Spotlight on once-monthly long-acting injectable aripiprazole and its potential as maintenance treatment for bipolar I disorder in adult patients

Vanessa Torres-Llenza, Pooja Lakshmin, Daniel Z Lieberman Department of Psychiatry and Behavioral Sciences, George Washington University School of Medicine and Health Sciences, Washington, DC, USA Abstract: The lack of long-term medication adherence is a challenge in the treatment of bipolar disorder, particularly during the maintenance phase when symptoms are less prominent. The rate of nonadherence is ~20%–60% depending on how strict a definition is used. Nonadherence worsens the course of bipolar disorder and can add hundreds of thousands of dollars to the lifetime cost of treating the illness. Long-acting injectable (LAI) medication is an attractive alternative to daily dosing of oral medication, especially among patients who are ambivalent about treatment. The purpose of this paper is to review the evidence for the safety and efficacy of LAI aripiprazole, which was recently approved for the treatment of bipolar disorder. The approval was based on a single double-blind, placebo-controlled, multisite trial that recruited participants from 103 sites in 7 countries. A total of 731 participants with bipolar disorder were enrolled in the study. Out of that total, 266 were successfully stabilized on LAI aripiprazole and entered the randomization phase. Treatment-emergent adverse events were, for the most part, mild to moderate. Akathisia was the most common adverse event, which, combined with restlessness, was experienced by 23% of the sample. At the end of the 52-week study period, nearly twice as many LAI-treated participants remained stable compared to those treated with placebo. Stability during the maintenance phase is arguably the most important goal of treatment. It is during this period of relative freedom from symptoms that patients are able to build a meaningful and satisfying life. The availability of a new treatment agent, particularly one that has the potential to enhance long-term adherence, is a welcome development. Keywords: antipsychotic, adherence, partial agonist, mood stabilizer, revie

Identifying harmful drinking using a single screening question in a psychiatric consultation-liaison population.

Background: Harmful drinking is common in medical inpatients, yet commonly missed due in part to time pressures. A screening question about past year heavy drinking recommended by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has been validated in primary care and emergency room settings. We tested the psychometric properties of a modified single screening question (SSQ) in hospitalized patients referred to a consultation-liaison service. Methods: A psychiatry attending (n = 40), a psychiatry resident (n = 30) and a medical student (n = 30) administered the SSQ, followed by a self-report 10-item Alcohol Use Disorders Identification Test (AUDIT) to a sample of 100 consultation-liaison patients who were able to give informed consent for participation. Results: Using the AUDIT as a reference, the sensitivity and specificity of the SSQ to detect harmful drinking in this sample were .96 and .82, respectively. Gender differences in specificity were not found. The single question also had a strong correlation with dependence (r b = .457, p \u3c .001), and harmful use (r b = .620, p \u3c .001) subscales of the AUDIT. Conclusion: The SSQ about past year heavy drinking can rapidly identify harmful drinking in alert nonpsychotic consultation-liaison patients. © 2011 The Academy of Psychosomatic Medicine

Motor-evoked potentials (MEP) during brainstem surgery to preserve corticospinal function

Brainstem surgery bears a risk of damage to the corticospinal tract (CST). Motor-evoked potentials (MEPs) are used intraoperatively to monitor CST function in order to detect CST damage at a reversible stage and thus impede permanent neurological deficits. While the method of MEP is generally accepted, warning criteria in the context of brainstem surgery still have to be agreed on

The risk for drug abuse, alcohol use disorder, and psychosocial dysfunction in offspring from high-density pedigrees : its moderation by personal, family, and community factors

Previous high-risk family designs in psychiatry have focused largely on offspring of affected parents. We take a pedigree-based approach and examine the social, psychological, and psychiatric features of offspring from extended pedigrees selected for high-densities of alcohol use disorder (AUD) or drug abuse (DA). We identified, from the Swedish population, 665,715 pedigrees containing a mean of 17.9 parents, aunts/uncles, grandparents, and cousins of a core full-sibship we term the pedigree offspring. We then derived 13 empirical classes of these pedigrees based on the density of cases of AUD and DA. High rates of AUD or DA in the pedigrees were associated in the offspring with lower levels of school achievement, educational attainment, and resilience, and higher rates of psychiatric illness, neighborhood deprivation, unemployment, social welfare, early retirement, and criminal convictions. Effect sizes were large in the offspring of the highest density pedigrees and were stronger in high-density DA than in high-density AUD pedigrees. Sensitivity to the pathogenic effects of membership in these high-risk sibships was substantially attenuated by high levels of school attainment and resilience, female sex, and absence of parental divorce. Offspring of pedigrees with a high density of AUD or DA are multiply disadvantaged and typically suffer from educational difficulties, social deprivation, socio-economic dysfunction, personality problems, and elevated rates of both psychiatric disorders and externalizing syndromes. Despite these difficulties, personal strengths, including improved school achievement and resilience, and an intact parental marriage can substantially buffer these adverse effects and might form a basis for prevention efforts

Disrupted regulation of social exclusion in alcohol dependence : an fMRI study

Alcohol-dependence is associated with cognitive and biological alterations, and also with interpersonal impairments. Although overwhelming in clinical settings and involved in relapse, these social impairments have received little attention from researchers. Particularly, brain alterations related to social exclusion have not been explored in alcohol-dependence. Our primary purpose was to determine the neural correlates of social exclusion feelings in this population. In all, 44 participants (22 abstinent alcohol-dependent patients and 22 paired controls) played a virtual game ('cyberball') during fMRI recording. They were first included by other players, then excluded, and finally re-included. Brain areas involved in social exclusion were identified and the functional connectivity between these areas was explored using psycho-physiological interactions (PPI). Results showed that while both groups presented dorsal anterior cingulate cortex (dACC) activations during social exclusion, alcohol-dependent participants exhibited increased insula and reduced frontal activations (in ventrolateral prefrontal cortex) as compared with controls. Alcohol-dependence was also associated with persistent dACC and parahippocampal gyrus activations in re-inclusion. PPI analyses showed reduced frontocingulate connectivity during social exclusion in alcohol-dependence. Alcohol-dependence is thus linked with increased activation in areas eliciting social exclusion feelings (dACC-insula), and with impaired ability to inhibit these feelings (indexed by reduced frontal activations). Altered frontal regulation thus appears implied in the interpersonal alterations observed in alcohol-dependence, which seem reinforced by impaired frontocingulate connectivity. This first exploration of the neural correlates of interpersonal problems in alcohol-dependence could initiate the development of a social neuroscience of addictive states.Neuropsychopharmacology advance online publication, 18 April 2012; doi:10.1038/npp.2012.54