William M. Glazer

Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: a prospective cohort study.

OBJECTIVE Most previous studies of the incidence of tardive dyskinesia with atypical antipsychotics compared with conventional antipsychotics have not had tardive dyskinesia as their primary focus. The current study aimed to compare the incidence of tardive dyskinesia with atypical vs conventional antipsychotics using methods similar to those from a previous prospective cohort study at our site in the 1980s. METHOD Three hundred fifty-two initially tardive dyskinesia-free psychiatric outpatients (diagnosed at baseline using the Structured Clinical Interview for DSM-IV) were examined for a new diagnosis of tardive dyskinesia (using the Abnormal Involuntary Movement Scale and Glazer-Morgenstern criteria) every 6 months for up to 4 years at a community mental health center. At baseline, subjects were receiving conventional antipsychotics only (23%), atypicals only (64%), or both (14%). Only 26 subjects had never received conventional antipsychotics. Baseline evaluations were conducted from November 2000 through May 2003. Follow-ups were conducted through February 2005. RESULTS Compared with subjects treated with conventional antipsychotics alone since the previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% CI, 0.29-1.64). The incidence and prevalence of tardive dyskinesia was similar to previous findings at this site in the 1980s. CONCLUSIONS The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it.

Assessment of tardive dyskinesia using the abnormal involuntary movement scale

Over a 10-month period, 33 patients with tardive dyskinesia (TD) were evaluated with the Abnormal Involuntary Movement Scale (AIMS) simultaneously and independently by two experienced and two inexperienced raters. The experienced raters generally had higher levels of agreement and their scores were more consistent over time. It is concluded that experience with TD influences AIMS inter-rater reliability and that it is useful to differentiate TD movements into the dimensions of quality, frequency, and amplitude, dimensions not currently used in the AIMS. The usefulness and difficulty of developing more specific guidelines for AIMS ratings are discussed.

Assessment and treatment selection for 'revolving door' inpatients with schizophrenia

Goals: The goals of this study are 1) to determine causes and patterns of relapse for a cohort of “revolving door” schizophrenia inpatients, and 2) to assess the feasibility of starting a new psychopharmacologic intervention before discharge, either depot therapy or an atypical antipsychotic. Methods: Consecutive admissions to an acute inpatient unit in New York City were screened for “revolving door” criteria. Patients had to have a primary diagnosis of schizophrenia or schizoaffective disorder and have either 1) two hospitalizations in the last year, or 2) three hospitalizations in the last three years. Patients were then assessed for probable causes of relapse for the index and prior two hospitalizations. Treatment selection, based on this information, was trichotomized to: 1) oral conventional antipsychotic, 2) depot conventional antipsychotic (either haloperidol or fluphenazine decanoate), or 3) atypical antipsychotic (either risperidone or clozapine). Results: Sixty-three out of 131 screened admissions met the above revolving door criteria. They were indeed “revolving”, having an average of 1.3 hospitalizations per year over the last 3 years and were only out of the hospital for five months (median) before index admission. The treatment selection process was hampered by lack of information about events leading to relapse, and by the lack of outpatient participation in the medication selection process. Of the 50 patients with complete histories about precipitants for the index episode, the most common reason for rehospitalization was judged to be medication non-compliance (n = 25; 50%), followed by medication nonresponse (n = 13; 26%). Not surprisingly, medication recommendations were closely linked to the assessed reason for relapse (depot therapy [n = 27; 49%] with medication non-compliance; atypical antipsychotic [n = 20; 37%] with medication nonresponse [X2 = 26.9, p<.001]).These two recommendations were implemented before discharge for about one-half of the cases. Patient refusal was a relatively greater problem for depot recommendation while constraints in the outpatient environment were more problematic for patients recommended for atypical antipsychotics. Conclusions: Medication noncompliance and medication nonresponse, in that order, were judged to be the most common causes of relapse for “revolving door” inpatients. Both depot therapy and atypical antipsychotics were commonly recommended and ultimately accepted by about 2/3rds of patients. Choice between depot and atypical was driven by the assessed cause of relapse. In summary, it seems possible to identify “revolving door” inpatients, and to target specific medication interventions within the time frame of an acute inpatient admission.

Depression and Social Adjustment Among Chronic Schizophrenic Outpatients

&NA; An examination of the relationship between symptoms and social adjustment among 98 chronic schizophrenic outpatients revealed that depressive mood contributed most to overall social dysfunction. Correlational patterns between depressive mood and factors of social dysfunction among these patients were found to be similar to those found among acutely depressed outpatients.

The effect of neuroleptic discontinuation on psychopathology, involuntary movements, and biochemical measures in patients with persistent tardive dyskinesia

As some of the pharmacological activities of neuroleptic medication may involve pathophysiological mechanisms underlying schizophrenia and tardive dyskinesia (TD), it is useful to study patients undergoing medication discontinuation. In this study, 19 stable, neuroleptic-maintained patients with persistent TD underwent taper and discontinuation of their neuroleptic medication over a 3-week period, and multiple behavioral and biochemical (plasma HVA, MHPG, and prolactin) measures were obtained. The major finding was that early relapsing patients had lower baseline and a significantly greater increase in plasma HVA levels after discontinuation than nonrelapsing patients. In addition, patients exhibiting withdrawal-exacerbated TD had significantly lower plasma MHPG levels than patients not exhibiting this phenomenon. The clinical and pharmacological implications of these findings are discussed.

Estrogen replacement and tardive dyskinesia

A double-blind randomized clinical trial was conducted among 10 post-menopausal women with tardive dyskinesia (TD) to test the effect of estrogen replacement of the severity of abnormal movements and other outcome variables. After 3 weeks of treatment, the mean Abnormal Involuntary Movement Scale (AIMS) score decreased by 38% in the estrogen group and by 9% in the placebo group; the difference between groups was marginally significant (p less than 0.10). However, the small sample size and the imbalance between groups in baseline AIMS scores do not allow us to rule out the confounding effects of other prognostic factors. There were no significant differences between treatment groups for parkinsonian and psychological symptoms at any visit or for changes in these variables between visits. The findings of this preliminary trial are consistent with the results of other human and animal investigations, and they support the need for future research to understand the role of estrogens in the neuropathology and treatment of TD.

Naltrexone augmentation of neuroleptics in schizophrenia

This study was conducted to determine whether the addition of naltrexone to ongoing neuroleptic treatment would facilitate the reduction in positive or negative symptoms in patients with schizophrenia. Twenty-one patients meeting DSM-III criteria for schizophrenia were enrolled; all patients had been stabilized for at least 2 weeks on their dosage of neuroleptic medicine before entering the study. Patients were randomized to receive either placebo or naltrexone 200 mg/day for 3 weeks in addition to their neuroleptic. Patients randomized initially into the placebo arm were crossed over to receive naltrexone in a single-blind fashion for 3 additional weeks. All patients were rated weekly with the Brief Psychiatric Rating Scale (BPRS). Fifteen patients received placebo and six received naltrexone in the first 3 weeks. No significant effects of naltrexone on total BPRS scores or BPRS subscale scores were observed. Patients who received naltrexone on a single-blind basis at the end of the placebo-controlled trial demonstrated a transient exacerbation in negative symptoms as reflected by the total BPRS score and the BPRS Withdrawal-Retardation subscale score. Repeated-measures analysis of variance (ANOVA) on the BPRS total score of the subsequent treatment with naltrexone showed a trend for a significance in the drug by time effect. Repeated-measures ANOVA on the BPRS Withdrawal-Retardation subscale of the subsequent treatment with naltrexone showed a significant drug by time effect. The current data failed to indicate a clinical benefit when naltrexone was added to the neuroleptic regimen. Other potential applications of naltrexone in schizophrenia are addressed.

The relationship of circulating estradiol to tardive dyskinesia in men and postmenopausal women.

In order to assess the relationship between tardive dyskinesia (TD) and baseline circulating concentrations of estradiol, prolactin and homovanillic acid, we studied 43 outpatient men and postmenopausal women on chronic antipsychotic medication. Serum estradiol did not correlate with severity of TD, antipsychotic medication dose, serum prolactin or plasma HVA. Multiple regression analysis indicated a significant relationship between plasma HVA and severity of TD in postmenopausal women. These findings support the hypothesis that estrogen might serve a protective role against neuroleptic-induced striatal dopamine pathology.

Predictors of tardive dyskinesia: Results of a cross-sectional study in an outpatient population

A cross-sectional study was conducted to identify predictors of tardive dyskinesia (TD) in a group of 180 psychiatric outpatients maintained on neuroleptic medications. The estimated prevalence of this involuntary movement disorder was 33% in the total study population. Using multiple logistic regression, we found that TD was independently related to five factors: being 55 yr of age and older; being male; using depot (injectable) neuroleptics; having 6 or more years of neuroleptic exposure; and having less than 6 months of psychiatric hospitalization. In addition, the effect of depot medication was much greater in white males than it was in other race-sex groups. We observed no other interaction effects between pairs of predictor variables, nor did we find significant independent effects of race, denture use, DSM III diagnosis, current neuroleptic dose and potency, percent time on neuroleptics, and recent use of antiparkinsonian drugs or lithium. This study is serving as a pilot investigation for a large prospective incidence study that has already begun among patients at risk of developing TD in the same source population.

The treatment of tardive dyskinesia with baclofen

Thirty-one psychiatric outpatients with tardive dyskinesia (TD) on neuroleptic medication were followed in a double-blind, randomized trial comparing baclofen (30–90 mg per day) to placebo. A repeated measures analysis of variance revealed no statistical difference between the baclofen-treated group and the placebo group for the group and the placebo group for the total Abnormal Involuntary Movement Scale (AIMS) scores. There was a trend (P=0.09) for an initial improvement, then a worsening of frequency counts across four visits. The authors attempt to explain this finding on the basis of information obtained from animal research.