Medication Options and Clinical Strategies for Treating Tardive Dyskinesia.

Valbenazine and deutetrabenazine are FDA-approved as treatment for tardive dyskinesia (TD). Both medications are vesicular monoamine transporter type 2 (VMAT2) inhibitors, and both are effective for reducing TD symptoms. Clinicians need to be aware of the adverse effects of valbenazine and deutetrabenazine, as well as other key differences between the two, in order to individualize treatment. Using the Abnormal Involuntary Movement Scale assists clinicians in assessing progress for each patient. Treating TD effectively with these new medications will reduce the burden of the condition for patients.

Activating and Sedating Properties of Medications Used for the Treatment of Major Depressive Disorder and Their Effect on Patient Functioning.

Although the sedative and extrapyramidal side effects associated with first-generation antipsychotics are well known, some second-generation antipsychotics are also associated with substantial sedation and activation effects. In this Academic Highlights article, 4 experts on depression from the fields of psychiatry and primary care take a closer look at activation and sedation effects of atypical antipsychotics in patients with MDD. They examine the likelihood of each agent to cause these effects; the impact of these effects on patient functioning, quality of life, and treatment adherence; and the question of whether leveraging activation and sedation to address acute symptoms is ever advisable.

Epidemiology, Prevention, and Assessment of Tardive Dyskinesia and Advances in Treatment.

​​ Tardive dyskinesia (TD) is a disorder characterized by involuntary movements, typically of the orofacial muscles and also of the extremities and other muscle groups. The condition is associated with exposure to dopamine receptor blocking agents, including antipsychotics. Because the indications and off-label uses for these agents have expanded over the last 2 decades, a larger number of patients are receiving antipsychotic medications than in the past. While evidence suggests that patients being treated with second-generation antipsychotics have less risk for developing TD than those treated with first-generation antipsychotics, the decreased risk is not as great as was originally expected. In addition, patients with chronic psychiatric conditions often require long-term use of antipsychotics, putting them at risk for TD. This article addresses the prevalence, risk factors, and prevention of TD; assessment strategies including diagnostic criteria and rating scales; and evidence for TD treatments, including 2 newly approved medications: deutetrabenazine and valbenazine. ​​​.

Comparing Treatments for Tardive Dyskinesia.

Many treatment interventions for tardive dyskinesia have been studied, but some have better evidence than others. Read this CME activity to get an expert's perspectives on the evidence for older and newer treatments so that you can minimize abnormal movements in your patients.

Risk of treatment-emergent diabetes mellitus in patients receiving antipsychotics.

BACKGROUND: Type 2 diabetes mellitus has been reported during antipsychotic treatment. OBJECTIVE: To quantify the potential risk of treatment-emergent diabetes mellitus among patients receiving antipsychotic medications. METHODS: The MEDLINE and Psychinfo databases were searched using the key words antipsychotic (including individual drug names), diabetes, risk, and incidence for all English-language articles published between 1966 and 2005. Risk calculations were performed using data obtained from pharmacoepidemiologic studies that met the following criteria: (1) cohort design, (2) determination of preexisting diabetes, (3) inclusion of antipsychotic monotherapy as an exposure variable, and (4) comparison with exposure to first-generation antipsychotics. Studies meeting these criteria were used to calculate incidence, attributable risk between agents, and number needed to harm. RESULTS: A total of 25 observational pharmacoepidemiologic studies were found comparing antipsychotics on the outcome of diabetes mellitus. Sufficient information was provided in 15 of the reports to be able to estimate attributable risk. Attributable risk for individual second-generation antipsychotics relative to first-generation antipsychotics ranged from 53 more to 46 fewer new cases of diabetes per 1000 patients. Little observable difference was noted between the individual second-generation antipsychotics versus first-generation antipsychotics on this outcome. However, few of the studies controlled for body weight, race or ethnicity, or the presence of diabetogenic medications. None adjusted for familial history of diabetes, levels of physical activity, or diet, as this information is not usually available in the databases used in pharmacoepidemiologic studies. CONCLUSIONS: Based on the published pharmacoepidemiologic reports reviewed, the avoidance of diabetes as an outcome cannot be predictably achieved with precision by choice of a second-versus a first-generation antipsychotic. Risk management for new-onset diabetes requires the assessment of established risk factors such as family history, advancing age, non-white ethnicity, diet, central obesity, and level of physical activity.

Intramuscular aripiprazole in the control of agitation.

OBJECTIVE: To evaluate response to intramuscular (IM) aripiprazole injections using secondary analyses from clinical trials. METHODS: Data from one trial in patients with bipolar I disorder and two trials in patients with schizophrenia were assembled and used for three secondary analyses. Analysis 1 looked at data from "nonsedated" patients (i.e., patients with scores < 8 [deep sleep] or 9 [unarousable] on the Agitation-Calmness Evaluation Scale [ACES]). In analysis 2, patients were subdivided into "higher" and "lower" agitation groups according to a median split on the baseline score for the Positive and Negative Syndrome Scale (PANSS) Excited Component (PEC) (median = 18). Analysis 3 looked at the patients who received a second injection within the 24-hour study period. In each analysis, the mean change from baseline in PEC scores was re-evaluated. RESULTS: Analysis 1 found that nonsedated patients with bipolar I disorder and schizophrenia showed significant decreases in PEC scores following treatment with aripiprazole IM (p < 0.005). Analysis 2 found that aripiprazole IM significantly reduced agitation compared with placebo in patients with bipolar I disorder who had lower baseline agitation (p < 0.01), while patients with bipolar I disorder who had higher baseline agitation showed similarly large PEC decreases with aripiprazole (-9.9) and placebo (-7.9). Patients with schizophrenia showed significant reductions in PEC scores compared with placebo regardless of baseline level of agitation (p < 0.01). Analysis 3 found that a second injection of aripiprazole IM significantly reduced agitation in patients with bipolar I disorder or schizophrenia (p < 0.05); repeated injections were safe and well tolerated. CONCLUSION: Improvements with aripiprazole IM appeared to be specific to core agitation symptoms, as opposed to nonspecific sedation, and to be independent of baseline level of agitation. Furthermore, patients benefited from a repeated aripiprazole injection when clinically warranted. These results address important clinical issues regarding use of aripiprazole IM in treating agitation.

Aggression and quantitative MRI measures of caudate in patients with chronic schizophrenia or schizoaffective disorder.

Caudate dysfunction is implicated in schizophrenia. However, little is known about the relationship between aggression and caudate volumes. Forty-nine patients received magnetic resonance imaging scanning in a double-blind treatment study in which aggression was measured. Caudate volumes were computed using a semiautomated method. The authors measured aggression with the Overt Aggression Scale and the Positive and Negative Syndrome Scale. Larger caudate volumes were associated with greater levels of aggression. The relationship between aggression and caudate volumes may be related to the iatrogenic effects of long-term treatment with typical antipsychotic agents or to a direct effect of schizophrenic processes on the caudate.

Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder.

The relationship between orbitofrontal cortex (OFC) volumes and functional domains in treatment-resistant patients with schizophrenia or schizoaffective disorder is poorly understood. OFC dysfunction is implicated in several of the behaviors that are abnormal in schizophrenia. However, little is known about the relationship between these behaviors and OFC volumes. Forty-nine patients received magnetic resonance imaging scanning as part of a double-blind treatment study in which psychiatric symptomatology, neuropsychological function, and aggression were measured. OFC volumes were manually traced on anatomical images. Psychiatric symptomatology was measured with the Positive and Negative Syndrome Scale (PANSS). Aggression was measured with the Overt Aggression Scale (OAS) and with the PANSS. Neuropsychological function was assessed using a comprehensive test battery. Larger right OFC volumes were associated with poorer neuropsychological function. Larger left OFC gray matter volumes and larger OFC white matter volumes bilaterally were associated with greater levels of aggression. These findings are discussed in the context of potential iatrogenic effects.

Aggression and psychopathology in treatment-resistant inpatients with schizophrenia and schizoaffective disorder.

Positive psychotic symptoms, such as threat/"control-override" delusions or command hallucinations, have been related to aggression in patients with schizophrenia. However, retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior. In this study, we monitored aggressive behavior and psychopathology prospectively and in close temporal proximity in 157 treatment-resistant inpatients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial. Aggressive behavior was rated with the overt aggression scale (OAS). Psychopathology was assessed using the positive and negative syndrome scale (PANSS). At baseline, subjects who would be aggressive during the study had higher scores on only two PANSS items: hostility and poor impulse control. During the study PANSS positive subscale scores were significantly higher in aggressive subjects. Total PANSS scores were higher within 3 days of an aggressive incident, as were positive and general psychopathology subscale scores. However, in a smaller subsample for whom PANSS ratings were available within 3 days before aggressive incidents, only scores on the PANSS positive subscale were significantly higher. These findings in chronic, treatment resistant inpatients support the view that positive symptoms may lead to aggression.

The increase in risk of diabetes mellitus from exposure to second-generation antipsychotic agents.

This is a review of the evidence for a link between exposure to second-generation antipsychotic agents and the development of type 2 diabetes mellitus. Most of this evidence comes from case series and retrospective pharmacoepidemiological studies. Exposure to second-generation antipsychotic agents increases the risk for diabetes mellitus compared to no exposure to antipsychotic drugs. The risk with second-generation antipsychotic agents compared to exposure to first-generation antipsychotics is smaller and not consistent. The differential risk among the second-generation antipsychotic agents has not yet been adequately established. Other risk factors for diabetes mellitus, such as advancing age, non-White ethnicity, family history, obesity, lack of physical activity and the diagnosis of schizophrenia, probably contribute more to the risk than exposure to any single antipsychotic drug. Clinicians are urged to manage risk by regularly monitoring all patients receiving second-generation antipsychotic agents for the emergence of diabetes mellitus.

Relationship of atypical antipsychotics with development of diabetes mellitus.

OBJECTIVE: To review the pharmacoepidemiologic evidence for the link between exposure to atypical antipsychotics and the development of diabetes mellitus. DATA SOURCES: A MEDLINE search (1990-March 2003) was conducted. STUDY SELECTION AND DATA EXTRACTION: The search was limited to articles that described findings from analyses of large databases and used the words diabetes or hyperglycemia, and antipsychotic or clozapine or olanzapine or risperidone or quetiapine or ziprasidone or aripiprazole in the title or abstract. The odds ratio or relative risk, together with their corresponding confidence interval, was extracted. DATA SYNTHESIS: Results are conflicting, and this variability may be due to the different populations studied, different study designs, and the possibility of publication bias related to funding by the pharmaceutical industry. Nevertheless, an increased risk for diabetes mellitus appears to be present for patients receiving atypical antipsychotics. However, differential risk among the atypical antipsychotics is difficult to ascertain. CONCLUSIONS: Clinicians are urged to manage risk by regularly monitoring all patients receiving atypical antipsychotics for the emergence of diabetes mellitus. Future studies should carefully control for confounding variables such as age, diagnosis, change in weight, activity level, family history, and ethnicity.

Characteristics of assaultive behavior among psychiatric inpatients.

OBJECTIVE: The purpose of this study was to assess the extent to which psychosis, disordered impulse control, and psychopathy contribute to assaults among psychiatric inpatients. METHODS: The authors used a semistructured interview to elicit reasons for assaults from assailants and their victims on an inpatient research ward. Video monitoring provided supplemental information to confirm participants' identities and activities before and during the assault. RESULTS: Consensus clinical ratings indicated that approximately 20 percent of the assaults in this sample were directly related to positive psychotic symptoms. Factor analysis revealed two psychosis-related factors, one related to positive psychotic symptoms and the other to psychotic confusion and disorganization, as well as a third factor that differentiated impulsive from psychopathic assaults. CONCLUSIONS: Information obtained from interviews with assailants can reveal the underlying causes of specific assaults. This information is potentially useful in the selection of rational antiaggressive treatment strategies.