Use Of Antiparkinsonian Medication Research Articles

Risk factors for 3-year mortality in selected patients with Parkinson's disease from a Romanian cohort.

This study aimed to identify and analyze factors associated with a higher risk of 3-year mortality in patients with Parkinson's disease (PD) within a Romanian cohort, focusing on individuals with more advanced disease stages as indicated by the Hoehn and Yahr scale. We conducted a cross-sectional observational study on 42 patients with PD treated at the Neurology Clinic I, Cluj-Napoca County Emergency Clinical Hospital, between October 2019 and January 2021. All participants were at stages 2.5 or 3 on the Hoehn and Yahr scale at baseline. Various clinical, neuropsychological, and neurophysiological assessments were performed, including evaluations for motor and non-motor symptoms such as anhedonia (via the Snaith-Hamilton Pleasure Scale - SHAPS) and cognitive impairment. The use of antiparkinsonian medications and antidepressants was also recorded. Factors associated with higher mortality risk included a higher anhedonia score (SHAPS > 34; P = 0.03), higher levodopa doses (cutoff = 937.5 mg; P = 0.001), and the administration of mirtazapine (P = 0.04). These findings indicate that non-motor symptoms like anhedonia, along with higher medication doses and specific treatments, play a significant role in influencing mortality risk in advanced PD. This study highlights the multifaceted nature of mortality risk in patients with PD, particularly emphasizing the role of non-motor symptoms and pharmacological treatment. Tailored therapeutic strategies, including closer monitoring of anhedonia and careful management of medication dosages, may be essential in reducing mortality and improving patient outcomes in advanced stages of PD.

Development of a Screening Tool for Assessing Sexual Difficulties Among Patients with Parkinson's Disease: The PD-SDS.

People with Parkinson's disease (PwPD) exhibit various sexual difficulties (SDs) that may be due to motor and/or nonmotor symptoms or the use of antiparkinsonian medication. SDs are often underreported by PwPD and underexplored by physicians. This study aimed to explore the SDs experienced by PwPD and create a scale for assessing them. A corpus of items was generated from semistructured interviews to represent the experience of PwPD as closely as possible. The number of items was reduced according to the psychometric properties, and the scale's structure was subsequently examined. The final phase consisted of measuring the scale's validity and reliability. After assessment of the original corpus of 59 items by PwPD and clinicians, a 25-item version was obtained. The analysis of item properties led to the removal of fifteen items. An exploratory factor analysis of the first 10-item version with a first PwPD sample identified four components of the SDs among PwPD: "low sexual esteem," "sexual displeasure," "impact on sexual position" and "hypersexuality." With a second PwPD sample, a confirmatory factor analysis demonstrated a satisfactory fit between the model with four components and the data. The 10-item scale had good internal consistency and good temporal reliability. The Parkinson's Disease Sexual Difficulties Scale (PD-SDS) is a valid screening tool that facilitates the investigation of and communication about PD-related SDs. It is intended to improve the identification of vulnerable PwPD and to target the domain of sexual experience impacted by PD to better support PwPD.

Clinical and Brain Morphometry Predictors of Deep Brain Stimulation Outcome in Parkinson’s Disease

Subthalamic deep brain stimulation (STN-DBS) is known to improve motor function in advanced Parkinson’s disease (PD) and to enable a reduction of anti-parkinsonian medication. While the levodopa challenge test and disease duration are considered good predictors of STN-DBS outcome, other clinical and neuroanatomical predictors are less established. This study aimed to evaluate, in addition to clinical predictors, the effect of patients’ individual brain topography on DBS outcome. The medical records of 35 PD patients were used to analyze DBS outcomes measured with the following scales: Part III of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) off medication at baseline, and at 6-months during medication off and stimulation on, use of anti-parkinsonian medication (LED), Abnormal Involuntary Movement Scale (AIMS) and Non-Motor Symptoms Questionnaire (NMS-Quest). Furthermore, preoperative brain MRI images were utilized to analyze the brain morphology in relation to STN-DBS outcome. With STN-DBS, a 44% reduction in the UPDRS-III score and a 43% decrease in the LED were observed (p<0.001). Dyskinesia and non-motor symptoms decreased significantly [median reductions of 78,6% (IQR 45,5%) and 18,4% (IQR 32,2%) respectively, p=0.001 – 0.047]. Along with the levodopa challenge test, patients’ age correlated with the observed DBS outcome measured as UPDRS-III improvement (ρ= -0.466 – -0.521, p<0.005). Patients with greater LED decline had lower grey matter volumes in left superior medial frontal gyrus, in supplementary motor area and cingulum bilaterally. Additionally, patients with greater UPDRS-III score improvement had lower grey matter volume in similar grey matter areas. These findings remained significant when adjusted for sex, age, baseline LED and UPDRS scores respectively and for total intracranial volume (p=0.0041- 0.001). However, only the LED decrease finding remained significant when the analyses were further controlled for stimulation amplitude. It appears that along with the clinical predictors of STN-DBS outcome, individual patient topographic differences may influence DBS outcome. Clinical Trial Registration Number: NCT06095245, registration date October 23, 2023, retrospectively registered

A retrospective study evaluating the use of anti-Parkinsonian medications in patients with advanced Parkinson's disease treated with Levodopa-Carbidopa Intestinal Gel and deep brain stimulation

Patients using deep brain stimulation (DBS) with adjunctive oral therapy may require additional therapies like levodopa-carbidopa intestinal gel (LCIG), known as CLES in the United States. We examine use of oral/transdermal anti-parkinsonian medications in advanced Parkinson's disease (APD) patients with history of or current treatment with DBS, receiving LCIG.

A Retrospective Study Evaluating the Use of Anti-Parkinsonian Medications in Patients with Advanced Parkinson’s Disease Who Are Treated with Levodopa-Carbidopa Intestinal Gel and Deep Brain Stimulation: The PD-DUAL Study (2347)

A Retrospective Study Evaluating the Use of Anti-Parkinsonian Medications in Patients with Advanced Parkinson’s Disease Who Are Treated with Levodopa-Carbidopa Intestinal Gel and Deep Brain Stimulation: The PD-DUAL Study (2347)

Characterization of Gastrointestinal Symptom Type and Severity in Parkinson's Disease: A Case-Control Study in an Australian Cohort.

While constipation is a well-known non-motor symptom which may precede the onset of the classical motor symptoms of PD, there have been few comprehensive studies of gastrointestinal (GI) symptoms in people with PD (PwP). To investigate the spectrum of GI symptoms in an Australian PwP cohort and their relationship to use of anti-parkinsonian medications dietary habits and smoking. The prevalence and severity of GI symptoms were compared in a group of 163 PwP and 113 healthy control subjects using the Gastrointestinal Symptom Rating Scale (GSRS). Corrected linear regression models were used to determine differences between PwP and controls, and to investigate the influence of different classes of anti-Parkinsonian medications. PwP reported a greater frequency of constipation and GI-associated illnesses when compared to healthy controls. Total GSRS scores (P < 0.0001), upper GI symptoms (P < 0.0001), and hypoactive GI Symptoms (P < 0.0001) were all significantly greater in the PD cohort than controls. Further analyses revealed a positive association between the use of anti-Parkinsonian medications and total GSRS scores (P < 0.001), as well as upper GI symptoms (P < 0.001) and hypoactive GI function (P < 0.001). This study illustrates the frequency and array of GI symptoms in a large PD cohort. The findings indicate that anti-parkinsonian medications play an important role in the presentation and development of GI symptoms.

Comparative Efficacy and Tolerability of 32 Oral Antipsychotics for the Acute Treatment of Adults With Multi-Episode Schizophrenia: A Systematic Review and Network Meta-Analysis.

(Reprinted with permission from the Lancet 2019; 394: 939-51).

Subthalamic nucleus deep brain stimulation with a multiple independent constant current-controlled device in Parkinson's disease (INTREPID): a multicentre, double-blind, randomised, sham-controlled study.

Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease. This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396. Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p<0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation. This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes. Boston Scientific.

Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis

SummaryBackgroundSchizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials.MethodsWe did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919.FindingsWe identified 54 417 citations and included 402 studies with data for 53 463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from −0·89 (95% CrI −1·08 to −0·71) for clozapine to −0·03 (−0·59 to 0·52) for levomepromazine (40 815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31 179 participants) varied from −0·69 (95% CrI −0·86 to −0·52) for amisulpride to −0·17 (−0·31 to −0·04) for brexpiprazole, for negative symptoms (32 015 participants) from −0·62 (−0·84 to −0·39; clozapine) to −0·10 (−0·45 to 0·25; flupentixol), for depressive symptoms (19 683 participants) from −0·90 (−1·36 to −0·44; sulpiride) to 0·04 (−0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause discontinuation (42 672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30 770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24 911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide). Mean differences compared to placebo for weight gain (28 317 participants) ranged from −0·16 kg (−0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21 569 participants) from −77·05 ng/mL (−120·23 to −33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15 467 participants) from −2·21 ms (−4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole). Conclusions for the primary outcome did not substantially change after adjusting for possible effect moderators or in sensitivity analyses (eg, when excluding placebo-controlled studies). The confidence in evidence was often low or very low.InterpretationThere are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences.FundingGerman Ministry of Education and Research and National Institute for Health Research

Efficacy, acceptability and tolerability of antipsychotics in patients with schizophrenia and comorbid substance use. A systematic review and meta-analysis

Patients with schizophrenia and substance related comorbidity or substance induced psychotic disorder are difficult to treat. Although the prevalence of a comorbid substance use is approximately 40% in schizophrenia, such patients are usually excluded from clinical trials. We therefore performed a random-effects meta-analysis of all randomized controlled antipsychotic drug trials in this patient subgroup. We searched multiple databases up to May, 2018. The primary outcome was the reduction of substance user; secondary outcomes were craving, mean reduction of substance use, overall change in schizophrenia symptoms, positive and negative symptoms, response, dropouts, quality of life, social functioning, weight gain, sedation, prolactin, extrapyramidal side effects and use of antiparkinsonian medication. We identified 27 references from 19 RCTs published from 1999 to March 2017 including 1742 participants. The most frequent types of substance abuse were cannabis (8 studies) and cocaine (6 studies) use/dependence. Clozapine was superior to other antipsychotics for reduction of substance use and risperidone to olanzapine for craving. Olanzapine, clozapine and risperidone showed superiority for symptom reduction compared to some other drugs. When reported, results of side-effects followed known patterns. The evidence-base is considerable (19 RCTs), however, firm conclusions cannot be drawn due to small sample sizes of individual studies and insufficient reporting.

Antipsychotic drugs for elderly patients with schizophrenia: A systematic review and meta-analysis

Elderly patients with schizophrenia are a particularly vulnerable group often excluded from clinical trials. Currently there is no evidence-synthesis about the efficacy and safety of antipsychotics in this subgroup.We reviewed all randomized-controlled-trials, about antipsychotics in elderly schizophrenics (last search Dec 12, 2017). Pairwise meta-analyses were conducted. The primary outcome was overall symptoms. Secondary outcomes included positive symptoms, negative symptoms, response, dropouts, quality of life, social functioning and side-effects.We included 29 references from 18 unique randomized-controlled-trials with 1225 participants published from 1958 to 2009. The definition of “elderly” was very heterogeneous across the studies (minimum age 46–65, mean age 57–73). There were evidence gaps for most drugs in many outcomes. In terms of efficacy paliperidone was associated with fewer dropouts due to inefficacy than placebo in the only placebo-controlled-trial. Olanzapine was superior to haloperidol in overall symptoms, negative symptoms and response, and it was associated with fewer dropouts than risperidone. Risperidone and haloperidol produced more prolactin increase than olanzapine, and olanzapine was associated with less use of antiparkinson medication than haloperidol.Although we found no marked differences of the effects of these drugs in the elderly, the evidence presented was based on very few usually small studies. To examine specifically whether there are differences in efficacy and side-effects in elderly, which differs in meaningful ways from the general population, studies in patients who are defined by critiera as truly geriatric, which incorporates older age together with multimorbidity and fraility dimensions, may be more informative.

Use of anti-Parkinson medication during pregnancy: a case series.

Experience about the use and safety of anti-Parkinson (anti-PD) medication during pregnancy is scarce. We have retrospectively evaluated the course and outcome of pregnancy in PD patients who used anti-PD medication during their pregnancy. 14 PD patients who used anti-PD medication during part or whole of their pregnancy were included. Dopamine agonists were used in 13 patients, levodopa/benserazide in 4, levodopa/carbidopa/entacapone in 1, rasagiline in 7, amantadine in 4, and biperiden in 1 patient. Nine patients were on combination treatment at the time of their pregnancy. During their whole pregnancy, dopamine agonists had been used in six patients, levodopa in four, and rasagiline in one. Four patients experienced adverse outcomes: one had spontaneous abortion while receiving pramipexole, one elderly mother gave birth to a child with Down syndrome, while receiving pramipexole and rasagiline, in one case, there was fetal distress under levodopa/benserazide, piribedil, and rasagiline which resolved spontaneously, in one case, one of the twins did not survive after the birth while the mother was receiving pramipexole and rasagiline. In none of these cases an association with the use of anti-PD medication and adverse outcomes was clearly established. In one patient, motor symptoms worsened despite high dose levodopa, four others experienced transient worsening upon dose reduction. Results in our case series suggest that levodopa, rasagiline, pramipexole, and ropinirole alone or in combination with each other may be considered relatively safe during pregnancy. Expected benefits and risks should be considered when prescribing anti-PD medication in pregnant women.

Amantadine and the Risk of Dyskinesia in Patients with Early Parkinson's Disease: An Open-Label, Pragmatic Trial.

Objective We examined whether amantadine can prevent the development of dyskinesia.Methods Patients with drug-naïve Parkinson’s disease (PD), younger than 70 years of age and in the early stage of PD (Hoehn and Yahr scale < 3), were recruited from April 2011 to December 2014. The exclusion criteria included the previous use of antiparkinsonian medication, the presence of dyskinesia, significant psychological disorders, and previous history of a hypersensitivity reaction. Patients were consecutively assigned to one of 3 treatment groups in an open label fashion: Group A-1, amantadine first and then levodopa when needed; Group A-2, amantadine first, dopamine agonist when needed, and then levodopa; and Group B, dopamine agonist first and then levodopa when needed. The primary endpoint was the development of dyskinesia, which was analyzed by the Kaplan-Meier survival rate.Results A total of 80 patients were enrolled: Group A-1 (n = 27), Group A-2 (n = 27), and Group B (n = 26). Twenty-four patients were excluded from the analysis due to the following: withdrawal of amantadine or dopamine agonist (n = 9), alternative diagnosis (n = 2), withdrawal of consent (n = 1), and breach in the protocol (n = 12). After exclusion, 5 of the 56 (8.93%) patients developed dyskinesia. Patients in Group A-1 and A-2 tended to develop dyskinesia less often than those in Group B (cumulative survival rates of 0.933, 0.929, and 0.700 for A-1, A-2, and B, respectively; p = 0.453).Conclusion Amantadine as an initial treatment may decrease the incidence of dyskinesia in patients with drug-naïve PD.

Dural Arteriovenous Fistula-Associated Reversible Parkinsonism with Presynaptic Dopaminergic Loss.

Dear Sir, Although the association between reversible parkinsonism with dementia and dural arteriovenous fistula (dAVF) is well documented, its pathophysiological mechanism has not been fully described. Moreover, its relationship to the presynaptic dopaminergic system has not been reported, aside from one case report of hemi-parkinsonism due to midbrain arteriovenous malformation. In this report, we describe a patient presenting as parkinsonism who was shown to have dAVF and presynaptic dopaminergic nerve terminal loss based on dopamine transporter imaging. Interestingly, the parkinsonism in this patient improved following the occlusion of the dAVF without anti-parkinsonian drug therapy. A 75-year-old male with a four-month history of progressive gait difficulty visited our clinic. Upon admission, he exhibited severe bradykinesia and rigidity involving the axial muscles and all four limbs. Gait was short step with decreased bilateral arm swing and mild postural instability. Both hands exhibited 4–5 Hz rest tremors. The subject’s mini-mental status examination score was 18/30 (disorientation in time, memory recall impairment, reduced attention span, and impaired calculation). He had constipation and a previous history of dream enactment behaviors that suggested rapid eye movement sleep behavior disorder (RBD). Visual hallucinations began approximately one month prior to the clinic visit. In addition, he complained of right occipital headache that was aggravated by daily activities. At the time of admission, his unified Parkinson disease rating scale motor score was 49. Brain magnetic resonance imaging (MRI) revealed hyperintensity signals in the thalamus, globus pallidus, and cerebellum, with numerous distended deep cerebral and cortical venous structures (Figure 1A). These observations were highly suggestive of dAVF, which was confirmed by conventional angiography (Figure 1A). Because our initial clinical assessment was probable dementia with Lewy bodies, we performed N-(3-[18F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane ([18F]FP-CIT) positron emission tomography to determine whether his parkinsonian symptoms were related to nigrostriatal dopaminergic degeneration. An early phase scan image, which was obtained during first 10 min following [18F]FP-CIT injection, showed perfusion decreases in the left hemisphere including in the basal ganglia, thalamus and cerebellum (Figure 1B). A late phase scan image, which was obtained after 150 min, showed symmetric bilateral decreases in uptake in the basal ganglia with an anteroposterior gradient (Figure 1B), which was not related to hemodynamic changes induced by dAVF (Figure 1C). Considering the risk of future intracranial hemorrhage and venous sinus thrombosis, an embolization of the dAVF was performed. Follow-up angiography showed complete occlusion of the feeding arteries and normalized filling of the straight sinus. There was an improvement in the T2 signal changes on a follow-up brain MRI following the dAVF occlusion. The subject showed gradual improvements in gait disturbance and parkinsonian motor symptoms, and he became able to perform daily activities without difficulty and without the use of anti-parkinson medication. At two months after embolization and without any drug treatment during that period, his parkinsonian speech, cognitive symptoms and hallucinations had spontaneously improved, but his RBD symptoms remained unchanged. Figure 1. A: Brain magnetic resonance imaging at admission. T2-weighted images (top) show a vasogenic edema in the left thalamocapsular region. Susceptibility-weighted images (middle) show hypointensity signals in the thalamus, cerebellum, and occipital lobe with ... Venous hypertension, which results from increased blood flow via draining veins or from obstruction to drainage, has been associated with the neurological deficits [1]. Reversal of parkinsonism associated with dAVF might be explained by the restoration of cerebral hypoperfusion; however, not all patients with dAVF develop parkinsonism, and there are only a few case reports of reversible parkinsonism in cases of dAVF [2-4]. There is one report of dopamine transporter imaging in supratentorial hemorrahge-associated parkinsonism. In that case, anatomical distortion and compression of the midbrain might have resulted in the decreased 18F-fluorodopa uptake in the side contralateral to the acute supratentorial hematoma. However, in that case, the possible mechanisms such as presynaptic dopaminergic degeneration related to hemodynamic alterations and the possibility of coincident Parkinson’s disease were not elucidated [5]. Our patient is the first reported case to show decreased [18F]FP-CIT uptake in dAVF-associated parkinsonism. He exhibited symptoms suggestive of RBD, which is a premotor sign of synucleinopathy. Thus, we inferred that this patient might have a premanifest parkinsonian disorder, most likely dementia with Lewy bodies or Parkinson’s disease. The early phase scan of our patient showed decreased perfusion, and the amount of dopamine that is released is reported to be dependent on the cerebral blood flow [6]. Thus, these findings suggest that hemodynamic impairment could cause parkinsonism via an accentuation of the underlying dopamine deficiency in subjects with preclinical stage parkinsonism [5]. Because cases with reversible parkinsonism in the presence of dAVF are rare, dopamine transporter imaging studies are warranted in future cases to elucidate the presynaptic dopaminergic alteration–related mechanism of this rare manifestation.

Validation of secondary data sources to identify Parkinson disease against clinical diagnostic criteria.

Parkinson disease (PD) is the second most common neurodegenerative disorder. Its diagnosis relies solely on a clinical examination and is not straightforward because no diagnostic test exists. Large, population-based, prospective cohort studies designed to examine other outcomes that are more common than PD might provide cost-efficient alternatives for studying the disease. However, most cohort studies have not implemented rigorous systematic screening for PD. A majority of epidemiologic studies that utilize population-based prospective designs rely on secondary data sources to identify PD cases. Direct validation of these secondary sources against clinical diagnostic criteria is lacking. The Framingham Heart Study has prospectively screened and evaluated participants for PD based on clinical diagnostic criteria. We assessed the predictive value of secondary sources for PD identification relative to clinical diagnostic criteria in the Framingham Heart Study (2001-2012). We found positive predictive values of 1.0 (95% confidence interval: 0.868, 1.0), 1.0 (95% confidence interval: 0.839, 1.0), and 0.50 (95% confidence interval: 0.307, 0.694) for PD identified from self-report, use of antiparkinsonian medications, and Medicare claims, respectively. The negative predictive values were all higher than 0.99. Our results highlight the limitations of using only Medicare claims data and suggest that population-based cohorts may be utilized for the study of PD determined via self-report or medication inventories while preserving a high degree of confidence in the validity of PD case identification.

Quetiapine versus other atypical antipsychotics for schizophrenia

In many countries, second-generation ('atypical') antipsychotic drugs have become the first-line drug treatment for people with schizophrenia. It is not clear how the effects of the various second-generation antipsychotic drugs differ. To evaluate the effects of quetiapine compared with other second-generation (atypical) antipsychotic drugs in the treatment of people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Group Trials Register (May 2010), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. We included all randomised controlled trials (RCTs) comparing oral quetiapine with other oral forms of atypical antipsychotic medication in people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For dichotomous data, we calculated risk ratios (RRs) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a random-effects model. We calculated number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For continuous data, we calculated mean differences (MDs), again based on a random-effects model. Efficacy data tended to favour the control drugs over quetiapine (Positive and Negative Syndrome Scale (PANSS) total score vs olanzapine: 11 RCTs, n = 1486, mean quetiapine endpoint score 3.67 higher, CI 1.95 to 5.39, low quality; vs risperidone: 13 RCTs, n = 2155, mean quetiapine endpoint score 1.74 higher, CI 0.19 to 3.29, moderate quality; vs paliperidone: 1 RCT, n = 319, mean quetiapine endpoint score 6.30 higher, CI 2.77 to 9.83, moderate quality), but the clinical meaning of these data is unclear. No clear mental state differences were noted when quetiapine was compared with clozapine, aripiprazole or ziprasidone. Compared with olanzapine, quetiapine produced slightly fewer movement disorders (7 RCTs, n = 1127, RR use of antiparkinson medication 0.51, CI 0.32 to 0.81, moderate quality) and less weight gain (8 RCTs, n = 1667, RR 0.68, CI 0.51 to 0.92, moderate quality) and glucose elevation, but increased QTc prolongation (3 RCTs, n = 643, MD 4.81, CI 0.34 to 9.28). Compared with risperidone, quetiapine induced slightly fewer movement disorders (8 RCTs, n = 2163, RR use of antiparkinson medication 0.5, CI 0.36 to 0.69, moderate quality), less prolactin increase (7 RCTs, n = 1733, MD -35.25, CI -43.59 to -26.91) and some related adverse effects but greater cholesterol increase (6 RCTs, n = 1473, MD 8.57, CI 4.85 to 12.29). On the basis of limited data, compared with paliperidone, quetiapine induced fewer parkinsonian side effects (1 RCT, n = 319, RR use of antiparkinson medication 0.64, CI 0.45 to 0.91, moderate quality) and less prolactin increase (1 RCT, n = 319, MD -49.30, CI -57.80 to -40.80) and weight gain (1 RCT, n = 319, RR weight gain of 7% or more of total body weight 2.52, CI 0.5 to 12.78, moderate quality). Compared with ziprasidone, quetiapine induced slightly fewer extrapyramidal adverse effects (1 RCT, n = 522, RR use of antiparkinson medication 0.43, CI 0.2 to 0.93, moderate quality) and less prolactin increase. On the other hand, quetiapine was more sedating and led to greater weight gain (2 RCTs, n = 754, RR 2.22, CI 1.35 to 3.63, moderate quality) and cholesterol increase when compared with ziprasidone. Available evidence from trials suggests that most people who start quetiapine stop taking it within a few weeks (around 60%). Comparisons with amisulpride, sertindole and zotepine do not exist. Although efficacy data favour olanzapine and risperidone compared with quetiapine, the clinical meaning of these data remains unclear. Quetiapine may produce fewer parkinsonian effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine.Quetiapine appears to have a similar weight gain profile to risperidone, as well as clozapine and aripiprazole (although data are very limited for the latter two comparators).Quetiapine may produce greater weight gain than ziprasidone and less weight gain than olanzapine and paliperidone. Most data that have been reported within existing comparisons are of very limited value because of assumptions and biases within them. Much scope is available for further research into the effects of this widely used drug.

Management of Neuropsychiatric Symptoms in Long-Term Care Residents with Parkinson’s Disease

The management of neuropsychiatric symptoms, including psychosis, in Parkinson's Disease (PD) is complicated by the fact that treatment with antipsychotics can worsen the movement disorder, which may necessitate changes to antiparkinsonian medications. The objectives of this study were to determine what antipsychotics are prescribed to residents in long-term care with PD and document subsequent changes in levodopa dosage. A retrospective cohort study using administrative health database information from Ontario, Canada, was conducted. PD diagnostic codes were obtained from the Ontario Health Insurance Plan (physician diagnostic codes) and the Canadian Institute of Health Information (hospitalization discharge diagnoses). The Ontario Drug Benefit database provided information on the use of antiparkinsonian medications and antipsychotics. Residents diagnosed with PD in long-term care were included if they were treated with stable doses of levodopa monotherapy and received a new prescription for an antipsychotic. The type of antipsychotic and the changes in levodopa dosage were determined. There were 479 residents who met inclusion criteria. The prescribed antipsychotics were quetiapine (n = 192; 40 %), risperidone (n = 185; 39 %) and olanzapine (n = 81; 17 %), and only 21 (4 %) received a prescription for a typical antipsychotic. The first levodopa dosage change was a dose reduction in 469 (98 %) patients, and a dose increase in ten (2 %) patients. Many PD patients in long-term care are treated with potentially inappropriate antipsychotic medications. However, there is no evidence that this treatment results in a prescribing cascade that leads to inappropriate increases in levodopa dosage.

Guideline-Concordant Antipsychotic Use and Mortality in Schizophrenia

To determine if care concordant with 2009 Schizophrenia Patient Outcomes Research Team (PORT) pharmacological recommendations for schizophrenia is associated with decreased mortality. We conducted a retrospective cohort study of adult Maryland Medicaid beneficiaries with schizophrenia and any antipsychotic use from 1994 to 2004 (N = 2132). We used Medicaid pharmacy data to measure annual and average antipsychotic continuity, to calculate chlorpromazine (CPZ) dosing equivalents, and to examine anti-Parkinson medication use. Cox proportional hazards regression models were used to examine the relationship between antipsychotic continuity, antipsychotic dosing, and anti-Parkinson medication use and mortality. Annual antipsychotic continuity was associated with decreased mortality. Among patients with annual continuity greater than or equal to 90%, the hazard ratio [HR] for mortality was 0.75 (95% confidence interval [CI] 0.57-0.99) compared with patients with annual medication possession ratios (MPRs) of less than 10%. The HRs for mortality associated with continuous annual and average antipsychotic continuity were 0.75 (95% CI 0.58-0.98) and 0.84 (95% CI 0.58-1.21), respectively. Among users of first-generation antipsychotics, doses greater than or equal to 1500 CPZ dosing equivalents were associated with increased risk of mortality (HR 1.88, 95% CI 1.10-3.21), and use of anti-Parkinson medication was associated with decreased risk of mortality (HR 0.72, 95% CI 0.55-0.95). Mental health visits were also associated with decreased mortality (HR 0.96, 95% CI 0.93-0.98). Adherence to PORT pharmacological guidelines is associated with reduced mortality among patients with schizophrenia. Adoption of outcomes monitoring systems and innovative service delivery programs to improve adherence to the PORT guidelines should be considered.

Comparing Tolerability of Olanzapine in Schizophrenia and Affective Disorders

Background: Olanzapine is prescribed for a number of psychiatric disorders, including schizophrenia, bipolar mania, and unipolar and bipolar depression. Olanzapine treatment is associated with tolerability issues such as metabolic adverse effects (e.g. weight gain, increase in blood glucose, triglycerides and total cholesterol levels), extrapyramidal symptoms [EPS] (e.g. parkinsonism, akathisia, tardive dyskinesia) and sedative adverse effects. Metabolic issues lead to some long-term consequences, which include cardiovascular diseases (CVD) and type 2 diabetes mellitus, and these complications cause high rates of mortality and morbidity among patients with severe mental illnesses. The expanded indications of olanzapine in psychiatry suggest a need to investigate whether there is a difference in the incidence and severity of adverse effects related to category diagnosis. Are the adverse effects expressed differently according to phenotype? Unfortunately, there are no reported studies that investigated these differences in adverse effects associated with olanzapine treatment in psychiatric patients with different phenotypes. Objective: The aim of the present meta-analysis is to separately examine olanzapine-induced cardiometabolic adverse effects and EPS in patients with schizophrenia and affective disorders. Data Sources: A search of computerized literature databases PsycINFO (1967–2010), PubMed (MEDLINE), EMBASE (1980–2010) and the clinicaltrials.gov website for randomized clinical trials was conducted. A manual search of reference lists of published review articles was carried out to gather further data. Study Selection: Randomized controlled trials were included in our study if (i) they assessed olanzapine adverse effects (metabolic or extrapyramidal) in adult patients with schizophrenia or affective disorders; and (ii) they administered oral olanzapine as monotherapy during study. Data Extraction: Two reviewers independently screened abstracts for choosing articles and one reviewer extracted relevant data on the basis of predetermined exclusion and inclusion criteria. It should be mentioned that for the affective disorders group we could only find articles related to bipolar disorder. Data Synthesis: Thirty-three studies (4831 patients) that address olanzapine monotherapy treatment of adults with schizophrenia or bipolar disorder were included in the analysis. The primary outcomes were metabolic adverse effects (changes in weight, blood glucose, low-density lipoprotein, total cholesterol and triglyceride levels). The secondary outcomes of our study were assessing the incidence of some EPS (parkinsonism, akathisia and use of antiparkinson medication). The tolerability outcomes were calculated separately for the schizophrenia and bipolar disorder groups and were combined in a meta-analysis. Tolerability outcomes show that olanzapine contributes to weight gain and elevates blood triglycerides, glucose and total cholesterol levels in both schizophrenia and bipolar disorder patients. However, olanzapine treatment produced significantly more weight gain in schizophrenia patients than in bipolar disorder patients. In addition, increases in blood glucose, total cholesterol and triglyceride levels were higher in the schizophrenia group compared with the bipolar disorder group, even though these differences were not statistically significant. Based on our results, the incidence of parkinsonism was significantly higher in the schizophrenia group than in the bipolar disorder group. Subgroup analysis and logistic regression were used to assess the influence of treatment duration, dose, industry sponsorship, age and sex ratio on tolerability outcome. Conclusions: Our results suggest that schizophrenia patients may be more vulnerable to olanzapine-induced weight gain. The findings may be explained by considering the fact that in addition to genetic disposition for metabolic syndrome in schizophrenia patients, they have an especially high incidence of lifestyle risk factors for CVD, such as poor diet, lack of exercise, stress and smoking. It might be that an antipsychotic induces severity of adverse effect according to the phenotype.

Association of Parkinson's disease with infections and occupational exposure to possible vectors

The ultimate causes of idiopathic Parkinson's disease (PD) are not fully known, but environmental and occupational causes are suspected. Postencephalitic parkinsonism has been linked to influenza, and other viral infections have also been suspected to relate to PD. We estimated the relationship between PD and both infections and possible vectors of infection (i.e., animal and human) in a population-based, case-control study in British Columbia, Canada. We recruited 403 cases detected by their use of antiparkinsonian medications and 405 controls from the registrants of the provincial universal health insurance plan. Severe influenza was associated with PD (odds ratio [OR]: 2.01; 95% confidence interval [CI]: 1.16-3.48), although this effect was attenuated when reports were restricted to those occurring 10 or more years before diagnosis. Childhood illnesses were inversely associated with PD, particularly red measles (OR: 0.65; 95% CI: 0.48-0.90). Several animal exposures were associated with PD, with statistically significant effects for cats (OR: 2.06; 95% CI: 1.09-3.92) and cattle (OR: 2.23; 95% CI: 1.22-4.09). Influenza infection may be associated with PD. The inverse relationships with childhood infections may suggest an increased risk with subclinical or asymptomatic childhood infections. Occupational exposure to animals may increase risk through transmission of infections or may indicate exposure to another agent of interest (e.g., bacterial endotoxin).