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Impact of Tardive Dyskinesia on Physical, Psychological, Social, and Professional Domains of Patient Lives: A Survey of Patients in the United States
Abstract
Objective: To assess the physical, psychological, social, and professional impact of tardive dyskinesia (TD) on patients in the United States. Methods: An online survey (April 2020-June 2021) to assess patient burden of TD was developed using targeted literature review and interviews with clinicians, patients, and caregivers. Survey participants (aged ≥ 18 years) with current diagnoses of TD and schizophrenia, bipolar disorder, or major depressive disorder rated the 7-day impact of TD on their physical, psychological, and social functioning via Likert scales (scored from 1 [least impact] to 5 [most impact]). Impact scores were calculated and summarized descriptively overall by self-reported disease severity and underlying disease. Participants also completed the Work Productivity and Activity Impairment Questionnaire and reported the impact of TD on their underlying psychiatric condition. Results: Overall, 269 patients (mean [SD] age = 40.6 years [9.9]; 74.7% employed) responded to the survey. Mean (SD) impact scores of 3.1 (0.9), 3.5 (1.0), and 3.2 (1.1) were reported in the physical, psychological, and social domains, respectively, and scores increased with reported TD symptom severity. Patients with underlying schizophrenia reported the highest burden for all domains. Patients reported 66.2% activity impairment because of TD. Employed patients (n = 193) indicated 29.1% absenteeism, 68.4% presenteeism, and 73.5% overall work impairment. Over one-third of patients reported skipping/reducing (48.4%) or stopping (39.3%) their antipsychotic medication and stopping visits to clinicians treating their underlying condition (35.7%) because of TD. Conclusion: TD imposes a substantial burden on patients' physical, psychological, social, and professional lives and impacts management of their underlying condition.
... The study was approved by Western Institutional Review Board (IRB) and informed consent was obtained from interview participants and survey respondents before their involvement in the study. This report focuses on caregiver responses to the surveys; results for the parallel survey study conducted with an independent patient population are reported separately [22]. ...
... These panels included healthy participants (including caregivers) as well as patients with various health conditions across the US who have agreed to receive invitations to participate in web-based surveys. Caregiver participants were required to be providing unpaid care for ≥ 3 months to a patient with current diagnoses of TD and SCZ, BD, and/or MDD and who, to the caregiver's knowledge, had not already participated in the patient portion of this study [22]. ...
Background
Tardive dyskinesia (TD) has a multidimensional impact on patients with TD and, as importantly, their caregivers. An online survey was developed and administered to assess patient and caregiver burden of TD. Survey participants were unpaid caregivers for patients with diagnoses of TD and schizophrenia, bipolar disorder, and/or major depressive disorder. Overall, 162 caregivers rated the 7-day impact of TD on the physical, psychological, and social functioning of patients and the impact of TD on these domains in their own lives and in their professional lives.
Results
Across physical, psychological, and social domains, most caregivers (82.7%) reported that TD had severe impact on the cared-for patients, and 23.5% reported severe impact of TD in their own lives. Caregivers experienced 46.4% activity impairment, and caregivers who were employed (n = 136) experienced 49.5% overall work impairment because of TD-related caregiving.
Conclusions
These results suggest that TD imposes substantial burden for both caregivers and patients.
Tardive dyskinesia (TD) is a syndrome that causes chronic, involuntary, and disruptive movements of the body and/or face that is a severe, potentially irreversible adverse effect of long-term antipsychotic use. It has wide-reaching effects on patients’ well-being, quality of life, 1 and treatment adherence. 2 Thus, TD is debilitating, leading to social withdrawal, 3 and workplace absenteeism. 1 Current data on tardive dyskinesia treatment are limited, and prevention, primarily through the modification of antipsychotic regimens, remains the most effective strategy. 4 Recent systematic review has shown valbenazine and vitamin E are the only treatments significantly more effective compared to placebo in treatment of TD, although valbenazine is associated with significant side effects. 5 We present a case of a 76-year-old female with a diagnosis of Bipolar II Disorder (BD) who developed TD after treatment with lurasidone for 10 years. After struggling with both her BD and TD symptoms for 3 years, she sought care at our clinic where we prescribed 300 mg daily of lithium. At her follow-up visit 5 weeks later, her TD symptoms were greatly improved, with sustained benefits observed at following visits. This article reviews the literature discussing the interplay between lithium and TD and presents a case report of TD improvement after lithium augmentation for treatment-resistant depression. While this case suggests a potential role in TD treatment, the role of lithium in TD treatment remains controversial.
Objectives
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.
Methods
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.
Results
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.
Conclusion
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.
Objective:
Antipsychotic 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.
Methods:
This was an experimental, randomized, blinded, digital survey in a general population sample. Participants were randomized 1:1 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.
Results:
Surveys 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).
Conclusion:
Professional 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.
Purpose
To understand similarities and differences in patient treatment goals as selected by US psychiatrists, adult patients with schizophrenia, and their caregivers in a real-world setting in the United States, including stratification by current medication and age.
Patients and Methods
Data were drawn from the Adelphi Schizophrenia Disease Specific Programme™, a point-in-time survey of psychiatrists and their consulting adult patients with schizophrenia, conducted from June to October 2019. Psychiatrists completed record forms for their next 8 consecutive outpatients and (where possible) 2 inpatients matching inclusion criteria. Participating psychiatrists, patients, and caregivers completed treatment goal questionnaires as part of the survey.
Results
Psychiatrists (n = 124) provided data on 1204 patients with schizophrenia, including 1135 on drug treatment (207 inpatients [18%] and 928 outpatients [82%]); questionnaires were completed by 555 patients and 135 caregivers. Decrease in disease symptoms was identified as the most important patient treatment goal by patients (64%), psychiatrists (selecting for 63% of patients), and caregivers (selecting for 68% of patients). Patients, psychiatrists, and caregivers similarly rated the least important goals (less sexual problems and less weight gain). Patients indicated their current medication helped to reach their most important goals: decrease in disease symptoms (68%) and thinking more clearly (39%). Findings based on analysis of treatment goals by treatment and age were similar to overall trends.
Conclusion
These findings, including identification of a primary consensus goal of decrease in disease symptoms, may help with discussions between patients with schizophrenia, psychiatrists, and caregivers to inform effective management strategies and encourage shared decision-making.
Purpose
Tardive dyskinesia (TD) is a hyperkinetic movement disorder in which patients experience abnormal involuntary movements that can have profound negative impacts on physical, cognitive, and psychosocial functioning. Use of measures to assess the functional impact of TD in routine clinical practice is lacking. To address this gap, an advisory panel of experts in psychiatry and movement disorder neurology was convened to develop consensus recommendations on assessment of the impact of TD on patients’ functioning that can be used in clinical practice.
Methods
An advisory panel provided recommendations using an iterative process, beginning with a narrative literature review regarding current practices for assessing the impact of TD in clinical settings. A detailed summary was generated, and the advisory panel provided comments about the content and answered questions about assessing TD impact in clinical practice. The panelists’ responses were discussed during a virtual meeting held on August 28, 2020. A second meeting on September 25, 2020, focused on developing and refining recommendations for assessment of the impact of TD in clinical practice. At the conclusion of the second meeting, general consensus was reached on all recommendation statements.
Results
As part of routine clinical practice, it is imperative to assess the impact of TD on the patient’s life to help guide treatment decisions. Key domains for assessing the overall impact of TD include social, physical, vocational, and psychological functioning and the impact of TD on the underlying psychiatric disorder. Assessment of TD impact should be performed at every patient visit. Impact assessments should include consultation with patients, caregivers, and family members. Shared decision-making to initiate TD treatment should consider impact.
Conclusion
The impact of TD should be assessed routinely, including the key domains of social, physical, vocational, and psychological functioning and the impact of TD on the underlying psychiatric disorder.
Purpose/background:
RE-KINECT (NCT03062033) was designed to assess the presence and impact of possible tardive dyskinesia (TD) in antipsychotic-treated outpatients.
Methods/procedures:
The study included adults with 3 or more months of lifetime antipsychotic exposure and 1 or more psychiatric disorder. Based on clinician observation and assessment, patients were assigned to cohort 1 (without involuntary movements or with non-TD involuntary movements) or cohort 2 (with involuntary movements confirmed by clinician as possible TD). Baseline assessments included the following: patient characteristics; location/severity of involuntary movements; and impact of possible TD on health-related quality of life, including the EuroQoL 5-Dimensions 5-Level questionnaire.
Findings/results:
Of 739 eligible patients, 204 (27.6%) had clinician-confirmed possible TD (cohort 2). Compared with cohort 1, patients in cohort 2 were significantly older (P < 0.0001), more likely to have schizophrenia or schizoaffective disorder (P < 0.0001) and longer lifetime exposure to antipsychotics (P < 0.0001), and less likely to be working or studying, based on clinician perception (P = 0.0010). Clinician- and patient-rated severity of possible TD movements was significantly correlated in each of 4 body regions (head/face, neck/trunk, upper extremities, lower extremities), for maximum severity in any region, and for total number of affected regions (P < 0.001 for all correlations). For the patient-rated EuroQoL 5-Dimensions 5-Level, the health state visual analog scale score was significantly lower (worse) in cohort 2 versus cohort 1 (66.8 vs 69.7; P = 0.0002), as was the utility index score (0.71 vs 0.76; P < 0.0175).
Implications/conclusions:
Results from this real-world population indicate that TD occurs frequently and can significantly reduce quality of life in patients with a psychiatric disorder.
Purpose
Tardive dyskinesia (TD) is a common but serious hyperkinetic movement disorder and side effect of antipsychotic medications used to treat bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ). The purpose of this study was to evaluate health-related quality of life (HRQoL) in a population with diagnoses for BD, MDD, or SZ by comparing patients with TD (n = 197) with those without TD (n = 219). HRQoL in each group was also compared with HRQoL of the general population.
Methods
This study employed a cross-sectional web-based survey. HRQoL was assessed by four instruments: the SF-12 Health Survey, Version 2 (SF-12v2), the Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form (Q-LES-Q-SF), the Social Withdrawal subscale of the Internalized Stigma of Mental Illness Scale (SW-ISMI); and two questions on movement disorders.
Results
Patients with TD had significantly worse HRQoL and social withdrawal than those without. The differences were more pronounced for physical HRQoL domains than for mental health domains. Patients with more-severe TD, assessed through either self-rating or clinician rating, experienced significantly worse HRQoL than did those with less-severe TD. The impact of TD was substantially greater in patients with SZ than in those with BD or MDD. Compared with the general population, patients with BD, MDD, or SZ experienced significantly worse HRQoL regardless of TD status, although this deficit in HRQoL was greater among those with TD.
Conclusions
The presence of TD is associated with worse HRQoL and social withdrawal. The most severe impact of TD is on physical aspects of patients’ HRQoL.
Purpose
Advanced non-small cell lung cancer (aNSCLC) impacts the lives of patients and their caregivers. This analysis examined the association between patient clinical characteristics and patient and caregiver humanistic burden.
Methods
Data for patients with aNSCLC and their informal caregivers in France, Germany and Italy, were collected between May 2015 and June 2016 via chart review and patient and caregiver surveys. Patients and caregivers completed validated instruments to evaluate their health state (EuroQol-5-dimensions-3-levels [EQ-5D-3L]), work and activity impairment (Work Productivity Activity Impairment [WPAI]) and health-related quality of life (HRQoL; European Organisation for Research and treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30]). Caregivers also completed the Zarit Burden Interview (ZBI). Univariate and regression analyses were stratified by patient Eastern Cooperative Group Performance Status (ECOG-PS 0, 1, 2 or 3/4).
Results
In total, 1030 patients and 427 accompanying informal caregivers participated. Regression analyses indicated that patients reported lower EQ-5D-3L utility index, EQ-VAS and EORTC QLQ-C30 global health status and greater work and activity impairment with worsening ECOG-PS (all p < 0.05). Caregivers also reported greater activity impairment and higher ZBI scores with worsening ECOG-PS of the patient they were providing care for (all p < 0.05).
Conclusions
As patients’ functionality deteriorates as measured by the ECOG-PS, so do their outcomes related to health utility, work productivity, activity impairment and HRQoL. This deterioration is also reflected in increased caregiver burden and activity impairment. There is a need for interventions to maintain patients’ physical function to relieve the humanistic burden of both patients and caregivers.
Background
Although depression and cognitive dysfunction are connected, limited tools exist to capture the patient’s perspective on cognitive dysfunction and its impact on major depressive disorder (MDD). We report results of a psychometric validation of the Perceived Deficits Questionnaire-Depression (PDQ-D), a self-report measure of cognitive dysfunction for use in MDD.
Methods
A non-interventional, prospective, panel-recruited, online survey was conducted using the PDQ-D in adults with and without MDD in the US and UK. Respondents were assessed at baseline and after 6 weeks (MDD only) (baseline: US n=418, UK n=437, 49% MDD; follow-up: US n=169, UK n=153, all MDD). The criterion measures included: Medical Outcomes Study Cognitive Functioning Scale-Revised-acute form (MOS COG-R), Patient Health Questionnaire-9 (PHQ-9), Patient Global Impression of Severity scale (PGI-Severity), Sheehan Disability Scale (SDS), Work Productivity and Activity Impairment Questionnaire: Specific-Health Problem (WPAI:SHP), and modified Lam Employment Absence and Productivity Scale (LEAPS). US and UK data were analyzed separately.
Results
Internal consistency was high for PDQ-D total scale and four subscales (Cronbach’s alpha 0.81–0.96). Convergent validity was good, with strong concordance with MOS COG-R and moderate/small correlations with PHQ-9, SDS, WPAI:SHP, LEAPS, and PGI-Severity. Significant differences (all P<0.001) existed for all PDQ-D subscale and total scores between MDD/non-MDD samples. The PDQ-D was responsive to changes in depression symptom severity. Confirmatory factor analysis supported scoring of a global overall scale for perceived cognitive dysfunction.
Conclusion
The PDQ-D provides a reliable and valid measure of subjective cognitive dysfunction in patients with MDD.
The recent approval of treatments for tardive dyskinesia (TD) has rekindled interest in this chronic and previously recalcitrant condition. A large proportion of patients with chronic mental illness suffer from various degrees of TD. Even the newer antipsychotics constitute a liability for TD, and their liberal prescription might lead to emergence of new TD in patient populations previously less exposed to antipsychotics, such as those with depression, bipolar disorder, autism, or even attention deficit hyperactivity disorder. The association of TD with activity limitations remains poorly understood. We review potential new avenues of assessing the functional sequelae of TD, such as the performance of instrumental activities of daily living, residential status, and employment outcomes. We identify several mediating aspects, including physical performance measures and cognition, that may represent links between TD and everyday performance, as well as potential treatment targets.
There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid (GABA), cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration (USFDA) has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms (EPS), weight gain, and hyperglycemia.
Neuro-QOL provides a clinically relevant and psychometrically robust health-related quality of life (HRQL) assessment tool for both adults and children with common neurological disorders. We now report the psychometric results for the adult tools.
An extensive research, survey and consensus process was used to produce a list of 5 priority adult neurological conditions (stroke, multiple sclerosis, Parkinson's disease, epilepsy and ALS). We identified relevant health related quality of life (HRQL) domains through multiple methods and data sources including a comprehensive review of the literature and literature search, expert interviews and surveys and patient and caregiver focus groups. The final domain framework consisted of 17 domains of Physical, Mental and Social health. There were five phases of item development: (1) identification of 3,482 extant items, (2) item classification and selection, (3) item review and revision, (4) cognitive interviews with 63 patients to assess their understanding of individual items and (5) field testing of 432 representative items. PARTICIPANTS AND PROCEDURES: Participants were drawn from the US general population and clinical settings, and included both English and Spanish speaking subjects (N = 3,246). Confirmatory factor analysis (CFA) was used to evaluate the dimensionality of unidimensional domains. Where the domain structure was previously unknown, the dataset was split and first analyzed with exploratory factor analysis and then CFA. Samejima's graded response model (GRM) was used to calculate IRT parameters. We further evaluated differential item functioning (DIF) on gender, education and age.
Thirteen unidimensional calibrated item banks consisting of 297 items were developed. All of the tested item banks had high reliability and few or no locally dependent items. The range of item slopes and thresholds with good information are reported for each of the item banks. The banks can support CAT and the development of short forms.
The Neuro-QOL measurement system provides item banks and short forms that enable PRO measurement in neurological research, minimizes patient burden and can be used to create multiple instrument types minimizing standard error. The 17 adult measures include 13 calibrated item banks, 3 item pools available for calibration work by others, and 1 stand-alone scale (index). The Neuro-QOL instruments provide a "common metric" of representative concepts for use across patient groups in different studies.
Objective
The objective of this survey was to assess patient outcomes and caregiver status by disease severity among patients with schizophrenia in the United States.
Methods
A point-in-time survey was conducted between July–October 2019 via the Adelphi Schizophrenia Disease Specific Programme. Psychiatrists reported on their next 10 eligible patients with schizophrenia including demographics, disease severity, treatment history and hospitalizations. Patients receiving treatment for schizophrenia were classified as mild, moderate or severe based on disease severity. Regression models adjusted for age, sex and race/ethnicity.
Results
Psychiatrists (n = 124) reported on 435 mild, 401 moderate and 247 severe patients. Greater severity of schizophrenia was associated with a greater number of hospitalizations related to schizophrenia relapse in the previous 12 months (moderate vs. mild: adjusted incidence rate ratio (aIRR)[95% CI] = 2.17 [1.60–2.94]; severe vs. mild: aIRR =5.45 [3.59–8.27]), lower full-time employment (moderate vs. mild: adjusted odds ratio (aOR)=0.15 [0.08–0.28]; severe vs. mild: aOR =0.02 [0.002–0.12]) and greater unemployment due to disability (moderate vs. mild: aOR =4.24 [3.02–5.97]; severe vs. mild: aOR =10.85 [6.85–17.17]). Patients with severe vs. mild schizophrenia had lower average quality of life (QoL) measured by the EuroQoL 5-dimension Health Index (difference=-0.16 [-0.23–-0.09]). Among patients requiring care, patients with severe vs. mild schizophrenia received more caregiver hours per week (aIRR =1.89 [1.25–2.84]).
Conclusions
Greater severity of schizophrenia was associated with a significantly greater number of hospitalizations and greater unemployment due to disability. Compared with mild schizophrenia, severe schizophrenia was associated with worse patient QoL and greater caregiver hours.
Background
Previous studies have shown that bipolar disorder (BD) patients frequently present with difficulties in interpersonal relationships, education or employment and suffer poorer quality of life. This study aimed to estimate the impact of BD on health-related quality of life (HRQOL), work productivity loss and indirect costs.
Methods
Data was from the online, self-administered 2019 National Health and Wellness Survey. Outcomes were compared for those who self-reported a physician diagnosis of BD (N=179), major depressive disorder (MDD, N=1,549) and controls who have never experienced BD, MDD and schizophrenia (N=27,485).
Results
The lifetime prevalence was estimated to be 0.60% for BD and 5.16% for MDD. Significantly lower Mental Component Summary (MCS), Role Component Summary (RCS) scores and EuroQol 5-dimension scale (EQ-5D-5L) summary index and significantly higher presenteeism, total work productivity impairment and activity impairment assessed by Work Productivity and Activity Impairment questionnaire and indirect costs for BD versus controls and BD PHQ-9≥10 versus PHQ-9<10 were observed. Compared to MDD patients, BD patients had significantly lower RCS score and greater work productivity loss and activity impairment. The national morbidity cost of BD in Japan was estimated to be Japanese yen 1,236 billion using a human-capital approach.
Limitations
The data used were self-reported and is cross-sectional in nature, thus causal relationship cannot be assumed.
Conclusion
BD patients and those with severe depressive symptoms experience significantly poorer HRQOL and greater work productivity loss and indirect costs. These findings highlight the importance of proper screening, diagnosis and treatment of BD and bipolar depression.
Objectives:
People with schizophrenia (SCZ) and bipolar illness (BPI) generate self-reports of their functioning that diverge from objective information. It has been suggested that these participants do not base such reports on daily experiences, relying on other information. We used ecological momentary assessment (EMA) to sample socially relevant daily activities in SCZ and BPI and related them to self-reported and observer-rated social functioning and social cognitive ability.
Methods:
71 people with (BPI) were compared to 102 people with SCZ. Participants were sampled 3 times per day for 30 days with a smartphone-based survey. Each survey asked where they were, with whom they were, what they were doing, and if they were sad. Participants and observers were asked to provide ratings on social functioning and social cognitive abilities at the end of the EMA period.
Results:
There was no association between being home or alone and self-reports of everyday social functioning. In contrast observer ratings were highly correlated with the momentary survey results. Reports of very low levels of sadness were associated with overestimated functioning and participants who were commonly home and alone rated their social functioning as better than participants who were commonly away in the presence of others.
Implications:
Both SCZ and BPI were marked by a disconnect between momentary experiences and self-reports. The largest effect was overestimation of functioning by participants who reported no sadness. Experience appears important, as participants who were routinely home and alone reported better social functioning than participants who spent more time others.
Clinical guidelines provide evidence-based recommendations to regulate pharmacological treatment of psychotic disorders. However, the quality of evidence, country of origin, and publication dates of such guidelines vary, which leads to discrepancies between recommendations. This systematic review aimed to examine consensus and disparities between clinical recommendations on the choice, dose, and duration of antipsychotic treatment for first- and multi-episode schizophrenia patients. A literature search through The Cochrane Library, Embase, Medline, PsycINFO, PubMed, Scopus, Web of Sciences, and relevant bibliographies revealed 24 guidelines that met the inclusion criteria. The guidelines indicated mostly consistent recommendations regarding the optimal dose range of antipsychotics, while guidance with regards to the choice and duration of treatment remains somewhat controversial. Current trends in guidelines emphasize that there is simply no ‘one-size-fits-all’ method to manage schizophrenia patients. Further research is needed not only to address discrepancies between guidelines, but also to justify the gap between theory and practice.
Tardive dyskinesia (TD) is a potentially permanent movement disorder resulting from chronic use of dopamine receptor blocking agents (DRBA). Identified risk factors include the type of antipsychotic agent, being greater for those of first generation antipsychotics (FGA), the duration of illness and cumulative dose of DRBA and advanced age. Female sex and African and Caucasian ethnicity are additional potential risk factors. Because only a subset of people taking DRBA's develops TD, genetics may play a role. Susceptibility gene candidates include those involved in DRBA metabolism and the targets or receptors of DRBA's. Although met with conflicting data, the following genes may be involved with TD development: the cytochrome P450 gene CYP2D6, involved with metabolism of most antipsychotics, Dopamine D2 and D3 receptor genes, serotonin 2A and 2C receptor genes, vesicular monoamine transporter 2 (VMAT 2) gene, involved with intracellular neurotransmitter packaging, and the manganese superoxide dismutase (MnSOD) gene, an antioxidant enzyme. Heparan sulfate proteoglycan 2 (HSPG 2) gene is another potential gene involved with development of TD. The pathogenesis of TD is unknown, however there are three main theories proposed: dopamine receptor supersensitivity resulting from chronic dopamine receptor blockade, oxidative stress and maladaptive synaptic plasticity each of which is discussed further in this article. Tardive dyskinesia (TD) is a potentially permanent and disabling adverse effect from certain medications. By definition TD is the insidious onset of rhythmic, repetitive, stereotypic movements of the face, mouth and tongue, often with involvement of the trunk and extremities that occur as a result of dopamine receptor blocking agents (DRBA) [1]. The term tardive refers to the delayed onset of the disorder. The mean prevalence of TD is estimated to be 25.3% in psychiatric patients taking antipsychotics [2]. Compared to the number of people taking these drugs, TD represents a minority. TD is a potentially permanent condition; stopping the offending agent does not always alleviate the condition. Therefore, prevention of TD by avoiding DRBA's if at all possible is ideal. However, there is no apparent way to predict who will develop TD and there are some cases in which DRBA's are necessary for treatment of chronic conditions. As TD has been present since the development of DRBA's, possible risk factors for its development have been studied. Solmi et al. (2018) [3] have written a comprehensive review on this subject.
Background:
Tardive dyskinesia (TD) is a movement disorder that causes involuntary, repetitive body movements and is commonly seen in patients who are on long-term treatment with antipsychotic medications. However, several other classes of medications with different mechanisms are also associated with TD.
Methods:
We conducted a PubMed search using keywords and combined word searches that involved medication-induced TD, as well as agents that are associated with causing or are used to treat medication-induced TD. We attempted to include as many recent (publication date of 2015 and later) articles as possible.
Results:
The reported incidence of TD seems to be reduced with the use of atypical antipsychotic drugs, yet the risk of developing TD remains with these medications. Furthermore, several other medication classes have a high prevalence of TD and yet are not commonly considered to be TD-inducing. This review highlights the need for a prevention-based focus of TD treatment that starts with a clinical consideration of pharmacologic choices related to each individual patient's history.
Conclusion:
This review offers the information current as of 2016 on the pathophysiology, etiology, and epidemiology of TD, as well as the medications associated with TD, mechanisms of medication-induced TD, and treatments for medication-induced TD.
The construct validity of a quantitative work productivity and activity impairment (WPAI) measure of health outcomes was tested for use in clinical trials, along with its reproducibility when administered by 2 different methods. 106 employed individuals affected by a health problem were randomised to receive either 2 self-administered questionnaires (self administration) or one self-administered questionnaire followed by a telephone interview (interviewer administration). Construct validity of the WPAI measures of time missed from work, impairment of work and regular activities due to overall health and symptoms, were assessed relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity and global measures of work and interference with regular activity. Multivariate linear regression models were used to explain the variance in work productivity and regular activity by validation measures. Data generated by interviewer-administration of the WPAI had higher construct validity and fewer omissions than that obtained by self-administration of the instrument. All measures of work productivity and activity impairment were positively correlated with measures which had proven construct validity. These validation measures explained 54 to 64% of variance (p less than 0.0001) in productivity and activity impairment variables of the WPAI. Overall work productivity (health and symptom) was significantly related to general health perceptions and the global measures of interference with regular activity. The self-administered questionnaire had adequate reproducibility but less construct validity than interviewer administration. Both administration methods of the WPAI warrant further evaluation as a measure of morbidity.