Showing papers on "Psychotropic drug published in 2014"

Assessing racial/ethnic disparities in treatment across episodes of mental health care.

Abstract: ObjectiveTo investigate disparities in mental health care episodes, aligning our analyses with decisions to start or drop treatment, and choices made during treatment. Study DesignWe analyzed whites, blacks, and Latinos with probable mental illness from Panels 9–13 of the Medical Expenditure Panel Survey, assessing disparities at the beginning, middle, and end of episodes of care (initiation, adequate care, having an episode with only psychotropic drug fills, intensity of care, the mixture of primary care provider (PCP) and specialist visits, use of acute psychiatric care, and termination). FindingsCompared with whites, blacks and Latinos had less initiation and adequacy of care. Black and Latino episodes were shorter and had fewer psychotropic drug fills. Black episodes had a greater proportion of specialist visits and Latino episodes had a greater proportion of PCP visits. Blacks were more likely to have an episode with acute psychiatric care. ConclusionsDisparities in adequate care were driven by initiation disparities, reinforcing the need for policies that improve access. Many episodes were characterized only by psychotropic drug fills, suggesting inadequate medication guidance. Blacks’ higher rate of specialist use contradicts previous studies and deserves future investigation. Blacks’ greater acute mental health care use raises concerns over monitoring of their treatment.

Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study

Abstract: Objective To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people. changes in antidepressant use were −31.0% (95% confidence interval −33.0% to −29.0%) among adolescents, −24.3% (−25.4% to −23.2%) among young adults, and −14.5% (−16.0% to −12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, −6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group.

Pharmacotherapy for Mood Disorders in Pregnancy: A Review of Pharmacokinetic Changes and Clinical Recommendations for Therapeutic Drug Monitoring

Abstract: Untreated mood disorders during pregnancy are associated with health risks to both mother and fetus, making the goal of euthymia paramount.1–4 Guidelines for the management of major depressive disorder and bipolar disorder during pregnancy stress the importance of preconception treatment planning and close clinical monitoring.2,5 Most women who discontinue maintenance antidepressants or mood-stabilizer pharmacotherapy for a pregnancy will experience a relapse during the pregnancy. Therefore, immediate and prophylactic treatment of many women with mood disorders will include pharmacologic treatment.6,7 Treatment during pregnancy is complicated by pharmacokinetic changes, which can result in lowered psychotropic drug levels and/or treatment efficacy. Therapeutic drug monitoring (TDM) is an integral aspect of the standard of care for medications with established therapeutic ranges, a narrow therapeutic index or significant pharmacokinetic variability, which includes some mood stabilizers and tricyclic antidepressants (TCAs). Given the evidence for changes in perinatal physiology and pharmacokinetics, TDM has the potential to optimize dosing by avoiding supratherapeutic doses that would increase drug exposure to the mother and fetus or subtherapeutic dosing that would expose the dyad to the consequences of undertreated psychiatric illness. A comprehensive discussion that includes the potential risks of undertreated mental illness for the mother and fetus, benefits of nonpharmacologic and potential risks, and benefits to psychopharmacologic treatment8–16 is essential to quality patient care. In cases of polypharmacy, TDM can be valuable in avoiding adverse effects due to drug-to-drug interactions. For medications without standardized therapeutic ranges, an individual woman’s drug level at a time when she is clinically asymptomatic that can be used as a target serum drug level during pregnancy may be useful.17,18 The objectives of this review are to summarize the evidence for changes in perinatal pharmacokinetics of psychotropic medications commonly used for mood disorders during pregnancy, consider the implications for clinical and TDM, and make clinical recommendations.

Pharmacological treatments prescribed to people with autism spectrum disorder (ASD) in primary health care

Abstract: Rationale Autism spectrum disorders (ASDs) affect 1 % of children, having significant impact on health and social outcomes. Psychotropic medication use by individuals with ASD in the USA increased over time, and polypharmacy occurred in >50 % of those prescribed. In the UK, no psychotropic drugs are approved in ASDs, and little is known about patterns of pharmacological treatment in the ASD population and associated co-morbidities. Methods We used The Health Improvement Network, a nationally representative primary care database, to assess the prevalence of ASD diagnoses, psychotropic drug

Medical marijuana and driving: a review

Abstract: Medical marijuana remains a highly debated treatment regimen despite removal of state penalties against care providers prescribing the drug and patients treated with the drug in many areas of the USA. The utility of marijuana in specific medical conditions has been studied at length, but its effects on driving performance and risk of motor vehicle collision remain unclear. As with other medications that affect psychomotor function, the healthcare provider should be informed of the potential risks of driver safety prior to prescribing this psychotropic drug to give appropriate anticipatory guidance for appropriate use. The goal of this narrative review is to assess the current literature regarding marijuana as it relates to driving performance and traffic safety. With a foundation in the pharmacology of cannabinoids, we consider the limitations of testing cannabinoid and metabolite concentration. In addition, we will review studies on driving performance and epidemiological studies implicating marijuana in motor vehicle collisions. The increasing prevalence of medical marijuana laws in the USA suggests that clinicians should be aware of marijuana’s influence on public safety. Patients should abstain from driving for 8 h if they achieve a subjective “high” from self-treatment with smoked marijuana and should be aware of the cumulative effects of alcohol and other psychoactive xenobiotics.

CYP2D6 variation, behaviour and psychopathology: implications for pharmacogenomics-guided clinical trials

Abstract: Individual and population differences in polymorphic cytochrome P450 enzyme function have been known for decades. The biological significance of these differences has now been deciphered with regard to drug metabolism, action and toxicity as well as disposition of endogenous substrates, including neuroactive compounds. While the cytochrome P450 enzymes occur abundantly in the liver, they are expressed in most tissues of the body, albeit in varying amounts, including the brain. The latter location of cytochrome P450s is highly pertinent for susceptibility to neuropsychiatric diseases, not to mention local drug metabolism at the site of psychotropic drug action in the brain. In the current era of personality medicine with companion theranostics (i.e. the fusion of therapeutics with diagnostics), this article underscores that such versatile biological roles of cytochrome P450s offer multiple points of entry for personalized medicine and rational therapeutics. We focus our discussion on CYP2D6, one of the most intensively researched drug and endogenous compound metabolism pathways, with a view to relevance for, and optimization of, pharmacogenomic-guided clinical trials. Working on the premise that CYP2D6 is related to human behaviour and certain personality traits such as serotonin and dopamine system function, we further suggest that the motivation of healthy volunteers to participate in clinical trials may in part be influenced by an under- or over-representation of certain CYP2D6 metabolic groups.

Therapeutic implications of adding the psychotropic drug escitalopram in the treatment of patients suffering from moderate-severe psoriasis and psychiatric comorbidity: a retrospective study.

Abstract: Background It is known that stress and/or psychiatric diseases can play an important role in determining psoriasis, including the well-known negative somato–psychiatric rebound that comes with the disease. Methods Samples of 38 subjects suffering from both moderate–severe psoriasis treated with anti-TNFα, and depressive and/or anxious mood disorders were studied. Part of them were additionally treated with escitalopram, whereas the other group only consulted to a dermatological and psychiatric follow-up. The aim of this study was to determine if an improvement in the dermatological manifestation as well as an improvement in the anxious–depressive disorder can be observed. Results The study revealed that patients treated with escitalopram had a reduction of psycho-diagnostic test scores that measure depression and anxiety levels as well as the values of pruritus. Conclusion Our study suggests that psychological interventions and antidepressant medications may improve perceived symptom severity, quality of life and major compliance to the treatment in selected patients (suffering from psoriasis and mood disturbance), without a clinician necessarily being able to see an impact on psoriasis severity.

Consumption of psychotropic drugs among adults who were in societal care during their childhood-A Swedish national cohort study.

Abstract: Background: Previous studies have demonstrated greatly increased risks of severe psychiatric morbidity for former child welfare clients. We investigated psychotropic medication in this population as a proxy indicator of less severe mental health problems. Methods: This register-based cohort study comprises the Swedish birth cohorts between 1973 and 1981, 765,038, including 16,986 former children from societal care and 1296 national adoptees. Estimates of risk of retrieval of prescribed psychotropic medications during 2009 were calculated in four categories (any such drug, neuroleptics, antidepressants and anxiolytics/hypnotics) as hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression analysis, adjusting for birth parental background including psychiatric morbidity. Results: 17–25% of men and 25–32% of the women with childhood experiences of societal care retrieved at least one prescription of a psychotropic drug, equivalent to age-adjusted HRs of between 2.1 and 3.3, compare...

The diminished pipeline for medications to treat mental health and substance use disorders.

Abstract: Objective:Psychotropic drug development is perceived to be lagging behind other pharmaceutical development, even though there is a need for more effective psychotropic medications. This study examined the state of the current psychotropic drug pipeline and potential barriers to psychotropic drug development.Methods:The authors scanned the recent academic and “grey” literature to evaluate psychotropic drug development and to identify experts in the fields of psychiatry and substance use disorder treatment and psychotropic drug development. On the basis of that preliminary research, the authors interviewed six experts and analyzed drugs being studied for treatment of major psychiatric disorders in phase III clinical trials.Results:Interviews and review of clinical trials of drugs in phase III of development confirmed that the psychotropic pipeline is slim and that a majority of the drugs in phase III trials are not very innovative. Among the barriers to development are incentives that encourage firms to foc...

The role of mental health problems and common psychotropic drug treatments in accidental injury at work: a case–control study

Abstract: Objectives Mental illness and psychotropic drugs have been linked with workplace injury, but few studies have measured exposures and outcomes independently or established their relative timings. To address this shortcoming, we conducted a case–control study nested within a database prospectively recording injury consultations, diagnoses and drug prescriptions. Methods The Clinical Practice Research Datalink logs primary care data for 6% of the British population, coding all consultations (by the Read system) and drug prescriptions. We identified 1348 patients aged 16–64 years from this database who had consulted a family doctor or hospital over a 20-year period for workplace injury (cases, 479 diagnostic codes) and 6652 age, sex and practice-matched controls with no such consultation. Groups were compared in terms of consultations for mental health problems (1328 codes) and prescription of psychotropic drugs prior to the case9s injury consultation using conditional logistic regression. Results In total, 1846 (23%) subjects had at least one psychiatric consultation before the index date and 1682 (21%) had been prescribed a psychotropic drug. The OR for prior mental health consultation was 1.44 (p Conclusions Mental health problems and psychotropic treatments may account for an important minority of workplace injuries.

Impact of TimeSlips creative expression program on behavioral symptoms and psychotropic medication use in persons with dementia in long-term care: a cluster-randomized pilot study.

Abstract: Objectives To evaluate whether involvement in TimeSlips, a creative storytelling program, reduced mood and behavioral symptoms as well as psychotropic medication use in persons with dementia. Methods A cluster-randomized pilot study compared two discrete dementia care units in one nursing home. The control cohort (N = 10) received standard-of-care activity programming, and the intervention cohort (N = 10) received standard-of-care plus two one-hour TimeSlips sessions per week for six weeks. Data on mood and behavioral symptoms and psychotropic drug prescriptions were collected, and within-group and between-group comparisons were performed. Results Between-group comparisons did not reveal statistically significant differences in mood and behavioral symptoms. No differences in psychotropic drug prescriptions were found. Conclusions Larger trials of longer duration are needed to determine whether involvement in TimeSlips reduces mood and behavioral symptoms that compromise quality of life for persons with dementia.

Use of SSRIs among Danish children: a nationwide study.

Abstract: Our objective was to describe the use of selective serotonin reuptake inhibitors (SSRIs) in the entire Danish population of children and adolescents from 1995 to 2011. Data on filled SSRIs were obtained for all children in Denmark aged 5–17 during 1995–2011. The amount and type of SSRIs filled were calculated as well as incidence rates and prevalence proportions. Furthermore, we looked at concurrent use of other psychotropic drug treatment duration. A total of 23,547 children aged 5–17 used SSRIs during the study period, most commonly sertraline followed by citalopram. Overall, the incidence rate increased from 0.57 per 1,000 person years in 1997 to 3.30 in 2010 and fell to 2.55 in 2011, while the prevalence proportion rose from 0.1 per 1,000 children at the end of 1995 to 3.3 at the end of 2011. However, these findings were driven entirely by an increase among adolescents (12–17 years), where the prevalence proportion rose from 0.11 and 0.36 to 4.64 and 8.52 per 1,000 boys and girls, respectively. A significant proportion of SSRI users used other psychotropic drugs concurrently, most notably antipsychotics (12–28 %) and psychostimulants (10–33 %). About 50 % of adolescents and 40 % of children discontinued treatment within 12 months of initiation. We found a marked increase in the use of SSRI drugs among adolescents in Denmark between 1995 and 2011. Whether this increase reflects a true increase in disorder occurrence, an increase in diagnostic intensity or more aggressive treatment remains uncertain.

The Israel Survey of Mental Health among Adolescents: prevalence of attention-deficit/hyperactivity disorder, comorbidity, methylphenidate use, and help-seeking patterns.

Abstract: Background The prevalence of ADHD is controversial, with many feeling that this disorder is over- or under-diagnosed. Objectives To study the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its association with sociodemographic characteristics, comorbid mental disorders, medical services, and methylphenidate use in the Israeli adolescent population. Methods The Israel Survey of Mental Health among Adolescents was conducted in a representative national sample of 14-17 year olds and their mothers. The Development and Well-Being Assessment was administered to identify DSM-IV diagnoses of ADHD and comorbid mental and learning disorders, and the results were verified by senior child psychiatrists. Respondents were also asked about their use of medical services and psychotropic drug intake in the past 12 months. Results Three percent of the adolescents met the DSM-IV criteria for ADHD. ADHD was significantly associated with gender (higher prevalence in boys than girls), ethnicity (higher prevalence in Jews than Arabs/Druze), referral to a medical professional, and maternal help-seeking for the emotional or behavioral problems of the adolescent. Medication was prescribed to 2.9% of adolescents: 34.6% with a diagnosis of ADHD had not been prescribed methylphenidate in the past year, and 34.6% of the medicated subjects did not have a diagnosis of ADHD. None of the Arab/Druze adolescents was receiving stimulants compared to 3.7% of the Jewish adolescents. Conclusions Despite advances in public awareness of mental disorders in youth, a substantial proportion of older Israeli adolescents, especially from minority groups, are under-diagnosed or untreated. At the same time, many, especially from the Jewish majority, are over-diagnosed and potentially over-treated. Ethnic disparities in rates of mental health care highlight the urgent need to identify and overcome barriers to the recognition and treatment of these conditions.

Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT interval in patients with schizophrenia.

Abstract: Risperidone (RIS) is a frequently used efficacious psychotropic drug. However, it prolongs the QTc interval and may cause fatal arrhythmia. Little is known on the determinants of this RIS side effect. RIS is metabolized by CYP2D6, and is subject to drug efflux by P-glycoprotein (P-gp) encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene. P-gp removes both RIS and its metabolite 9-OH-RIS from cardiac tissue. To investigate the effect of RIS metabolism and ABCB1 gene polymorphisms on QTc, steady-state plasma RIS and 9-OH-RIS levels, and QTc were measured. CYP2D6, ABCB1 C3435T and G2677T/A genotypes were determined in 66 schizophrenia patients on RIS. QTc was significantly longer in patients with ABCB1 3435CT+3435 TT than in those with 3435CC (P=0.006). ABCB1 G2677T/A genotype did not affect QTc. Multiple regression analysis showed that C/T or T/T genotypes at the ABCB1 C3435T locus, lower weight, and older age prolonged QTc. In summary, the T allele of the ABCB1 C3435T genotype should be considered in future diagnostic development efforts for RIS-associated QT.

Extreme Procalcitonin Elevation without Proven Bacterial Infection Related to Amphetamine Abuse.

Abstract: Systemic inflammatory response with rhabdomyolysis and consequent multiorgan failure is a known sequela of psychotropic drug abuse. However, in cases with uncertain past medical history the initial diagnosis can be challenging. Here we report the case of a 21-year-old male who was admitted to the intensive care unit with severe neurological impairment caused by amphetamine intoxication. First laboratory investigations revealed extremely high serum procalcitonin (PCT) levels reaching a maximum concentration of 1640 ng/mL on the second day of observation. Although PCT has high sensitivity and specificity in differentiating bacterial sepsis from nonbacterial inflammation, our case report shows for the first time that it can be extremely elevated following serious amphetamine intoxication without bacterial infection.

Prescribing in prison: minimizing psychotropic drug diversion in correctional practice.

Abstract: Correctional facilities are a major provider of mental health care throughout the United States. In spite of the numerous benefits of providing care in this setting, clinicians are sometimes concerned about entering into correctional care because of uncertainty in prescribing practices. This article provides an introduction to prescription drug use, abuse, and diversion in the correctional setting, including systems issues in prescribing, commonly abused prescription medications, motivation for and detection of prescription drug abuse, and the use of laboratory monitoring. By understanding the personal and systemic factors that affect prescribing habits, the clinician can develop a more rewarding correctional practice and improve care for inmates with mental illness.

Prevalence and correlates of psychotropic drug use in community-dwelling people with young-onset dementia: the NeedYD-study

Abstract: BACKGROUND: Young-onset dementia (YOD) is defined as dementia that develops before the age of 65 years. The prevalence and type of neuropsychiatric symptoms (NPS) in YOD differ from patients with late onset dementia. NPS in dementia patients are often treated with psychotropic drugs. The aim of this study was to investigate psychotropic drug use (PDU) in Dutch community-dwelling YOD patients and the association between age, gender, dementia etiology and severity, symptoms of depression, disease awareness, unmet needs, and type of NPS. METHODS: Psychotropic drug use in 196 YOD patients was registered. Drugs were categorized according to the Anatomical Therapeutical Chemical classification. The association between age, gender, dementia type, dementia stage, type of NPS, depressive symptoms, disease awareness, and amount of unmet needs on total PDU was analyzed using binomial logistic regression analysis. RESULTS: Fifty-two percent of the patients were prescribed at least one psychotropic drug; 36.2% of patients used one drug, and 12.2% used two different drugs. Antidepressants (36.2%) and antipsychotic drugs (17.3%) were the most frequently prescribed psychotropic drugs. Anti-dementia drugs were prescribed in 51.5% of the patients. Increasing age and moderate to severe depressive symptoms were positively associated with the total use of psychotropic drugs. CONCLUSIONS: Community-dwelling YOD patients have a high prevalence of PDU. More research is needed to study the association between unmet needs, NPS, and PDU, and psychosocial interventions have to be developed to limit the use of psychotropic drugs in YOD.

Shadows of Beauty - Prevalence of Body Dysmorphic Concerns in Germany is Increasing: Data from Two Representative Samples from 2002 and 2013.

Abstract: Body dysmorphic disorder (BDD) is a psychosomatic disease associated with reduced quality of life and suicidal ideations. Increasing attention to beauty and the development of beauty industries lead to the hypothesis that BDD is increasing. The aim of this study was to test this hypothesis in two representative samples of Germans, assessed in 2002 and 2013. In 2002, n = 2,066 and in 2013, n = 2,508 Germans were asked to fill in the Dysmorphic Concern Questionnaire (DCQ), which assesses dysmorphic concerns. Subclinical and clinical dysmorphic concerns increased from 2002 to 2013 (subclinical from 0.5% to 2.6%, OR = 5.16 (CI95% = 2.64; 10.06); clinical from 0.5% to 1.0%, OR = 2.20 (CI95% = 1.03; 4.73). Women reported more dysmorphic concerns than men, with rates of 0.7% subclinical and 0.8 clinical BDD in women and 0.3% subclinical and 0.1% clinical BDD in men in 2002. In 2013, 2.8% subclinical and 1.2% clinical BDD were found in women and 2.4% subclinical and 0.8% clinical BDD in men. Further studies should assess predictors for developing a BDD and evaluate factors determining the efficacy of disease-specific psychotherapeutic and psychotropic drug treatments.

Emerging trends in clinical psychology

Abstract: 227 A recent paper by a leading American clinical psychologist, James Overholser1, discusses some critical areas of development of the discipline. A fundamental characteristic of clinical psychology is its deep roots into clinical practice, unlike other fields of psychology. The major advances in psychological assessment and treatment that have been introduced by clinical psychologists in the past decades have found their inspiration from their activities in the front-lines delivery of clinical services. Overholser is very concerned by the increasing number of clinical psychologists in the US who do not provide such services and are thus not familiar with many important clinical issues to be developed in research projects1. Such problem, however, also applies to psychiatry and other clinical specialties2. The weight and potential growth of clinical psychology lie in its capacity to maintain a strong clinical focus in research and to progress in emerging lines of research that have been developed. The first line is concerned with psychological assessment. Clinical psychologists in the seventies found a role as experts in psychological testing (particularly the IQ, or MMPI and the Rorschach in doubtful diagnostic case) at a time when there was very little emphasis on psychiatric diagnosis. In those years, however, a clinical psychologist, Jean Endicott, and a psychiatrist, Robert Spitzer, developed the Research Diagnostic Criteria that paved the ground for the advent of DSM-III and subsequent refinements. This renewed emphasis on symptomatic assessment apparently decreased the role of clinical psychologists, because of the shared ground with psychiatry. It seemed that not much could be added to the practical implications of a DSM diagnosis. The validity and reliability of MMPI and projective testing faded, and neuropsychologists took over cognitive assessment. However, in due course, the substantial limitations and clinical inadequacies of this approach emerged2. Exclusive reliance on diagnostic criteria has impoverished the clinical process and does not reflect the complex thinking that underlies decisions in psychiatric practice2. Paul Emmelkamp and other clinical psychologists3 have introduced the concept of macro-analysis (a relationship between co-occurring syndromes and problems is established on the basis of where treatment should commence in the first place). It is supplemented by micro-analysis, a detailed analysis of specific symptoms, which can be accomplished by the use of questionnaires and rating scales2,3. This approach supplants the obsolete notion of psychometric battery to be administered to everyone, which is still fashionable, for instance, in neuropsychology. A second line of research is concerned with psychobiologic exploration of clinical states. Current diagnostic definitions of psychiatric disorders based on symptoms collection encompass very heterogeneous populations and are thus likely to yield spurious results when exploring biological correlates of mental disturbances. The customary clinical taxonomy in psychiatry, which emphasizes reliability at the cost of clinical validity, does not include effects of comorbid subclinical conditions, timing of phenomena, rate of progression of illness, responses to previous treatments, and other distinctions that demarcate major prognostic and therapeutic differences among patients who otherwise seem to be deceptively similar since they share the same psychiatric diagnosis2. Clinical psychology may provide the missing link between clinical states and biomarkers, building pathophysiological bridges from clinical manifestations to their neurobiologic counterparts4. Clinical pharmacopsychology is an area of clinical psychology which is concerned with the psychological effects of medications (including behavioral toxicity and iatrogenic comorbidity) and the interaction of drugs with specific and non-specific treatment ingredients5. A third line of research is concerned with psychotherapy. In the past two decades, unprecedented refinements of the technical components of psychotherapy have occurred, with clinical results from randomized controlled trials that are in striking contrast with the disillusionments that have characterized psychotropic drug development and use5. Clinical psychology is the leading force underlying psychotherapy research and practice, including its organization in clinical services within the National Health Systems in the UK and German countries. These emerging trends of clinical psychology provide important opportunities for development and may be an antidote to oversimplified models that derive from biological reductionism, neglect individual responses to treatment and clash with clinical reality.

Molecular analysis of potassium ion channel genes in sudden death cases among patients administered psychotropic drug therapy: are polymorphisms in LQT genes a potential risk factor?

Abstract: Psychotropic drugs can pose the risk of acquired long QT syndrome (LQTS). Unexpected autopsy-negative sudden death in patients taking psychotropic drugs may be associated with prolonged QT intervals and life-threatening arrhythmias. We analyzed genes that encode for cardiac ion channels and potentially associated with LQTS, examining specifically the potassium channel genes KCNQ1 and KCNH2 in 10 cases of sudden death involving patients administered psychotropic medication in which autopsy findings identified no clear cause of death. We amplified and sequenced all exons of KCNQ1 and KCNH2, identifying G643S, missense polymorphism in KCNQ1, in 6 of the 10 cases. A study analysis indicated that only 11% of 381 healthy Japanese individuals carry this polymorphism. Reports of previous functional analyses indicate that the G643S polymorphism in the KCNQ1 potassium channel protein causes mild I(Ks) channel dysfunction. Our present study suggests that administering psychotropic drug therapy to individuals carrying the G643S polymorphism may heighten the risk of prolonged QT intervals and life-threatening arrhythmias. Thus, screening for the G643S polymorphism before prescribing psychotropic drugs may help reduce the risk of unexpected sudden death.

Proteomic Investigation of the Hippocampus in Prenatally Stressed Mice Implicates Changes in Membrane Trafficking, Cytoskeletal, and Metabolic Function

Abstract: Prenatal stress influences the development of the fetal brain and so contributes to the risk of the development of psychiatric disorders in later life. The hippocampus is particularly sensitive to prenatal stress, and robust abnormalities have been described in the hippocampus in schizophrenia and depression. The aim of this study was to determine whether prenatal stress is associated with distinct patterns of differential protein expression in the hippocampus using a validated mouse model. We therefore performed a comparative proteomic study assessing female hippocampal samples from 8 prenatally stressed mice and 8 control mice. Differential protein expression was assessed using 2-dimensional difference in gel electrophoresis and subsequent mass spectrometry. The observed changes in a selected group of differentially expressed proteins were confirmed by Western blotting. In comparison to controls, 47 protein spots (38 individual proteins) were found to be differentially expressed in the hippocampus of prenatally stressed mice. Functional grouping of these proteins revealed that prenatal stress influenced the expression of proteins involved in brain development, cytoskeletal composition, stress response, and energy metabolism. Western blotting was utilized to validate the changes in calretinin, hippocalcin, profilin-1 and the signal-transducing adaptor molecule STAM1. Septin-5 could not be validated via Western blotting due to methodological issues. Closer investigation of the validated proteins also pointed to an interesting role for membrane trafficking deficits mediated by prenatal stress. Our findings demonstrate that prenatal stress leads to altered hippocampal protein expression, implicating numerous molecular pathways that may provide new targets for psychotropic drug development.

Utilization of psychotropic drugs prescribed to persons with and without HIV infection: a Danish nationwide population-based cohort study.

Abstract: Objectives The objective was to estimate the utilization of psychotropic drugs in HIV-infected individuals compared with that in the background population. Methods Using data obtained from the Danish HIV Cohort Study and the Danish National Prescription Registry, we analysed aggregated data on redeemed prescription of psychotropic drugs during 1995–2009. We primarily focused our analyses on HIV-infected individuals with no history of injecting drug use (IDU) or hepatitis C virus (HCV) infection. Drug utilization was expressed as defined daily doses per 1000 person-days (DDD/1000PD). The utilization rate ratio (URR) was calculated as utilization in the HIV-infected cohort compared with that in the comparison cohort. We estimated longitudinal trends in utilization and potential associations with HIV and exposure to highly active antiretroviral therapy (HAART), especially efavirenz. Results During 1995–2009, 54.5% of the HIV-infected cohort (3615 non-IDU/non-HCV-infected HIV-infected individuals) and 29.2% of the comparison cohort (32 535 individuals) had at least one prescription of a psychotropic drug. HIV infection was associated with a URR of 1.13 for antipsychotics, 1.76 for anxiolytics, 4.42 for hypnotics and sedatives, and 2.28 for antidepressants. Antidepressants were confined primarily to men who have sex with men (MSM). Older age, more recent calendar time, and increased time after HIV diagnosis were associated with increased drug utilization. However, no association with exposure to HAART or efavirenz was found. Conclusions HIV-infected individuals had a higher utilization of psychotropic drugs than the background population, which was not confined to individuals with a history of IDU or HCV infection. This emphasizes the need to focus on diagnosis of, and appropriate psychopharmacological interventions for, mental disorders in this population.

Reliability and validity of the Severity of Dependence Scale in a Chinese sample of treatment-seeking ketamine users.

Abstract: Objective: Despite growing popularity of ketamine misuse in Asia, there is a lack of a validated instrument to measure the severity of ketamine dependence. Psychometric properties of Chinese Severity of Dependence Scale for ketamine (C-SDS-K) were examined in a sample of treatment-seeking ketamine users in Hong Kong.Methods: A total of 80 treatment-seeking ketamine users were recruited from 3 treatment centres. The C-SDS-K was administered to assess their severity of dependence on ketamine in the previous month. The diagnosis of their ketamine misuse as per the DSM-IV criteria, and the count of dependence criteria fulfilled in the previous month were determined by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I).Results: The C-SDS-K showed high internal consistency (? = 0.74) and test-retest reliability (intraclass correlation coefficient = 0.95). Total score of C-SDS-K correlated positively with frequency (rs = 0.73, p Conclusion: The findings support SDS as a reliable and valid tool for measuring the severity of dependence in the treatment-seeking population of Chinese ketamine users.Key words: Ketamine; Substance-related disorders; Treatment outcomeIntroductionKetamine is a non-competitive N-methyl-D-aspartate receptor antagonist developed as an anaesthetic in 1962.1 Manufactured under the trade name "Ketalar", ketamine has found its place within several areas of medicine.2 However, its propensity to produce "emergence phenomenon" in patients recovering from ketamine anaesthesia, characterised by delusion, hallucination, delirium and mind-body dissociation, has prevented it from becoming a mainstream anaesthetic. Ironically, these adverse effects that limit ketamine's medical use have paved its way to non-medical use.3 Recreational drug users value it for the dream-like hallucinations, floating sensations, perceptions of increased efficiency and creativity, feelings of arousal and euphoria, as well as the mystical experiences of self-transcendence.4Soon after ketamine was developed, its illegal manufacture, distribution, and misuse were reported in the West Coast of the United States.5 Some have suggested that it may have been linked to veterans returning from Vietnam War who had experienced it on the field.6 Until the 1980s, ketamine misuse was mainly restricted to North America, being linked to groups of individuals who were most often involved in the medical field.7,8 In the 1990s, ketamine gained mass popularity among young drug users with the global rise of dance-club culture.9,10 Along with MDMA (3,4-methyl enedioxy-N-methylamphetamine, or known as the "ecstasy"), ketamine became a new addition to the thriving "poly-pharmacy" of dance scene drug use.11The escalation in popularity of ketamine misuse in Hong Kong is probably unmatched internationally. In fact, it is deemed the single most abused psychotropic drug in Hong Kong according to data from Central Registry of Drug Abuse, which documents drug users who come into contact with authorities and health care professionals. In the past decade, ketamine has been the most commonly used psychotropic drug in Hong Kong, more than doubling the figure of second-placed amphetamines (31.5% vs. 14.0% in the year 2011).12 The percentage of ketamine use in reported drug users aged under 21 years reached 85% by 2008, which implied that vast majority of emerging young drug users in the city were using ketamine.12Dominance of ketamine misuse in Hong Kong is also reflected by its burden on the local health care system. Ketamine users represented 16% of all drug users attending the Accident and Emergency Departments of all public hospitals in 2005; the proportion rose to 40% in 2008. …