Use Of Antiparkinsonian Drugs Research Articles

Voiding dysfunction in patients with Parkinson's disease: Impact of neurological impairment and clinical parameters

We assessed the lower urinary tract symptoms (LUTS) of patients with Parkinson's disease (PD) and their association with different clinical parameters. We prospectively evaluated 110 patients (84 men), with a mean age of 61.8 +/- 9.6 years. Mean duration of the disease was 12.3 +/- 7.2 years. Neurological impairment was assessed by the Hoehn-Yahr and the Unified Parkinson Disease Rating scales. LUTS were assessed by the International Continence Society questionnaire. We evaluated the impact of age, PD duration, neurological impairment, gender, and use of anti-Parkinsonian drugs on the voiding function. On multivariate analysis, voiding dysfunction increased with the neurological impairment, but not with patient's age or disease duration. Quality of life (QOL) was affected by the severity of LUTS, and the symptoms with the worst impact were frequency and nocturia. Sixty-three (57.2%) patients were symptomatic. They did not differ with the asymptomatic as to age and disease duration, but had more severe neurological impairment. No impact on LUTS was associated with the use of levodopa, anticholinergics, and dopamine receptor agonists. Men and women were similarly affected by urinary symptoms. The severity of the neurological disease is the only predictive factor for the occurrence of voiding dysfunction, which affects men and women alike.

Does the Association Between Anxiety and Parkinsons Disease Really Exist? A Literature Review

Introduction: Although anxiety is a common psychiatric complication of Parkinsons disease (PD), it has received little attention compared to depression in PD, being still an under-recognized and under-diagnosed condition in clinical practice. Objective: To review general aspects of the association between anxiety and PD concerning prevalence, etiopathogenesis, clinical characteristics, comorbidities, and treatment. Method: The basic and clinical literature on anxiety and PD was reviewed via the Pubmed, Lilacs and Scielo indexing services, using the keywords anxiety, etiology, prevalence, treatment, Parkinson, and Parkinsons disease. Moreover, complementary information was extracted from the reference lists of the articles found in the search. Results: Up to 67% of PD patients present clinically significant anxiety levels. Oscillations in anxious symptoms may be related to the use of anti-Parkinson drugs and motor fluctuations. The association between anxiety in PD and depressive disorders sleep disturbances, and cognitive impairment has also been proposed as a possible explanation for this psychiatric complication. Thus far, few data on the treatment of anxiety disorders in PD are available. Conclusions: More studies investigating aspects such as prevalence, etiopathogenesis, comorbidities, impact on life quality, and treatment are necessary and opportune in order to facilitate the recognition and diagnosis of anxiety disorders in PD.

Antidopaminergic therapy for managing comorbidities in patients with Parkinson’s disease

A literature evaluation of antidopaminergic therapies in patients with Parkinson's disease (PD) who have developed psychosis, nausea, vomiting, and hiccups was conducted. Complications associated with the use of antiparkinsonian drugs make PD management more difficult given the need for antidopaminergic therapy, which worsens motor functioning in patients with PD. For psychosis, clozapine is the only atypical antipsychotic that has proven effective without worsening motor function in PD patients. However, its use requires the monitoring of agranulocytosis. Newer atypical antipsychotics such as quetiapine have been claimed to be safe in terms of motor functioning, but evidence about their effectiveness is not compelling. The emergency treatment of psychosis in PD would require parenteral administration, only available for olanzapine and ziprasidone. However, no randomized controlled trials have been conducted to establish the efficacy and safety in this setting. For nausea and vomiting, very little domperidone crosses the blood-brain barrier. As a result, the risk of developing extrapyramidal adverse effects is minimal. Metoclopramide blocks central dopamine receptors and worsens motor parkinsonian symptoms. Chlorpromazine, the first-line treatment of intractable hiccups, is contraindicated in PD. Baclofen could be considered as a first-line alternative. Although clozapine can be used to treat psychosis in patients with PD, managing nausea, vomiting, hiccups, and emergent psychotic symptoms in these patients remains a challenge due to a lack of evidence for currently available options.

Thioridazine for schizophrenia.

Thioridazine is an antipsychotic that can still be used for schizophrenia although it is associated with the cardiac arrhythmia, torsades de pointe. To review the effects of thioridazine for people with schizophrenia. For this 2006 update, we searched the Cochrane Schizophrenia Group's Register (June 2006). We included all randomised clinical trials comparing thioridazine with other treatments for people with schizophrenia or other psychoses. We reliably selected, quality rated and extracted data from relevant studies. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) on an intention-to-treat basis. This review currently includes 42 RCTs with 3498 participants. When thioridazine was compared with placebo (total n=668, 14 RCTs) we found global state outcomes favoured thioridazine (n=105, 3 RCTs, RR 'no change or worse' by 6 months 0.33 CI 0.2 to 0.5, NNT of 2 CI 2 to 3). Thioridazine is sedating (n=324, 3 RCTs, RR 5.37 CI 3.2 to 9.1, NNH 4 CI 2 to 74). Generally, thioridazine did not cause more movement disorders than placebo.Twenty-seven studies (total n=2598) compared thioridazine with typical antipsychotics. We found no significant difference in global state (n=743, 11 RCTs, RR no short-term change or worse 0.98 CI 0.8 to 1.2) and medium-term assessments (n=142, 3 RCTs, RR 0.99, CI 0.6 to 1.6). We found no significant differences in the number of people leaving the study early 'for any reason' (short-term, n=1587, 19 RCTs, RR 1.07 CI 0.9 to 1.3). Extrapyramidal adverse events lower for those allocated to thioridazine (n=1082, 7 RCTs, RR use of antiparkinsonian drugs 0.45 CI 0.4 to 0.6). Thioridazine did seem associated with cardiac adverse effects (n=74, 1 RCT, RR 'any cardiovascular adverse event' 3.17 CI 1.4 to 7.0, NNH 3 CI 2 to 5). Electrocardiogram changes were significantly more frequent in the thioridazine group (n=254, 2 RCTs, RR 2.38, CI 1.6 to 3.6, NNH 4 CI 3 to 10). Six RCTs (total n=344) randomised thioridazine against atypical antipsychotics. Global state rating did not reveal any short-term difference between thioridazine and remoxipride and sulpiride (n=203, RR not improved or worse 1.00 CI 0.8 to 1.3). Limited data did not highlight differences in adverse event profiles. Although there are shortcomings, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used antipsychotics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems and higher level of ECG changes. We would advocate the use of alternative drugs, but if its use in unavoidable, cardiac monitoring is justified.

Effects of switching from conventional antipsychotics to risperidone in Japanese patients with chronic schizophrenia

Atypical antipsychotics are rapidly evolving to become the standard pharmacotherapy in schizophrenia; however, the trend of switching to such drugs is not necessarily progressing quickly in East Asia. This might be due to the scarcity of evidence for the efficacy of switching from conventional to atypical antipsychotics, which prompted the authors to examine effects of switching from conventional antipsychotics to an atypical drug, risperidone, in Japanese patients. Fifty patients with chronic schizophrenia completed the study in which combination therapy with other antipsychotics was allowed if monotherapy with risperidone was not tolerated. Symptoms were assessed with the brief psychiatric rating scale (BPRS). Switching to monotherapy was achieved in 34 patients (68%). The number of antipsychotics prescribed to each patient was reduced (from 2.1 to 1.4 drugs; P < 0.001) and the use of antiparkinsonian drugs decreased (P < 0.001). The mean BPRS score was also reduced 6 months after initiation of the switch (P < 0.001). Failure in switching to monotherapy was associated with higher dosage of antipsychotics at baseline. Switching from conventional antipsychotics to risperidone reduced schizophrenia symptoms, antiparkinsonian medication, and polypharmacy. However, a portion of patients, particularly those who receive an excessive dosage of antipsychotics, might not tolerate such switching.

Impact of second-generation antipsychotics on the use of antiparkinson agents in nursing homes and assisted-living facilities

Background: It is not known whether the reduced risk of motor adverse effects with second-generation antipsychotics (SGAPs) translates into less use of antiparkinson drugs (APDs). Objective: This study sought to estimate national rates of concomitant prescribing of APDs and antipsychotic drugs among elderly Medicare beneficiaries without Parkinson's disease (PD) who were residing in institutional settings from 1997 to 2000, a period during which the use of SGAPs increased greatly. Methods: This was a retrospective, cross-sectional, descriptive analysis using the Medicare Current Beneficiary Survey database. The population of interest was residents of nursing homes (NHs) and assisted-living facilities (ALFs) who received concomitant antipsychotic drugs and APDs but did not have PD. The primary objective of the study was to estimate the prevalence of concomitant APD and antipsychotic drug use for each study year, by use of first-generation antipsychotics (FGAPs) and SGAPs in each setting. A secondary objective was to compare concomitant use of APDs and individual antipsychotic agents (ie, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, haloperidol, and thioridazine). We computed population-level annual prevalence rates for APD use and tested for statistically significant differences in APD use between FGAPs and SGAPs at the 5% significance level. Results: In NH residents, concomitant use of APDs and antipsychotics decreased from 20.7% in 1997 to 9.0% in 2000 ( P < 0.005). APD use in NH residents declined similarly among users of FGAPs (from 23.2% in 1997 to 13.3% in 2000; P < 0.005) and SGAPs (from 18.4% in 1997 to 8.1% in 2000; P < 0.005). In ALF residents, concomitant use of APDs and antipsychotics decreased from 24.5% in 1997 to 21.1% in 2000 ( P < 0.005). ADP use in ALF residents receiving FGAPs decreased from 26.9% in 1997 to 24.2% in 2000 ( P < 0.005); there was no significant change in ADP use among ALF residents receiving SGAPs (from 21.0% in 1997 to 21.7% in 2000). Conclusions: These results provide the first nationally representative estimate of the concomitant use of APDs and antipsychotic drugs among older individuals in long-term care settings. The decrease in concomitant use of APDs and antipsychotics when SGAPs were used in NHs suggests an association between the use of SGAPs and a reduction in the prescribing cascade, in which one drug is used to treat the adverse effects of another. The results also suggest that some Medicare beneficiaries in ALFs may be continued on APDs despite changes in the prescribing of antipsychotic agents, implying a need for better medication-management practices in these institutions.

Use of antiparkinsonian drugs in Denmark: Results from a nationwide pharmacoepidemiological study

The objective of the present study was to record the use of antiparkinsonian drugs (APD) in Denmark and discuss estimates of the incidence and prevalence rates of Parkinson's disease (PD). The main indication for treatment with APD is idiopathic PD. The use of APD is, therefore, an indicator of the epidemiology of PD and Parkinsonism. We used a drug tracer design, which previously has been found applicable in estimating the frequency of PD. From a national prescription database, all persons who purchased APD from 1995 to 2002 could be identified on an individual level. Results show an age-standardized prevalence rate for APD purchase of 164.0 persons per 100,000, and an incidence rate of 55.9 persons per 100,000. The total number of persons purchasing APD was 11,656 per year on average. Our results showed higher figures of persons purchasing APD than the estimated prevalence of idiopathic PD in Denmark, which is approximately 100 persons per 100,000, corresponding to 5,000 to 6,000 persons. The differences might in part be explained by other indications for APD prescription in addition to PD and in part by misdiagnosis. However, the possibility of somewhat higher incidence and prevalence rates of PD than hitherto estimated should be considered.

Hallucinations and sleep disturbances in Parkinson’s disease

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.

Evaluation of antiparkinsonian drugs in pharmacy records as a marker for Parkinson's disease.

The aim of this study was to determine whether use of antiparkinsonian drugs in pharmacy records can be used as a marker for patients with Parkinson's disease (PD). Data were obtained from the Rotterdam Study, a community-based prospective cohort study among people aged 55 years or older who were all screened for PD. For 5510 persons, of whom 74 had PD, pharmacy records were available. Stepwise logistic regression analysis was used to evaluate whether age, sex and use of the antiparkinsonian drugs amantadine, anticholinergics, dopamine agonists, levodopa and selegiline, were predictive variables for PD. For each individual a probability for having PD was calculated. Sensitivity, specificity and positive predictive value (PPV) were calculated at different cut-off values based on calculated probabilities. More than 90% of the users of levodopa, bromocriptine, selegiline, and users of at least two different antiparkinsonian drugs had PD. Age, use of amantadine, anticholinergics, bromocriptine, levodopa, and selegiline were predictive variables for PD. After application of different cut-off values, sensitivity was at most 66.2%, and specificity was at least 99.8%. A PPV of higher than 90% was obtained at higher probabilities. Based on the high PPV of our predictive model, antiparkinsonian drugs can be used as a reliable marker for PD in pharmacy records. Because sensitivity is low, pharmacy records cannot be used to estimate prevalence of PD.

Factors affecting levodopa effects in Parkinson's disease.

Levodopa is the gold standard for the treatment of Parkinson's disease (PD) because of its outstanding clinical efficacy. However, the majority of patients experience various adverse reactions, including the wearing-off phenomenon, the on-off phenomenon, dyskinesia and psychiatric symptoms. The response to levodopa depends not only on the intrinsic responsiveness of the patients, but also on various other important factors including the type of levodopa preparation, its absorption/metabolism, the blood-brain barrier, age at onset of disease and concomitant use of anti-parkinsonian drugs. This review summarizes factors which influence the effects of levodopa in PD. To minimize levodopa-induced adverse reactions and to relieve long-term parkinsonian symptoms, levodopa therapy should be conducted by taking these factors into consideration.

Prevalence of orthostatic hypotension in Parkinson’s disease

OBJECTIVESTo investigate the prevalence of orthostatic hypotension and the nature of the postural events related to a fall in blood pressure in patients with Parkinson’s disease.METHODSBlood pressure was measured first...

Trihexyphenidyl (Artane) Dependence: A Controlled Investigation between Users and Abusers

This controlled study aims to identify the socioclinical factors predisposing psychiatric patients to abuse trihexyphenidyl (artane) and to document the extrapyramidal symptoms in artane abusers and users. Thirty patients (n=30), with mainly two major functional psychoses and who were abusing trihexyphenidyl, were compared with 90 artane user patients (n=90), who were matched for both the diagnosis and treatment. Besides a detailed clinical interview, each patient was assessed by using DSM-IIIR criteria, Brief Psychiatric Rating Scale, Simpson and Angus Scale, and Abnormal Involuntary Movement Scale. The analysis of data showed that, compared with users, trihexyphenidyl abusers were significantly characterized by being unmarried, unemployed, smokers and having past and concurrent history of multiple drug abuse, and genetic loading of mental disorders. Both groups of patients were prescribed antipsychotic drugs and trihexyphenidyl on a longer basis. Besides other socioclinical parameters, premorbid personalities, stressful life events and extrapyramidals, including tardive dyskinesias, we did not differentiate between the two groups. Artane abusers, when compared with users, were significantly characterized by less negative psychopathology. However, other psychopathological domains, in particular, the positive symptoms and depression, did not differentiate between abusers and users. In conclusion, patients having these socioclinical profiles tend to develop trihexyphenidyl abuse. The mental health professionals should not prescribe trihexyphenidyl indiscriminately or for a long time to such patients, who indeed require long-term antipsychotic maintenance medications.

Usage and Side Effects of Neuroleptics in Elderly Japanese Patients

The authors assessed the use and side effects of neuroleptics (especially tardive dyskinesia [TD]) in elderly patients in Japan (N = 73; mean age 76 years, 32 men and 41 women) admitted for the first time to six psychiatric hospitals. The comparison group was 74 elderly patients with dementia admitted to nursing homes or psychiatric hospitals and not treated with neuroleptics. The mean dose of neuroleptics in the Japanese elderly patients was lower than that in Western countries; however, the prevalence of side effects was higher, possibly because of polypharmacy. The total number of psychotropic drugs correlated significantly with the number of side effects. Incidence of dyskinesia in the patients treated with neuroleptics (for a mean of 20 months) was significantly greater (44%) than that in non-neuroleptic-treated patients (14%). A significant risk factor for TD was long-term neuroleptic therapy, whereas age, gender, psychiatric diagnosis, neuroleptic dose, and antiparkinsonian drug use were not risk factors.

Drug-Induced Parkinsonism in the Aged

Drug-induced Parkinsonism is a frequent adverse effect of numerous drugs interfering with dopamine function at the basal ganglionic level. It accounts for 4% of all patients with Parkinsonism seen in neurology clinics. Pharmacological agents implicated in the production of this disorder have a wide range of applications in medicine, beyond the treatment of psychiatric illnesses. Antipsychotics, substituted benzamides and calcium channel blockers are the drugs most commonly involved. The aged population is at an increased risk of drug-induced Parkinsonism due to intrinsic factors and because they often receive multiple drugs, including those from self-medication. Lack of knowledge in the medical profession of the potential hazards involved in the use of certain drugs plays a contributory role in the development of drug-induced Parkinsonism. Physicians should be always alert in order to detect, as early as possible, the presence of extrapyramidal symptoms in patients exposed to medications with antidopaminergic properties. Whenever possible, withdrawal of the medication will help resolve symptoms; complete remission takes place within 6 to 18 months in the majority of patients. The use of anti-Parkinsonian drugs is only advisable if the symptomatology is disabling. The best available treatment is prevention.

Prophylactic Antiparkinson Drug Use: II. Withdrawal After Long‐Term Maintenance Therapy

Although the efficacy of long-term neuroleptic treatment of schizophrenic patients is generally accepted, the use of concurrent antiparkinson drugs is less well defined. The value of prolonged antiparkinson drug use in preventing extrapyramidal side effects is controversial. More than 30 studies of antiparkinson drug withdrawal have attempted to answer this question. The authors reviewed all double-blind, placebo-controlled studies, and found most to contain serious methodologic or statistical flaws. There is evidence to support the long-term use of these agents in preventing extrapyramidal side effects. The authors offer an analysis of the benefits and risks that are involved with prophylactic antiparkinson drug use, and conclude that most patients would benefit from maintenance therapy.

Prophylactic Antiparkinson Drug Use: I. Initial Prophylaxis and Prevention of Extrapyramidal Side Effects

The use of prophylactic antiparkinson medications during neuroleptic treatment is controversial. Although the efficacy of these agents in the treatment of extrapyramidal side effects is well established, the questions of when to initiate therapy and for how long remain unanswered. There are only a few double-blind, placebo-controlled studies on the value of concurrent antiparkinson drug use at the beginning of neuroleptic treatment. The authors reviewed all studies on initial prophylaxis, and found most to be methodologically deficient. There is evidence to support the use of these agents to prevent acute dystonic reactions. Further work needs to focus on other types of extrapyramidal symptoms. In light of the inability to predict who will experience these side effects, the authors conclude that initial prophylaxis is beneficial for most patients who are starting neuroleptic medications.

Predictors of tardive dyskinesia: Results of a cross-sectional study in an outpatient population

A cross-sectional study was conducted to identify predictors of tardive dyskinesia (TD) in a group of 180 psychiatric outpatients maintained on neuroleptic medications. The estimated prevalence of this involuntary movement disorder was 33% in the total study population. Using multiple logistic regression, we found that TD was independently related to five factors: being 55 yr of age and older; being male; using depot (injectable) neuroleptics; having 6 or more years of neuroleptic exposure; and having less than 6 months of psychiatric hospitalization. In addition, the effect of depot medication was much greater in white males than it was in other race-sex groups. We observed no other interaction effects between pairs of predictor variables, nor did we find significant independent effects of race, denture use, DSM III diagnosis, current neuroleptic dose and potency, percent time on neuroleptics, and recent use of antiparkinsonian drugs or lithium. This study is serving as a pilot investigation for a large prospective incidence study that has already begun among patients at risk of developing TD in the same source population.

Neuroleptics, extrapyramidal symptoms, and serum-calcium levels

A prospective study of 34 new admissions to a psychiatric center revealed an 80% incidence of extrapyramidal symptoms among patients receiving only neuroleptic drugs (N = 24) during the first 2 weeks of hospitalization. The occurrence of acute dystonic reactions and parkinsonian symptoms (but not akathisia) in this group was significantly associated with a decrease in serumcalcium levels. The findings suggest the need for (1) prophylactic use of antiparkinsonian drugs during the initial stages of neuroleptic treatment and (2) further research into the possible role of calcium metabolism in the production of extrapyramidal side effects.

Controlled Study of Pimozide vs. Placebo in Tourette's Syndrome

This double-blind, crossover, prospective study compared the efficacy and safety of pimozide to placebo in 20 patients with Tourette's syndrome (TS). The study included a 2–week drug-free period, random assignment to pimozide or placebo for 6 weeks and crossover to the alternate medication for a second 6–week period. Multiple dependent measures of efficacy at endpoint by the clinician, patient and judges were all highly significant (most p values = 0.0001). Adverse reactions, commonly encountered with antipsychotic drugs, were related to dosage and generally could be managed by careful titration of dosage and use of antiparkinson drugs, except for an abnormal ECG in one patient. This study confirms previous reports in the literature that pimozide is an effective drug for the treatment of TS. Future controlled studies should be conducted to evaluate whether pimozide is more effective and has less adverse effects than haloperidol and other drugs.

Limitations of long term use of antiparkinson drugs.

Effective control of parkinsonian symptoms can be achieved in a substantial number of patients by the judicious use of dopaminergic agents. To a considerable extent these drugs produce optimal therapeutic effects during the first 3-5 years of their use. Subsequently, efficacy diminishes with reemergence of parkinsonian symptoms as well as a number of untoward responses. The nature, frequency and mechanisms underlying the limitations of long term use of presently available anti-parkinson agents are discussed in this presentation.