Parkinson Disease: Friedman JH

Friedman JH. · No affiliation provided · Neurology. · Pubmed #19171841 No free full text.

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Black KJ, Friedman JH. · No affiliation provided · Neurology. · Pubmed #17030743 No free full text.

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Friedman JH. · No affiliation provided · Med Health R I. · Pubmed #16184821 No free full text.

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Friedman JH, Millman RP. · Neuro Health Parkinson's Disease and Movement Disorders, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. · CNS Spectr. · Pubmed #18323762 links to  free full text

Abstract: Although Parkinson's disease is defined by its motor symptoms, the symptoms that are most devastating to patients and caregivers are dementia and psychosis. In addition, sleep has a tremendous impact on patient well being and quality of life. Eighty percent to 90% of Parkinson's disease patients have a sleep disorder affecting their ability to fall asleep, ability to stay asleep, dreams, motor activity during sleep, post-sleep behavior, or daytime somnolence. Treatment plans for patients with Parkinson's disease who experience sleep disorders aim to improve nighttime sleep or daytime wakefulness, and treatment options vary by sleep disorder.

Borek LL, Chou KL, Friedman JH. · Neurohealth Alzheimer's Disease and Movement Disorders Center, and Department of Geriatric Psychiatry, Butler Hospital, Warren Alpert Medical School of Brown University, RI, USA. · Expert Rev Neurother. · Pubmed #17563253 No free full text.

Abstract: Parkinson's disease is a progressive and debilitating movement disorder that is diagnosed by its motor signs. The behavioral manifestations of Parkinson's disease are prevalent and frequently complicate the course of the disease. These may be due to the illness itself or its treatment and are often more disabling than the motor symptoms. This review focuses on the management of the most common behavioral symptoms of Parkinson's disease, including depression, anxiety, psychosis, dementia, delirium, sleep disorders, fatigue, apathy, emotionalism and compulsive behaviors.

Chou KL, Borek LL, Friedman JH. · Department of Clinical Neurosciences, Warren Alpert Medical School of Brown University, Providence, RI, USA. · Expert Opin Pharmacother. · Pubmed #17472539 No free full text.

Abstract: Psychosis may be seen with several movement disorders. As pharmacological treatments can sometimes worsen movement disorders, psychosis in these situations can be complex for clinicians to manage. This review covers the management of psychosis in three different movement disorders: Parkinson's disease, dementia with Lewy bodies and Huntington's disease.

Friedman JH, Brown RG, Comella C, Garber CE, Krupp LB, Lou JS, Marsh L, Nail L, Shulman L, Taylor CB, Anonymous00113. · NeuroHealth, Warwick, Rhode Island 02886, USA. · Mov Disord. · Pubmed #17133511 No free full text.

Abstract: Fatigue is a common problem in Parkinson's disease (PD), often the most troubling of all symptoms. It is poorly understood, generally under-recognized, and has no known treatment. This article reviews what is known about the symptom, putting it into the context of fatigue in other disorders, and outlines a program for developing better understanding and therapy.

Borek LL, Amick MM, Friedman JH. · Department of Geriatric Psychiatry, Brown University School of Medicine, Providence, RI, USA. · CNS Spectr. · Pubmed #16816793 links to  free full text

Abstract: Parkinson's disease is primarily considered to be a movement disorder and is defined by its motor signs. Yet, the behavioral manifestations of the disease are often more debilitating than its motor complications. This review will focus on the non-motor aspects of Parkinson's disease, including mood, psychosis, cognitive, sleep, fatigue, apathy, delirium, and repetitive disorders, that may occur. The phenomenology, pathology, and treatment of the behavioral symptoms of Parkinson's disease will be discussed.

Friedman JH, Chou KL. · Division of Neurology, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA. · Parkinsonism Relat Disord. · Pubmed #15109584 No free full text.

Abstract: Sleep disorders and fatigue are common problems in Parkinson's disease (PD). Although they frequently appear together, they are often distinct symptoms that must be understood separately. Fatigue has been reported to be the most bothersome aspect of PD in about one-third of patients, yet it is poorly understood and not clearly treatable. Sleep disorders, while more common, are less bothersome to the patients and often responsive to therapy. An overview of sleep disorders in PD and an approach to therapy will also be outlined. The little that is known about fatigue in PD will be reviewed.

Fernandez HH, Trieschmann ME, Friedman JH. · Department of Clinical Neurosciences, Brown University School of Medicine, Providence, Rhode Island, USA. · Drug Saf. · Pubmed #12814332 No free full text.

Abstract: 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.

Friedman JH. · Division of Neurology, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860, USA. · Psychoneuroendocrinology. · Pubmed #12504071 No free full text.

Abstract: 'Typical' antipsychotic agents can lead to a variety of extrapyramidal symptoms (EPS), including parkinsonism. The efficacy of a number of atypical antipsychotics in reducing psychosis without a detrimental effect on motor function has been studied in the group of patients most vulnerable to EPS, those who already have parkinsonian symptoms. Multiple open-label studies with clozapine strongly suggested that at low doses the drug was an effective antipsychotic and did not impair motor function. This was confirmed by two double-blind, placebo-controlled studies. A disadvantage of clozapine is that it can cause agranulocytosis and therefore patients require ongoing hematological monitoring. Studies with both risperidone and olanzapine have produced conflicting results, with some patients showing an overall improvement and others exhibiting severe deterioration of motor function. As with clozapine, multiple open-label studies with quetiapine have consistently demonstrated that it improves psychosis without impairing motor function. Double-blind trials are yet to be performed: however, the existing data, coupled with the lack of required blood monitoring, have led some experts to recommend quetiapine as the drug of choice for treatment of drug-induced psychosis in patients with parkinsonism. The atypical antipsychotics have also been tested in the largest group of EPS-vulnerable patients, the demented elderly. Results from a number of trials are described here. These data are more difficult to interpret as the number of variables is far greater than for the population with parkinsonism. However, the evidence to date indicates a generally low incidence of tardive dyskinesia with atypical antipsychotics.

Friedman JH, Fernandez HH. · Department of Clinical Neurosciences, Brown University School of Medicine, Providence, Rhode Island, USA. · J Geriatr Psychiatry Neurol. · Pubmed #12230086 No free full text.

Abstract: Drug-induced iatrogenic hallucinations and psychosis occur in about 30% of Parkinson's disease (PD) patients and are the single most important precipitant for nursing home placement, which carries a grave prognosis. In addition, parkinsonism is a frequent accompaniment to the more common dementing syndromes, Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies (DLB). The five most recent antipsychotic drugs approved by the Food and Drug Administration in the United States have been marketed as "atypical" antipsychotics (AA) due to their relative freedom from extrapyramidal symptoms when used in schizophrenia patients. The use of these newer antipsychotic drugs in PD and other parkinson-sensitive populations represents the most stringent test to their freedom from motor side effects. To date, clozapine, risperidone, olanzapine, and quetiapine have been studied in parkinson-vulnerable populations. This article reviews the data and highlights the differences that these four drugs have on motor function. It also emphasizes the challenges in evaluating the available data on the motor effects of AA, especially on the non-PD elderly and cognitively impaired population. Suggestions are made for future research to improve the interpretability of these studies.

Friedman JH, Factor SA. · Memorial Hospital of Rhode Island, Pawtucket 02860, USA. · Mov Disord. · Pubmed #10752567 No free full text.

Abstract: Our experience with atypical antipsychotics in patients with PD is that their motor effects are not predictable. The multiple reports concerning clozapine's beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias all underscore this observation. However, the appearance of even minor degrees of parkinsonism in normal volunteers or schizophrenics should suggest that an antipsychotic will not be well-tolerated in patients with PD. The treatment of PD is probably the most stringent test of a drug's freedom from parkinsonian side effects. The data from trials in schizophrenia concerning parkinsonian effects cannot always be confidently interpreted. Virtually all subjects in these trials have been treated with typical neuroleptics until shortly before study entry. Because the parkinsonian side effects of these drugs may persist for several months, patients may still show declining levels of parkinsonism even when placed on a drug that induces it if this effect is milder than that induced by the pre-study neuroleptic. Depending on the pre-study drug used and the duration of the study, distinguishing placebo from a low-potency neuroleptic may be impossible. Furthermore, the standard measure of parkinsonism in psychiatric studies is the Simpson-Angus scale which is heavily weighted toward rigidity and may underscore bradykinesia, gait, and posture abnormalities. The prolactin response to an antipsychotic drug may turn out to be a good predictor of its freedom from parkinsonian side effects. That would fit with the data presented above of clozapine and quetiapine having less parkinsonian effects, olanzapine having more but variable effects and risperidone being poorly tolerated. With the data presented above, comprising a current review of all reports of the use of atypical antipsychotics in PD that we could locate, we can say little with certainty. The only drug with confirmed benefit without worsening parkinsonism is clozapine. Open-label trials involving over 400 patients and two multicenter, placebo-controlled, double-blind trials have demonstrated that it is effective in treating the psychosis. It improves tremor, does not worsen other motor functions to any significant extent, and is safe at low doses. Limited data provide conflicting information on both risperidone and olanzapine. Quetiapine seems to be well-tolerated with some, but definitely less, worsening of PD motor features than risperidone and olanzapine. Based on the current literature, our personal experience, and anecdotal experience of other PD specialists which we solicited, we will venture our own interpretation and recommendations. We think risperidone is poorly tolerated and should be used only as a last resort; that olanzapine is better than risperidone but will, in a majority of patients with PD, worsen motor function. We are optimistic, but not yet convinced, that quetiapine may prove to be as effective and better tolerated than clozapine. It will not require cumbersome monitoring because it does not induce a blood dyscrasia. We therefore recommend that DP be treated in the following manner. First, the anti-PD medications should be simplified and reduced as much as tolerated. We think, in general, side effects multiply more with increasing numbers of drugs than with drug dose, so that patients are more likely to tolerate a higher dose of levodopa than a lower dose of levodopa combined with other adjunctive anti-PD medications. In reducing anti-PD medications, we recommend tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. Anticholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own. Finally, levodopa is reduced. Generally, a point is reached at which the anti-PD medications cannot be reduced without jeopardizing motor function. If psychosis persists at this point, then an antipsychotic is added. (ABS

Shetty N, Friedman JH, Kieburtz K, Marshall FJ, Oakes D. · Department of Clinical Neurosciences, Brown University School of Medicine, Providence, Rhode Island, USA. · Clin Neuropharmacol. · Pubmed #10442249 No free full text.

Abstract: Our objective was to study the placebo response in Parkinson's disease (PD). We conducted a literature search in which placebo response was measured in all studies of PD from 1969 to April 1996. Strict criteria were defined to include or exclude published reports in our survey. The Parkinson Study Group database for Deprenyl & Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) was reviewed and placebo "responders" were compared to placebo "nonresponders" by age, race, religion, level of education, duration of PD, and gender. A significant difference between the efficacy of placebo and that of active drug was reported in 61% (22 of 36) of the articles meeting the required criteria; DATATOP analysis showed no statistically significant epidemiologic differences between 140 placebo responders and 58 placebo nonresponders except in PD effect on current job. Although there is clearly a placebo response in PD patients, our review suggests that the variation in placebo response does not correlate with demographic factors such as age, gender, religion, level of education, or duration of PD.

Fernandez HH, Lannon MC, Trieschmann ME, Friedman JH. · Department of Clinical Neuroscience, Brown University School of Medicine, Providence, RI, USA. · Med Sci Monit. · Pubmed #15232500 No free full text.

Abstract: BACKGROUND: Freezing of Gait (FOG) can be a serious problem in Parkinson's disease (PD) and is usually refractory to medical treatment. Botulinum toxin (BTX) type A has been reported to relieve FOG in small open label studies. MATERIAL/METHODS: We performed a double-blind, placebo-controlled, parallel-group study using BTX-B injections on the soleus-gastrocnemius muscle complex of the predominantly affected leg in freezing. Patients were evaluated at baseline and monthly thereafter until endpoint was reached. UPDRS parts II and III, Visual Analog Scale (VAS), Clinical Global Impression Scale (CGIS) and Modified Webster Step-Seconds test were the used to measure efficacy. RESULTS: 14 out of 17 patients screened with idiopathic PD and FOG refractory to medical treatment met inclusion criteria for the study. 9 patients were randomized to 5,000 U of BTX-B treatment and 5 patients to placebo. Our cohort had a mean age of 74 years, and average PD duration of 10 years. Based on the CGIS, 1 patient was much improved, 2 patients had minimal improvement, 9 were unchanged from baseline and 2 were minimally worse. There was no significant difference between the treatment and placebo arms in the number of patients improved versus unchanged. There were no significant differences between the treatment and placebo arms in the UPDRS II and III, VAS, or Modified Webster Step-Seconds scores between the treatment and placebo arms, at baseline and after treatment. CONCLUSIONS: 5,000 U of BTX-B injected in one leg did not significantly improve FOG. However, since the power of the study was low, a small beneficial effect may have been missed.

Fernandez HH, Trieschmann ME, Friedman JH. · Department of Neurology, University of Florida College of Medicine, Gainesville, FL 32610, · Clin Neuropharmacol. · Pubmed #15090928 No free full text.

Abstract: Aripiprazole is the newest atypical antipsychotic (AA) drug to be released in the US. It is the only AA that is a partial agonist at the D2 and 5HT1a receptors and an antagonist at 5HT2a receptors. It also has a high 5HT2/D2 ratio and may therefore carry a low risk of extrapyramidal side effects and alleviate psychosis in Parkinson-vulnerable populations. We report our preliminary experience in 8 patients with probable Parkinson disease (PD) treated with aripiprazole for drug-induced psychosis. Two patients were neuroleptic-naive, 5 patients were "quetiapine failures", and 1 patient was switched from olanzapine to aripiprazole. Aripiprazole was started at 5 mg to 10 mg a day and slowly increased over 3 to 7 days until side effects or improvement of psychosis occurred. Only 2 out of 8 patients experienced near complete resolution of their psychosis using aripiprazole. The other six patients discontinued aripiprazole within 40 days, 2 of whom discontinued due to motor worsening. Our preliminary experience with aripiprazole is mixed but not very encouraging. Controlled studies are needed to evaluate aripiprazole in parkinsonian patients.

Factor SA, Feustel PJ, Friedman JH, Comella CL, Goetz CG, Kurlan R, Parsa M, Pfeiffer R, Anonymous00282. · Albany Medical Center, NY 12205, USA. · Neurology. · Pubmed #12796526 No free full text.

Abstract: OBJECTIVES: To examine the long-term outcome of PD patients with psychosis requiring antipsychotic therapy; to explore predictors of mortality, nursing home placement, dementia, and persistent psychosis; and to compare outcomes of those with persistent psychosis vs those whose psychosis resolved. METHODS: Baseline data available from 59 patients enrolled in the PSYCLOPS (PSychosis and CLOzapine in PD Study) trial included age, age at onset of PD, duration of PD and psychosis, character of psychosis, medications, living setting, and scores for Mini-Mental State Examination (MMSE), Unified Parkinson's Disease Rating Scale, Hoehn and Yahr Scale, and Clinical Global Impression Scale. Longitudinal data were collected 26 months later regarding four outcomes: death, nursing home placement, diagnosis of dementia, and persistence of psychosis. Logistic regression was used to explore whether any baseline characteristics were associated with an increased likelihood of one of these outcomes. RESULTS: At baseline, 56% of patients had an MMSE score of <25, 12% were in a nursing home, 95% had hallucinations, and 60% had paranoia. On follow-up, 25% were dead, nursing home placement occurred in 42%, psychosis was persistent in 69%, and dementia was diagnosed in 68%. Select baseline characteristics predicted individual outcomes: Nursing home placement was associated with the presence of paranoia and older age; persistent psychosis was associated with younger age at onset of PD and longer disease duration; dementia was associated with older age at PD onset and lower initial MMSE score; no characteristics predicted death. Whether psychosis persisted or not had no significant effect on the development of the other three outcomes. The prevalence of hallucinations at follow-up was not different between groups currently receiving antipsychotics vs those on no treatment. CONCLUSIONS: Psychosis in PD requiring antipsychotic therapy is frequently associated with death, nursing home placement, development and progression of dementia, and persistence of psychosis. Still, it appears the prognosis has improved with atypical antipsychotic therapy based on the finding that 28% of NH patients died within 2 years compared with 100% in a previous study done prior to availability of this treatment.

Garber CE, Friedman JH. · Bouvé College of Health Sciences, Department of Cardiopulmonary and Exercise Sciences, Northeastern University, Boston, MA 02115, USA. · Neurology. · Pubmed #12682317 No free full text.

Abstract: OBJECTIVE: To characterize the relationships between symptoms of fatigue, physical activity, physical function, and functional capacity in patients with idiopathic PD. METHODS: Thirty-seven patients with PD underwent evaluation of physical activity, physical function, functional capacity, and fatigue. Physical activity and fatigue were measured by standard questionnaires (Godin Leisure Activity Questionnaire, Yale Physical Activity Questionnaire, and Fatigue Severity Scale); physical function was measured by the Up and Go Test and the Six-Minute Walk; and functional capacity was measured by a maximal oxygen uptake exercise test (VO(2max)). RESULTS: Increased levels of fatigue were associated with decreased levels of leisure physical activity, lower frequency of vigorous physical activity, less time spent moving about performing daily tasks each day, lower diastolic blood pressure and VO(2max), longer Up and Go performance time, and carbidopa-levodopa (CL) use. A multiple regression analysis was performed to determine factors predicting fatigue (Fatigue Severity Scale). The Up and Go Test, Leisure Activity Score, CL use, VO(2max), and diastolic blood pressure were the best predictor variables of fatigue. The Up and Go Test and CL use contributed independently to the model, whereas the other variables appeared to moderate the relationships between these variables. CONCLUSIONS: PD patients with more severe fatigue are more sedentary and have poorer functional capacity and physical function compared with patients with less fatigue.

Breier A, Sutton VK, Feldman PD, Kadam DL, Ferchland I, Wright P, Friedman JH. · Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. · Biol Psychiatry. · Pubmed #12242060 No free full text.

Abstract: BACKGROUND: Studies in elderly patients demonstrate antipsychotic efficacy and favorable safety profiles for olanzapine. We report results from two placebo-controlled, double-blind studies of olanzapine for treatment of dopamimetic drug-induced psychosis in patients with Parkinson's disease (PD). METHODS: Patients were treated with olanzapine or placebo for 4 weeks while dopamimetic therapy was held constant. Olanzapine was initiated at 2.5 mg/day, with 2.5-mg/day increases allowed every 3 to 4 days up to the maximum dose of 15 mg/day. RESULTS: Olanzapine patients showed significant improvements from baseline on positive symptoms and most efficacy measures, but no significant treatment-group differences were observed. Olanzapine performed significantly worse than placebo in both studies on the Unified Parkinson's Disease Rating Scale (UPDRS) total, Motor, and Activities of Daily Living scales, but not the UPDRS Tremor item or Complications scores. Corrected QT interval, vital signs, and body weight were not significantly different from placebo. CONCLUSIONS: These findings did not demonstrate superior efficacy of olanzapine for treatment of dopamimetic-induced psychosis in PD. The initial dose-titration schedule and mild baseline levels of psychosis may account for these findings. Future studies involving gradual dose titration are needed to explore further olanzapine's optimum use for patients with PD with treatment-related psychosis.

Fernandez HH, Trieschmann ME, Burke MA, Friedman JH. · Department of Clinical Neurosciences, Brown University School of Medicine, Providence, RI, USA. · J Clin Psychiatry. · Pubmed #12088163 No free full text.

Abstract: BACKGROUND: Most clinicians perceive psychosis in dementia with Lewy bodies (DLB) as more difficult to treat than Parkinson's disease, yet there are no reports comparing the antipsychotic response between the 2 disorders. METHOD: All charts of Parkinson's disease and DLB patients at our Movement Disorders Center, Memorial Hospital of Rhode Island, Pawtucket, given quetiapine for psychosis were reviewed. Demographic data, including type and severity of psychosis, before and after Unified Parkinson's Disease Rating Scale (UPDRS)-motor scores, motor worsening, and treatment response (recorded as poor/none, partial, or total), were obtained. The chi-square test was used to assess differences in efficacy and tolerability of quetiapine between Parkinson's disease and DLB patients. RESULTS: Eighty-seven Parkinson's disease and 11 DLB patients with psychosis were analyzed. No significant difference in mean age, levodopa dose, quetiapine dose, duration of quetiapine use, or baseline UPDRS-motor score was noted between Parkinson's disease and DLB patients. Eighty percent (70/87) of Parkinson's disease patients and 90% (10/11) of DLB patients had partial to complete resolution of psychosis using quetiapine (p = .40). Motor worsening was noted at one point in 32% (28/87) of Parkinson's disease and 27% (3/11) of DLB patients over the duration of quetiapine use (p = .74). CONCLUSION: Long-term quetiapine use was generally well tolerated in this geriatric Parkinson's disease and DLB population. Mild motor worsening occurred in some patients. No significant difference in long-term efficacy and motor worsening associated with quetiapine treatment was noted between the 2 disorders.

Factor SA, Friedman JH, Lannon MC, Oakes D, Bourgeois K, Anonymous00168. · Albany Medical College, New York, USA. · Mov Disord. · Pubmed #11215574 No free full text.

Abstract: OBJECTIVE: To report the results of the 12-week, prospective, open label extension of the 4-week, multicenter, placebo-controlled, double-blind PSYCLOPS (PSYchosis and CLOzapine in the treatment of Parkinsonism) trial. This extension examined the chronic safety and efficacy of clozapine in the treatment of drug-induced psychosis in Parkinson's disease (PD). BACKGROUND: Psychosis is a serious late complication of PD and may be a harbinger to increased mortality. Clozapine, the first atypical antipsychotic, was shown in several small open label studies to improve psychosis without worsening of motor symptoms. This was recently confirmed in the double-blind PSYCLOPS trial. METHODS: The 53 patients who completed the double-blind portion of PSYCLOPS were evaluated on their original randomized treatment (clozapine or placebo), then had study medication stopped. All were started on clozapine. The patients from both treatment groups were evaluated every 4 weeks over a 12-week period using standardized measures for psychosis and PD. RESULTS: The mean dose of clozapine was 28.78 mg/day. Those originally treated with placebo improved significantly in Brief Psychiatric Rating Scale and clinical global scores for psychosis to the same degree as the group originally randomized to clozapine in the double-blind study. Both groups maintained their response to week 16 (end of the combined double-blind and open label portions). There was no worsening of motor features as measured by the Unified Parkinson's disease rating scale. Eighteen patients were either hospitalized or died during the trial. The most common reasons were pulmonary. CONCLUSIONS: Low-dose clozapine is effective in treating drug-induced psychosis without worsening motor features of PD, and the response is maintained for at least 4 months. Patients with psychosis and PD were previously described as a group with high risk for morbidity and mortality. The high risk continues despite antipsychotic therapy.

Fernandez HH, Friedman JH, Jacques C, Rosenfeld M. · Department of Neurology, Brown University School of Medicine, Memorial Hospital of Rhode Island, Pawtucket 02860, USA. · Mov Disord. · Pubmed #10348474 No free full text.

Abstract: Quetiapine is an atypical antipsychotic with clozapine-like pharmacology but without associated agranulocytosis. We report our complete experience with quetiapine for the treatment of drug-induced psychosis (DIP) in Parkinson's disease (PD). Thirty-five patients with PD and DIP aged 75 years (range, 58-89) with a mean PD duration of 8.4 years on an average of 427 mg levodopa per day received a mean dose of 40.6 mg quetiapine daily. Twenty of 24 neuroleptic-naive patients reported marked improvement of psychosis without a decline in motor function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS-motor). Ten patients had a baseline and 4-week follow-up assessment using the Mini-Mental Status Examination (MMSE) and Brief Psychiatric Rating Scale (BPRS). The improvement in BPRS score (32.6 versus 22.8) was clinically and statistically significant (p = 0.024). Three of 24 were unable to tolerate quetiapine because of orthostatic hypotension, headache, nausea, and persistence of hallucinations. One patient died of an unrelated cause. We also tried to switch 11 psychiatrically stable patients on clozapine (eight) and olanzapine (three). Five patients made this transition without a loss of effect as measured on BPRS and MMSE. Six did not (five on clozapine, one on olanzapine) because of confusion, erratic behavior, and increased hallucinations. No crossover failure had worsened PD except for increased tremor in one. Quetiapine is useful and well-tolerated as a first drug to treat DIP in PD but must be used cautiously to replace other atypical antipsychotic drugs.

Friedman JH. · No affiliation provided · Med Health R I. · Pubmed #19288681 No free full text.

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Friedman JH. · No affiliation provided · Med Health R I. · Pubmed #19093377 No free full text.

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Grace J, Amick MM, Friedman JH. · Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #18931006 No free full text.

Abstract: OBJECTIVE: To study the efficacy and safety of galantamine hydrobromide ER for the enhancement of cognition in non-demented Parkinson's patients (PD). METHODS: Sixty-nine non-demented PD participants were randomised in a double-blind, placebo-controlled study of galantamine or placebo. Galantamine was administered over 16 weeks (8 mg/day for 4 weeks, a therapeutic dose of 16 mg/day for 6 weeks and a maximum dose of 24 mg/day for 6 weeks). Outcome measures were neuropsychological (attention, verbal fluency, executive, memory, visuospatial), behavioural (Frontal Systems Behavior Scale, Neuropsychiatric Inventory-Questionnaire, PDQ-39) and motor (Unified Parkinson's Disease Rating Scale motor scale). RESULTS: 26 individuals on active medication and 28 individuals on placebo were included in the outcome analyses. No significant differences were found between the active and placebo groups on cognitive, behavioural or motor outcome measures. Most common adverse events were gastrointestinal and self-reported worsening of PD symptoms. CONCLUSIONS: Contrary to our hypotheses, galantamine treatment did not improve attention/executive, memory or visuospatial performance in non-demented PD patients. Further, there was a high, statistically significant drop-out rate in the treatment group due to gastrointestinal side effects and self-reported worsening of PD symptoms. Treatment with galantamine did not enhance self-perception of mental sharpness or quality of life. No negative behavioural change such as hallucinations or apathy was found with treatment.