Bharath Holla

High doses of Baclofen as suicide attempt in patients with alcohol use disorders - A serious concern

Baclofen is increasingly being used as an off label anti-craving agent in alcohol use disorders in various parts of the world. The lack of proper recommendations regarding the dosage has important implications for safety in clinical management. In this context, we report two patients who were started with Baclofen as an anti-craving agent, and later developed serious complications following acute self inflicted overdose. We also highlight the important mechanisms of such complications and precautions that needs to be exerted while prescribing.

Karnataka state telemedicine project: Utilization pattern, current, and future challenges

Background: The Telemedicine Network Project in the state of Karnataka was introduced in the year 2001. This is a value added service from the health department of the government of Karnataka. There is no data on its utilization pattern or its future challenges. This study was conducted from a nodal center in order to understand the above two issues. Materials and Methods: We used a 51-item survey questionnaire that captured data on infrastructure, technical aspects, and connectivity parameters, tele-consultations including emergency services, human resources, and coordination aspects both at the client as well as the nodal centers. Results: Services are operational in 25 district hospitals across the state for the past 3.3 (2.1) years. Space was ear-marked across all the client centers. Back-up power supply was present only in 10 (40%) of the client centers. Quality of satellite connection was acceptable in 18 (72%) centers. Approximately, 3.0 (1.8) phone calls had to be made to the nodal centers to obtain one appointment. Monthly maximum and minimum cases done over the past 2 year period were reported as 58.2 (66.2) and 13.5 (16.2) respectively. Each consultation lasted for 26.1 (13.9) min. Tele-consultation advices from nodal centers were carried out completely in only 9 (36%) centers. Only in 13 (52%) client centers, did doctors keep up with appointment regularly. All technicians reported that the training they received was inadequate. 16 (64%) technicians were asked to do works that were not pertaining to telemedicine. 19 (76%) technicians had frequently felt insecurities about their jobs. Conclusions: The telemedicine service has been largely under-utilized and has failed to deliver the promise in Karnataka state. At present, the obstacles reflect both inherent limitations in the technology and also improper use of human resources. Successful implementation of the given recommendations may in the long run help optimal utilization and reach all end-users.

Course and outcome of schizophrenia in asian countries: review of research in the past three decades.

Considerable variation has been observed in the course and outcome of schizophrenia. With regard to epidemiology of schizophrenia, papers from different Asian countries have reported findings which are in contrast with literature from the western countries. In this background we undertook a narrative review of literature regarding course and outcome of schizophrenia in Asian countries. We conducted Medline search for English-language papers on long-term course and outcome of schizophrenia conducted in Asia in the past 3 decades. We also reviewed data pertaining to Asian countries from the World Health Organizations International Study of Schizophrenia (ISoS). In addition to ISoS, we retrieved 14 reports from 9 Asian countries. While ISoS used comparable methodology across the countries, non-ISoS studies differed substantially in their aims, sampling, follow-up rates and assessment tools used for studying the course and outcome. Overall, the percentage of patients who experienced clinical and functional outcome in the Asian countries were largely comparable to those in the western studies. We observed significant variations in the long-term outcome and mortality in schizophrenia even among the Asian countries. In conclusion, there is substantial variation in the long-term course and outcome and mortality across different Asian countries. The reason for this remains unexplored. Cross-national studies exploring biological and cultural explanations for this variation may provide clues, which may have heuristic, translational and public-health significance.

Visual Image-induced Craving for Ethanol (VICE): Development, validation, and a pilot fmri study

Background: Craving induction in a controlled environment is helpful in the research of craving mechanism and its role in development of alcohol dependence (AD). We describe a novel tool Visual Image-induced Craving for Ethanol (VICE) and its effects on brain activation with pilot functional magnetic resonance imaging (fMRI). Materials and Methods: Alcohol-related visual cues (ARCs) in 5 scenarios were photographed, which included pictures of bars, alcoholic beverage bottles, pouring of alcohol into glasses, glasses filled with alcohol, and scenes of people sipping alcohol, counterbalanced with neutral pictures (involving water, milk etc.,). Craving scores were obtained from 15 hospitalized patients with AD to validate this tool. In the pilot fMRI (3-Tesla) study, 5 patients were examined using VICE in a symptom provocation model. Group level-fixed effect analysis of brain activation differences was done using SPM8. Results: VICE showed a high internal consistency with Cronbachs α coefficient of 0.86, which confirmed its reliability. Concurrent validity of VICE was demonstrated via its convergence with the Penn Alcohol Craving Scale. ARCs had significantly greater mean craving scores than neutral cues in all the 5 scenarios (intentional validity). In the pilot fMRI, patients were found to have greater activation while viewing ARCs compared to the neutral cues in right insular cortex and deficient activation in right orbitofrontal cortex. Conclusions: The VICE is a reliable and valid measure of alcohol craving with promising clinical and translational research implications. Preliminary fMRI findings indicate it can be used as a symptom provocation tool for fMRI experiments.

Modafinil for the Treatment of Antipsychotic-Induced Excessive Daytime Sedation: Does It Exacerbate Tics?

To the Editor: Excessive daytime sedation (EDS) is a common and disabling side effect of antipsychotics (AP). We report on a case of a 17-year-old patient with difficultto-treat symptoms of obsessivecompulsive disorder, chronic tic disorder, and primary derealization syndrome, whose compliance was noted to be poor because of AP-induced EDS. We successfully used modafinil for the treatment of this AP-related EDS, but with initial exacerbation of tics. This report highlights the need for careful dose-titration of modafinil, especially in those with past or family history of tic disorders. Excessive daytime sedation (EDS) is a common and disabling side effect of antipsychotics (AP), often leading to treatment noncompliance. EDS can be treated with activating agents such as modafinil or stimulants or by stopping the sedating APs. We report on a case with successful use of modafinil for the treatment of AP-induced EDS, but with initial worsening of tics. A 17-year-old boy presented to the hospital outpatient services with a 3-year history of derealization, pathological doubts, aggressive and superstitious obsessions, re-reading and re-writing compulsions; and excessive blinking, facial grimacing, quick movements of the arms and legs, and grunting sounds. There was a family history of tic disorder in the mother and maternal aunt. He was diagnosed with obsessive-compulsive disorder (OCD), chronic tic disorder, and primary derealization syndrome. He was treated with fluvoxamine 200 mg/day and risperidone 2 mg/day. Compliance was noted to be poor because of sedation. Treatment was changed to fluoxetine 40 mg/day and haloperidol 2 mg/day. With this, there was 90% improvement in his tics and significant improvement in OCD. In view of the patient’s continuing complaint of lack of alertness during the day, modafinil 200 mg/day was added. After adding modafinil, a worsening of tics was noted; hence, the dose was decreased to 150 mg/day. In the next follow-up, after 2 months, the patient reported 80% improvement in tics. The score on the Naranjo ADR Probability Scale was 8, which scores as Probable. The total tic score on the Yale Global Tic Severity Scale was 15/50 (before modafinil), 40/50 (on modafinil), and 16/50 (after reducing modafinil dose). Modafinil has been traditionally used to reduce excessive sleepiness in patients with narcolepsy and shiftwork sleep disorder. There is preliminary evidence for its successful use in AP-induced EDS. In this patient, addition of modafinil at 200 mg/day led to significant improvement in EDS, but was associated with worsening of tics. However, with a titration of its dose down to 150 mg/day, tics were brought under control. There are reports of stimulantassociated exacerbation of tics, but causal relationship has been debatable. Use of a nonstimulant like modafinil in appropriate dosage can lead to effective amelioration of EDS without marked worsening of tics, as demonstrated in our report. The precise pathophysiological link behind exacerbation of tics and modafinil’s mechanism in promoting wakefulness remains unclear. It is believed that it increases synaptic dopamine following blockade of dopamine transport. This leads to increased tonic firing and downstream effects on neurotransmitters involved in wakefulness, as against phasic dopamine firing seen with classic stimulants like amphetamine and methylphenidate, promoting reinforcement and abuse. Tonic dopamine leads to release of histamine from the tuberomamillary nucleus of the posterior hypothalamus and then further activation of the lateral hypothalamus, with orexin release to stabilize wakefulness. This increase in synaptic dopamine is also believed to be associated with exacerbation of tics. This can be managed by careful titration of modafinil dosage and also the use of Dopamine-2 receptor antagonists.

Piracetam treatment in patients with cognitive impairment

Piracetam is a cognitive-enhancing agent that is used for the treatment of cognitive impairments of various etiologies. Little is known about its side effect profile, especially in those with psychiatric illness. We herewith present two cases with cognitive impairment who had contrasting responses to piracetam. One of them with organic amnestic syndrome had significant improvement, whereas the other who had an organic personality change as well as a family history of mental illness had significant worsening of behavioral problems after piracetam was introduced. This report highlights the need for caution in the use of piracetam, especially in those with past or family history of psychiatric illness.

Disrupted Resting Brain Graph Measures in Individuals at High Risk for Alcoholism

Familial susceptibility to alcoholism is likely to be linked to the externalizing diathesis seen in high-risk offspring from high-density alcohol use disorder (AUD) families. The present study aimed at comparing resting brain functional connectivity and their association with externalizing symptoms and alcoholism familial density in 40 substance-naive high-risk (HR) male offspring from high-density AUD families and 30 matched healthy low-risk (LR) males without a family history of substance dependence using graph theory-based network analysis. The HR subjects from high-density AUD families compared with LR, showed significantly reduced clustering, small-worldness, and local network efficiency. The frontoparietal, cingulo-opercular, sensorimotor and cerebellar networks exhibited significantly reduced functional segregation. These disruptions exhibited independent incremental value in predicting the externalizing symptoms over and above the demographic variables. The reduction of functional segregation in HR subjects was significant across both the younger and older age groups and was proportional to the family loading of AUDs. Detection and estimation of these developmentally relevant disruptions in small-world architecture at critical brain regions sub-serving cognitive, affective, and sensorimotor processes are vital for understanding the familial risk for early onset alcoholism as well as for understanding the pathophysiological mechanism of externalizing behaviors.

Brain Functional Magnetic Resonance Imaging Cue-reactivity Can Predict Baclofen Response in Alcohol Use Disorders

Objective Baclofen is a promising treatment for alcohol use disorders (AUD), although its clinical response in humans is mixed. The present study aimed at investigating the impact of baclofen treatment on cue-induced brain activation pattern and its relationship with relapse outcomes. Methods Twenty-three inpatients with AUD underwent a functional magnetic resonance imaging cue-reactivity task before beginning medication with baclofen and 2 weeks later. Twelve additional inpatients with AUD, who did not receive any anticraving medications, formed the control group. All subjects were prospectively followed up for 90 days post-discharge or until lapse to first alcohol use. Results Whole-brain linear mixed effects analysis revealed a significant group-by-time interaction with greater activation of the bilateral dorsolateral pre-frontal cortex and right anterior cingulate cortex (ACC) following baclofen treatment in comparison with the control group. Further, cox regression analysis revealed that increased activation of ACC and deactivation of insular cortex (IC) was associated with longer time to first alcohol use only in the baclofen treatment group but not in the control group. Conclusion This study provides preliminary evidence for the neural predictors of baclofen treatment response in AUD. Baclofen treatment in AUD was associated with changes in cue-reactivity at critical brain regions within the incentive-salience network. Importantly, baclofen treatment-related specific activation of regions involved in cognitive control (ACC) and deactivation of regions involved in reward anticipation (IC) prolonged the time to first alcohol drink.

Altered brain cortical maturation is found in adolescents with a family history of alcoholism: Brain CTh in familial AUDs

Substance‐naïve offspring from high‐density alcohol use disorder (AUD) families exhibit altered subcortical brain volumes structurally and altered executive‐functioning and emotion‐processing functionally, compared with their peers. However, there is a dearth of literature exploring alterations of cortical thickness (CTh) in this population. T1‐weighted structural brain MRI was acquired in 75 substance‐naïve male offspring of treatment‐seeking early onset (<25 years) AUD patients with high familial loading of AUDs (≥2 affected relatives) (FHP) and 65 age‐matched substance‐naïve male controls with negative family history from the community. Surface‐based CTh reconstruction was done using FreeSurfer. Univariate general linear models were implemented at each vertex using SurfStat, controlling for age (linear and quadratic effects), and head size, to examine the main effect of familial AUD risk on CTh and its relationship with externalizing symptom score (ESS). A Johnson–Neyman procedure revealed that the main effect of familial AUD risk on CTh was seen during adolescence, where the FHP group had thicker cortices involving bilateral precentral gyri, left caudal middle frontal gyrus (MFG), bilateral temporo‐parietal junction, left inferior‐frontal gyrus and right inferior‐temporal gyrus. Thicker cortices in left MFG and inferior‐parietal lobule were also associated with greater ESS within both groups. More importantly, these group differences diminished with age by young adulthood. Familial AUD risk is associated with age‐related differences in maturation of several higher order association cortices that are critical to ongoing development in executive function, emotion regulation and social cognition during adolescence. Early supportive intervention for a delay in alcohol initiation during this critical phase may be crucial for this at‐risk population.

Profile of male forensic psychiatric inpatients in South India

Aim: The study explored the socio-demographic, clinical and legal profile of forensic psychiatric inpatients in an attempt to improve the existing mental health services for prisoners within the prison and in psychiatric hospitals. Methodology: A chart review of 135 forensic psychiatric inpatients admitted between January 2005 and December 2009 was done. A structured data-extraction tool was used for data collection and a descriptive approach for analyses. Results: Subjects were referred either directly from prison (62.2%) or from court (37.8%) for diagnosis, treatment or certification. References to the Mental Health Act 1987, charges and inclusion of first investigation report and behavioural observation report was lacking in most. The majority of prisoners (85.7%) were under trial, murder being the most common charge. Psychiatric diagnosis was made in 90.3%, the most common being psychosis. Substance use (nicotine, alcohol, cannabis) and high-risk behaviours were also common. Conclusion: There is a need to streamline the procedure of referral and to sensitize the referral authorities about the Mental Health Act and mental illnesses, and the need to enclose first investigation reports and behavioural observation reports. De-addiction services and facilities need to be established within prison premises so that the inmates get the benefit of treatment at the earliest opportunity.