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)

Clozapine (CZP) is an atypical antipsychotic drug that does not appear to block striatal dopamine receptors. In six patients who met the criteria of HIV-associated psychosis and who had previously developed moderate parkinsonism as a result of the use of typical neuroleptic agents, CZP was added in an open, rising dose study. Subjects were evaluated at baseline after at least 7 days without neuroleptic drugs and then monthly for 3 months of the experimental treatment using three rating scales: Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and motor examination of the Unified Parkinson's Disease Rating Scale (UPDRS). A significant reduction in psychopathology as represented in the BPRS total score (54.2 at baseline versus 23.9 at month 3) and CGI (2 and 8, respectively) was obtained with a mean CZP dose of 27.08 mg/day. Parkinsonism also improved by an average of 76.5% at the end of the study. One patient did not complete the study as a result of a progressive decrease in leukocyte count while on CZP. These preliminary results suggest that the pharmacologic properties of CZP may be of value in the management of HIV-psychotic patients.
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PMID:Pilot study with clozapine in patients with HIV-associated psychosis and drug-induced parkinsonism. 991 55

Dopamine is a biogenic amine synthesized in the hypothalamus, in the arcuate nucleus, the caudad, and various areas of the central and peripheral nervous system. It has been widely established that dopamine and its agonists play an important role in cardiovascular, renal, hormonal, and central nervous system regulation through stimulation of alpha and beta adrenergic and dopaminergic receptors. There are several agonists of dopamine-2 (DA 2 ) dopaminergic receptors, such as bromocriptine, pergolide, lisuride, quinpirole, and carmoxirole, which inhibit norepinephrine release and produce a decrease in arterial blood pressure; in some cases, bromocriptine and pergolide also reduce heart rate. From a therapeutic point of view, the above-mentioned agonists are used for treating Parkinson's disease, acting over DA 2 dopaminergic receptors of the nigrostriatal system. Bromocriptine and the other dopaminergic agonists mentioned act over DA 2 receptors of the tuberoinfundibular system, inhibiting prolactin release and decreasing hyperprolactinemia and tumor size. Among DA 1 receptor agonists, we can mention fenoldopam, piribedil, ibopamine, SKF 3893, and apomorphine (nonspecific). Activation of these receptors decreases peripheral resistance, inducing lowering of arterial blood pressure and increases in heart rate, sympathetic tone, and activity of the renin aldosterone system. Among DA 2 receptor antagonists, we can mention metoclopramide, domperidone, sulpiride, and haloperidol. From a therapeutic point of view, metoclopramide and domperidone are used in gastric motility disorders, and haloperidol is used in psychotic alterations. Antagonists of DA 1 receptors are SCH23390 and clozapine. Clozapine is used for treating schizophrenia.
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PMID:Dopamine: pharmacologic and therapeutic aspects. 1009 36

Patients with essential tremor (ET) may not respond to commonly used drugs. Clozapine, an atypical neuroleptic drug, has been reported to improve postural Parkinson's disease tremor clinically resembling ET. The effects of a single dose of 12.5 mg clozapine and placebo were evaluated in a randomized, double-blind, crossover study in 15 drug-resistant patients with ET. Patient responders with more than 50% improvement after a single dose of clozapine subsequently received the drug (39+/-9 mg up to 50 mg) unblinded for a period of 15.8+/-7.7 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients (p <0.01). Sedation was the only side effect reported during the clozapine test; however, the time course of sedation and of the antitremor effect were not coincident. A significant reduction of tremor was reported with chronic clozapine treatment (p <0.01) with no tolerance to drug antitremor effect, whereas sedation markedly decreased after 6-7 weeks of therapy. No clozapine-induced hematologic side effects were observed in our cohort of patients during long-term treatment. Our results suggest that in selected drug-resistant ET cases, clozapine should be considered before resorting to neurosurgical options.
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PMID:Acute and chronic effects of clozapine in essential tremor. 1034 71

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.
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PMID:Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy. 1042 93

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.
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PMID:Quetiapine as an alternative to clozapine in the treatment of dopamimetic psychosis in patients with Parkinson's disease. 1048 24

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.
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PMID:Worsening of motor features of parkinsonism with olanzapine. 1058 79

Tremor is the most common initial symptom and one of the cardinal features of Parkinson's disease. Mild tremor causes only minimal disability, but severe tremor causes more significant disability and distress for the patient than rigidity and/or bradykinesia. Anticholinergic agents, levodopa/DCI and dopamine agonists are most common and beneficial in parkinsonian tremor, but efficacies of these medications are variable among patients. Rigidity and bradykinesia are more responsive to levodopa/DCI therapy than tremor. Clozapine is an atypical neuroleptic agent, not on the market in Japan, and has been reported to decrease or ameliorate parkinsonian tremor through the studies of open label and double blind crossover as a new drug for parkinsonian tremor.
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PMID:[Pharmacological treatment of parkinsonian tremor]. 1106 52

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.
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PMID:Leucopenia induced by low dose clozapine in Parkinson's disease recedes shortly after drug withdrawal. Clinical case descriptions with commentary on switch-over to olanzapine. 1121 59

Clozapine is known to be beneficial for the treatment of dopamine agonist-induced psychotic states in patients with Parkinson's disease (PD). Many reports have suggested that it may also be efficacious for the treatment of parkinsonian tremor. We describe a patient with schizophrenia in whom early-onset PD appeared after treatment with antipsychotic drugs. When the parkinsonian symptoms proved resistant to anticholinergic agents, we introduced a trial with up to 50 mg clozapine daily, which yielded a prompt and dramatic response. Thereafter, the parkinsonian symptoms reappeared each time the patient discontinued clozapine and rapidly disappeared on its repeat initiation. There was also a marked improvement in his psychotic and depressive symptoms. This report suggests that some patients with concomitant schizophrenia and PD-a difficult treatment challenge-may benefit from clozapine treatment alone for both disorders.
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PMID:Low-dose clozapine for the treatment of Parkinson's disease in a patient with schizophrenia. 1130 50

A patient in stage 3-4 of the Unified Parkinson's Disease Rating Scale (UPDRS), or in stage 4-5 of Hoehn and Yahr staging scale, or a patient with 0-50% activities of daily living scale of Schwab and England is considered a Late Parkinson's Disease (LPD) patient. The prevalence of disturbed sleep in Parkinson's Disease (PD) was found to vary according to an objective rating, from 60 to 98%. The factors predicting the quality of life in PD patients are: depression, sleep disturbances and dependence. The present article proposes the insertion of the following items as a chapter in a revised UPDRS based on updated knowledge in sleep arousal disturbances in PD. V. SLEEP-AROUSAL DISTURBANCES: Sleep disturbances 43. Light fragment sleep (LFS) 44. Sleep-related breathing disorders (SRBD) 45. Restless legs-periodic leg movements during sleep (RLS-PLM) 46. REM behavioral disorders (RBD) 47. Sleep-related hallucinations (SRH) 48. Sleep-related psychotic behavior (SRPB) Arousal disturbances 49. Sleep attacks (SA) 50. Excessive daytime sleepiness (EDS). Approaching the treatment of disturbed sleep in LPD means postponement of the institutionalization of the LPD patient, allowing the spouse or the caregiver a quiet nights sleep. This approach consists of three steps, each one of major importance. (1) Correct diagnosis based on detailed anamnesis of the patient, of the spouse or of the caregiver; a one week recording on a symptom diary (log) by the patient or the caregiver; excluding co morbidities. Then choosing the most appropriate sleep test, if necessary: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), actigraphy or video-PSG. This first step allows the diagnosis of one of the above mentioned sleep-arousal disturbances. (2) The non-specific therapeutic approach consists of: (a) checking the sleep effect on motor performance: beneficial, worse or neutral. (b) Dopaminergic adjustment is necessary due to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals which alter the normal modulator mechanisms of motor centers in LPD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and non-REM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates LPD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. L-Dopa has also an arousal effect on Non-REM sleep, repeatedly awakening the patient and enhancing the fragmentation due to the involuntary movements. (c) Socio-physical assistance. (3) The specific therapy consists of: LFS-Sinemet CR, Tolcapone, Intranasal Desmopressin, Domperidon, Cisapride and neurosurgery; SRBD-CPAP, UPPP, nasal interventions, losing weight; RLS-PLM-Benzodiazepine (Clonazepam), Opioid, Apomorphine infusion; RBD-Clonazepam and dopaminergic agonists; SRH-Clozapine, Risperidone; SRPD-Nortriptyline, Clozapine, Olanzepine; SA-adjustment; EDS-arousing drugs. Each therapeutic approach must be tailored to the individual LPD patient.
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PMID:Approaching disturbed sleep in late Parkinson's Disease: first step toward a proposal for a revised UPDRS. 1148 77


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