The Melkersson-Rosenthal syndrome: a retrospective study of biopsied cases.
J Neurol. 2013 Jan;260(1):138-43
Authors: Elias MK, Mateen FJ, Weiler CR
Melkersson-Rosenthal syndrome (MRS) is a rare neuromucocutaneous syndrome marked by the triad of recurrent nonpitting orofacial edema, fissured dorsal tongue (lingua plicata), and lower motoneuron facial paralysis. Large case series including treatment are limited. A retrospective records review was performed for the diagnoses Melkersson-Rosenthal syndrome, granulomatous cheilitis, and orofacial granulomatosis, confirmed by noncaseating granulomas on biopsy, at the Mayo Clinic in Rochester, Minnesota (1979-2009). There were 72 patients [51 women (71 %), mean age at presentation 39 years (range 8-79)] identified with facial edema with noncaseating granulomas on skin biopsy. Lingua plicata occurred in 34 cases (47 %, 95 % confidence interval 35.3-59.3 %). Unilateral or partial facial nerve palsy occurred in 14 cases (19.4, 95 % confidence interval 11.4-30.8 %). Comorbidities among those with facial edema included periodontal disease (n = 10, 14 %), history of allergic disease (n = 10, 14 %), Crohn's Disease (n = 6, 8 %), migraine headaches (n = 5, 7 %), and systemic lupus erythematosus (n = 2, 3 %). There were no patients who had low C1q or C4 levels among those who were tested. Overall, the full triad canonical of Melkersson-Rosenthal syndrome was observed in nine patients (seven female, median age at symptomatic presentation 35 years (range 10-74 years), 13 %, (95 % confidence interval 6.2-22.9 %) with a median time from first symptoms to diagnosis of 4 years (range 1-35). The medication treatments attempted in the nine patients with the full triad of symptoms included non-steroidal anti-inflammatory drugs, oral and intra-lesional steroids, metronidazole, dapsone, acyclovir, methotrexate, and thalidomide with no consistent treatment responses. The Melkersson-Rosenthal syndrome may present over the course of most of the lifespan and may require several years of observation to be diagnosed. Neurologists who observe a combination of facial edema and facial palsy in a patient should consider the diagnosis of MRS and proceed to a diagnostic skin biopsy and a trial of steroid treatment for their patient.
PMID: 22836908 [PubMed - in process]
[New diagnosis for kids with temper tantrum].
Dtsch Med Wochenschr. 2013 Apr;138(16):822-3
Authors: Schenk M
PMID: 23720832 [PubMed - indexed for MEDLINE]
[Medication of the month. asenapine (Sycrest].
Rev Med Liege. 2013 Apr;68(4):196-200
Authors: Pitchot W
Asenapine is a new atypical antipsychotic. Like other atypicals, asenapine acts as an antagonist at both dopamine D2 and serotonin 5-HT2A receptors. The efficacy of asenapine monotherapy in the treatment of bipolar disorder manic episodes in adults has been demonstrated in two similarly designed randomized placebo-controlled flexible-dose trials of 3 weeks' duration, using olanzapine as active reference. Asenapine is associated with a good tolerability profile. In particular, asenapine induces a moderate weight gain, and does not increase serum levels of lipids or fasting glucose.
PMID: 23755711 [PubMed - in process]
Epidemiology of suicide in bipolar disorders: a systematic review of the literature.
Bipolar Disord. 2013 Jun 12;
Authors: Pompili M, Gonda X, Serafini G, Innamorati M, Sher L, Amore M, Rihmer Z, Girardi P
OBJECTIVE: Suicidal behavior is a major public health problem worldwide, and its prediction and prevention represent a challenge for everyone, including clinicians. The aim of the present paper is to provide a systematic review of the existing literature on the epidemiology of completed suicides in adult patients with bipolar disorder (BD). METHODS: We performed a Pubmed/Medline, Scopus, PsycLit, PsycInfo, and Cochrane database search to identify all relevant papers published between 1980 and 2011. A total of 34 articles meeting our inclusion criteria were included in the present review. RESULTS: Several prospective follow-up contributions, many retrospective analyses, and a few psychological autopsy studies and review articles investigated the epidemiology of completed suicides in patients with BD. The main finding of the present review was that the risk for suicide among BD patients was up to 20-30 times greater than that for the general population. CONCLUSION: Special attention should be given to the characteristics of suicides in patients with BD. Better insight and understanding of suicide and suicidal risk in this very disabling illness should ultimately help clinicians to adequately detect, and thus prevent, suicidal acts in patients with BD.
PMID: 23755739 [PubMed - as supplied by publisher]
Suicide risk in people with epilepsy taking antiepileptic drugs.
Bipolar Disord. 2013 Jun 12;
Authors: Mula M, Sander JW
OBJECTIVES: The standardized mortality ratio for suicide in people with epilepsy is reported as 5.1 [95% confidence interval (CI): 3.9-6.6], but this is only partially explained by the high rates of psychiatric comorbidity. This issue was revived when, in 2008, the Food and Drug Administration (FDA) issued an alert on an increased risk of suicide in people taking antiepileptic drugs (AEDs). We discuss and elaborate on available evidence on the interplay among epilepsy, suicide, and AEDs, taking into account the phenomenology of mood disorders in people with epilepsy and the psychotropic potential of AEDs. METHODS: Articles were identified by searches of Medline/PubMed using the terms epilepsy, antiepileptic drugs, and suicide. Only papers published in English in international peer-reviewed journals were considered. The reference lists of relevant articles were hand-searched for additional publications (e.g., book chapters or review papers) if relevant to the discussion. RESULTS: The results of studies supporting or opposing the FDA conclusions have been inconsistent. This may be due to a number of methodological limitations, such as the failure to adjust for past suicidality and the confounding effect of epilepsy. CONCLUSIONS: A subgroup of people with epilepsy appears to be at risk of developing treatment-emergent psychiatric adverse effects of AEDs independently of the specific mechanism of action of the drug. Clinicians need to pay attention not only to seizure patterns when choosing the appropriate AED but also to a number of different parameters, not least the mental state of the individual patient.
PMID: 23755740 [PubMed - as supplied by publisher]
Meta-analysis confirms a functional polymorphism (5-HTTLPR) in the serotonin transporter gene conferring risk of bipolar disorder in European populations.
Neurosci Lett. 2013 Jun 8;
Authors: Jiang HY, Qiao F, Xu XF, Yang Y, Bai Y, Jiang LL
The serotonin transporter (5-HTT) is a candidate risk gene for bipolar disorder, and a functional polymorphism of 44-bp insertion/deletion (5-HTTLPR) located in the promoter region of this gene has been investigated for the association with the illness extensively among worldwide populations, but overall results were inconsistent and its role in the disorder remains unclear. The present study attempts to find its potential association with bipolar disorder using meta-analyzes that maximize the statistical power. We applied meta-analysis techniques by combining all available case-control studies of 5-HTTLPR and bipolar disorder in samples of European ancestry (with a total of 3778 cases and 4997 controls), and we assessed the evidence for allelic associations, heterogeneity among different studies, influence of each single study, and potential publication bias. The short allele (S allele) of 5-HTTLPR showed a significant association with bipolar disorder in our meta-analysis (odds ratio=1.10, p-value=0.005), suggesting it is likely a risk polymorphism for the illness, and the observed OR is consistent with other susceptibility loci identified through recent large-scale genetic association studies on bipolar disorder, which could be regarded simply as a small but detectable effects.
PMID: 23756178 [PubMed - as supplied by publisher]
HIV/AIDS and serious mental illness: a risky conclusion.
Psychiatr Serv. 2012 Dec;63(12):1261; author reply 1261-2
Authors: Cournos F, Guimarães MD, Wainberg ML
PMID: 23203364 [PubMed - indexed for MEDLINE]
Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia.
Schizophr Res. 2013 Jun 6;
Authors: Severance EG, Gressitt KL, Stallings CR, Origoni AE, Khushalani S, Leweke FM, Dickerson FB, Yolken RH
The origin of inflammation in psychiatric disorders is not well understood. The translocation of commensal microbiota across the gastrointestinal barrier can result in a persistent state of low-grade immune activation and/or inflammation. We measured serological surrogate markers of bacterial translocation (soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP)) in two psychiatric cohorts and compared these levels to C-reactive protein (CRP), body mass index (BMI), and food-related and autoimmune antibodies. The two cohorts were composed of the following: (1) n=141 schizophrenia, n=75 bipolar disorder, n=78 controls; (2) n=78 antipsychotic-naïve first-episode schizophrenia, n=38 medicated first-episode schizophrenia. sCD14 seropositivity conferred a 3.1-fold increased odds of association with schizophrenia (multivariate regressions, OR=3.09, p<0.0001) compared to controls. Case-control differences in sCD14 were not matched by LBP. Quantitative levels of LBP, but not sCD14, correlated with BMI in schizophrenia (R(2)=0.21, p<0.0001). sCD14 and LBP also exhibited some congruency in schizophrenia with both significantly correlated with CRP (R(2)=0.26-0.27, p<0.0001) and elevated in females compared to males (p<0.01). Antipsychotic treatment generally did not impact sCD14 or LBP levels except for significant correlations, especially sCD14, with gluten antibodies in antipsychotic-naïve schizophrenia (R(2)=0.27, p<0.0001). In bipolar disorder, sCD14 levels were significantly correlated with anti-tissue transglutaminase IgG (R(2)=0.37, p<0.001). In conclusion, these bacterial translocation markers produced discordant and complex patterns of activity, a finding that may reflect an imbalanced, activated innate immune state. Whereas both markers may upregulate following systemic exposure to Gram-negative bacteria, non-lipopolysaccharide-based monocyte activation, autoimmunity and metabolic dysfunction may also contribute to the observed marker profiles.
PMID: 23746484 [PubMed - as supplied by publisher]
Is Aberrant Functional Connectivity A Psychosis Endophenotype? A Resting State Functional Magnetic Resonance Imaging Study.
Biol Psychiatry. 2013 Jun 5;
Authors: Khadka S, Meda SA, Stevens MC, Glahn DC, Calhoun VD, Sweeney JA, Tamminga CA, Keshavan MS, O'Neil K, Schretlen D, Pearlson GD
BACKGROUND: Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives. METHODS: We investigated resting state functional magnetic resonance imaging in 70 schizophrenia and 64 psychotic bipolar probands, their respective first-degree relatives (n = 70 and 52), and 118 healthy subjects. We used independent component analysis to identify components representing various resting state networks and assessed spatial aspects of functional connectivity within all networks. We first investigated group differences using five-level, one-way analysis of covariance (ANCOVA), followed by post hoc t tests within regions displaying ANCOVA group differences and correlation of such functional connectivity measures with symptom ratings to examine clinical relationships. RESULTS: Seven networks revealed abnormalities (five-level one-way ANCOVA, family-wise error correction p < .05): A) fronto-occipital, B) midbrain/cerebellum, C) frontal/thalamic/basal ganglia, D) meso/paralimbic, E) posterior default mode network, F) fronto-temporal/paralimbic and G) sensorimotor networks. Abnormalities in networks B and F were unique to schizophrenia probands. Furthermore, abnormalities in networks D and E were common to both patient groups. Finally, networks A, C, and G showed abnormalities shared by probands and their relative groups. Negative correlation with Positive and Negative Syndrome Scale negative and positive scores were found in regions within network C and F respectively, and positive correlation with Positive and Negative Syndrome Scale negative scores was found in regions in network D among schizophrenia probands only. CONCLUSIONS: Schizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes.
PMID: 23746539 [PubMed - as supplied by publisher]
The utilization of psychopharmacological treatment and medication adherence among Medicaid enrolled children and adolescents with bipolar depression.
J Affect Disord. 2013 Jun 6;
Authors: Bhowmik D, Aparasu RR, Rajan SS, Sherer JT, Ochoa-Perez M, Chen H
BACKGROUND: To examine the psychotropic medication utilization and compare adherence to treatment regimens in pediatric bipolar depression patients. METHODS: 2003-2007 MAX data from four geographically diverse states were used. According to the regimen received by the patients (6-18 years) in the first month after the index bipolar depression diagnosis, patients were categorized into six mutually exclusive groups. The month to month change of treatment regimen in each group was then assessed during the 6 month post-index bipolar depression diagnosis. Adherence to each regimen was measured as continuation of the initial regimen, switch to a new regimen, augmentation with medication from a different therapeutic category, and discontinuation of all pharmacotherapies. Repeated measure analysis was conducted to compare the trend of each adherence measure across the study groups. RESULTS: Of the 5,460 subjects identified, 15.39% received antipsychotic monotherapy, 9.43% received mood stabilizer monotherapy, 5.77% received antidepressant monotherapy, 26.48% received mood stabilizer-antipsychotic polytherapy, 22.51% received antidepressant polytherapy, and 19.89% received antipsychotic-mood stabilizer-antidepressant polytherapy. At the end of the follow-up period, over 50% of the 1st month polytherapy users and less than 50% of the monotherapy users were continuing their initial regimen. Repeated measure analysis using antipsychotic monotherapy as the reference group suggested differences in trend slopes (p<0.05). LIMITATIONS: In absence of structured clinical evaluation, bipolar disorder diagnoses cannot be ascertained in this study. CONCLUSIONS: Bipolar depression patients were predominantly treated with combinations of psychotropic drugs. Potentially questionable practice, such as antidepressant monotherapy was used only in a small fraction of patients. Combination regimens had better adherence as compared to monotherapies.
PMID: 23747210 [PubMed - as supplied by publisher]
Lack of association of EGR2 variants with bipolar disorder in Japanese population.
Gene. 2013 Jun 4;
Authors: Balan S, Yamada K, Iwayama Y, Toyota T, Ohnishi T, Maekawa M, Toyoshima M, Iwata Y, Suzuki K, Kikuchi M, Ujike H, Inada T, Kunugi H, Ozaki N, Iwata N, Nanko S, Kato T, Yoshikawa T
The early growth response gene 2 (EGR2) has been recently reported to be associated with bipolar disorder in Korean population. However replication studies in independent cohorts of same and different ethnicities are essential for establishing the credibility of a genotype-phenotype association. With this notion, in the present study we have performed a replication study of the reported association of SNPs in EGR2 in a case-control study comprising of 867 unrelated Japanese bipolar disorder patients and 895 age-, sex- and ethnicity-matched controls. Results showed no significant differences in allele and genotype frequencies of EGR2 SNPs between bipolar disorder patients and controls and also in a sex-stratified genetic analysis. The haplotype and meta-analyses also showed no significant association with bipolar disorder. In conclusion, this is the first replication study of the previously reported association of EGR2 with bipolar disorder in a larger sample set and the results showed that the EGR2 gene is unlikely to contribute to the susceptibility of bipolar disorder in Japanese cohort.
PMID: 23747400 [PubMed - as supplied by publisher]
Biomarkers of bipolar disorder: specific or shared with schizophrenia?
Front Biosci (Elite Ed). 2013;E5:845-63
Authors: Bellivier F, Geoffroy PA, Scott J, Schurhoff F, Leboyer M, Etain B
Kraepelin's observations of the differences in the course and outcome of dementia praecox and manic depression fundamentally influenced thinking about bipolar disorder (BP) and schizophrenia (SZ) for over a century. In modern times, there is increasing awareness that a greater understanding of the similarities between these two highly prevalent and disabling conditions can teach us as many lessons about the pathophysiology of severe mental disorders as does the pursuit of differentiating factors. We review publications on developmental, genetic, epidemiological, and outcome research that challenges the Kraepelian dichotomy. We highlight the increasing evidence of the overlap in genetic susceptibility. Neuro-developmental studies provide evidence of shared early pathological processes, whilst neurophysiological investigations also suggest that different genes may have a role in the development of both phenotypes. There is also evidence of overlapping neurocognitive phenotypes. It has become increasingly clear that a simple binary classification of these disorders represents an oversimplification. It may be more apposite to think in terms of genetic in?uences on six continuous symptom dimensions: neurobiological, cognitive, positive, negative, depressive and manic symptoms.
PMID: 23747901 [PubMed - in process]
[Thinking organization and defense mechanisms in bipolar disorders. Clinical and psychopathological study on bipolar I and bipolar II].
Riv Psichiatr. 2013 Mar-Apr;48(2):0
Authors: Lo Baido R, Di Blasi M, Alfano P, Audino P, Bellavia C, Blando AA, Merendino A, Messina R, Poma ML, La Grutta S
Aim. The aim of this research is to explore the psychical functioning in bipolar I or bipolar II disorder people through the analysis and comparison of their thought styles and defense patterns. Methods. 29 bipolar I and bipolar II people afferent to Palermo University Policlinical Psychriatic Hospital Department were selected during the whole 2009-2010 year. The following tests were administred: Wechsler Adult Intelligent Scale-R (WAIS-R) in order to measure the general cognitive function; Defense Mechanisms Inventory (DMI) in order to measure defense patterns. Afterwards, the results of the two tests were analysed and compared. Outcome. Bipolar disorder people use cognitive mechanisms and defense strategies that are very different from standard population. Bipolar I subjects show both wider and more serious cognitive deterioration and stricter defense mechanisms than bipolar II subjects. Generally bipolar patients show an immature personality based on archaic mechanisms that can be found in all the spheres of their personality: emotions, cognition, Ego-strength, adaptability to reality. Discussion. The peculiar achieved cognitive and defense profile leads to important considerations about how psychological strategies can contribute to use "bespoke" treatments for these patients.
PMID: 23748719 [PubMed - in process]
[Olanzapine in manic/mixed patients with or without substance abuse].
Riv Psichiatr. 2013 Mar-Apr;48(2):0
Authors: Sani G, Simonetti A, Serra G, Solfanelli A, Girardi N, Janiri D, Danese E, Rapinesi C, Tatarelli R, Girardi P
Aim. To evaluate the efficacy of olanzapine in patients in their manic/mixed phase with or without comorbidity with substance abuse/dependence disorder. Methods. In this observational, controlled, prospective study, 60 patients with a DSM-IV-TR diagnosis of bipolar disorder, manic/mixed episode (30 patiens with and 30 patient without comorbidity with a substance abuse/dependence disorder) were treated with olanzapine, evaluated at discharge, and followed-up for 8 weeks. Efficacy of olanzapine was assessed by comparing the proportion of responders (an at least 50% drop in Young Mania Rating Scale [YMRS] score from baseline) and remitters (YMRS ?12 and Hamilton Depression Rating Scale [HAM-D] ?8) in both groups. Craving and days of abuse/use were assessed with Visual Analogue Scale (VAS) and Time-line Follow-Back (TLFB), respectively. Results. Differences in response and remission percentages were statistically not significant at discharge and during follow-up. A reduction of days of abuse has been observed in the drug-abuse group, while craving was only slightly decreased. Discussion. These results suggest that olanzapine is effective in both groups and its efficacy in reducing the days of abuse appears to be independent from its action on craving.
PMID: 23748724 [PubMed - in process]
Distribution of the glucocorticoid receptor in the human amygdala; changes in mood disorder patients.
Brain Struct Funct. 2013 Jun 8;
Authors: Wang Q, Verweij EW, Krugers HJ, Joels M, Swaab DF, Lucassen PJ
Exposure to stress activates the hypothalamic-pituitary-adrenal (HPA) axis that stimulates glucocorticoid (GC) release from the adrenal. These hormones exert numerous effects in the body and brain and bind to a.o. glucocorticoid receptors (GR) expressed in the limbic system, including the hippocampus and amygdala. Hyperactivity of the HPA axis and disturbed stress feedback are common features in major depression. GR protein is present in the human hypothalamus and hippocampus, but little is known-neither in healthy subjects nor in depressed patients-about GR expression in the amygdala, a brain structure involved in fear and anxiety. Since chronic stress in rodents affects GR expression in the amygdala, altered GR protein level in depressed versus healthy controls can be expected. To test this, we investigated GR-? protein expression in the post-mortem human amygdala and assessed changes in ten major or bipolar depressed patients and eight non-depressed controls. Abundant GR immunoreactivity was observed in the human amygdala, both in neurons and astrocytes, with a similar pattern in its different anatomical subnuclei. In major depression, GR protein level as well as the percentage of GR-containing astrocytes was significantly higher than in bipolar depressed patients or in control subjects. Taken together, the prominent expression of GR protein in the human amygdala indicates that this region can form an important target for corticosteroids and stress, while the increased GR expression in major, but not bipolar, depression suggests possible involvement in the etiology of major depression.
PMID: 23748930 [PubMed - as supplied by publisher]
[Madrid study on the prevalence and characteristics of outpatients with dual pathology in community mental health and substance misuse services].
Authors: Arias F, Szerman N, Vega P, Mesias B, Basurte I, Morant C, Ochoa E, Poyo F, Babín F
The objective was to quantify the prevalence of dual diagnosis and to evaluate the characteristics of these patients from community mental health and substance misuse services in Madrid. The sample consisted of 837 outpatients from Madrid, 208 from mental health services and 629 from substance misuse services. We used the Mini International Neuropsychiatric Interview (MINI) and Personality Disorder Questionnaire (PDQ4+) to evaluate disorders from axis I and II. It was considered that 517 (61.8%) patients had dual pathology (current diagnoses of axis I or II disorders and an addictive disorder): 36,1% in mental health services and 70,3% in substance misuse services. There were fewer males amongst the dual patients and it was also found that they had a worse employment situation, along with higher figures of alcohol and cannabis dependence than addicts without dual diagnoses (n=194). When comparing them with patients with mental disorder diagnoses only, excluding substance use disorder (n=126), there were differences in all socio-demographic characteristics analyzed, and dual patients were associated with diagnoses of bipolar disorder, agoraphobia, generalized anxiety disorder, post-traumatic stress disorder, and had more suicide risk and different personality disorders. Thus, dual pathology is higher in patients who are in treatment and have differential characteristics (higher suicide risk, worse employment situation) that suggest greater severity that could be of help in the planning of care resource policies for these patients.
PMID: 23748940 [PubMed - in process]
Pharmacological Management of Bipolar Depression: Acute Treatment, Maintenance, and Prophylaxis.
CNS Drugs. 2013 Jun 9;
Authors: Vieta E, Valentí M
Although the most distinctive clinical feature of bipolar disorder is the pathologically elevated mood, it does not usually constitute the prevalent mood state of bipolar illness. The majority of patients with bipolar disorder spend much more time in depressive episodes, including subsyndromal depressive symptoms, and bipolar depression accounts for the largest part of the morbidity and mortality of the illness. The pharmacological treatment of bipolar depression mostly consists of combinations of at least two drugs, including mood stabilizers (lithium and anticonvulsants), atypical antipsychotics, and antidepressants. Antidepressants are the most frequently prescribed drugs, but recommendations from evidence-based guidelines are not conclusive and do not overtly support their use. Among antidepressants, best evidence exists for fluoxetine, but in combination with olanzapine. Although some guidelines recommend the use of selective serotonin reuptake inhibitors or bupropion in combination with antimanic agents as first-choice treatment, others do not, based on the available evidence. Among anticonvulsants, the use of lamotrigine is overall recommended as a first-line choice, but acute monotherapy studies have failed. Valproate is generally mentioned as a second-line treatment. Lithium monotherapy is also suggested by most guidelines as a first-line treatment, but its efficacy in acute use is not totally clear. Amongst atypical antipsychotics, quetiapine, in monotherapy or as adjunctive treatment, is recommended by most guidelines as a first-line choice. Olanzapine monotherapy is also suggested by some guidelines and is approved in Japan. Armodafinil, pramipexole, ketamine, and lurasidone are recent proposals. Long-term treatment in bipolar disorder is strongly recommended, but guidelines do not recommend the use of antidepressants as a maintenance treatment. Lithium, lamotrigine, valproate, olanzapine, quetiapine, and aripiprazole are the recommended first-line maintenance options.
PMID: 23749421 [PubMed - as supplied by publisher]
Bipolar disorder and disruptive mood dysregulation in children and adolescents: assessment, diagnosis and treatment.
Evid Based Ment Health. 2013 Jun 8;
Authors: Krieger FV, Stringaris A
PMID: 23749629 [PubMed - as supplied by publisher]
Adverse Clinical Events Among Medicare Beneficiaries Using Antipsychotic Drugs: Linking Health Insurance Benefits and Clinical Needs.
Med Care. 2013 Jul;51(7):614-621
Authors: Fung V, Price M, Busch AB, Landrum MB, Fireman B, Nierenberg A, Dow WH, Hui R, Frank R, Newhouse JP, Hsu J
OBJECTIVE:: Medicare Part D provides formulary protections for antipsychotics but does not exempt these drugs from cost-sharing. We investigated the impact of Part D coverage on antipsychotic drug spending, adherence, and clinical outcomes among beneficiaries with varying indications for use. METHODS:: We conducted a historical cohort study of Medicare Advantage beneficiaries who received antipsychotic drugs, with diagnoses of schizophrenia or bipolar disorder or with no mental health diagnoses (N=10,190). Half had a coverage gap; half had no gap because of low-income subsidies. Using fixed effects regression models, we examined changes in spending and adherence as beneficiaries experienced cost-sharing increases after reaching the gap. We examined changes in hospitalizations and emergency department visits using proportional hazard models. RESULTS:: Across all diagnostic groups, total monthly expenditure on antipsychotic drugs decreased with cost-sharing increases in the gap compared with those with no gap (eg, schizophrenia: -$123 95% confidence interval [-$138, -$108]), and out-of-pocket spending increased (eg, schizophrenia: $104 [$98, $110]). Adherence similarly decreased, with the largest declines among those with schizophrenia (-20.6 percentage points [-22.3, -18.9] in proportion of days covered). Among beneficiaries with schizophrenia and bipolar disorder, hospitalizations and emergency department visit rates increased with cost-sharing increases (eg, schizophrenia: hazard ratio=1.32 [1.06, 1.65] for all hospitalizations), but did not among subjects without mental health diagnoses. Clinical event rates did not change among beneficiaries with low-income subsidies without gaps. CONCLUSIONS:: There is evidence of interruptions in antipsychotic use attributable to Part D cost-sharing. Adverse events increased among beneficiaries with approved indications for use, but not among beneficiaries without such indications.
PMID: 23752219 [PubMed - as supplied by publisher]
The societal cost of bipolar disorder in Sweden.
Soc Psychiatry Psychiatr Epidemiol. 2013 Jun 11;
Authors: Ekman M, Granström O, Omérov S, Jacob J, Landén M
PURPOSE: There is a lack of comprehensive cost-of-illness studies in bipolar disorder, in particular studies based on patient-level data. The purpose of this study was to estimate the societal cost of bipolar disorder and to relate costs to disease severity, depressive episodes, hospitalisation and patient functioning. METHODS: Retrospective resource use data in inpatient and outpatient care during 2006-2008, as well as ICD-10 diagnoses and Global Assessment of Functioning (GAF) scores, were obtained from the Northern Stockholm psychiatric clinic with a catchment area including 47 % of the adult inhabitants in Stockholm. This dataset was combined with national register data on prescription pharmaceuticals and sick leave to estimate the societal cost of bipolar disorder. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. RESULTS: The average annual cost per patient was <euro>28,011 in 2008 (n = 1,846). Indirect costs due to sick leave and early retirement represented 75 %, inpatient costs 13 %, outpatient costs 8 %, pharmaceuticals 2 % and community care another 2 % of the total cost. Total costs were considerably higher during mood episodes (six times higher than in remission), for hospitalised patients (<euro>55,500 vs. <euro>22,200) and for patients with low GAF scores. CONCLUSIONS: The high cost of bipolar disorder is driven primarily by indirect costs. Costs were strongly associated with mood episodes, hospitalisations and low GAF scores. This suggests that treatment that reduces the risk for relapses and hospitalizations and improve functioning may decrease both the societal cost of bipolar disorder and patient suffering.
PMID: 23754681 [PubMed - as supplied by publisher]
mhGAP Intervention Guide for Mental, Neurological and Substance Use Disorders in Non-Specialized Health Settings: Mental Health Gap Action Programme (mhGAP)
The mhGAP Intervention Guide (mhGAP-IG) for mental, neurological and substance use disorders for non-specialist health settings, is a technical tool developed by WHO to assist in implementation of mhGAP. The Intervention Guide has been developed through a systematic review of evidence followed by an international consultative and participatory process. The mhGAP-IG presents integrated management of priority conditions using protocols for clinical decision-making. The priority conditions included are: depression, psychosis, bipolar disorders, epilepsy, developmental and behavioural disorders in children and adolescents, dementia, alcohol use disorders, drug use disorders, self-harm/suicide and other significant emotional or medically unexplained complaints. The mhGAP-IG is a model guide and has been developed for use by health-care providers working in non-specialized health-care settings after adaptation for national and local needs.
Genetics in neural toxicities of drugs.
Cent Nerv Syst Agents Med Chem. 2012 Dec;12(4):250-3
Authors: Lu DY, Lu TR, Zhu PP
Adverse side effects or toxicities of a drug were previously regarded as a manifestation of drug's own characterizations, such as the chemical structure and property of a drug. More recently, increasing experimental or clinical data and modern ideas suggest that human's genetic factors also play indispensable roles in resulting neural side effects of a drug, especially in antidepressant-induced suicide and antibiotics-induced hearing loss. However, there are many questions and technological obstacles (including high costs and limited samples) in these kinds of researches and this makes genetic study of drug toxicities in its initial stage. In this review, we in depth address and analysis of this matter from some new perspectives and propose some new initiatives to improve this type of researches in future. It is also highly needed to expedite the translation of these pharmacogenetic concepts from bench to bedside.
PMID: 22846044 [PubMed - indexed for MEDLINE]
Toward a systems biology of mood disorder.
Biol Psychiatry. 2013 Jan 15;73(2):107-8
Authors: McIntosh AM
PMID: 23245950 [PubMed - indexed for MEDLINE]
[Affective disorders in women with reproductive cancer (to the problem of somatoreactive cyclothymia).]
Zh Nevrol Psikhiatr Im S S Korsakova. 2013;113(4):13-17
Authors: Samushiia MA, Barinov VV
Based on the observation of 26 female patients, authors present a specific subtype of bipolar disorder - a somatoreactive cyclothymia which develops concomitantly with cancer. The affective disorder manifests itself as an acceptor of the clinical rhythm of cancer: the first and recurrent affective episodes coincide with the key stages of the disease.
PMID: 23739434 [PubMed - as supplied by publisher]
Loxapine Inhalation Powder: A Review of its Use in the Acute Treatment of Agitation in Patients with Bipolar Disorder or Schizophrenia.
CNS Drugs. 2013 Jun 6;
Authors: Keating GM
Loxapine is a well-established, first-generation antipsychotic agent. Loxapine inhalation powder (Adasuve(®)) was recently approved in the USA and the EU for use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia. Inhaled loxapine is delivered by a hand-held, single-dose, single-use device that uses the Staccato(®) drug delivery system. With Adasuve(®), maximum plasma loxapine concentrations are reached in a median of 2 min. In two randomized, double-blind, placebo-controlled, multicentre trials, inhaled loxapine 5 or 10 mg significantly reduced agitation (assessed using Positive and Negative Syndrome Scale-Excited Component scores) in patients with bipolar I disorder or schizophrenia, with the onset of effect seen within 10 min of administration. Inhaled loxapine was generally well tolerated in phase III trials (which excluded patients with clinically significant acute or chronic pulmonary disease), with the most commonly occurring adverse events including dysgeusia and sedation. Inhaled loxapine is contraindicated in patients with airways disease associated with bronchospasm or acute respiratory signs or symptoms. In conclusion, inhaled loxapine provides a novel new option for use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia, combining a rapid onset of effect with a noninvasive route of administration.
PMID: 23740380 [PubMed - as supplied by publisher]
Lamotrigine in epilepsy, pregnancy and psychiatry--a drug for all seasons?
J Clin Neurosci. 2013 Jan;20(1):13-6
Authors: Vajda FJ, Dodd S, Horgan D
Lamotrigine has been demonstrated to be effective as both an antiepileptic drug and a mood stabiliser. For epilepsy it is less efficacious than valproate in primary generalised epilepsy, but it is comparable to some traditional drugs in partial epilepsy. In psychiatry it has significant advantages over other mood stabilisers for the treatment and prevention of depressive phases of bipolar illness, but not for the treatment of mania. It has a more benign adverse effect profile than older antiepileptic agents and is not a proven teratogen. Risk of adverse reactions is reduced by commencing treatment at a markedly reduced dose that is gradually increased.
PMID: 23036173 [PubMed - in process]
Neuropsychological performance and family history in children at age 7 who develop adult schizophrenia or bipolar psychosis in the New England Family Studies.
Psychol Med. 2013 Jan;43(1):119-31
Authors: Seidman LJ, Cherkerzian S, Goldstein JM, Agnew-Blais J, Tsuang MT, Buka SL
BACKGROUND: Persons developing schizophrenia (SCZ) manifest various pre-morbid neuropsychological deficits, studied most often by measures of IQ. Far less is known about pre-morbid neuropsychological functioning in individuals who later develop bipolar psychoses (BP). We evaluated the specificity and impact of family history (FH) of psychosis on pre-morbid neuropsychological functioning.
METHOD: We conducted a nested case-control study investigating the associations of neuropsychological data collected systematically at age 7 years for 99 adults with psychotic diagnoses (including 45 SCZ and 35 BP) and 101 controls, drawn from the New England cohort of the Collaborative Perinatal Project (CPP). A mixed-model approach evaluated full-scale IQ, four neuropsychological factors derived from principal components analysis (PCA), and the profile of 10 intelligence and achievement tests, controlling for maternal education, race and intra-familial correlation. We used a deviant responder approach (<10th percentile) to calculate rates of impairment.
RESULTS: There was a significant linear trend, with the SCZ group performing worst. The profile of childhood deficits for persons with SCZ did not differ significantly from BP. Neuropsychological impairment was identified in 42.2% of SCZ, 22.9% of BP and 7% of controls. The presence of psychosis in first-degree relatives (FH+) significantly increased the severity of childhood impairment for SCZ but not for BP.
CONCLUSIONS: Pre-morbid neuropsychological deficits are found in a substantial proportion of children who later develop SCZ, especially in the SCZ FH+ subgroup, but less so in BP, suggesting especially impaired neurodevelopment underlying cognition in pre-SCZ children. Future work should assess genetic and environmental factors that explain this FH effect.
PMID: 22575089 [PubMed - indexed for MEDLINE]
Acta Psychiatr Scand. 2013 Jan;127(1):84
Authors: Ghaemi N, Phelps J
PMID: 23145842 [PubMed - indexed for MEDLINE]
False positives and false negatives: is the answer relatively simple?
Acta Psychiatr Scand. 2013 Jan;127(1):83
Authors: Vella S, Pai N
PMID: 23171234 [PubMed - indexed for MEDLINE]
Abstracts of the Tenth International Conference on Bipolar Disorder. June 13-16, 2013. Miami Beach, Florida, USA.
Bipolar Disord. 2013 Jun;15 Suppl 1:9-163
PMID: 23721539 [PubMed - in process]