Abnormal Involuntary Movement Scale Scores Research Articles

Transcranial direct current stimulation improves tardive dyskinesia in long-term hospitalized patients with chronic schizophrenia

ObjectiveThis study aimed to evaluate the efficacy and safety of transcranial direct current stimulation (tDCS) in chronic schizophrenia patients with tardive dyskinesia (TD) who were long-term hospitalized. MethodsSixty-four inpatients who met the DSM-IV diagnostic criteria for schizophrenia and TD were randomly assigned to either the active (N=35) or sham (N=29) group. Treatment was given 15 times, with each session lasting for 30 min, and an intensity of 2 mA. The anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right supraorbital region. Primary outcome was measured by the changes in Abnormal Involuntary Movements Scale (AIMS) score. Secondary outcomes were measured using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Adverse effects of tDCS were assessed with an experimenter-administered open-ended questionnaire throughout the experiment. ResultsOf the 64 patients, 52 (81.25%) completed the study. Compared to the sham group, patients in the active group exhibited a significant reduction in both the total AIMS score and the facial-oral subscore (P<0.05). An improvement of at least 30% in total AIMS scores was observed in the active group (14 patients, 50%) compared to the sham group (2 patients, 8.3%) after treatment (P<0.01). There were no between-group differences in the PANSS and SANS total scores. However, there was a significant difference between the two groups in the occurrence of the reported adverse effect of tingling sensation (P<0.05). ConclusionsTDCS may be an effective and safe treatment for improving the facial-oral motor symptoms of TD in chronically hospitalized patients with schizophrenia. SignificanceThis study provides a novel perspective for the clinical treatment of patients with TD.

Tardive Dyskinesia with Antipsychotic Medication in Children and Adolescents: A Systematic Literature Review.

Tardive dyskinesia (TD) is a persisting, and potentially irreversible, movement disorder associated with treatment with dopamine receptor antagonists. Few data are available on the risk of TD in children and adolescents treated with antipsychotic medication. To review the literature on incidence, risk factors, and treatment options for antipsychotic-associated TD in children and adolescents (aged < 18 years). Relevant articles were identified through a systematic search of Embase and Medline performed in January 2024. Methodological quality was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute Critical Appraisal tools. Thirteen studies were identified. The reported TD point prevalence was 5-20%, with higher rates in studies involving typical antipsychotics. Lower estimates (around 1%) emerged from analyses of clinical database data suggesting underdiagnosis in clinical practice. Risk factors included treatment with typical antipsychotics, higher doses, longer duration of exposure, older age, female gender, higher baseline Abnormal Involuntary Movements Scale (AIMS) scores, intellectual impairment, and perinatal complications. Although relatively few cases have been reported in children and adolescents, TD remains a risk in this population. Individuals receiving antipsychotics should be monitored carefully for the emergence of abnormal movements. Other than dose reduction, discontinuation, or switch to a lower-risk antipsychotic, few interventions have demonstrated efficacy. The strongest evidence for pharmacological treatment is for VMAT-2 inhibitors (valbenazine and deutetrabenazine), but these drugs are not licensed for use in children. To reduce risk, antipsychotics should be prescribed only if necessary, at the minimum effective dose and for the minimum necessary duration.

Analysis of schizophrenia-associated genetic markers in the HLA region as risk factors for tardive dyskinesia.

The pathology of Tardive Dyskinesia (TD) has yet to be fully understood, but there have been proposed hypotheses for the cause of this condition. Our team previously reported a possible association of TD with the Complement Component C4 gene in the HLA region. In this study, we explored the HLA region further by examining two previously identified schizophrenia-associated HLA-region single-nucleotide polymorphisms (SNPs), namely rs13194504 and rs210133. The SNPs rs13194504 and rs210133 were tested for association with the occurrence and severity of TD in a sample of 172 schizophrenia patients who were recruited for four studies from three different clinical sites in Canada and USA. The rs13194504 AA genotype was associated with decreased severity for TD as measured by Abnormal Involuntary Movement Scale (AIMS) scores (p=0.047) but not for TD occurrence. SNP rs210133 was not significantly associated with either TD occurrence or AIMS scores. Our findings suggest that the rs13194504 AA genotype may play a role in TD severity, while SNP rs210133 may not have a major role in the risk or severity of TD.

Association of dopamine receptor D3 polymorphism with Levodopa-induced Dyskinesia: A study on Parkinson’s disease patients from India

IntroductionLevodopa-induced dyskinesia (LID) is a debilitating motor feature in a subset of patients with Parkinson’s disease (PD) after prolonged therapeutic administration of levodopa. Preliminary animal and human studies are suggestive of a key role of dopamine type 3 (D3) receptor polymorphism (Ser9Gly; rs6280) in LID. Its contribution to development of LID among Indian PD patients has remained relatively unexplored and merits further investigation. Methods and materials200 well-characterised PD patients (100 without LID and 100 with LID) and 100 age-matched healthy controls were recruited from the outpatient department of Institute of Neurosciences Kolkata. MDS-UPDRS (Unified Parkinson’s Disease Rating Scale from International Movement Disorder Society) Part III and AIMS (abnormal involuntary movement scale) were performed for estimation of severity of motor features and LID respectively in the ON state of the disease. Participants were analysed for the presence of Ser9Gly single nucleotide variant (SNV) (rs6280) by polymerase chain reaction followed by restriction fragment length polymorphism techniques. ResultsThe frequency of AA genotype (serine type) was more frequently present in PD patients with LID compared to PD patients without LID (50 % vs 28 %; P = 0.002; OR = 2.57, 95 % CI: 1.43 – 4.62). The abnormal involuntary movement scale score was significantly higher in PD patients with AA genotype compared to carriers of glycine allele (AG + GG) (4.08 ± 3.35; P = 0.002). ConclusionWe observed a significant association of serine type SNV (rs6280) in D3 receptor gene in a cohort of PD patients with LID from India. More severe motor severity was found in patients with glycine substitution of the same SNV. The current study emphasised the role of D3 receptor in the pathogenesis of LID.

Buspirone and Zolmitriptan Combination for Dyskinesia: A Randomized, Controlled, Crossover Study.

Preclinical evidence suggests that co-administration of the 5-HT1A agonist buspirone and the 5-HT1B/1D agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone. Assess the therapeutic potential of a fixed-dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa-induced dyskinesia. Single-center, randomized, placebo-controlled, two-way crossover study (NCT02439203) of a fixed-dose buspirone/zolmitriptan regimen (10/1.25 mg three times a day) in 30 patients with PD experiencing at least moderately disabling peak-effect dyskinesia. Seven days of treatment with buspirone/zolmitriptan added to levodopa significantly reduced dyskinesia as assessed by Abnormal Involuntary Movement Scale scores versus placebo (mean treatment effect vs. placebo: -4.2 [-6.1, -2.3]) without significantly worsening Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON) scores (mean treatment effect vs. placebo: 0.6 [-0.1, 1.3]). No serious adverse events were reported. In this proof-of-concept study, addition of buspirone/zolmitriptan to the patients' PD medication regimen significantly reduced dyskinesia severity without worsening motor function. © 2024 International Parkinson and Movement Disorder Society.

Homocysteine Levels and Clinical Outcomes in Schizophrenia—A Pilot Randomized Controlled Trial

Objectives: To find out the relation between homocysteine levels in peripheral blood and the effectiveness as well as the safety of haloperidol and olanzapine in schizophrenia treatment. Materials and Methods: A prospective randomized parallel-group open-label interventional clinical trial was conducted on 40 mild to moderate schizophrenia patients. To compare the efficacy of olanzapine and haloperidol Brief Psychiatric Rating Scale (BPRS) score was used. Homocysteine levels of peripheral blood and Abnormal Involuntary Movement Scale scores were evaluated. Results: BPRS score improved in both groups on day 14 and day 28. But significantly more with olanzapine ( P value =.001). The olanzapine group showed a higher reduction (13.91±0.47 to 9.74±0.5) in homocysteine levels than the haloperidol group. Also, the BPRS scores negatively correlated ( r = –0.66) to homocysteine levels. Conclusion: Therefore, our study shows that peripheral blood homocysteine levels can be used to predict and assess the treatment outcome in schizophrenia patients. Biomarker driven approach in schizophrenia will allow the patients to be treated promptly with the right drug. In this light, personalized treatment holds great potential in the future.

Effects of Long-Term Deutetrabenazine Treatment in Patients with Tardive Dyskinesia and Underlying Psychiatric or Mood Disorders

Deutetrabenazine is FDA-approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal trials (ARM-TD/AIM-TD), deutetrabenazine significantly improved Abnormal Involuntary Movement Scale (AIMS) scores and was well-tolerated. This post hoc analysis examined the efficacy and safety of long-term deutetrabenazine treatment in TD patients with comorbid psychiatric illness, including schizophrenia/schizoaffective disorder and mood disorders (bipolar/depression/other). Patients who completed ARM-TD or AIM-TD enrolled in the 3-year, open-label extension (OLE) study. Deutetrabenazine was titrated based on dyskinesia control and tolerability. Change from baseline in total motor AIMS score, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and adverse events (AEs) were analyzed in subgroups by comorbid psychiatric illness. A total of 337 patients in the OLE study were included in the analysis: 205 patients with schizophrenia/schizoaffective disorder (mean age, 55years; 50% male; 6.4years since diagnosis; 92% taking DRA) and 131 patients with mood disorders (mean age, 60years; 35% male;4.6years since diagnosis; 50% taking DRA). At week 145, mean±SE dose was 40.4±1.1mg/day for schizophrenia/schizoaffective disorder (n=88) and 38.5±1.2mg/day for mood disorders (n=72). Mean±SE change from baseline in AIMS score at week 145 was -6.3±0.49 and -7.1±0.58, 56% and 72% achieved PGIC treatment success, and 66% and 82% achieved CGIC treatment success in schizophrenia/schizoaffective disorder and mood disorder patients, respectively. Overall AE incidence (exposure-adjusted incidence rates [incidence/patient-years]) was low: any, 1.02 and 1.71; serious, 0.10 and 0.12; leading to discontinuation, 0.07 and 0.05). Long-term deutetrabenazine treatment provided clinically meaningful improvements in TD-related movements, with a favorable safety profile, regardless of underlying comorbid psychiatric illness. Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.

CPNP 2022 Annual Meeting Poster Abstracts

CPNP 2022 Annual Meeting Poster Abstracts

Minimal clinically important change in Abnormal Involuntary Movement Scale score in tardive dyskinesia as assessed in pivotal trials of deutetrabenazine

IntroductionDeutetrabenazine is approved by the US Food and Drug Administration to treat tardive dyskinesia (TD) based on 2 pivotal, 12-week, placebo-controlled studies (ARM-TD and AIM-TD) evaluating safety and efficacy in patients with baseline total motor Abnormal Involuntary Movement Scale (AIMS) score ≥6. This analysis estimated the minimal clinically important change (MCIC) in total motor AIMS score in TD patients treated with deutetrabenazine. MethodsThe pooled analysis population included all patients in ARM-TD and AIM-TD who received study drug and had ≥1 postbaseline AIMS assessment. MCIC analyses were performed using Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) as anchors. MCIC was defined as the mean change from baseline in total motor AIMS score in patients treated with deutetrabenazine who were rated minimally improved on PGIC or CGIC at Week 12. ResultsThis analysis included 295 patients (deutetrabenazine, n = 197; placebo, n = 98). At Week 12, the MCIC in deutetrabenazine-treated patients was −2.4 based on the PGIC and −2.1 based on the CGIC. Mean change from baseline in total motor AIMS score for placebo-treated patients rated minimally improved was −1.4 based on the PGIC and −1.5 based on the CGIC. The proportion of deutetrabenazine-treated patients who achieved improvement in total motor AIMS score by ≥2 and ≥3 points was 66% and 55%, respectively. ConclusionUsing anchor-based methodology, the MCIC on the AIMS for deutetrabenazine in patients with TD was approximately −2, suggesting that a reduction in total motor AIMS score of ∼2 is associated with clinically meaningful improvement in TD symptoms.

An Experimental Study to Assess the Professional and Social Consequences of Tardive Dyskinesia.

ObjectiveAntipsychotic medications may cause tardive dyskinesia (TD), an often-irreversible movement disorder characterized by involuntary movements that are typically stereotypic, choreiform, or dystonic and may impair quality of life. This study evaluated others’ perceptions of abnormal TD movements in professional and social situations.MethodsThis was an experimental, randomized, blinded, digital survey in a general population sample. Participants were randomized 11 into a test or control group to view a video of a professional actor simulating TD movements or no TD movements prior to completing surveys on employment, dating, and friendship domains. Assessments for mild-to-moderate and moderate-to-severe TD movements were conducted separately. Authenticity of abnormal movements and Abnormal Involuntary Movement Scale (AIMS) scores were evaluated by physician experts.ResultsSurveys were completed by 2,400 participants each for mild-to-moderate and moderate-to-severe TD. In all domains, participants responded significantly less favorably to persons with TD movements (both mild-to-moderate and moderate-to-severe) than those without TD movements. Fewer participants in the test versus control group for mild-to-moderate and moderate-to-severe TD, respectively, considered the candidate as a potential employee (29.2% and 22.7% fewer), found him/her attractive (20.5% and 18.7% fewer), and were interested in becoming friends with him/her (12.3% and 16.5% fewer).ConclusionProfessional actors simulating TD movements were perceived more negatively than those without TD movements in employment, dating, and friendship domains. To our knowledge, this is the first randomized study to quantify professional and social stigma associated with TD movements that may reduce opportunities for gainful employment, marital status, and an effective support system.

Long-Term Deutetrabenazine Treatment for Tardive Dyskinesia Is Associated With Sustained Benefits and Safety: A 3-Year, Open-Label Extension Study.

BackgroundDeutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia (TD) in adults. In two 12-week pivotal studies, deutetrabenazine demonstrated statistically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores, with favorable safety/tolerability in TD patients. This study reports long-term efficacy and safety of deutetrabenazine in a 3-year, single-arm, open-label extension (OLE) study.MethodsPatients who completed the pivotal studies could enroll in this single-arm OLE study, titrating up to 48 mg/day based on dyskinesia control and tolerability. Efficacy was assessed based on change from baseline in total motor AIMS score, Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change (PGIC), and quality of life (QOL) assessments. Safety evaluation included adverse event (AE) incidence, reported using exposure-adjusted incidence rates, and safety scales.Results343 patients enrolled in the study (6 patients were excluded). At Week 145 (mean dose: 39.4 ± 0.83 mg/day), mean ± SE change from baseline in total motor AIMS score was −6.6 ± 0.37 and 67% of patients achieved ≥50% improvement in total motor AIMS score. Based on CGIC and PGIC, 73% and 63% of patients achieved treatment success, respectively. QOL improvements were also observed. Deutetrabenazine was generally well tolerated, with low rates of mild-to-moderate AEs and no new safety signals; most safety scales remained unchanged over time.ConclusionsLong-term deutetrabenazine treatment was associated with sustained improvement in AIMS scores, indicative of clinically meaningful long-term benefit, and was generally well tolerated. Results suggest deutetrabenazine may provide increasing benefit over time without increases in dose.

Long-Term Safety and Efficacy of Deutetrabenazine in Younger and Older Patients With Tardive Dyskinesia

To assess long-term safety and efficacy of deutetrabenazine in younger (<55 years) and older (≥55 years) adult participants with tardive dyskinesia (TD). Three-year, single-arm, open-label extension (OLE) study enrolling participants who completed the 12-week, pivotal ARM-TD or AIM-TD studies. Seventy-six centers in the United States and Europe. A total of 337 participants with TD (119 younger and 218 older). Deutetrabenazine was initiated at 12 mg/day and titrated once weekly by 6 mg/day using a response-driven dosing regimen until adequate dyskinesia control was reached or a clinically significant adverse event occurred. This post hoc analysis assessed change and percent change from baseline in total motor Abnormal Involuntary Movement Scale (AIMS) score, response rates for ≥50% AIMS improvement, Clinical Global Impression of Change (CGIC), Patient Global Impression of Change (PGIC), and safety in younger and older participants with TD. After 3 years of open-label treatment, mean deutetrabenazine dose was ∼39.5 mg/day in both groups. Mean±SE changes from baseline in total motor AIMS score were -6.7 ± 0.62 and -6.5 ± 0.47 in younger and older participants, respectively (percent changes: -61.4% ± 4.10% and -54.6% ± 3.01%); 76% of younger and 62% of older participants achieved ≥50% AIMS response. Most younger and older participants achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%). Deutetrabenazine was generally well tolerated in both groups. Deutetrabenazine treatment was associated with sustained improvements in total motor AIMS score, treatment success, and improved quality of life, and was well tolerated in younger and older adults with TD in this 3-year OLE study.

Effect of Varenicline on Tardive Dyskinesia: A Pilot Study.

ObjectiveAlthough evidence implicates striatal cholinergic impairment as a mechanism underlying tardive dyskinesia, trials of nonspecific cholinergic agents have been inconclusive. As a partial agonist at specific nicotinic receptor subtypes, varenicline reduces drug-induced dyskinesias in animal models suggesting promise as a treatment for tardive dyskinesia.MethodsThree schizophrenia patients with tardive dyskinesia who were smokers underwent an open trial of varenicline. After a 2-week baseline, subjects received varenicline 1 mg twice daily. Changes from baseline on the Abnormal Involuntary Movement Scale were measured after a 4-week varenicline stabilization period, and 6 weeks after the smoking quit date in one patient.ResultsVarenicline had no effect on mean Abnormal Involuntary Movement Scale scores after 4 weeks. Although smoking decreased after 4 weeks on varenicline and diminished further in one patient after 10 weeks, this also appeared to have no effect on ratings of tardive dyskinesia.ConclusionIn contrast to animal models, no significant change in tardive dyskinesia occurred in response to varenicline replacement in three schizophrenia patients. Further investigations of cholinergic mechanisms in tardive dyskinesia are worthwhile as agents for specific cholinergic targets become available for treatment. In addition, treatment trials of tardive dyskinesia should control for smoking status, while patients on antipsychotics receiving nicotine replacement therapies for smoking should be studied further for changes in movement.

Long-Term Deutetrabenazine Treatment Is Associated With Continued Improvement in Tardive Dyskinesia in the Completed 3-Year Open-Label Extension Study

The 12-week ARM-TD and AIM-TD studies in tardive dyskinesia (TD) patients showed statistically significant improvements in TD symptoms with deutetrabenazine. The completed open-label extension (OLE) study (SD-809-C-20) evaluated long-term efficacy and safety of deutetrabenazine in TD. Patients who completed ARM-TD or AIM-TD enrolled in the OLE study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score was assessed by local site raters. Treatment success was evaluated locally as patients being "much improved" or "very much improved" on Clinical Global Impression of Change (CGIC). 343 patients enrolled in the OLE study; 6 patients were excluded from analyses. At Week 54 (n=249; dose [mean±SE]: 38.7±0.66mg/day), mean change from baseline in AIMS score was -4.8±0.28; 66% of patients experienced treatment success. At Week 106 (n=194; dose: 39.3±0.75mg/day), mean change from baseline in AIMS score was -5.4±0.33; 65% of patients experienced treatment success. At Week 145 (n=160; dose: 39.4±0.83mg/day), mean change from baseline in AIMS score was -6.6±0.37; 73% of patients experienced treatment success. Treatment was generally well tolerated across 723 patient-years of exposure through Week 158, and exposure-adjusted incidence rates (incidence/patient-years) for akathisia/restlessness were 0.01, somnolence/sedation were 0.07, and symptoms which may represent parkinsonism or depression were 0.08 each. Patients who received long-term treatment with deutetrabenazine achieved sustained improvement in AIMS scores. Findings from this open-label trial with response-driven dosing suggest the possibility of increasing benefit over time. Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.

Minimal Clinically Important Difference in AIMS Score Based on CGIC and PGIC in Patients With Tardive Dyskinesia Treated With Deutetrabenazine

Deutetrabenazine is FDA approved for tardive dyskinesia (TD) based on two 12-week, placebo-controlled studies evaluating safety and efficacy in patients with baseline Abnormal Involuntary Movement Scale (AIMS) score ≥6. Deutetrabenazine reduced overall AIMS scores compared with placebo in ARM-TD (-3.0 vs -1.6, P=0.019) and AIM-TD (24 mg/day, -3.2 vs -1.4, P=0.003; 36 mg/day, -3.3 vs -1.4, P=0.001). This analysis assessed Minimal Clinically Important Difference (MCID) in AIMS score in patients with TD treated with deutetrabenazine. MCID is the smallest change from baseline in AIMS score that is meaningful for patients. MCID analyses were performed based on Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) as anchors described by Hauser et al., where MCID is the difference between patients treated with deutetrabenazine who were minimally improved and patients treated with placebo who were unchanged. Additional MCID definitions were explored: difference between patients who demonstrated treatment improvement versus those who did not (Method 2); difference between patients who demonstrated treatment success versus those who did not (Method 3). 295 patients were analyzed. Based on PGIC, the suggested MCID was -2.8. Results were similar for Method 2 (75% of patients had treatment improvement; MCID = -2.8) and Method 3 (38% of patients had treatment success; MCID = -2.6). Based on CGIC, the suggested MCID was -2.6. Results were similar for Method 2 (76% of patients had treatment improvement; MCID = -2.8) and Method 3 (41% of patients had treatment success; MCID = -3.0). Therefore, the suggested MCID for deutetrabenazine is -3. The MCID for change in AIMS score based on PGIC and CGIC for deutetrabenazine was -3 regardless of the analytical method. Findings suggest an AIMS score reduction of ~3 is associated with clinically meaningful improvement in TD symptoms. Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.

Long-Term Safety and Efficacy of Deutetrabenazine in Younger and Older Patients With Tardive Dyskinesia

Tardive dyskinesia (TD) is an involuntary movement disorder that is more prevalent in older patients. However, there is limited information on TD treatment for this population. In two 12-week pivotal trials (ARM-TD and AIM-TD), TD patients demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) score with deutetrabenazine versus placebo. Patients who completed ARM-TD or AIM-TD enrolled in an open-label extension (OLE) study. This post hoc analysis assessed change and percent change from baseline in AIMS score, response rates for ≥50% AIMS improvement, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety in younger (<55years) and older (≥55 years) patients. This analysis included 119 younger and 218 older patients enrolled in the OLE. Data presented at Week 145 (mean±SE): total deutetrabenazine dose was 39.4±1.39mg/day and 39.5±1.04mg/day in younger and older patients, respectively. Changes from baseline in AIMS score were -6.7±0.62 and -6.5±0.47, respectively (percent changes of -61.4%±4.10% and -54.6%±3.01%). The majority of younger and older patients achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%) and achieved ≥50% AIMS response (76% and 62%). Deutetrabenazine was generally well tolerated in both groups. Exposure-adjusted incidence rates (incidence/patient-years) were <0.01 and 0.02 for akathisia, 0.07 (both) for somnolence and sedation, 0.04 and 0.11 for parkinson-like events, and 0.06 and 0.09 for depression in younger and older patients, respectively. Deutetrabenazine treatment was associated with sustained improvements in AIMS score and was well tolerated in both younger and older TD patients. Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.

Altered interhemispheric synchrony in Parkinson\u2019s disease patients with levodopa-induced dyskinesias

Levodopa-induced dyskinesias are common motor complication of Parkinson’s disease after 4–6 years of treatment. The hallmarks of dyskinesias include unilateral onset and the tendency to appear on the more affected body sides. There is a growing literature documenting the lateralization abnormalities are associated with the emergence of dyskinesias. Our investigation aimed to explore interhemispheric functional and its corresponding morphological asymmetry. A total of 22 dyskinetic patients, 23 nondyskinetic patients, and 26 controls were enrolled. Resting-state functional magnetic resonance imaging scans were performed twice before and after dopaminergic medication. Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer were employed to assess the synchronicity of functional connectivity and structural alternations between hemispheres. During OFF state, dyskinetic patients showed desynchronization of inferior frontal cortex (IFC) when compared to nondyskinetic patients. And during ON state, dyskinetic patients showed desynchronization of IFC and pre-supplementary motor area (pre-SMA) when compared to nondyskinetic patients. However, there was no corresponding significant asymmetries in cortical thickness. Moreover, the degree of desynchronization of IFC and pre-SMA in dyskinetic pateients during ON state were negatively correlated with the Abnormal Involuntary Movement Scale (AIMS) scores. Notably, among patients who showed asymmetrical dyskinesias, there was a significant negative correlation between VMHC values of IFC and dyskinesias symptom asymmetry. Our findings suggested that uncoordinated inhibitory control over motor circuits may underlie the neural mechanisms of dyskinesias in Parkinson’s disease and be related to its severity and lateralization.

Initiating clozapine treatment service and characteristics of clozapine-treated patients in a general hospital in Addis Ababa, Ethiopia.

BackgroundAt least one-third of patients with schizophrenia suffer from treatment-resistant schizophrenia needing treatment with clozapine. This is the first report on the experience of initiating clozapine service in Ethiopia.AimThe aim of this study was to report the experience of setting up clozapine service and describe characteristics of patients treated with clozapine.SettingThis study was conducted in a general hospital in Addis Ababa, Ethiopia.MethodsDescriptive summary of the clozapine treatment service and review of characteristics of patients treated with clozapine were conducted. Clinical Global Impression (CGI) Scale and Abnormal Involuntary Movement Scale (AIMS) score were used to measure outcome. Quantitative data were analysed using Statistical Package for the Social Sciences (SPSS) Version 24.ResultsIt was possible to provide clozapine treatment in a general hospital using the national guideline. During the first year of initiation of the service, a total of 22 patients were treated. The majority were men (20/22, 90.9%) and in the age group of 30–44 years (11/22, 50%). Indications for clozapine were treatment-resistant schizophrenia (15/22, 68.2%) and tardive dyskinesia (7/22, 31.8%). The average dose of clozapine was 350 mg/day. Common side effects included sedation, constipation and excessive salivation. On CGI Scale, mean severity index score dropped from 5.18 at admission to 3.68 during discharge, and average AIMS score changed from 16.8 to 6.5. None of the patients developed agranulocytosis; however, three patients discontinued because of adverse effects.ConclusionEstablishing clozapine treatment service was possible in a general hospital in Ethiopia where psychiatric service run by psychiatrists was available. Mechanisms should be in place to ensure adherence to the national guideline.

Valbenazine and deutetrabenazine: Vesicular monoamine transporter 2 inhibitors for tardive dyskinesia.

The purpose of this review is to summarize the current evidence for valbenazine and deutetrabenazine use for the treatment of tardive dyskinesia (TD). A literature search was conducted to gather relevant data regarding the use of valbenazine and deutetrabenazine for TD management. PubMed, MEDLINE, and ClinicalTrials.gov were searched using the following keywords and MeSH terms: valbenazine, deutetrabenazine, tardive dyskinesia, VMAT2 inhibitors, and vesicular monoamine transporter 2 inhibitors. Randomized, double-blind, placebo-controlled trials and meta-analyses published in English from April 2015 to August 2019 were included. Valbenazine 40-80 mg and deutetrabenazine 12-36 mg per day have been evaluated for the treatment of TD. Abnormal Involuntary Movement Scale (AIMS) scores decline similarly (by 2-5 points) with use of either agent. AIMS response rates, defined by a 50% decline in symptoms, range from 33% to 50%. Both agents are well tolerated, with somnolence and akathisia reported most frequently (at low rates). Agent selection may be guided by manufacturer labeling recommendations for special populations and cost considerations. Valbenazine and deutetrabenazine were demonstrated to be effective in decreasing AIMS scores and were well tolerated in randomized controlled trials. These treatments may be considered as a next-line option when traditional strategies are not feasible or are ineffective. Head-to-head studies are warranted to decipher if either agent is preferable in terms of efficacy or tolerability.

Drug-Induced Dyskinesia Outpatient Suspected to be Induced by Risperidone Management with Yigan-san with Citri Pericarpium and Pinelliae Rhizoma (modified Yigan-san, Yokukan-san Kachimpihang), Electro-Acupuncture at GB34, and Stopping Suspected Medication: A Case Report

Objectives Drug-induced Parkinsonism has similar symptoms to Parkinson’s disease, but each has different causes. Drug-induced Parkinsonism accounts for the largest proportion of secondary Parkinsonism We report a outpatient case of drug-induced Parkinsonism after taking Risperidone, an atypical antipsychotic. Method With discontinuing of antipsychotic drug, modified Yigan-san extract was administered for 12 weeks, and acupuncture and electroacupuncture procedures were performed 20 times. Results Abnormal Involuntary Movement Scale (AIMS) score decreased from 23 to 3 during 59 days of treatment period without adverse events and worsening of depression. The Patient was highly satisfied. Conclusion Modified Yigan-san and electroacupuncture (GB34) can be used as an treatment option in patients with drug-induced Parkinsonism Keywords: Korean medicine, Yigan-san, Yokukan-san, case report, herbal medicine, drug induced Parkinsonism