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

Psychotic symptoms occur in up to 40% of patients with Parkinson's disease (PD). Clozapine and quetiapine, two atypical antipsychotic drugs, at doses markedly lower than those effective in schizophrenia, which, nevertheless, still cause sedation, hypotension, and other side effects, are widely used to treat psychotic symptoms in patients with PD psychosis (PDP), although quetiapine has never been shown to be effective in a placebo-controlled study. The demonstrated efficacy of clozapine in PDP has been attributed to serotonin (5-HT(2A)) receptor blockade. We postulated that pimavanserin (ACP-103), a highly selective 5-HT(2A) inverse agonist, would attenuate psychosis in patients with PDP, but avoid motoric worsening and non-motoric side effects. In this double-blind, randomized multicenter 28-day study, the tolerability and efficacy of pimavanserin was compared with placebo in 60 patients with L-DOPA or dopamine (DA) agonist-induced PDP. Motor function was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. Antipsychotic efficacy was evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS) and a UPDRS Part I psychosis-relevant item. Pimavanserin did not differentiate from placebo with regard to motor impairment, sedation, hypotension, or other side effects. The principal measures of efficacy of antipsychotic response to pimavanserin, the SAPS total domain score, only showed a trend. However, the pimavanserin-treated patients showed significantly greater improvement in some but not all measures of psychosis, including SAPS global measures of hallucinations and delusions, persecutory delusions, and the UPDRS measure of delusions and hallucinations. Pimavanserin showed significantly greater improvement in psychosis in patients with PDP at a dose which did not impair motor function, or cause sedation or hypotension Thus, pimavanserin may represent a novel treatment for PDP. Furthermore, these results support the hypothesis that attenuation of psychosis secondary to DA receptor stimulation in PDP may be achieved through selective 5-HT(2A) receptor antagonism.
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PMID:Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of parkinson's disease psychosis. 1990 17

Although Parkinson's disease (PD) is considered mainly a movement disorder, robust information accumulated during the last 30 years has shown that about 30% of PD patients may also suffer from psychosis, which deeply affects their quality of life and eventually brings them to permanent hospitalization in nursing homes. PD psychosis (PDPsy) mainly occurs after 10 or more years of treatment. The main features of PDPsy include recurrent and continuous hallucinations and delusions for at least 1 month. In addition, a recent consensus of the National Institute of Neurological Disorders and Stroke and National Institute of Mental Health Working Group also included illusions and a false sense of presence as "minor symptoms" supporting the diagnosis. In addition, accumulated clinical data have shown that "minor symptoms" and benign hallucinations also imply a bad prognosis with time. In the diagnostic criteria for PDPsy, it is considered that patients suffer from PD for at least more than 1 year before psychosis develops. If this is not the case, there is an unsolved problem of an overlapping diagnosis with Dementia with Lewy Bodies. Most clinicians consider that the main cause of psychosis is chronic exposure to dopaminergic medication. However, from an operational point of view there remain difficulties in defining a specific time of exposure and dose of treatment and the occurrence of PDPsy. Specific rating scales have been developed for the evaluation of PDPsy, such as the Parkinson Psychosis Rating Scale. The Scale for the Assessment of Positive Symptoms usually applied in schizophrenic patients has also proved useful for scoring psychotic symptomatology in PD. Clozapine in low doses has been proven to be the most effective antipsychotic medication for PDPsy. However, its use may cause neutropenia. Therefore, new atypical antipsychotic drugs with serotonin 5-HT2A receptor inverse agonist properties have been developed. Recently, pimavanserin--a 5-HT2A inverse agonist--has been studied. We hope that soon we will have the possibility to include new agents for the management of PDPsy.
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PMID:Hallucinations and psychosis in Parkinson's disease. 2012 47

It has recently been reported that psychotic symptoms in patients such as those with Parkinson's disease dementia (PDD) and Lewy body dementia (LBD) may worsen following treatment with memantine, a non-competitive NMDA receptor antagonist. Prepulse inhibition (PPI) of the acoustic startle response (ASR) is used as a measure for sensorimotor gating and it has been reported that PPI is disrupted by memantine. However, the mechanism of memantine-induced PPI disruption remains unclear. In the present study, we investigated the effects of memantine on PPI of the ASR in mice. Memantine (1.25-20mg/kg, intraperitoneally) increased the ASR and dose-dependently decreased PPI for all prepulse intensities tested. This effect of memantine on PPI was attenuated by pretreatment with the antipsychotics clozapine (3 and 6 mg/kg), risperidone (0.3mg/kg) and haloperidol (0.5mg/kg), the selective D(2) antagonist sulpiride (40 mg/kg) and 5-HT(2A/2C) antagonist ketanserin (2 and 4 mg/kg) but not with the selective D(1) antagonist SCH23390 (0.05 and 0.1mg/kg). Clozapine (6 mg/kg) and risperidone (0.3 mg/kg) significantly attenuated the increased startle amplitude in the memantine-treated groups. These results suggest that involvement of dopaminergic and/or serotonergic neurotransmission may play a crucial role in memantine-induced PPI disruption, and additionally, indicate that blockade of either the D(2) or 5-HT(2A) receptor may prevent disruption of PPI induced by memantine in mice. Conceivably, memantine may exacerbate psychotic symptoms in patients with PDD and LBD.
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PMID:Pharmacological characterizations of memantine-induced disruption of prepulse inhibition of the acoustic startle response in mice: involvement of dopamine D2 and 5-HT2A receptors. 2113 Aug 10

Psychosis (delusions and/or hallucinations) is a common nonmotor feature of Parkinson's disease (PD). Use of the older 'typical' antipsychotic drugs led to worsening of motor symptoms. The introduction of 'atypical' antipsychotics opened up a range of therapeutic options. These agents include clozapine, risperidone, olanzapine, aripiprazole and quetiapine. All have been used to treat psychosis in PD with varying success. Clozapine is the only drug with proven efficacy. We review the evidence for the efficacy of quetiapine. Eight open-label studies have assessed quetiapine use in 191 patients, with improvement in psychosis recorded in 152 (80%). In addition to the open-label studies, there have been two single-blind, randomized trials comparing quetiapine and clozapine. These studies suggest that quetiapine has similar efficacy to clozapine in controlling psychosis. Following the promising results of the open-label and clozapine comparison studies, five randomized, controlled trials (RCTs) have been performed to further establish the efficacy of quetiapine. Unfortunately, the results have been disappointing. The only positive placebo-controlled study excluded patients with delusions, which seem to be harder to treat than hallucinations. The four negative RCTs discussed seriously undermine the evidence from the open-label studies. The differences in design and interpretation of the RCTs emphasizes the need for further large, well-controlled trials, using strict inclusion criteria, appropriate psychosis rating scales, carer input and clinical significance. Currently, many physicians continue to cautiously offer a trial of low-dose quetiapine empirically. Clozapine should be considered in patients who can tolerate the required blood monitoring.
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PMID:Quetiapine in the treatment of psychosis in Parkinson's disease. 2117 95

A case of parkinson's disease starting 7 yrs. ago in 1993 with 2 episodes of mania is presented. The 1st episode (1993) was of 1-1/2 months duration, when early parkinsons symptoms had already set in. This was treated with anti-psychotic medications for a month, the picture was complicated with stroke and post-stroke sequlae for 5-6 months, where anti-psychotics were continued. He developed dyskinesia, when antipsychotics were stopped. The patient was on selegiline for Parkinson's disease for 2 years and off all medications subsequently. The 2nd episode of mania occurred after 7 years in January 2000. This episode of mania lasting for 2 months duration was treated with divalproate sodium and I-dopa for Parkinson's. Treatment emergent dyskinesia had to be treated with Clozapine. This unusual combination of bipolar-l disorer (2 episodes of mania) with Parkinson's disease and treatment emergent dyskinesia is presented with management strategy.
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PMID:Mania in Parkinson's disease with treatment emergent dyskineisa : a case report. 2140 84

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.
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PMID:Treatment of Parkinson's disease. Psychological disorders: striking a balance in order to optimise antiparkinsonian treatment. 2197 92

The objective was to update previous evidence-based medicine reviews of treatments for motor symptoms of Parkinson's disease published between 2002 and 2005. Level I (randomized, controlled trial) reports of pharmacological, surgical, and nonpharmacological interventions for the motor symptoms of Parkinson's disease between January 2004 (2001 for nonpharmacological) and December 2010 were reviewed. Criteria for inclusion, clinical indications, ranking, efficacy conclusions, safety, and implications for clinical practice followed the original program outline and adhered to evidence-based medicine methodology. Sixty-eight new studies qualified for review. Piribedil, pramipexole, pramipexole extended release, ropinirole, rotigotine, cabergoline, and pergolide were all efficacious as symptomatic monotherapy; ropinirole prolonged release was likely efficacious. All were efficacious as a symptomatic adjunct except pramipexole extended release, for which there is insufficient evidence. For prevention/delay of motor fluctuations, pramipexole and cabergoline were efficacious, and for prevention/delay of dyskinesia, pramipexole, ropinirole, ropinirole prolonged release, and cabergoline were all efficacious, whereas pergolide was likely efficacious. Duodenal infusion of levodopa was likely efficacious in the treatment of motor complications, but the practice implication is investigational. Entacapone was nonefficacious as a symptomatic adjunct to levodopa in nonfluctuating patients and nonefficacious in the prevention/delay of motor complications. Rasagiline conclusions were revised to efficacious as a symptomatic adjunct, and as treatment for motor fluctuations. Clozapine was efficacious in dyskinesia, but because of safety issues, the practice implication is possibly useful. Bilateral subthalamic nucleus deep brain stimulation, bilateral globus pallidus stimulation, and unilateral pallidotomy were updated to efficacious for motor complications. Physical therapy was revised to likely efficacious as symptomatic adjunct therapy. This evidence-based medicine review updates the field and highlights gaps for research.
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PMID:The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the motor symptoms of Parkinson's disease. 2202 Nov 73

Clozapine is the best treatment option in several clinical circumstances, including treatment-resistant schizophrenia, non treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. However, clozapine is associated with many serious side effects. Furthermore, monitoring requirements, i.e., frequent blood draws and frequent visits, discourage clozapine use. Therefore, the drug is underused. The only way to avoid the underuse of clozapine is full awareness of its side effects and competence to minimize them. The aim of the paper is reviewing the safety profile of clozapine and the suggested strategies in the management of its side effects, including neutropenia, eosinophilia, seizures, myocarditis, weight gain, diabetes, metabolic syndrome, hypersalivation, fever, constipation, ileus, urinary incontinence, sweating. The neuropsychiatric side effects of clozapine are not discussed in this review.
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PMID:Clozapine safety, 35 years later. 2212 92

Clozapine is, and will remain in the coming years, an irreplaceable drug in psychiatry which has elective indication in treatment-resistant schizophrenia, suicide risk in schizophrenia spectrum disorders, aggressiveness or violence in psychiatric patients, psychosis in Parkinson's disease, prevention and treatment of tardive dyskinesia. Unfortunately, the drug is largely underused for many and serious side effects. Only a good knowledge of these side effects and of the main strategies to prevent their occurrence or minimize their impact can allow overcoming the underutilization of this valuable therapy. The article describes the clinical and epidemiological features of the non-motor side effects of clozapine including blood dyscrasias, constipation, diabetes, enuresis, fever, hepatitis, hypersalivation, ileus, myocarditis, nephritis, priapism, seizures, serositis, weight gain and metabolic syndrome. The paper suggests several strategies, supported by scientific evidence, in the management of these side effects. The neuropsychiatric side effects of clozapine are not discussed in this review.
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PMID:Clozapine safety, 40 years later. 2480 63

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.
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PMID:Novel pharmaceuticals in the treatment of psychosis in Parkinson's disease. 2530 32


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