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----------------------------------------------------------------------- ABSTRACT: 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. Adv Neurol 1995;65:115-138 Factor SA, Molho ES, Podskalny GD, Brown D Albany Medical College, Department of Neurology, New York, 12208, USA PMID: 7872135, MUID: 95176970 ------------------------------------------------------------------------ ABSTRACT: OBJECTIVE: To determine factors that are predictive for the=20 development of hallucinations associated with Parkinson disease (PD). ------------------------------------------------------------------------ BACKGROUND: Hallucinations are a common difficulty for patients with established PD, and hallucinations and psychosis may be the most common causes for= nursing home placement. The characteristics of the hallucinations associated with PD differ from the hallucinations associated with schizophrenia or cocaine= abuse. Multiple factors have been suggested as causal. DESIGN AND METHODS: A total of 214 consecutive patients were interviewed during routine visits to the Parkinson's Disease Clinics in Columbus, Ohio, and Miami, Fla, using a hallucination questionnaire, Folstein Mini-Mental State Examination, and an attempt to correlate age, duration of disease,= medication, and psychological or sleep disorders with the hallucinations. RESULTS: Hallucinations were almost exclusively visual and were present in 55 of the 214 patients. Dementia, age, duration of disease, history of depression, or history of sleep disorder were strongly associated with the hallucinations. CONCLUSIONS: While reduction in levodopa and anticholinergic medication doses is appropriate in the management of hallucinations, the factors that predispose patients to hallucinations include dementia and advancing age. The phenomena of visual hallucinations associated with PD, while not fully explained, are unique enough to be of interest to all neurologists and neuroscientists. Arch Neurol 1996 Dec;53(12):1265-1268 Sanchez-Ramos JR, Ortoll R, Paulson GW Department of Neurology, University of Miami School of Medicine, Fla, USA. PMID: 8970453, MUID: 97125374 ----------------------------------------------------------------------- ABSTRACT: Drug treatment of PD in the 1990s ------------------------------------------------------------------------ Advances in the medical treatment of Parkinson's disease have improved the disability related to complications of long term levodopa therapy, including motor fluctuations, dyskinesias and neuropsychiatric toxicity. A range of= new dopamine agonists are in various stages of preclinical and clinical development. Cabergoline appears to be effective in improving moderate motor= fluctuations, and a number of dopamine partial agonists that can act as either agonists or antagonists depending on the degree of denervation and receptor sensitivity are being investigated. Apomorphine represents a significant advance in the treatment of well developed motor fluctuations in selected patients who are able to master the technique of subcutaneous administration. The catecholamine-O-methyl transferase inhibitors are proving useful in= phase III studies in the management of patients with moderate motor fluctuations. A role for glutamate antagonists is supported by animal and early clinical data, although the poor therapeutic index associated with the currently available nonselective, noncompetitive glutamate antagonists has prompted a search for more selective antagonists with less toxicity. The management of levodopa-induced dyskinesias remains a major therapeutic challenge. Some reports of dopamine partial agonists, selective D2 receptor antagonists and atypical antipsychotics being useful await confirmation. Neuropsychiatric toxicity probably remains the major dose-limiting adverse effect of levodopa and is a major reason for parkinsonian patients being admitted to nursing homes. The development of new atypical antipsychotics= with improved therapeutic indices, along with the possible use of serotonergic antagonists, may improve management of this difficult problem. The challenge will be to fit these new forms of treatment into our present range of available drugs and to assess their relative role within the emerging framework of functional neurosurgery for parkinsonian disability. Drugs 1997 Feb;53(2):195-205 Hughes AJ Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia. PMID: 9028741, MUID: 97180565 ------------------------------------------------------------------------- ABSTRACT: Drug-Induced Psychosis + Delirium in PD ------------------------------------------------------------------------ Parkinson's disease (PD) is a progressive neurological condition that causes considerable disability in the elderly. Drugs used to treat PD, such as levodopa, offer symptomatic relief but often have neuropsychiatric adverse effects, most prominently psychosis and delirium. Aged patients and those= with dementia are particularly vulnerable to these adverse effects. Evaluating PD patients with drug-induced neuropsychiatric adverse effects is made difficult by their complex clinical presentations. The treatment of= drug- induced psychosis and delirium begins with manipulating the antiparkinsonian drug regimen, but this frequently worsens motor function. Atypical antipsychotics such as clozapine have been successfully employed to treat the psychosis without worsening the motor disability. Patient intolerance of clozapine therapy has prompted open-label studies with newer agents such= as risperidone, remoxipride, zotepine, mianserin and ondansetron. Drugs Aging 1997 May;10(5):367-383 Young BK, Camicioli R, Ganzini L Portland Veterans Affairs Medical Center, Oregon, USA. PMID: 9143857, MUID: 97288925 ------------------------------------------------------------------------ ABSTRACT: Inappropriate Medication Prescribing ------------------------------------------------------------------------ OBJECTIVE: To estimate the prevalence of inappropriate medications prescribed by office-based physicians for patients 65 years or older. DESIGN: A nationwide cross-sectional survey of office visits by the elderly. SETTING: The National Ambulatory Medical Care Survey (NAMCS) 1992, a= national probability sample survey of office visits by ambulatory patients within the continental US. SUBJECTS: A national probability sample of patients 65 years or older= visiting office-based physicians. National estimates are based on the National Center for Health Statistics weighting procedure for the NAMCS sample. MAIN OUTCOME MEASURES: Prevalence of 20 inappropriate medications that should be entirely avoided in the elderly, using criteria developed by a panel of national experts in geriatric medicine and geriatric pharmacology. RESULTS: In the US during 1992, an estimated 8.47 million (95% CI 7.66= million to 9.28 million) office visits by the elderly indicated prescribing of at least 1 of the 20 inappropriate medications. Approximately 7.75 million (95% CI= 6.98 million to 8.52 million) visits by the elderly involved 1 inappropriate medication and 0.72 million (95% CI 0.51 million to 0.93 million) visits included 2 inappropriate medications. According to the NAMCS, office-based physicians prescribed at least 1 inappropriate medication to 7.58% of the elderly who received prescriptions. The most frequently prescribed inappropriate medications were propoxyphene, amitriptyline, dipyridamole, diazepam, and chlorpropamide. Elderly patients rarely received prescriptions from office-based physicians for drugs such as secobarbital, isoxsuprine, trimethobenzamide,= and carisoprodol. Furthermore, office-based physicians did not prescribe cyclandelate, pentobarbital, or phenylbutazone for the elderly. CONCLUSIONS: The prescribing of inappropriate medications by office-based physicians raises concerns regarding the quality of care for the elderly in ambulatory settings. The crux of improving patient care in ambulatory= settings rests with collaborative efforts between physicians and pharmacists. Ann Pharmacother 1997 Jul;31(7-8):823-829 Aparasu RR, Fliginger SE College of Pharmacy, South Dakota State University, Brookings 57007 USA. [log in to unmask] PMID: 9220038, MUID: 97363746 ----------------------------------------------------------------------- ABSTRACT: Psychotic Disorders in the Elderly ------------------------------------------------------------------------ OBJECTIVE: To review the epidemiology, phenomenology, and treatment of psychotic disorders in late life. METHOD: The literature relating to psychotic symptoms in the elderly is reviewed, with a focus on the following categories: primary psychotic disorders, mood disorders, delirium, Parkinson's disease (PD), and somatic hallucinoses (including Charles Bonnet syndrome [CBS] and musical hallucinosis).= Practical clinical treatment implications are discussed. RESULTS: The prevalence of psychotic symptoms increases with age, largely because of underlying medical illnesses such as dementia, delirium, and= other neurological disorders that are exacerbated by sensory deficits coupled with social isolation. Treatment with the traditional high-potency neuroleptics= is complicated by extrapyramidal symptoms, and sedation, postural hypotension, and anticholinergic effects complicate the use of low-potency traditional= agents.=7F Although clozapine may have a narrow use in the treatment-resistant schizophrenia and PD, it is poorly tolerated in the elderly. Risperidone has= a wider use in this population and has a favourable clinical profile (at low doses). Other new neuroleptics await more formal evaluation in the elderly. CONCLUSION: Psychotic disorders in old age have more organic associations, which cause greater difficulty in their treatment. Further Evaluation of the use= of atypical agents in this elderly group is indicated. Can J Psychiatry 1997 Jun;42 Suppl 1:19S-27S Thorpe L Department of Psychiatry, University of Saskatchewan, Saskatoon. PMID: 9220126, MUID: 97363834 ------------------------------------------------------------------------ ABSTRACT: Clozapine + Drug-Induced Psychosis in PD ------------------------------------------------------------------------ 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. Mov Disord 1997 Jul;12(4):483-496 Factor SA, Friedman JH Albany Medical College, Department of Neurology, New York, USA. PMID: 9251065, MUID: 97394752 ------------------------------------------------------------------------ ABSTRACT: Drug-induced psychosis is a serious late complication=20 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. J Neuropsychiatry Clin Neurosci 1995;7(3):304-307 Factor SA, Molho ES, Brown DL Albany Medical College, Department of Neurology, New York 12208, USA. PMID: 7580188, MUID: 96076000 ----------------------------------------------------------------------- [log in to unmask]