 Parkinson's disease patients strongly suggest that quetiapine is well tolerated and effective. Unlike clozapine, it does not improve tremor and may induce mild deterioration of motor function. Recently, cholinesterase inhibitors have been reported to alleviate psychosis in Parkinson's disease. Although ondansetron, an antiemetic with antiserotonergic properties, has been reported to relieve psychosis in Parkinson's disease, its prohibitive cost has prevented further study in this population. Electroconvulsive treatment is generally reserved for the patient with psychotic depression who is unable to tolerate any pharmacological therapy.
 ...
PMID:Treatment of psychosis in Parkinson's disease: safety considerations. 1281 32

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.
 ...
PMID:[Clozapine for the treatment of psychosis in 3 elderly patients with Parkinson's disease]. 1561 68

Clozapine was one of the major advances in the treatment of schizophrenia since the introduction of the classic antipsychotic agent chlorpromazine in the 1950s. Over the past 10 years, clozapine has become the reference compound for the development of new antipsychotics, and new drugs have been developed which have also claimed atypical status. The indications of clozapine were recently extended to Psychosis in Parkinson's disease and harmonized in the European Union. This provides the opportunity to update the data on clozapine in the treatment of schizophrenia. In this article we review current clinical evidence in schizophrenia to address the following issues: 1) Efficacy in refractory/positive symptoms: a systematic and critical analysis of 14 double-blind clinical trials in comparison with both standard and novel antipsychotics show consistent findings in favour of clozapine, with all but three of the reports demonstrating superiority. The review of studies allow us to say little about the predictors of treatment response, time to clozapine response and about the impact of clozapine on the quality of patients'life and longer-term outcome. Treatment options for clozapine non-responders are reviewed. 2) Risk of EPS: clozapine is considered to have a minimal risk of EPS and in all studies where a valid methodology was used, a clear superiority over the other neuroleptics is demonstrated. It is pointed out that, if the prevalence and incidence of EPS with clozapine is low, it is not zero. All the studies assessing clozapine treatment for TD have major methodological limitations, so no final conclusion can be drawn. 3) Efficacy for primary and secondary negative symptoms and neurocognitive effects: the data of clinical studies where negative symptoms scales were used favour clozapine in terms of improvement. However most of the studies were carried out in populations with predominantly positive symptoms. With regard to the need to distinguish primary and secondary symptoms, data are conflicting regarding the benefit of clozapine. Due to the lack of studies with a valid methodology, no definitive conclusion can be drawn about the efficacy on clozapine on the deficit syndrome and on neurocognitive disorders. 4) Impact on suicide risk: 4 out of 6 retrospective studies provide evidence for the ability of clozapine therapy to reduce suicidal behaviour. The results of a recent randomized, parallel-group study designed to compare clozapine versus olanzapine in preventing suicide attempts seems to confirm this hypothesis. We also address the tolerability and safety data, especially haematologic, comitial, cardiovascular and metabolic side-effects. The effectiveness of blood monitoring for the management of neutropenia and agranulocytosis demands that the recommendations are strictly followed. The use of clozapine at doses higher than 600 mg daily should follow published recommendations, in order to minimize the risk of seizures; these include anticonvulsant regimens based on blood levels. With regard to the cardiovascular mortality, if clozapine therapy has negligible effects on QT interval, its association with potential fatal myocarditis cannot be excluded in young patients who should be investigated if they develop cardiac symptoms in the first weeks of treatment. Available data support the notion that the frequency of bodyweight gain is high with several new antipsychotics, including clozapine. Potential long term effects of bodyweight gain on mortality and morbidity have to be taken into consideration. The pharmacological mechanisms underlying the "unique clozapine profile" is discussed. Clozapine remains the only antipsychotic with efficacy at relatively low D2 receptor occupancy. The pharmacogenetic and pharmacokinetic aspects are also reviewed. Finally, the place of clozapine in the current treatment of schizophrenia is highlighted to inform the development of guidelines for clinical management.
 ...
PMID:[Leponex, 10 years after -- a clinical review]. 1562 52

The study of human gait has expanded and diversified to the extent that it is now possible to identify a substantive literature concerning a variety of gait tasks, such as gait initiation [Halliday SE, Winter DA, Frank JS, Patla AE, Prince F. The initiation of gait in young, elderly, and Parkinson's disease subjects. Gait Posture 1998;8:8-14; Mickelborough J, van der Linden ML, Tallis RC, Ennos AR. Muscle activity during gait initiation in normal elderly people. Gait Posture 2004;19:50-57], stepping over and across obstacles [Patla AE, Prentice SD, Robinson C, Newfold J. Visual control of locomotion: strategies for changing direction and for going over obstacles. J Exp Psych 1991;17:603-34; Chen, HC, Ashton-Miller JA, Alexander NB, Schultz AB. Effect of age and available response time on ability to step over an obstacle. J Gerontol 1994;49:227-33; Sparrow WA, Shinkfield AJ, Chow S, Begg RK. Gait characteristics in stepping over obstacles. Hum Mov Sci 1996;15:605-22; Begg RK, Sparrow WA, Lythgo ND. Time-domain analysis of foot-ground reaction forces in negotiating obstacles. Gait Posture 1998;7:99-109; Patla AE, Rietdyk S. Visual control of limb trajectory over obstacles during locomotion: effect of obstacle height and width. Gait Posture 1993;1:45-60] negotiating raised surfaces such as curbs and stairs [Begg RK, Sparrow WA. Gait characteristics of young and older individuals negotiating a raised surface: implications for the prevention of falls. J Gerontol Med Sci 2000;55A:147-54; Mcfayden BJ, Winter DA. An integrated biomechanical analysis of normal stair ascent and descent. J Biomech 1988;21:733-44]. In addition, increasing research interest in age-related declines in gait that might predispose individuals to falls has engendered a very extensive literature concerning ageing effects on gait. While rapid locomotor adjustments are common in the course of daily activities there has been no previous review of the findings concerning gait adaptations when walking is terminated both rapidly and unexpectedly. The aims of this review were first, to summarise the key research findings and methodological considerations from studies of termination. The second aim was to demonstrate the effects of ageing and gait pathologies on termination with respect to the regulation of step characteristics, lower-limb muscle activation patterns and foot-ground reaction forces.
 ...
PMID:Gait termination: a review of experimental methods and the effects of ageing and gait pathologies. 1627 20

Parkinson's disease is frequently associated with psychological disorders, especially depression, psychotic disorders, and dementia. We examined the management of psychological disorders in Parkinson's disease, including the use of psychotropic drugs, by reviewing the literature using the standard Prescrire methodology. About one-third of patients with Parkinson's disease experience visual hallucinations. Other hallucinations and delusions can also occur. Dose reduction or withdrawal of certain antiparkinsonian drugs sometimes improves psychotic disorders, providing an acceptable level of symptom control. Clozapine is effective and does not worsen parkinsonian symptoms, but it carries a risk of severe adverse effects, including agranulocytosis. Other neuroleptics are ineffective or worsen motor status. Mood disorders and depression are frequent during the course of Parkinson's disease. Pramipexole, an antiparkinsonian dopamine agonist, improved depressive symptoms in patients with Parkinson's disease in one trial. Its main adverse effects are ocular disorders. Several trials have shown that some tricyclic antidepressants improve depression in Parkinson's patients, but these drugs can worsen cognitive status and cause postural hypotension. Data on selective serotonin reuptake inhibitor antidepressants (SSRIs) are unconvincing. A meta-analysis of three trials showed that treatment withdrawals due to adverse events were similarly frequent with tricyclics and SSRIs. Dementia is frequent in end-stage Parkinson's disease. When severe cognitive disorders occur, it is advisable to withdraw any drugs capable of worsening the situation, especially drugs with antimuscarinic effects and benzodiazepines. Cholinesterase inhibitors have a negative harm-benefit balance in this setting. When a Parkinson's patient presents with a psychological disorder, the first step is to optimise antiparkinsonian treatment by striking a balance between motor control and psychological adverse effects. In the few situations in which drug treatment is likely to be beneficial, it should be remembered that psychotropic drugs are at best only moderately effective and should be used with care, monitoring patients for adverse effects.
 ...
PMID:Treatment of Parkinson's disease. Psychological disorders: striking a balance in order to optimise antiparkinsonian treatment. 2197 92

This publication offers a review of the pharmacological interventions studied for Parkinson's disease psychosis. Before initiating drug therapy for psychosis, possible contribution of antiparkinsonian medications to psychosis must be minimized by reducing their dose and completely switching them to levodopa if indicated. As a group, second- generation antipsychotics have been studied the most for Parkinson's disease psychosis. Evidence of efficacy for psychosis and safety for motor side effects is strongest for clozapine but routine use of clozapine is limited by its potential to cause agranulocytosis and the stringent monitoring requirements. Based on several open-label studies, quetiapine appeared to be a reasonable alternative, but recent double-blind studies create uncertainty about its efficacy. Olanzapine and aripiprazole have limited efficacy and are associated with worsening of motor symptoms. Literature is limited and lacks clarity about the utility of risperidone and ziprasidone in this scenario. Recently, encouraging literature has emerged on the use of donepezil and rivastigmine in patients with Parkinson's disease dementia and psychosis. There is a considerable need to further study the existing drugs and explore other pharmacotherapies in Parkinson's disease psychosis. Future research should ensure sound methodological quality and control for confounding variables to provide results that could be used reliably in clinical practice.
 ...
PMID:Psychosis in Parkinson's disease: therapeutic options. 2201 66


<< Previous 1 2 3 Next >>