Metoclopramide-associated tardive dyskinesia. An analysis of 67 cases.

OBJECTIVE: To summarize information regarding the frequency, risk factors, clinical characteristics, treatment, and course of metoclopramide hydrochloride-associated tardive dyskinesia obtained from an analysis of 67 case reports. DATA SOURCES: All the case reports of metoclopramide-associated tardive dyskinesia involving human patients in the literature in English obtained by using Index Medicus and Med-Search. The indexing terms used were as follows: metoclopramide, tardive dyskinesia, dyskinesia, parkinsonism, and extrapyramidal side effects. STUDY SELECTION: For a patient to be included, the main published research criteria had to be met based on the information provided. These criteria included exposure to metoclopramide for at least 30 days before the onset of dyskinesia. Fifty-two patients met these criteria. DATA EXTRACTION: One author independently extracted the data. DATA SYNTHESIS: The incidence and prevalence of tardive dyskinesia associated with metoclopramide have not been well studied. The mean (+/- SD) length of treatment with metoclopramide before the onset of symptoms was 20 +/- 15 months. The most common location of the dyskinetic movements was the face (28 [60%] of 47) followed by the tongue (21 [45%] of 47). In 15 (71%) of 21 patients on whom long-term follow-up was provided, the symptoms were still present 6 months or more after discontinuation of metoclopramide. CONCLUSION: Persistent tardive dyskinesia is a serious potential side effect associated with metoclopramide treatment.     

Serendipity in biological psychiatry--a myth?

It is often stated that major biological treatments in psychiatry were discovered by accident or serendipity. Tracing the history of the concept of serendipity, we find that serendipity has been subjected to greatly divergent interpretations. According to the current usage, it is a discovery in which chance was a necessary and/or sufficient condition. With this definition, none of the discoveries of major biological treatments in psychiatry can be labeled serendipitous. The necessary factors common to these discoveries were creative minds that were variably influenced by the zeitgeist and that were persistent in their search for answers. Another important prerequisite was the availability of crucial basic knowledge of many related sciences. We conclude that chance cannot substitute for long-term research and that the latter is the most likely way to lead to valuable discoveries.     

A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia

OBJECTIVE: The number of older patients with chronic schizophrenia is increasing. There is a need for empirically validated psychotherapy interventions for these patients. Cognitive behavioral social skills training teaches cognitive and behavioral coping techniques, social functioning skills, problem solving, and compensatory aids for neurocognitive impairments. The authors compared treatment as usual with the combination of treatment as usual plus cognitive behavioral social skills training. METHOD: The randomized, controlled trial included 76 middle-aged and older outpatients with chronic schizophrenia, who were assigned to either treatment as usual or combined treatment. Cognitive behavioral social skills training was administered over 24 weekly group sessions. Blind raters assessed social functioning, psychotic and depressive symptoms, cognitive insight, and skill mastery. RESULTS: After treatment, the patients receiving combined treatment performed social functioning activities significantly more frequently than the patients in treatment as usual, although general skill at social functioning activities did not differ significantly. Patients receiving cognitive behavioral social skills training achieved significantly greater cognitive insight, indicating more objectivity in reappraising psychotic symptoms, and demonstrated greater skill mastery. The overall group effect was not significant for symptoms, but the greater increase in cognitive insight with combined treatment was significantly correlated with greater reduction in positive symptoms. CONCLUSIONS: With cognitive behavioral social skills training, middle-aged and older outpatients with chronic schizophrenia learned coping skills, evaluated anomalous experiences with more objectivity (achieved greater cognitive insight), and improved social functioning. Additional research is needed to determine whether cognitive insight mediates psychotic symptom change in cognitive behavior therapy for psychosis.     

Assessment of capacity to consent to research among older persons with schizophrenia, Alzheimer disease, or diabetes mellitus: comparison of a 3-item questionnaire with a comprehensive standardized capacity instrument

CONTEXT: Considerable discussion surrounds issues related to the capacities of neuropsychiatric patients to consent to research, yet few empirical investigations have directly compared decisional capacity among patients with a serious mental illness with that among patients with neurologic or medical conditions. Also, as requirements for formal assessment of decisional capacity are becoming more common, there is a clear need to identify efficient screening methods. OBJECTIVES: To compare decisional capacity among 3 diagnostic groups, and to examine the degree to which impaired understanding can be detected with a brief set of screening questions. SETTING: Outpatient veterans hospital clinic and university-based neuropsychiatric research centers. DESIGN/ PARTICIPANTS: Cross-sectional comparison of decisional capacity among older (>/=60 years) outpatients with schizophrenia (n = 35), mild to moderate Alzheimer disease (n = 30), and type 2 diabetes mellitus (n = 36), and determination of sensitivity and specificity of a screening measure. MAIN OUTCOME MEASURES: Three-item decisional capacity questionnaire and the MacArthur Competence Assessment Tool for Clinical Research. RESULTS: Patients with diabetes mellitus performed the best on the capacity instruments, patients with Alzheimer disease had the worst performance, and patients with schizophrenia were intermediate. However, there was considerable heterogeneity within each group. Even within diagnostic groups, the level of cognitive functioning (measured with the Mini-Mental State Examination) was generally the best predictor of decisional capacity (particularly in the understanding component). The 3-item questionnaire was sensitive to impaired understanding as measured with the MacArthur Competence Assessment Tool for Clinical Research understanding subscale. CONCLUSIONS: Decisional capacity differed among the 3 groups; there was considerable heterogeneity even within each diagnostic group, so individualized consideration of capacity may be warranted. The level of cognitive deficits is 1 potential marker of which participants should receive comprehensive capacity evaluations, but sensitive brief questionnaires targeting key aspects of disclosed information may also provide an effective means of screening for participants warranting comprehensive capacity evaluations.     

Tri-ethnic variations of co-morbid substance and alcohol use disorders in schizophrenia

OBJECTIVES: This study examined the differential prevalence of substance and alcohol use disorders among European Americans, African Americans, and Latinos with schizophrenia (n = 6424) who received public mental health services in San Diego County during fiscal year 2002-2003. METHODS: Data were obtained from the public mental health database used by the San Diego County Mental Health System. Chi-Square analyses and stepwise logistic regression analyses were used to examine differences regarding the prevalence of substance and alcohol use among clients with schizophrenia and schizoaffective disorder, and to analyze the sociodemographic variables associated with this co-morbidity. RESULTS: Significant differences in the prevalence of diagnosed co-morbidity were found across the ethnic groups. Rates of co-morbid diagnosis among African Americans (25%) were significantly higher than those among European Americans (22%) and Latinos (19%). Logistic regression results revealed ethnicity was a significant predictor of co-morbid substance and alcohol use, as was being homeless and male. Among Latinos, language preference was also a significant predictor. Latinos who denoted English as their primary language were 1.7 times more likely to be diagnosed with co-morbid substance or alcohol use disorders than Latinos who denoted Spanish. CONCLUSIONS: Among people with schizophrenia, there were significant differences in prevalence rates and predictors of diagnosed co-morbid substance and alcohol use disorders. Future research is needed to examine the relationship among language preference, level of acculturation, and subsequent diagnosing barriers for Latinos. Among African Americans, the reasons behind increased co-morbidity rates need to be examined, and homelessness should be carefully addressed among all three ethnic groups.     

Review of longitudinal functional neuroimaging studies of drug treatments in patients with schizophrenia

We systematically reviewed twenty-one functional neuroimaging studies that used longitudinal designs to investigate the effects of medication treatments on brain functioning among patients with schizophrenia. The studies reviewed were comprised of functional magnetic resonance imaging and positron emission tomography research using a baseline and at least one follow-up. The present review summarizes the different effects of medication and disease status on brain function, with attention to functional normalization, specific drug effects, and comparisons of typical versus atypical antipsychotics. Particular emphasis is given to methodological limitations in the existing literature, including lack of reliability data, clinical heterogeneity among studies, and inadequate study designs and statistics. Suggestions are made for improving future longitudinal neuroimaging studies of treatment effects in schizophrenia.     

Abnormal brain response of chronic schizophrenia patients despite normal performance during a visual vigilance task

Deficits of attention are common among individuals with schizophrenia (SZ) and are related both to genetic liability to the disorder and to functional outcome among patients. To explore the brain systems underlying these attentional abnormalities, we compared the response of nine patients with chronic SZ or schizoaffective disorder to that of 10 matched healthy individuals performing a simple visual vigilance task during functional magnetic resonance imaging. The two groups performed equivalently on the task. When the blood oxygen level dependent (BOLD) signal during identification of a target letter among similar-looking letters was compared to the response during fixation trials, both groups showed multiple clusters of significant brain response in widespread cortical regions. Compared with healthy participants, SZ patients showed a diminished response in the inferior frontal cortex and an abnormally enhanced response in right postcentral gyrus, right medial temporal lobe and left cerebellum. The results suggest that abnormalities of functional brain response to attentional tasks can be observed among patients with SZ even when behavioral performance is unimpaired, and provide further evidence that brain systems related to attention are likely to be involved in the pathophysiology of the disorder.     

Proxy and surrogate consent in geriatric neuropsychiatric research: update and recommendations

OBJECTIVE: The ethics of involving decisionally incapable adults in research will continue to grow in importance as more research is conducted to address the problems of decisionally impaired persons, especially elderly persons. The authors provide an updated discussion, critique, and recommendations regarding the need for clear legal and regulatory policy on this issue. METHOD: The authors summarize and build on discussions of a workshop on proxy and surrogate consent in geriatric neuropsychiatric research sponsored by the Aging Research Consortium of the National Institute of Mental Health. They incorporate the views of various stakeholders present at the workshop as well as review recent federal and state initiatives, recent empirical research and media reports, and various commission reports and relevant regulations. RESULTS: Despite a wave of initiatives in the late 1990s to clarify policy, surrogate consent for research continues to be a murky legal area and incapable subjects in the United States still lack clear regulatory protection. There is evidence that conservative risk management strategies by institutional review boards and their institutions may severely restrict research with decisionally impaired subjects. A passive approach to this problem may no longer be feasible. A recent federal advisory report on human research protections and legislative initiatives in some states could begin to provide a blueprint for future policy making. Interim recommendations for various stakeholders are given. CONCLUSIONS: It is imperative that the scientific community, patients and their advocates, and policy makers at all levels establish a constructive dialogue to clarify ethical and legal standards in the area of proxy and surrogate consent for research.     

Association of diabetes with dyskinesia in older psychosis patients

Rationale Older patients treated with antipsychotics are more likely to develop tardive dyskinesia (TD) than younger individuals. Advanced age is also an important risk factor for diabetes, which may be associated with TD. These observations suggest that older diabetic patients may be particularly vulnerable to developing TD.Objective To examine whether older psychosis patients with diabetes exhibit more severe dyskinesia than well-matched patients without diabetes and to test whether there are differences in dyskinesia severity between diabetic patients treated with conventional versus atypical antipsychotics versus those not taking antipsychotic medications.Method Sixty-one psychosis patients with diabetes and 122 case-matched non-diabetic comparison patients were studied. Observer-based and quantitative instrumental measures were administered to assess prevalence and severity of dyskinesia. Raters were unaware of patients diabetes status.Results Diabetic patients exhibited significantly more severe TD than non-diabetic comparison patients. Groups did not differ in terms of severity of parkinsonism. Significantly more diabetic (27.9%) than non-diabetic (14.6%) patients met research diagnostic criteria for TD. Diabetic patients treated with atypical antipsychotics at the time of assessment had significantly more severe TD than all other patient subgroups, including patients treated with conventional antipsychotics. Results from the instrumental measures of force steadiness were consistent with observer-based severity ratings.Conclusion The deleterious effect of diabetes on TD in the absence of any effect of parkinsonism supports preclinical studies of glucose-related dopamine hyperfunction and has implications for the pharmacologic management of psychosis in patients with pre-existing diabetes.