Showing papers on "Psychotropic drug published in 2012"

Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America

Abstract: Every psychiatrist encounters the antipsychiatry movement. It is encountered in the skeptical colleague who wonders why you wasted your medical degree, in the relative who asks if you still perform lobotomies on everyone, and in the patient who insists that they would never take a psychiatric medication but wants alprazolam. The stigma surrounding the mentally ill and those who treat them endures. So why should you consider reading a provocative book whose dust jacket compares psychotropic drugs to a phrenology chart? After spending a week alternately wanting to throw this book across the room in disgust and excitedly researching the studies it cites, I found three reasons. First, Whitaker reviews decades of studies, explores novel mental health programs, and interviews many people with mental illness. Whitaker raises important questions about the misuse and overuse of psychotropic drugs and introduced me to the thought-provoking longitudinal studies conducted by Ross Baldessarini and Martin Harrow. Second, the book is being compared to Rachel Carson’s Silent Spring, andWhitaker hopes to spark an analogous reform movement. Whitaker has spoken at multiple conferences, delivered a grand rounds presentation at the Massachusetts General Hospital Department of Psychiatry, and founded a nonprofit organization called the Foundation for Excellence in Mental Health Care. Whitaker is advancing his argument, and psychiatrists should respond. Finally, his book is an object lesson in the hazards of interpretation. Whitaker begins by making two observations. He observes a startling rise in the rates of psychiatric disability from 1987, when 1 in every 184 Americans was disabled by mental illness as defined by receiving Supplemental Security Income or Social Security Disability Insurance payments, to 2007, when 1 in every 76 Americans was disabled by mental illness. As Whitaker notes, the rates of disability because of mental illness more than doubled by this measure. He also observes a dramatic increase in the prescriptions of psychiatric drugs over roughly the same period of time. He then asks an important questionV that of how these two observations are relatedVbefore settling for a simple answer: the latter causes the former. Whitaker believes that, as psychiatrists prescribed more psychotropic drugs, they caused more Americans to become mentally disabled. His thesis seems easy to dismiss, but Whitaker is a fluent writer who synthesizes interviews, depositions, case reports, cohort studies, randomized controlled trials, and basic science studies into a single story. As I read the book, recommended to me by a psychiatry intern who was shaken by its claims, I was unsettled. Whitaker criticizes the rigor of key studies, summarizes concerns that the DSM increases psychiatric diagnoses, details the compromising relationships between academic psychiatry and the pharmaceutical industry, and shows how the selective reporting of data skews perceptions of the efficacy and safety of psychotropic drugs. The trouble is that, while there is merit to many of these criticisms, Whitaker’s argument is totalizing. He does not simply criticize the use of alprazolam for anxiety, something many psychiatrists second, but he criticizes the use of every psychotropic drug for every chronic mental illness. Each agent he considersVantipsychotic, antidepressant, benzodiazepine, lithium, and stimulantsVare ultimately ‘‘pathological agents.’’ In his conclusion, he acknowledges that medications can be used for ‘‘some people’’ but then demands that psychiatry ‘‘admit that the drugs, rather than fix chemical imbalances in the brain, perturb the normal functioning of neurotransmitter pathways’’ (p. 333). In this statement, the expansive sweep of Whitaker’s interpretation becomes clear: I know of no serious psychiatrist who believes that psychotropic drugs ‘‘fix chemical imbalances in the brains’’ of their patients. The problem is, as it so often is in antipsychiatry literature, that the assumption that the critical factor in any bad outcome is the psychiatrist. In this book, Whitaker never seriously considers the changes in government definitions of disability, diagnostic standards, family structures, alcohol and illicit drug use, incarceration rates for the mentally ill, economic inequality, a shift throughout medicine to prescribe, the prescribing of psychotropic drugs by nonpsychiatrists, or any other possible confounder. If I proposed to resolve the fascinating question Whitaker posesVthe relationship between psychiatric disability and psychotropic prescriptionsVin the manner he does, my study would be summarily rejected for publication for never considering these other possible confounders. The result is a book that is a well-narrated collection of interpretations that advance a singular argument. Whitaker lingers over observational studies but crudely summarizes a complex, well-controlled, government-funded studyV like the Clinical Antipsychotic Trials of Intervention Effectiveness study trialVin two sentences, to the effect that none of the drugs worked. This is a shame because you could write a complex book on the dangers of polypharmacy, on the benefits of stopping and starting psychotropic medications gradually, on trying to decide who needs psychotropic drugs and who does not, on the need for well-designed long-term studies of the consequences of using psychotropic drugs, on whether (and which) psychosocial interventions are more or less helpful than psychotropic drugs, and on the need to reform the relationships between psychiatrists and the pharmaceutical industry. The data gathered by Whitaker would inform that book, a book that acknowledges the limits of psychiatric knowledge and the irreducible complexity of people with mental illness. Instead, Whitaker is just as crass a materialist as the psychiatrists he caricatures, settling for a simple but crude interpretation: those drugs messed you up.

Psychotropic drug-induced falls in older people: a review of interventions aimed at reducing the problem.

Abstract: Falls are a common health problem for older people, and psychotropic medications have been identified as an important independent fall risk factor. The objective of this paper was to review the literature relating to the effect of psychotropic medications on falls in older people, with a particular focus on evidence supporting minimization of their use to reduce risk of falls. A literature search identified 18 randomized trials meeting the inclusion criteria for the review of effectiveness of psychotropic medication withdrawal studies, including four with falls outcomes. One of these, which targeted reduced psychotropic medication use in the community, reported a 66% reduction in falls, while the other studies demonstrated some success in reducing psychotropic medication use but with mixed effects on falls. Other randomized trials evaluated various approaches to reducing psychotropic medications generally or specific classes of psychotropic medications (e.g. benzodiazepines), but did not report fall-related outcomes. Overall, these studies reported moderate success in reducing psychotropic medication use, and a number reported no or limited worsening of key outcomes such as sleep quality or behavioural difficulties associated with withdrawal of psychotropic medication use. Reduced prescription of psychotropic medications (e.g. seeking non-pharmacological alternatives to their use in place of prescription in the first place or, for those patients for whom these medications are deemed necessary, regular monitoring and efforts to cease use or wean off use over time) needs to be a strong focus in clinical practice for three reasons. Firstly, psychotropic medications are commonly prescribed for older people, both in the community and especially in the residential care setting, and their effectiveness in a number of clinical groups has been questioned. Secondly, there is strong evidence of an association between substantially increased risk of falls and use of a number of psychotropic medications, including benzodiazepines (particularly, the long-acting agents), antidepressants and antipsychotic drugs. Finally, the largest effect of any randomized trial of falls prevention to date was achieved with a single intervention consisting of weaning psychotropic drug users off their medications.

The STAT5 Inhibitor Pimozide Displays Efficacy in Models of Acute Myelogenous Leukemia Driven by FLT3 Mutations

Abstract: Activation of the transcription factor STAT5 is essential for the pathogenesis of acute myelogenous leukemia (AML) containing the FLT3 internal tandem duplication (ITD) mutation. FLT3 ITD is a constitutively active tyrosine kinase that drives the activation of STAT5, leading to the growth and survival of AML cells. Although there has been some success in identifying tyrosine kinase inhibitors that block the function of FLT3 ITD, there remains a continued need for effective treatment of this disease. We have identified the psychotropic drug pimozide as an effective inhibitor of STAT5 function. Pimozide inhibits the tyrosine phosphorylation of STAT5, leading to the death of AML cells through the induction of apoptosis. Pimozide shows a combinatorial effect with the tyrosine kinase inhibitors midostaurin (PKC412) and sunitinib in the inhibition of STAT5 tyrosine phosphorylation and the induction of apoptosis. Significantly, pimozide reduces the tumor burden in a mouse model of FLT3-driven AML. Therefore, identifying STAT5 inhibitors may provide a new avenue for the treatment of AML, and these may be effective alone or in combination with tyrosine kinase inhibitors.

Suppression of alcohol dependence using baclofen: a 2-year observational study of 100 patients.

Abstract: Aims: The purpose of this study was to examine the long-term effects of baclofen in a large cohort of alcohol-dependent patients compliant to baclofen treatment. Methods: A hundred patients with alcohol dependence, resistant to usual treatments, were treated with escalating doses of baclofen (no superior limit). Alcohol consumption (in grams) and craving for alcohol were assessed before treatment and at 3, 6, 12 and 24 months. Assessments were simply based on patients’ statements. The outcome measure was the consumption of alcohol, rated according to the World Health Organization criteria for risk of chronic harm. Results: While all patients were rated “at high risk” at baseline, approximately half of them were rated “at low risk” at 3, 6, 12 and 24 months. The sum of patients who were at “low risk” and at “moderate risk” (improved patients) was 84% at 3 months, 70% at 6 months, 63% at 1 year and 62% at 2 years. The constancy of improvement over the 2 years was remarkable. The average maximal dose of baclofen taken was 147mg/day. 92% of patients reported that they experienced the craving-suppressing effect of baclofen. Significant relationships were found between the amount in grams of alcohol taken before treatment and the maximal dose of baclofen required, and between the existence of a mental disorder and a lesser effect of baclofen. Conclusions: Baclofen produces an effortless decrease or suppression of alcohol craving when it is prescribed with no superior limit of dose. Potential limitations in the effectiveness of baclofen include the coexistence of a mental disorder, the concomitant use of other psychotropic drugs, a lack of real motivation in patients to stop drinking, and the impossibility to reach the optimal dose of baclofen because of unbearable side-effects (sometimes possibly related to too sharp a protocol of dose escalation).

Clinically significant psychotropic drug-drug interactions in the primary care setting.

Abstract: In recent years, the growing numbers of patients seeking care for a wide range of psychiatric illnesses in the primary care setting has resulted in an increase in the number of psychotropic medications prescribed. Along with the increased utilization of psychotropic medications, considerable variability is noted in the prescribing patterns of primary care providers and psychiatrists. Because psychiatric patients also suffer from a number of additional medical comorbidities, the increased utilization of psychotropic medications presents an elevated risk of clinically significant drug interactions in these patients. While life-threatening drug interactions are rare, clinically significant drug interactions impacting drug response or appearance of serious adverse drug reactions have been documented and can impact long-term outcomes. Additionally, the impact of genetic variability on the psychotropic drug’s pharmacodynamics and/or pharmacokinetics may further complicate drug therapy. Increased awareness of clinically relevant psychotropic drug interactions can aid clinicians to achieve optimal therapeutic outcomes in patients in the primary care setting.

Impact of socioeconomic deprivation on maternal perinatal mental illnesses presenting to UK general practice.

Abstract: Background Although maternal perinatal mental illnesses commonly present to and are primarily treated in general practice, few population-based estimates of this burden exist, and the most affected socioeconomic groups of pregnant women remain unclear. Aim To provide estimates of maternal depression, anxiety and serious mental illness (SMI) in UK general practice and quantify impacts of socioeconomic deprivation. Design and setting Cross-sectional analysis of prospectively recorded general practice records from a UK-wide database. Method A pregnancy ending in live birth was randomly selected for every woman of childbearing age, 1994–2009. Prevalence and diagnostic overlap of mental illnesses were calculated using a combination of medical diagnoses and psychotropic drug prescriptions. Socioeconomic deprivation was assessed using multivariate logistic regression, adjusting for calendar period and pregnancy history. Results Among 116 457 women, 5.1% presented with antenatal depression and 13.3% with postnatal depression. Equivalent figures for anxiety were 2.6% and 3.7% and for SMI 1/1000 and 2/1000 women. Socioeconomic deprivation increased the risk of all mental illnesses, although this was more marked in older women. Those age 35–45 years in the most deprived group had 2.63 times the odds of antenatal depression (95% confidence interval [CI] = 2.22 to 3.13) compared with the least deprived; in women aged 15–25 years the increased odds associated with deprivation was more modest (odds ratio = 1.35, 95% CI = 1.07 to 1.70). Similar patterns were found for anxiety and SMI. Conclusion Strong socioeconomic inequalities in perinatal mental illness persist with increasing maternal age. Targeting detection and effective interventions to high-risk women may reduce inequity and avoid substantial psychiatric morbidity.

Trajectories of mental health before and after old-age and disability retirement: a register-based study on purchases of psychotropic drugs.

Abstract: Objectives Retirement from paid work is a major life event facing increasingly large numbers of people in the coming years. We examined trajectories of mental health five years before and five years after old-age and disability retirement using data on purchases of psychotropic drugs. Methods The study included all employees from the City of Helsinki, Finland, retiring between 2000–2008 due to old age (N=4456) or disability (N=2549). Purchases of psychotropic drugs were analyzed in 20 3-month intervals before and after retirement using graphical methods and growth curve models. Results Old-age retirement was unrelated to purchases of psychotropic drugs. Among disability retirees, psychotropic medication tripled before retirement. The average increase was 0.95 [95% confidence interval (95% CI) 0.73–1.16] daily defined doses (DDD) 5–1.5 years before retirement; from 1.5 years until retirement it was 5.68 DDD (95% CI 5.33–6.03) for each 3-month interval. After disability retirement, purchases of antidepressants decreased on average by 0.40 DDD (95% CI 0.57–0.23) for each 3-month interval, those of hypnotics and sedatives increased by 0.30 DDD (95% CI 0.12–0.47), and no changes were seen for other psychotropic drugs. The changes before and after retirement were largest among those who retired due to mental disorders and those whose retirement had been granted as temporary. Conclusions While no overall decrease in psychotropic medication after retirement was observed, purchases of antidepressants decreased after disability retirement. Long-term trajectories suggest that disability retirement might be prevented if mental health problems were tackled more efficiently earlier in the pre-retirement period.

Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment

Abstract: Langle G, Steinert T, Weiser P, Schepp W, Jaeger S, Pfiffner C, Frasch K, Eschweiler GW, Messer T, Croissant D, Becker T, Kilian R. Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment. Objective: Evaluating the effects of different types of psychotropic polypharmacy on clinical outcomes and quality of life (QOL) in 374 patients with schizophrenia and schizoaffective disorder in routine care. Method: Psychotropic regimen, clinical outcomes, and QOL were assessed before discharge and after 6, 12, 18, and 24 months. Data were analyzed by mixed-effects regression models for longitudinal data controlling for selection bias by means of propensity scores. Results: At baseline 22% of participants received antipsychotic monotherapy (APM) (quetiapine, olanzapine, or risperidone), 20% more than one antipsychotic drug, 16% received antipsychotics combined with antidepressants, 16% antipsychotics plus benzodiazepines, 11.5% had antipsychotics and mood stabilizers, and 16% psychotropic drugs from three or more subclasses. Patients receiving APM had better clinical characteristics and QOL at baseline. Patients receiving i) antipsychotics plus benzodiazepines or ii) antipsychotics plus drugs from at least two additional psychotropic drug categories improved less than patients with APM. Conclusion: Combinations of antipsychotics with other psychotropic drugs seem to be effective in special indications. Nevertheless, combinations with benzodiazepines and with compounds from multiple drug classes should be critically reviewed. It is unclear whether poorer outcomes in patients with such treatment are its result or its cause.

Psychotropic Drug–Drug Interactions Involving P-Glycoprotein

Abstract: Multidrug resistance P-glycoprotein (P-gp; also known as MDR1 and ABCB1) is expressed in the luminal membrane of the small intestine and blood–brain barrier, and the apical membranes of excretory cells such as hepatocytes and kidney proximal tubule epithelia. P-gp regulates the absorption and elimination of a wide range of compounds, such as digoxin, paclitaxel, HIV protease inhibitors and psychotropic drugs. Its substrate specificity is as broad as that of cytochrome P450 (CYP) 3A4, which encompasses up to 50 % of the currently marketed drugs. There has been considerable interest in variations in the ABCB1 gene as predictors of the pharmacokinetics and/or treatment outcomes of several drug classes, including antidepressants and antipsychotics. Moreover, P-gp-mediated transport activity is saturable, and is subject to modulation by inhibition and induction, which can affect the pharmacokinetics, efficacy or safety of P-gp substrates. In addition, many of the P-gp substrates overlap with CYP3A4 substrates, and several psychotropic drugs that are P-gp substrates are also CYP3A4 substrates. Therefore, psychotropic drugs that are P-gp substrates may cause a drug interaction when P-gp inhibitors and inducers are coadministered, or when psychotropic drugs or other medicines that are P-gp substrates are added to a prescription. Hence, it is clinically important to accumulate data about drug interactions through studies on P-gp, in addition to CYP3A4, to assist in the selection of appropriate psychotropic medications and in avoiding inappropriate combinations of therapeutic agents. There is currently insufficient information available on the psychotropic drug interactions related to P-gp, and therefore we summarize the recent clinical data in this review.

Impact of the Food and Drug Administration’s antipsychotic black box warning on psychotropic drug prescribing in elderly patients with dementia in outpatient and office-based settings

Abstract: Background Most patients with dementia also suffer from behavioral and psychological symptoms of dementia, for which there is no Food and Drug Administration-approved treatment. Objectives To determine whether the Food and Drug Administration's black box warning in April 2005 has led to a decline in prescriptions of atypical antipsychotics for behavioral and psychological symptoms of dementia, as well as whether prescriptions for other psychotropic drugs, including antidepressants, anxiolytics, and antiepileptics, as substitutes, have increased. Methods Data on outpatient visits by elderly dementia patients were obtained from two large national surveys from 2003 to 2008. Any psychotropic drug mentions were identified. Percentage utilization statistics were calculated. Results The percentage of visits mentioning an atypical antipsychotic decreased from 12.5% prewarning to 11.5% postwarning. Postwarning, 34.4% of patients were taking none of the study medications, as opposed to 26.1% prewarning. Conclusions After the warning, there was a small decline in the use of atypical antipsychotics and no evidence of substitution of other psychotropic medications.

Sudden Death of Cardiac Origin and Psychotropic Drugs

Abstract: Mortality rate is high in psychiatric patients versus general population. An important cause of this increased mortality is sudden cardiac death (SCD) as a major side-effect of psychotropic drugs. These SCDs generally result from arrhythmias occurring when the posology is high and may attain a toxic threshold but also at dosages within therapeutic range, in the presence of risk factors. There are three kinds of risk factors: physiological (e.g.: low cardiac rate of sportsmen), physiopathological (e.g.: hepatic insufficiency, hypothyroidism) and "therapeutic" (due to interactions between psychotropic drugs and other medicines). Association of pharmacological agents may increase the likelihood of SCDs either by i) a pharmacokinetic mechanism (e.g.: increased torsadogenic potential of a psychotropic drug when its destruction and/or elimination are compromised) or ii) a pharmacodynamical mechanism (e.g.: mutual potentiation of proarrhythmic properties of two drugs). In addition, some psychotropic drugs may induce sudden death in cases of pre-existing congenital cardiopathies such as i) congenital long QT syndrome, predisposing to torsade de pointes that eventually cause syncope and sudden death. ii) a Brugada syndrome, that may directly cause ventricular fibrillation due to reduced sodium current through Nav1.5 channels. Moreover, psychotropic drugs may be a direct cause of cardiac lesions also leading to SCD. This is the case, for example, of phenothiazines responsible for ischemic coronaropathies and of clozapine that is involved in the occurrence of myocarditis. The aims of this work are to delineate: i) the risk of SCD related to the use of psychotropic drugs; ii) mechanisms involved in the occurrence of such SCD; iii) preventive actions of psychotropic drugs side effects, on the basis of the knowledge of patient-specific risk factors, documented from clinical history, ionic balance and ECG investigation by the psychiatrist.

Striatal dopamine release and genetic variation of the serotonin 2C receptor in humans.

Abstract: Mesoaccumbal and nigrostriatal projections are sensitive to stress, and heightened stress sensitivity is thought to confer risk for neuropsychiatric disorders. Serotonin 2C (5-HT 2C ) receptors mediate the inhibitory effects of serotonin on dopaminergic circuitry in experimental animals, and preclinical findings have implicated 5-HT 2C receptors in motivated behaviors and psychotropic drug mechanisms. In humans, a common missense single-nucleotide change (rs6318, Cys23Ser) in the 5-HT 2C receptor gene ( HTR2C ) has been associated with altered activity in vitro and with clinical mood disorders. We hypothesized that dopaminergic circuitry would be more sensitive to stress in humans carrying the Ser23 variant. To test this hypothesis, we studied 54 healthy humans using positron emission tomography and the displaceable D 2 /D 3 receptor radiotracer [ 11 C]raclopride. Binding potential (BP ND ) was quantified before and after a standardized stress challenge consisting of 20 min of moderate deep muscular pain, and reduction in BP ND served as an index of dopamine release. The Cys23Ser variant was genotyped on a custom array, and ancestry informative markers were used to control for population stratification. We found greater dopamine release in the nucleus accumbens, caudate nucleus, and putamen among Ser23 carriers, after controlling for sex, age, and ancestry. Genotype accounted for 12% of the variance in dopamine release in the nucleus accumbens. There was no association of Cys23Ser with baseline BP ND . These findings indicate that a putatively functional HTR2C variant (Ser23) is associated with greater striatal dopamine release during pain in healthy humans. Mesoaccumbal stress sensitivity may mediate the effects of HTR2C variation on risk of neuropsychiatric disorders.

Involvement of 5‐HT2A receptor and α2‐adrenoceptor blockade in the asenapine‐induced elevation of prefrontal cortical monoamine outflow

Abstract: The psychotropic drug asenapine is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. Asenapine exhibits higher affinity for several 5-HT receptors and α(2)-adrenoceptors than for D(2) receptors. Noteworthy, blockage of both the 5-HT(2A) and α(2)-adrenergic receptors has been shown to enhance prefrontal dopamine release induced by D(2) receptor antagonists. Previous results show that asenapine, both systemically and locally, increases dopamine, noradrenaline, and serotonin release in the medial prefrontal cortex (mPFC), and that the increased dopamine release largely depends on an intracortical action. Using reverse microdialysis in freely moving rats, we here assessed the potency of low concentrations of asenapine to cause a pharmacologically significant blockage in vivo of 5-HT(2A) receptors and α(2)-adrenoceptors within the mPFC, and thus its ability to affect cortical monoamine release by these receptors. Intracortical administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), a 5-HT(2A/2C) receptor agonist, increased cortical monoamine release, effects that were antagonized both by asenapine and the selective 5-HT(2A) antagonist M100907. Application of clonidine, an α(2)-adrenoceptor agonist, significantly reduced monoamine release in the mPFC. The selective α(2)-adrenoceptor antagonist idazoxan blocked, whereas asenapine partially blocked clonidine-induced cortical dopamine and noradrenaline decrease. The effects of asenapine and idazoxan on clonidine-induced serotonin decrease were less pronounced. Our results propose that low concentrations of asenapine in the mPFC exhibit a pharmacologically significant 5-HT(2A) and α(2) receptor antagonistic activity, which may contribute to enhance prefrontal monoamine release in vivo and, secondarily, its clinical effects in schizophrenia and bipolar disorder.

Drug-Drug Interactions Between Warfarin and Psychotropics: Updated Review of the Literature

Abstract: As the number of psychotropics on the market expands, the likelihood increases that a patient requiring anticoagulation with warfarin will receive concurrent treatment with a psychotropic drug. Because warfarin undergoes hepatic metabolism and is highly protein bound, it is particularly prone to drug interactions; in addition, its relatively narrow therapeutic window places patients at risk of either hemorrhagic or thrombotic complications. Although warfarin's interactions with other drugs have long been studied, the most recent review of the literature of warfarin's interactions with psychotropics was over a decade ago. Thus, we conducted a systematic review of the literature documenting the interaction between warfarin and psychotropics, with a focus on interactions mediated through the cytochrome P450 system and protein binding. A search of the MEDLINE database was performed, and reports of warfarin interactions with psychotropics were identified. The results suggest that interactions between warfarin and psychotropic drugs are important and likely underrecognized. They also have notable implications for both safety and drug compliance. When certain psychotropics are started or discontinued in patients receiving warfarin therapy, or when warfarin is introduced to a patient receiving a stable dose of a psychotropic, clinicians should monitor a patient's international normalized ratio (INR) closely to ensure it remains within therapeutic range. Psychotropics that pose a particular risk of increasing the INR when used with warfarin include fluoxetine, fluvoxamine, quetiapine, and valproic acid. Psychotropics that may significantly decrease the INR when used with warfarin include trazodone, St. John's wort, carbamazepine, and the polycyclic aromatic carbons in tobacco cigarettes; however, nicotine itself, as in nicotine replacement strategies, is not known to alter warfarin's anticoagulant effect. In certain cases, the need for anticoagulation may also necessitate switching to a different psychotropic.

A systematic review of psychotropic drug prescribing for prisoners

Abstract: Objective: To conduct a review of the literature on prescribing psychotropic drugs for prisoners.Methods: Articles were retrieved from nine databases, reference lists, citations, governmental prison websites, and contact with authors. The articles included were written in English, focused on adults’ time as prisoners, included at least one drug of interest, and discussed prescribing. Thirty-two articles met these inclusion criteria.Results: Five main themes were identified from the reviewed studies: polypharmacy, high-dose therapy, duration of treatment, documentation and monitoring, and issues associated with the prisoners’ environment.Conclusions: Consideration of these themes within the included studies identified areas for future research, particularly models of good practice, as numerous descriptions of poor practice exist. Policy-makers and prescribers should review current systems and practices, to ensure the care being offered to prisoners is optimal.

Psychotropic Medication Use in Children With Autism in the Kentucky Medicaid Population

Abstract: This study reviewed Kentucky Medicaid claims data for children with autism spectrum disorders to determine psychotropic drug (PTD) use in this population. Children with autism spectrum disorders (ICD-9 code 299.XX) in 3 different age-groups from 2005 to 2008 were identified; PTD use was defined as at least 1 prescription per year. PTD use in all age ranges was higher than in previously reported studies. High PTD use in children between 1 and 5 years is particularly of concern and may reflect perceived inadequacies of comprehensive educational/behavioral services for these children.

Who seeks primary care for sleep, anxiety and depressive disorders from physicians prescribing homeopathic and other complementary medicine? Results from the EPI3 population survey

Abstract: Objectives To describe and compare patients seeking treatment for sleep, anxiety and depressive disorders (SADD) from physicians in general practice (GPs) with three different practice preferences: strictly conventional medicine (GP-CM), mixed complementary and conventional medicine (GP-Mx) and certified homeopathic physicians (GP-Ho). Design and setting The EPI3 survey was a nationwide, observational study of a representative sample of GPs and their patients, conducted in France between March 2007 and July 2008. Participants 1572 patients diagnosed with SADD. Primary and secondary outcomes The patients’ attitude towards complementary and alternative medicine; psychotropic drug utilisation. Results Compared to patients attending GP-CM, GP-Ho patients had healthier lifestyles while GP-Mx patients showed similar profiles. Psychotropic drugs were more likely to be prescribed by GP-CM (64%) than GP-Mx (55.4%) and GP-Ho (31.2%). The three groups of patients shared similar SADD severity. Conclusion Our results showed that patients with SADD, while differing principally in their sociodemographic profiles and conventional psychotropic prescriptions, were actually rather similar regarding the severity of SADD in terms of comorbidities and quality of life. This information may help to better plan resource allocation and management of these common health problems in primary care.

Understanding insomnia in older adults.

Abstract: Objective: The aims of this study were to determine the true frequency of primary insomnia (PI), sleep disorder related to another mental disorder (SDMD) and sleep disorder due to a general medical condition (SDMC) in older adults and to establish their differentiating characteristics. Methods: This is a cross-sectional study. Participants were randomly selected samples of 951 subjects who are 65 years or older. Main measures were as follows: presence (according to DSM-IV-TR diagnostic criteria) of PI, SDMD, SDMC or other sleep disorders, co-morbidity and psychotropic consumption. Results: Of the subjects, 36.1% reported having sleep problems (95%CI:33.0–39.2) and 37.0% reported regularly consuming a psychotropic drug. The prevalence of PI was 8.9% (95%CI: 7.1–11.0), and according to the criteria for differential diagnosis, the prevalence of SDMD was 9.3% (95%CI: 7.5–11.4) and that of SDMC was 7.0% (95%CI: 5.4–8.9). A higher percentage of PI subjects had problems in falling asleep on most days (52.5%), had frequent night-time awakenings (66.3%) and early awakenings (51.3%). In subjects with any type of insomnia, the variables that showed a statistically significant association were female gender (OR: 2.21), consumption of psychotropic drugs (OR: 1.83), presence of four or more health problems (OR: 1.88) and being single, widowed or divorced (OR: 1.43). Conclusions: Our results provide a true picture of the prevalence of insomnia in older adults on the basis of diagnostic criteria and indicate that it is a widespread, significant health problem. The peculiarities of PI, SDMD and SDMC need to be appropriately differentiated in clinical practice, and each needs a different approach to obtain the best outcome. Copyright © 2011 John Wiley & Sons, Ltd.

Psychotropic drug effects on gene transcriptomics relevant to Parkinson's disease.

Abstract: Objectives Psychotropic drugs are widely prescribed in Parkinson's disease (PD) without regard to their pathobiological effects, and these drugs affect the transcription of a large number of genes. Effects of these drugs on PD risk gene transcription were therefore surveyed. Methods Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression evident in published data for 70 genes linked to PD risk. Results Psychotropic drugs can meaningfully affect PD risk gene mRNA transcription, including antipsychotics (upregulate dopamine receptors D2 and D3 (DRD2, DRD3); downregulate low-density lipoprotein receptor-related protein 8 (LRP8), ubiquitin carboxyl-terminal esterase L1 (UCHL1, also known as PARK5)), haloperidol (upregulates DRD3, parkin (PRKN, also known as PARK2), DRD2; downregulates brain-derived neurotrophic factor (BDNF)), risperidone (upregulates monoamine oxidase B (MAOB), DRD2), olanzapine (upregulates transmembrane protein 163 (TMEM163), BDNF, glutathione S-transferase mu 1 (GSTM1), MAOB, DRD2, solute carrier organic anion transporter family, member 3A1 (SLCO3A1)), aripiprazole (upregulates DRD2), quetiapine, paliperidone, lurasidone, carbamazepine, and many antidepressants (upregulate BDNF), lithium and bupropion (downregulate BDNF), amitriptyline (upregulates DRD3, DRD2), imipramine (upregulates BDNF, DRD3, DRD2), desipramine (upregulates BDNF, DRD3), and fluoxetine (upregulates acid beta-glucosidase (GBA), coiled-coil domain containing 62 (CCDC62), BDNF, DRD3, UCHL1, unc-13 homolog B (UNC13B), and perhaps huntingtin interacting protein 1 related (HIP1R); downregulates microtubule-associated protein tau (MAPT), methylcrotonoyl-coenzyme A carboxylase I (MCCC1), GSTM1, 28 kDa calbindin 1 (CALB1)). Fluoxetine effects on BDNF and UCHL1 in GEO Profiles were statistically robust. Conclusions This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on PD-relevant genes. Antipsychotics and serotoninergic antidepressants may potentially attenuate PD risk, and lithium and bupropion may augment risk, through MAPT, GBA, CCDC62, HIP1R, BDNF, and DRD2 transcription, with MAPT, GBA, and CCDC62 being strongly associated with PD risk in recent meta-analyses. Limitations of these findings and a research agenda to better relate them to the nigrostriatum and PD are discussed.

Psychotropic drug and polypharmacy use among adolescents and young adults: findings from the Finnish 1981 Nationwide Birth Cohort Study.

Abstract: Background: Little is known about the timing of the start of psychotropic drug use and psychotropic polypharmacy use. Aims: This study describes these patterns in a Finnish representative cohort aged between 12 and 25. Methods: 5525 subjects born in 1981 were followed up between 1994 and 2005 using the Finnish National Prescription Register. Results: Survival analysis revealed that the cumulative incidence of any psychotropic drug use was 1.3% by age 15, 6.1% by age 20 and 15.2% by age 25. Antidepressants and benzodiazepines were the most used drug groups, with cumulative incidences of 12.2% and 5.2%, respectively, by age 25. The cumulative incidence of polypharmacy was 0.02% by age 15, 0.9% by age 20 and 4.1% by age 25, i.e. having purchased at least two psychotropic drugs from different classes during the same day. Polypharmacy occurred among the majority of antipsychotic and benzodiazepine users, but among a minority of antidepressant users. More females than males had used any psychotropic drug, antid...

Subjective sleep problems in young women suffering from premenstrual dysphoric disorder.

Abstract: Premenstrual syndrome (PMS) is a common disorder that affects nearly 9–72% women across studies.[1–3] Premenstrual dysphoric disorder (PMDD) is the more severe form of the PMS and its prevalence ranges between 3% and 30%.[2,4] Sleep problems form an integral part of the problem as they are included in the diagnostic criteria for PMDD.[5] A number of studies have tried to find association between PMS or PMDD with sleep pattern and quality of sleep in the past. Sleep was examined using subjective as well as objective measures.[6–10] Majority of the studies have recorded sleep using a polysomnograph across various phases of menstrual cycle.[6–10] However, many of the patients experience first-night effect while sleeping in a sleep laboratory and this may adversely affect polysomnographic data.[11,12] Subjective perception of sleep-related parameters may not match the objective data, and resultantly the patient often complains of subjectively poor-quality sleep despite a good sleep on polysomnograph.[13] The common example is the paradoxical insomnia. Subjective perception of sleep which affects the clinical picture to a greater extent was examined by only a handful of these studies.[6,10] Though as scientists we rely more on objective evidences, still the subjective parameters cannot be overlooked as they are stronger determinants of quality of life. Hence, the present study was planned to assess subjective sleep problems in PMDD subjects and to compare them with the non-PMDD group. We further hypothesized that subjective sleep parameters would also affect the daytime functioning. This questionnaire-based study was done in a nursing college after seeking approval of the institutional ethics committee and permission of college administration. All the female students were invited to participate in the study. Female teachers who took the responsibility to get the questionnaires filled were explained the purpose of the study beforehand. They were also explained what kind of information was intended from each question in a training session. The questionnaire was distributed among the girls with the help of female teachers. Hence, the authors were blinded regarding the identity of participants. This blinding helped to motivate the participants. Teachers then explained the purpose of study to all students and encouraged them to volunteer the information. Verbal informed consent was taken from the participants and those who were not interested in participating in the study were excluded. The girls who were taking any kind of psychotropic drug or hormonal therapy were also advised not to participate in this study. The survey questionnaire was designed in Hindi language. It contained instructions regarding intended information. First part of the questionnaire contained instructions and the exclusion criteria as mentioned above. The next part contained questions regarding participants’ demographic data and changes observed in their sleep patterns prior to 1 week of onset of menstruation as compared to other days of the month during past 3 months. These questions included: “change in total sleep time” (responses were increased, as usual, decreased); “time to bed” (advanced, as usual, or delayed); “quality of sleep” (poor, as usual, better); etc. Subjects were supposed to choose the response that best described their condition. Screening for the PMDD was based upon DSM-IV-TR criteria.[5] The question was as follows: “Did you notice any change in your mood (depressed, as usual, better) 1 week prior to onset of your menstruation as compared to other days of the month?”. Similar questions were asked regarding other symptoms e.g. irritability (increased, as usual, worse); ability to concentrate (better, as usual, poor) etc.” In this manner, all the 11 criteria mentioned in DSM-IV-TR were changed in the question form. Subjects responded by marking the option that best explained their condition on that item. As per the DSM-IV-TR criteria, subjects who fulfilled 5 of the 11 criteria with at least 1 from the first 4 criteria during past 3 months were considered PMDD. However, DSM requires prospective charting of symptoms for the diagnosis of PMDD; hence, these cases were termed as possible-PMDD. Students were provided explanation if they had any difficulty in understanding the meaning of any of the items. The questionnaires were then collected and analyzed. Statistical analysis was done with the help of SPSS version 17.0. Cohort was divided into two groups – those with PMDD and those not fulfilling the criteria of PMDD. Chi-square test was used to compare non-parametric variables. The study sample consisted of 269 subjects. The average age of students was 19.06 years (±1.56 years). 37.5% students met the criteria for possible-PMDD. Possible-PMDD subjects reported that their sleep quality was worse before the onset of their menstruation, as compared to subjects who did not fulfill the criteria for PMDD. Table 1 depicts the other details of sleep-related variables. Table 1 Comparison of sleep-related variables between possible-PMDD and no PMDD groups No difference was reported in dream frequency between these groups. However, emotions associated with dreams were reported to differ between the two groups. Possible-PMDD group reported higher frequency of anxiety and anger in their dreams, as compared to the other group (χ2 = 24.93, df = 3, P < 0.001). However, no difference was observed in the frequency of parasomnia (sleep talking, sleepwalking) and snoring between these groups. Possible-PMDD group complained of fatigue during the day (χ2 = 36.68, df = 3, P < 0.001) and daytime sleepiness (χ2 = 18.16, df = 3, P < 0.001). Our study found that possible-PMDD group had poor sleep as compared to non-PMDD group on several measures of sleep including bed time, sleep quality, sleep-onset latency, sleep maintenance, and wake time. Similarly, daytime fatigue and daytime sleepiness was also reported by possible-PMDD group. This is in concordance with the results of earlier studies. Mauri et al.[10] have reported that women with severe PMS complain of increased sleepiness and fatigue before menstruation as compared to other periods of their own menstrual cycle as well as with reference to the control group. An increase in daytime sleepiness was the only factor that was able to differentiate between women with and without PMS in another study.[14] Severe PMS has been known to worsen the sleep quality, increase the daytime sleepiness, and is associated with reduced alertness during the day.[9] Thus, these studies reported that the fatigue, sleepiness, and alertness during the day may be used to differentiate PMDD group from non-PMDD group. However, unlike the present study, these studies failed to find any difference in nocturnal sleep. This association between PMS and disturbed subjective sleep parameters (increased nocturnal awakenings, unpleasant dreams, delayed wake time, and morning tiredness) was reported by only one study which was conducted long back.[10] As the quest for the objectivity has increased, most of the work in this area during past decade was done using objective parameters, which may not find any difference despite subjective symptoms.[15] Thus, as a clinician, it is important to consider patients’ symptoms rather than just look for the laboratory reports. Further, as a scientist, these results promote us to search for the factors that are responsible for the difference between subjective and objective quality of sleep in this specialized group. We also found an increased frequency of daytime symptoms in possible–PMDD group, which could have been an influence of nocturnal sleep. Considering the example of paradoxical insomnia, in future, it will be interesting to examine the relationship between PMDD, subjective sleep quality, objective sleep parameters, and daytime symptoms. This may guide us in the management of PMDD. We would like to mention that in this study, subjects without possible PMDD also reported sleep problems. This suggests that sleep problems are not governed by PMDD; rather, they are related to menstrual cycle. In the past, one study reported that poor sleep quality was seen not only in PMDD group but also among non-PMDD women; however; other factors remained unaffected.[6] Manber et al.[14] also reported that sleep disturbance, e.g. increased sleep latency, reduced sleep efficiency, and poor sleep quality, was not limited to PMS group; rather, it was found in all women before menstruation. One reason for these results could be fluctuation in plasma melatonin level and sleep–wake rhythms across menstrual cycle, even in healthy females.[7] These evidences suggest that poor sleep could be a trait marker of premenstrual period rather than a state marker of PMS or PMDD. In other words, sleep changes may be an inherent property of menstrual cycle and PMDD sufferers could have an exaggeration of sleep-related problems during late luteal phase. Like any other study, this study also had some methodological limitations. First, it was a survey and questionnaire can be used to screen only. Secondly, surveys are always associated with recall bias. Thirdly, DSM-IV-TR suggests that PMDD should be diagnosed prospectively, which was not done in the present study. Nonetheless, this study shows important findings in this area and is probably the first Indian study to address this important but yet unrecognized issue. In addition, this study adds up to the scarcely available literature that has examined subjective sleep parameters in PMDD subjects. In conclusion, possible-PMDD sufferers have problems with their night sleep and also bear daytime symptoms. These symptoms negatively affect their ability to accomplish daily chores.

Psychotropic drug effects on gene transcriptomics relevant to Alzheimer disease.

Abstract: Psychotropics are widely prescribed in Alzheimer disease (AD) without regard to their pathobiological effects. Results summarize a comprehensive survey of psychotropic effects on messenger ribonucleic acid (mRNA) expression for 52 genes linked to AD. Pending future investigations, current data indicate that atypical antipsychotics, lithium, and fluoxetine reduce AD risk, whereas other drug classes promote risk. Risk may be attenuated by antipsychotics and lithium (down-regulate TNF), atypical antipsychotics (down-regulate TF), risperidone (down-regulates IL1B), olanzapine (up-regulates TFAM, down-regulates PRNP), fluoxetine (up-regulates CLU, SORCS1, NEDD9, GRN, and ECE1), and lithium coadministered with antipsychotics (down-regulates IL1B). Risk may be enhanced by neuroleptics (up-regulate TF), haloperidol (up-regulates IL1B and PION), olanzapine (down-regulates THRA and PRNP, up-regulates IL1A), and chlorpromazine, imipramine, maprotiline, fluvoxamine, and diazepam (up-regulate IL1B). There were no results for dextromethorphan-plus-quinidine. Fluoxetine effects on CLU, NEDD9, and GRN were statistically robust. Drug effects on specific variants, polymorphisms, genotypes, and other genes (CCR2, TF, and PRNP) are detailed. Translational AD risk applications and their limitations related to specific genes, mutations, variants, polymorphisms, genotypes, brain site, sex, clinical population, AD stage, and other factors are discussed. This report provides an initial summary and framework to understand the potential impact of psychotropic drugs on AD-relevant genes.