Personalized prescribing: a new medical model for clinical implementation of psychotropic drugs.
Dialogues Clin Neurosci. 2016 Sep;18(3):313-322
Authors: Eap CB
The use of pharmacogenetic tests was already being proposed in psychiatry in the early 2000s because genetic factors were known to influence drug pharmacokinetics and pharmacodynamics. However, sufficient levels of evidence to justify routine use have been achieved for only a few tests (eg, major histocompatibility complex, class I, B, allele 1502 [HLA-B*1502] for carbamazepine in epilepsy and bipolar disorders); many findings are too preliminary or, when replicated, of low clinical relevance because of a small effect size. Although drug selection and dose adaptation according to cytochrome P450 genotypes are sound, a large number of patients need to be genotyped in order to prevent one case of severe side effect and/or nonresponse. The decrease in cost for genetic analysis shifts the cost: benefit ratio toward increasing use of pharmacogenetic tests. However, they have to be combined with careful clinical evaluations and other tools (eg, therapeutic drug monitoring and phenotyping) to contribute to the general aim of providing the best care for psychiatric patients.
PMID: 27757065 [PubMed - in process]
Chemokine and Chemokine Receptor Polymorphisms in Bipolar Disorder.
Psychiatry Investig. 2016 Sep;13(5):541-548
Authors: Tokac D, Tuzun E, Gulec H, Y?lmaz V, Bireller ES, Cakmakoglu B, Kucukali CI
OBJECTIVE: Bipolar disorder (BD) is a debilitating psychiatric disease with unknown etiology. Recent studies have shown inflammation as a potential contributing factor of BD pathogenesis. However, potential associations between chemokine and chemokine receptor polymorphisms and BD have been fundamentally understudied. To identify participation of chemokines in BD pathogenesis, we examined genetic variants of several chemokine and chemokine receptor genes.
METHODS: The study population comprised 200 patients with BD and 195 age- and sex-matched healthy controls. Genotyping of monocyte chemotactic protein 1 (MCP-1) A2518G, CCR2 V64I, CCR5 ?32, CCR5 A55029G, stromal cell-derived factor 1 (SDF-1) 3'A, and CXCR4 C138T polymorphisms was performed using polymerase chain reaction and restriction enzyme digestion.
RESULTS: We found that CCR5-?32 II and CXCR4-C138T C+ genotype frequencies contributed to an increased risk for BD. However, no statistical significance could be obtained with these genotypes after Bonferroni correction. A significant asssociation was only found with MCP-1 GG and G+ genotypes, which were markedly more prevalent in patients with BD and these genotypes seemed to significantly increase the risk for BD even after Bonferroni correction.
CONCLUSION: Our findings indicate an association between genetic variants of certain chemokine and chemokine receptor (especially MCP-1) genes and BD. The exact mechanisms by which these variants contribute to BD pathogenesis and their clinical implications need to be further investigated.
PMID: 27757133 [PubMed - in process]
Bipolar and Related Disorders Induced by Sodium 4-Phenylbutyrate in a Male Adolescent with Bile Salt Export Pump Deficiency Disease.
Psychiatry Investig. 2016 Sep;13(5):580-582
Authors: Vitale G, Simonetti G, Pirillo M, Taruschio G, Andreone P
Bile Salt Export Pump (BSEP) Deficiency disease, including Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2), is a rare disease, usually leading within the first ten years to portal hypertension, liver failure, hepatocellular carcinoma. Often liver transplantation is needed. Sodium 4-phenylbutyrate (4-PB) seems to be a potential therapeutic compound for PFIC2. Psychiatric side effects in the adolescent population are little known and little studied since the drug used to treat children and infants. So we described a case of Caucasian boy, suffering from a late onset PFIC2, listed for a liver transplant when he was sixteen and treated with 4-FB (200 mg per kilogram of body weight per day). The drug was discontinued for the onset of bipolar and related disorders. This case illustrates possible psychiatric side effects of the drug.
PMID: 27757140 [PubMed - in process]
Psychometric properties and validation of a four-item version of the Strauss-Carpenter scale in bipolar disorder.
Int J Bipolar Disord. 2016 Dec;4(1):22
Authors: Alberich S, Barbeito S, González-Ortega I, Ugarte A, Vega P, de Azúa SR, López P, Zorrilla I, González-Pinto A
BACKGROUND: Bipolar disorder is a chronic illness that impairs functioning and affects the quality of life of patients. The onset of this illness usually occurs at an early age, and the risk of relapse remains high for decades. Thus, due to the great clinical relevance of identifying long-term predictors of functioning in bipolar disorder, Strauss and Carpenter developed a scale composed of items known to have prognostic value.
METHODS: To determine the clinical usefulness of the four-item Strauss-Carpenter scale in bipolar disorder, a 1-year prospective follow-up study was carried out. The internal consistency, convergent and discriminant validity, and test-retest reliability of the scale were assessed. We also compared the Strauss-Carpenter scale with the reference scales Global Assessment Functioning (GAF), Clinical Global Impression for Bipolar Disorder, the Modified Version (CGI-BIP-M) and the Sheehan Disability Scale (Sheehan). Additionally, a cut-off point for remission was established.
RESULTS: The total sample was composed of 98 patients with a diagnosis of bipolar disorder. The four-item version of the Strauss-Carpenter scale showed to have appropriate psychometric properties, comparable to those of reference scales. The best cut-off point for remission was 14.
CONCLUSIONS: The four-item version of the Strauss-Carpenter scale has suitable validity and reliability for the assessment of functioning in patients with bipolar disorder.
PMID: 27757849 [PubMed - in process]
The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 patients with bipolar depression, mixed-state, mania and catatonic features.
Curr Neuropharmacol. 2016 Oct 17;
Authors: Perugi G, Medd P, Medd P, Toni C, Mariani MG, Socci C, Mauri M
OBJECTIVE: We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features.
METHOD: 522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features.
RESULTS: Of the original sample only 22 patients were excluded for the occurrence of side effects or consent withdrawal. After the ECT course, 344 (68.8%) patients were considered responders (final CGIi score ?3) and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic features. Length of current episode and global severity of the illness were the only statistically significant predictors of nonresponse.
CONCLUSIONS: ECT resulted to be an effective and safe treatment for all the phases of severe and drug-resistant BD. Positive response was observed in approximately two-thirds of the cases and in 80% of the catatonic patients. The duration of the current episode was the major predictor of nonresponse. The risk of ECT-induced mania is virtually absent and mood destabilization very unlikely. Our results clearly indicate that current algorithms for the treatment of depressive, mixed, manic and catatonic states should be modified and, at least for the most severe patients, ECT should not be considered as a "last resort".
PMID: 27758708 [PubMed - as supplied by publisher]
Relationship between childhood adversity and bipolar affective disorder: systematic review and meta-analysis.
Br J Psychiatry. 2016 Oct 6;:
Authors: Palmier-Claus JE, Berry K, Bucci S, Mansell W, Varese F
BACKGROUND: The relationship between childhood adversity and bipolar affective disorder remains unclear.
AIMS: To understand the size and significance of this effect through a statistical synthesis of reported research.
METHOD: Search terms relating to childhood adversity and bipolar disorder were entered into Medline, EMBASE, PsycINFO and Web of Science. Eligible studies included a sample diagnosed with bipolar disorder, a comparison sample and a quantitative measure of childhood adversity.
RESULTS: In 19 eligible studies childhood adversity was 2.63 times (95% CI 2.00-3.47) more likely to have occurred in bipolar disorder compared with non-clinical controls. The effect of emotional abuse was particularly robust (OR = 4.04, 95% CI 3.12-5.22), but rates of adversity were similar to those in psychiatric controls.
CONCLUSIONS: Childhood adversity is associated with bipolar disorder, which has implications for the treatment of this clinical group. Further prospective research could clarify temporal causality and explanatory mechanisms.
PMID: 27758835 [PubMed - as supplied by publisher]
Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort.
Bipolar Disord. 2016 Sep;18(6):520-527
Authors: Gonzalez S, Gupta J, Villa E, Mallawaarachchi I, Rodriguez M, Ramirez M, Zavala J, Armas R, Dassori A, Contreras J, Flores D, Jerez A, Ontiveros A, Nicolini H, Escamilla M
OBJECTIVES: Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD.
METHODS: A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations.
RESULTS: Associations of eight a priori GWAS SNPs with BD were replicated with nominal (P?.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction.
CONCLUSIONS: These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD.
PMID: 27759212 [PubMed - in process]
Early report on brain arousal regulation in manic vs depressive episodes in bipolar disorder.
Bipolar Disord. 2016 Sep;18(6):502-510
Authors: Wittekind DA, Spada J, Gross A, Hensch T, Jawinski P, Ulke C, Sander C, Hegerl U
OBJECTIVES: The arousal regulation model of affective disorders attributes an important role in the pathophysiology of affective disorders to dysregulation of brain arousal regulation. According to this model, sensation avoidance and withdrawal in depression and sensation seeking and hyperactivity in mania can be explained as auto-regulatory attempts to counteract a tonically high (depression) or unstable (mania) arousal. The aim of this study was to compare brain arousal regulation between manic and depressive bipolar patients and healthy controls. We hypothesized that currently depressed patients with bipolar disorder show hyperstable arousal regulation, while currently manic patients show unstable arousal regulation.
METHODS: Twenty-eight patients with bipolar disorder received a 15-min resting electroencephalogram (EEG) during a depressive episode and 19 patients received the same during a manic/hypomanic episode. Twenty-eight healthy control subjects were matched for age and sex. The Vigilance Algorithm Leipzig (VIGALL), which classifies 1-s EEG segments as one of seven EEG-vigilance substages, was used to measure brain arousal regulation.
RESULTS: Manic patients showed more unstable EEG-vigilance regulation as compared to the control sample (P = .004) and to patients with a depressive episode (P ? .001). Depressive patients had significantly higher mean vigilance levels (P = .045) than controls.
CONCLUSIONS: A clear difference was found in the regulation of brain arousal of manic patients vs depressive patients and controls. These data suggest that brain arousal might depend on the current mood state, which would support the arousal regulation model of affective disorders.
PMID: 27759213 [PubMed - in process]
Neuroprogression and episode recurrence in bipolar I disorder: A study of gray matter volume changes in first-episode mania and association with clinical outcome.
Bipolar Disord. 2016 Sep;18(6):511-519
Authors: Kozicky JM, McGirr A, Bond DJ, Gonzalez M, Silveira LE, Keramatian K, Torres IJ, Lam RW, Yatham LN
OBJECTIVES: Bipolar I disorder (BD-I) is associated with gray matter volume (GMV) alterations in neural regions important for emotional regulation. Reductions found in patients with multiple episodes are not seen at illness onset, suggesting that changes occur with illness progression, although no prospective studies to date have examined this. In the present study, we assessed GMV at baseline and one year following a first manic episode, examining the impact of episode recurrence on the trajectory of change.
METHODS: A total of 41 recently remitted first manic episode patients with BD-I and 25 healthy subjects (HS) underwent 3T magnetic resonance imaging at baseline and one year later. Using voxel-based morphometry, we compared GMV change between HS, patients who experienced a recurrence of a mood episode (BDrecurr ), and patients in sustained remission (BDwell ).
RESULTS: The GMV change from baseline to one year did not differ significantly between HS and the full BD-I group or BDwell and HS. However, the BDrecurr group had greater GMV loss than HS in left frontal and bilateral temporal regions, and BDwell patients involving bilateral frontal, temporal and left parietal regions.
CONCLUSIONS: GMV change early in the course of BD-I is associated with clinical outcome, such that neuroprogression found in patients who experience a recurrence of a mood episode is not seen in those with sustained remission. These findings have important implications for the treatment of BD-I as they suggest that prevention of recurrence might minimize neuroprogression of the disease, possibly requiring a multipronged early intervention approach to achieve this goal.
PMID: 27759214 [PubMed - in process]
Psychiatric disorders prior to amyotrophic lateral sclerosis.
Ann Neurol. 2016 Oct 19;:
Authors: Turner MR, Goldacre R, Talbot K, Goldacre MJ
It is recognized that neuropsychiatric conditions are over-represented in ALS patient kindreds and psychiatric symptoms may precede the onset of motor symptoms. Using a hospital record linkage database, hospitalization with a diagnosis of schizophrenia, bipolar disorder, depression or anxiety was significantly associated with a first diagnosis of ALS within the following year. This is likely to specifically reflect the clinicopathological overlap of ALS with frontotemporal dementia. A diagnosis of depression was significantly associated with a first record of ALS five or more years later, in keeping with growing evidence for major depressive disorder as an early marker of cerebral neurodegeneration. This article is protected by copyright. All rights reserved.
PMID: 27761925 [PubMed - as supplied by publisher]
Feasibility and Acceptability of the 'HABIT' Group Programme for Comorbid Bipolar and Alcohol and Substance use Disorders.
Clin Psychol Psychother. 2016 Oct 20;:
Authors: Biseul I, Icick R, Seguin P, Bellivier F, Scott J
OBJECTIVES: We investigated the feasibility and acceptability of an integrated group therapy (called HABIT) for comorbid bipolar disorder (BD) and alcohol and substance use disorders (ASUD) (BD-ASUD), a disabling clinical presentation for which no specific treatment has been validated. The 14-session HABIT programme employs psychoeducation-oriented cognitive-behaviour therapy (CBT) followed by mindfulness-based relapse prevention (MBRP) therapy.
METHOD: Potential group participants were recruited from adult clients with a DSM-IV diagnosis of BD and an ASUD who were referred by their treating clinician. Observer-rated changes in mood symptoms and ASUD, attendance rates and subjective feedback are reported.
RESULTS: Eight of 12 clients referred to the programme initially agreed to join the group, six attended the first group session and five clients completed the programme. Group mean scores for mood symptoms improved over time, with slightly greater reductions in depression during the first module. About 50% of individuals showed clinically significant improvement (?30% reduction) in alcohol and substance use. Attendance rates showed some variability between individuals and across sessions, but the average attendance rate of the group was marginally higher for the first module (86%) as compared with the second module (77%). Most clients reported high levels of general satisfaction with a group specifically targeted at individuals with BD-ASUD.
CONCLUSION: This small pilot study suggests our intensive group therapy is acceptable and feasible. If findings are replicated, we may have identified a therapy that, for the first time, leads to improvement in both mood and substance use outcomes in clients with difficult-to-treat comorbid BD-ASUD. Copyright © 2016 John Wiley & Sons, Ltd. Key Practitioner Message Comorbidity between bipolar and alcohol and substance use disorders (BD-ASUD) is frequent and highly disabling; Therapeutic research on approaches that can simultaneously help BD and ASUD is lacking; Previous research highlights the need for integrated treatment of both conditions but showed improvements limited to either element of the comorbid disorder; This pilot study supports the feasibility and acceptability of an intensive, 14-session group therapy programme that integrates CBT and mindfulness approaches.
PMID: 27761983 [PubMed - as supplied by publisher]
Structural Brain Changes in First Episode Mania with and without Psychosis: Data from Systematic Treatment Optimization Program for Early Mania (STOP-EM).
World J Biol Psychiatry. 2016 Oct 20;:1-30
Authors: Keramatian K, Dhanoa T, McGirr A, Lang DJ, Honer WG, Lam RW, Yatham LN
OBJECTIVES: The neurobiological underpinnings of bipolar I disorder are not yet understood. Previous structural neuroimaging studies of bipolar disorder have produced rather conflicting results. We hypothesize that clinical sub-phenotypes of bipolar I disorder defined by their psychotic symptoms, especially those with mood-incongruent psychotic features, may have more extensive structural brain abnormalities.
METHODS: We investigated structural brain alterations in patients with first-episode mania (n?=?55) with mood-congruent (n?=?16) and mood-incongruent (n?=?32) psychotic features, as well as those without psychotic symptoms (n?=?7), relative to healthy subjects (n?=?56).
RESULTS: Total intracranial volume was significantly reduced in patients with mood-incongruent psychosis compared to healthy subjects while cerebrospinal fluid (CSF) volume was significantly increased. Patients with mood-congruent psychosis showed significant reduction in total white matter volume and significant CSF volume increase. Patients with psychosis had significant volume reduction in anterior cingulate and medial prefrontal cortices. Relative to mood-congruent psychotic features, mood-incongruent psychotic features were associated with volume reduction in the left middle temporal gyrus, right inferior parietal gyrus, right fusiform gyrus, left middle orbitofrontal gyrus, and cerebellum.
CONCLUSIONS: While preliminary, our findings suggest that the presence and type of psychosis in first-episode mania may be phenotypic markers of underlying biological variants of bipolar disorder.
PMID: 27762161 [PubMed - as supplied by publisher]
Factors associated with use of psychiatric intensive care and seclusion in adult inpatient mental health services.
Epidemiol Psychiatr Sci. 2016 Oct 20;:1-11
Authors: Cullen AE, Bowers L, Khondoker M, Pettit S, Achilla E, Koeser L, Moylan L, Baker J, Quirk A, Sethi F, Stewart D, McCrone P, Tulloch AD
AIMS: Within acute psychiatric inpatient services, patients exhibiting severely disturbed behaviour can be transferred to a psychiatric intensive care unit (PICU) and/or secluded in order to manage the risks posed to the patient and others. However, whether specific patient groups are more likely to be subjected to these coercive measures is unclear. Using robust methodological and statistical techniques, we aimed to determine the demographic, clinical and behavioural predictors of both PICU and seclusion.
METHODS: Data were extracted from an anonymised database comprising the electronic medical records of patients within a large South London mental health trust. Two cohorts were derived, (1) a PICU cohort comprising all patients transferred from general adult acute wards to a non-forensic PICU ward between April 2008 and April 2013 (N = 986) and a randomly selected group of patients admitted to general adult wards within this period who were not transferred to PICU (N = 994), and (2) a seclusion cohort comprising all seclusion episodes occurring in non-forensic PICU wards within the study period (N = 990) and a randomly selected group of patients treated in these wards who were not secluded (N = 1032). Demographic and clinical factors (age, sex, ethnicity, diagnosis, admission status and time since admission) and behavioural precursors (potentially relevant behaviours occurring in the 3 days preceding PICU transfer/seclusion or random sample date) were extracted from electronic medical records. Mixed effects, multivariable logistic regression analyses were performed with all variables included as predictors.
RESULTS: PICU cases were significantly more likely to be younger in age, have a diagnosis of bipolar disorder and to be held on a formal section compared with patients who were not transferred to PICU; female sex and longer time since admission were associated with lower odds of transfer. With regard to behavioural precursors, the strongest predictors of PICU transfer were incidents of physical aggression towards others or objects and absconding or attempts to abscond. Secluded patients were also more likely to be younger and legally detained relative to non-secluded patients; however, female sex increased the odds of seclusion. Likelihood of seclusion also decreased with time since admission. Seclusion was significantly associated with a range of behavioural precursors with the strongest associations observed for incidents involving restraint or shouting.
CONCLUSIONS: Whilst recent behaviour is an important determinant, patient age, sex, admission status and time since admission also contribute to risk of PICU transfer and seclusion. Alternative, less coercive strategies must meet the needs of patients with these characteristics.
PMID: 27763251 [PubMed - as supplied by publisher]
Memory performance predicts recurrence of mania in bipolar disorder following psychotherapy: A preliminary study.
J Psychiatr Res. 2016 Oct 11;84:207-213
Authors: Bauer IE, Hautzinger M, Meyer TD
OBJECTIVE: Cognitive complaints are common features of bipolar disorder (BD). Not much is, however, known about the potential moderator effects of these factors on the outcome of talking therapies. The goal of our study was to explore whether learning and memory abilities predict risk of recurrence of mood episodes or interact with a psychological intervention.
METHOD: We analyzed data collected as part of a clinical trial evaluating relapse rates following Cognitive Behavioral Therapy (CBT) and Supportive Therapy (ST) (Meyer and Hautzinger, 2012). We included cognitive (Auditive Verbal Learning Test, general intelligence - Leistungsprüfsystem) and clinical measures from 76 euthymic patients with BD randomly assigned to either 9 months of CBT or ST and followed up for 2 years.
RESULTS: Survival analyses including treatment condition, AVLT measures, and general intelligence revealed that recurrence of mania was predicted by verbal free recall. The significant interaction between therapy condition and free recall indicated that while in CBT recurrence of mania was unrelated to free recall performance, in ST patients with a better free recall were more likely to remain euthymic, and those with a poorer free recall were less likely to remain mania-free.
CONCLUSIONS: These findings constitute first evidence that, when considering treatment outcome in BD, differences in verbal free recall might interact with the kind of psychotherapy provided. More research is needed to determine what other areas of cognitive functioning are related to outcome in psychological interventions.
PMID: 27764692 [PubMed - as supplied by publisher]
Factors associated with relapse after a response to electroconvulsive therapy in unipolar versus bipolar depression.
J Affect Disord. 2016 Oct 11;208:113-119
Authors: Itagaki K, Takebayashi M, Shibasaki C, Kajitani N, Abe H, Okada-Tsuchioka M, Yamawaki S
BACKGROUND: While electroconvulsive therapy (ECT) treatment for depression is highly effective, the high rate of relapse is a critical problem. The current study investigated factors associated with the risk of relapse in mood disorders in patients in which ECT was initially effective.
METHOD: The records of 100 patients with mood disorders (61 unipolar depression, 39 bipolar depression) who received and responded to an acute ECT course were retrospectively reviewed. Associations between clinical variables and relapse after responding to acute ECT were analyzed. The Ethics Committee of NHO Kure Medical Center approved the study protocol.
RESULTS: After one year, the percentage of relapse-free patients was 48.7%. There was no significant difference between patients with either unipolar or bipolar depression who were relapse-free (unipolar: 51.1%, bipolar: 45.5%, P=0.603). Valproate maintenance pharmacotherapy in unipolar depression patients was associated with a lower risk of relapse compared to patients without valproate treatment (multivariate analysis, hazard ratio: 0.091; P=0.022). Lithium treatment, reportedly effective for unipolar depression following a course of ECT, tended to lower the risk of relapse (hazard ratio: 0.378; P=0.060). For bipolar depression, no treatment significantly reduced the risk of relapse.
LIMITATIONS: The current findings were retrospective and based on a limited sample size.
CONCLUSIONS: The relapse-free rate was similar between unipolar and bipolar depression. Valproate could have potential for unipolar depression patients as a maintenance therapeutic in preventing relapse after ECT.
PMID: 27764738 [PubMed - as supplied by publisher]
CBHSQ Data Review
The National Survey on Drug Use and Health (NSDUH), conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA), is one of the primary sources of data for population-based estimates of mental health indicators in the United States. From 2008 to 2012, SAMHSA conducted the Mental Health Surveillance Study (MHSS) clinical study, in which clinicians administered semistructured diagnostic interviews to a subsample of NSDUH adult respondents to assess the presence of selected mental disorders. The MHSS clinical study was primarily designed for use in the development of a statistical model to apply to the full NSDUH sample that would generate estimated percentages of serious mental illness among civilian, noninstitutionalized adults aged 18 years or older at national and state levels. In addition, data from the MHSS clinical study also can be used to estimate the percentage and number of adults affected by each specific mental disorder. This report provides the first release of national estimates of specific mental disorders based on these clinical interviews, both for all civilian, noninstitutionalized adults as well as by sociodemographic characteristics such as age and gender. Specific disorders covered include mood disorders (major depressive disorder, bipolar I disorder, and/or dysthymic disorder), anxiety disorders (posttraumatic stress disorder, panic disorder with and without agoraphobia, agoraphobia without history of panic disorder, social phobia, specific phobia, obsessive compulsive disorder, and/or generalized anxiety disorder), eating disorders (anorexia nervosa and/or bulimia nervosa), substance use disorders (alcohol abuse, alcohol dependence, illicit drug abuse, and/or illicit drug dependence), intermittent explosive disorder, adjustment disorder, as well as psychotic symptoms (delusions and/or hallucinations).
Quetiapine-induced hyperglycemic crisis and severe hyperlipidemia: a case report and review of the literature.
Psychosomatics. 2014 Nov-Dec;55(6):686-91
Authors: Wu CY, Mitchell SR, Seyfried LS
PMID: 25497507 [PubMed - indexed for MEDLINE]
Historical perspectives: a snapshot of women admitted to psychiatric facilities with psychosis or mania after childbirth in the late Victorian and inter-war periods.
J Adv Nurs. 2015 Dec;71(12):2799-810
Authors: Jefferies D, Duff M, Burns E, Nicholls D
AIM: This study analysed historical healthcare records to investigate how women diagnosed with mania or psychosis and admitted to two mental health facilities in Australia following childbirth, were described in the late Victorian (1885-1895) and inter-war period (1925-1935).
BACKGROUND: Although historians have examined the history of mental health systems in Australia, there is no published scholarship that considers the healthcare records of these women. This was a unique opportunity to explore these documents.
DESIGN: An historical study examining healthcare records. The data collection occurred in 2012.
METHODS: Women admitted to mental health facilities with a diagnosis of psychosis or mania were identified in the admission registers found in the State Record Office of New South Wales and, if available, their healthcare record was transcribed verbatim. The records were imported into NVivo 10 for content analysis to determine the range and scope of information. A further textual analysis was conducted to see if the woman's diagnosis was congruent with the outcome of her admission.
RESULTS/FINDINGS: 155 cases were identified across the two periods. Although, demographic data and the description of the women on admission were remarkably similar, 17% of women were physically, rather than mentally, ill and died soon after admission. The findings demonstrate the importance of current practices such as taking a comprehensive healthcare assessment and the use of antibiotics and sanitary measures during labour and in the postnatal period.
CONCLUSION: Historical investigations of healthcare records provide legitimacy for current healthcare practices.
PMID: 26315153 [PubMed - indexed for MEDLINE]
Gut dysbiosis in mania: A viable therapeutic target?
Aust N Z J Psychiatry. 2016 Feb;50(2):185
Authors: Jacka FN, Berk M
PMID: 26497701 [PubMed - indexed for MEDLINE]
Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression.
J Psychiatr Res. 2016 Sep 30;84:113-118
Authors: Park M, Newman LE, Gold PW, Luckenbaugh DA, Yuan P, Machado-Vieira R, Zarate CA
Several pro-inflammatory cytokines have been implicated in depression and in antidepressant response. This exploratory analysis assessed: 1) the extent to which baseline cytokine levels predicted positive antidepressant response to ketamine; 2) whether ketamine responders experienced acute changes in cytokine levels not observed in non-responders; and 3) whether ketamine lowered levels of pro-inflammatory cytokines, analogous to the impact of other antidepressants. Data from double-blind, placebo-controlled studies of patients with major depressive disorder (MDD) or bipolar disorder (BD) who received a single infusion of sub-anesthetic dose ketamine were used (N = 80). Plasma levels of the eight cytokines were measured at baseline and at 230 min, 1 day, and 3 days post-ketamine. A significant positive correlation was observed between sTNFR1 and severity of depression at baseline. Cytokine changes did not correlate with changes in mood nor predict mood changes associated with ketamine administration. Ketamine significantly increased IL-6 levels and significantly decreased sTNFR1 levels. IL-6 and TNF-? levels were also significantly higher-and sTNFR1 levels were significantly lower-in BD compared to MDD subjects. The functional significance of this difference is unknown. Changes in cytokine levels post-ketamine were not related to antidepressant response, suggesting they are not a primary mechanism involved in ketamine's acute antidepressant effects. Taken together, the results suggest that further study of cytokine levels is warranted to assess their potential role as a surrogate outcome in the rapid antidepressant response paradigm.
PMID: 27718369 [PubMed - as supplied by publisher]
DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/?-catenin signaling.
Mol Psychiatry. 2016 Oct 18;:
Authors: Martin PM, Stanley RE, Ross AP, Freitas AE, Moyer CE, Brumback AC, Iafrati J, Stapornwongkul KS, Dominguez S, Kivimäe S, Mulligan KA, Pirooznia M, McCombie WR, Potash JB, Zandi PP, Purcell SM, Sanders SJ, Zuo Y, Sohal VS, Cheyette BN
Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/?-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/?-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/?-catenin pathway.Molecular Psychiatry advance online publication, 18 October 2016; doi:10.1038/mp.2016.184.
PMID: 27752079 [PubMed - as supplied by publisher]
Factors Associated With Antidepressant Dosing in Asia: Findings From the Research on Asian Psychotropic Prescription Study.
J Clin Psychopharmacol. 2016 Oct 5;
Authors: Rajaratnam K, Xiang YT, Tripathi A, Chiu HF, Si TM, Chee KY, Avasthi A, Grover S, Chong MY, Kuga H, Kanba S, He YL, Lee MS, Yang SY, Udomratn P, Kallivayalil RA, Tanra AJ, Maramis M, Shen WW, Sartorius N, Kua EH, Tan CH, Mahendran R, Shinfuku N, Sum MY, Baldessarini RJ, Sim K
In this study, we sought to examine factors associated with dosing of antidepressants (ADs) in Asia. Based on reported data and clinical experience, we hypothesized that doses of ADs would be associated with demographic and clinical factors and would increase over time. This cross-sectional, pharmacoepidemiological study analyzed data collected within the Research Study on Asian Psychotropic Prescription Pattern for Antidepressants from 4164 participants in 10 Asian countries, using univariate and multivariate methods. The AD doses varied by twofold among countries (highest in PR China and RO Korea, lowest in Singapore and Indonesia), and averaged 124 (120-129) mg/d imipramine-equivalents. Average daily doses increased by 12% between 2004 and 2013. Doses were significantly higher among hospitalized patients and ranked by diagnosis: major depression > anxiety disorders > bipolar disorder, but were not associated with private/public or psychiatric/general-medical settings, nor with age, sex, or cotreatment with a mood stabilizer. In multivariate modeling, AD-dose remained significantly associated with major depressive disorder and being hospitalized. Doses of ADs have increased somewhat in Asia and were higher when used for major depression or anxiety disorders than for bipolar depression and for hospitalized psychiatric patients.
PMID: 27753726 [PubMed - as supplied by publisher]
Subjective Versus Objective Weight Gain During Acute Treatment With Second-Generation Antipsychotics in Schizophrenia and Bipolar Disorder.
J Clin Psychopharmacol. 2016 Oct 5;
Authors: Gao K, Fang F, Wang Z, Calabrese JR
OBJECTIVES: To compare objective and subjective weight gain of second-generation antipsychotics in schizophrenia and bipolar disorder.
METHODS: English-language literature published and cited in PubMed (MEDLINE) from January 1966 to December 2015 was searched with the keywords antipsychotic, atypical antipsychotic, or generic/brand name of atypical antipsychotics, and schizophrenia, bipolar disorder, bipolar mania, or bipolar depression, and safety, tolerability, weight gain, and randomized, placebo-controlled clinical trials. The absolute risk increases and the numbers needed to treat to harm (NNH) for ?7% weight gain (objective) and self-report weight gain (subjective) were estimated.
RESULTS: In schizophrenia, the NNH for 7% or greater weight gain ranged from 5 to 62, and the NNH for self-reported weight gain was from 11 to -224. The ratio of self-reported NNH to 7% or greater NNH was from 1.5 to 8.0. In bipolar mania, the NNH for 7% or greater weight gain ranged from 7 to -101 and the NNH for self-reported weight gain was from 13 to 84. The ratio of self-reported NNH to 7% or greater NNH was from 0.9 to 2.5. In bipolar depression, the NNH for 7% or greater weight gain ranged from 5 to 69, and the NNH for self-reported weight gain was from 8 to 17. The ratio of self-reported NNH to 7% or greater NNH was 1.2 to 1.6.
CONCLUSIONS: Subjective reporting underestimated the risk of antipsychotic-related weight gain compared with objectively measured weight change. Self-awareness of antipsychotic-related weight gain was lower in patients with schizophrenia than in patients with bipolar disorder. Measuring weight change during antipsychotic treatment should be a routine practice.
PMID: 27753728 [PubMed - as supplied by publisher]
Long-term safety and tolerability of asenapine: A double-blind, uncontrolled, long-term extension trial in adults with an acute manic or mixed episode associated with bipolar I disorder.
J Affect Disord. 2016 Oct 14;207:384-392
Authors: Ketter TA, Durgam S, Landbloom R, Mackle M, Wu X, Mathews M
BACKGROUND: Asenapine (ASN) is approved in the United States as monotherapy and adjunctive therapy (to lithium or valproate) in adults with bipolar mania, and as monotherapy in pediatric patients with bipolar mania. This is the first long-term study evaluating safety and tolerability of ASN fixed doses in this population.
METHODS: After completing a 3-week, randomized, placebo (PBO)-controlled acute trial, patients could enroll in this 26-week, fixed-dose (5 or 10mg twice daily), double-blind extension study. Select predefined treatment-emergent adverse events (TEAEs) and metabolic parameters were reported.
RESULTS: Overall, 164 patients were treated; 88 completed the study. The incidence of ?1 TEAE was greater for PBO/ASN 5mg (68.3%) versus ASN 5mg/ASN 5mg (54.7%) and ASN 10mg/ASN 10mg (51.0%) with sedation, headache, somnolence, akathisia, and dizziness occurring as the most prevalent TEAEs. Predefined TEAEs were more common for PBO/ASN 5mg (33.3%) versus ASN 5mg/ASN 5mg (15.1%) and ASN 10mg/ASN 10mg (15.7%). Weight gain (?7% increase from baseline to endpoint) was more frequent for ASN 10mg/ASN 10mg (16.3%) versus ASN 5mg/ASN 5mg (13.7%) and PBO/ASN 5mg (8.9%). No clinically significant metabolic changes were observed. The incidence of serious AEs was low and primarily related to underlying bipolar I disorder.
LIMITATIONS: This study lacked a comparator group and was not powered for direct comparisons of ASN regimens. Results may not be applicable to the general bipolar population.
CONCLUSIONS: ASN was generally safe and well tolerated in adults with an acute manic or mixed episode associated with bipolar I disorder.
PMID: 27755982 [PubMed - as supplied by publisher]
Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders.
J Affect Disord. 2016 Oct 11;208:94-100
Authors: Hafeman D, Bebko G, Bertocci MA, Fournier JC, Chase HW, Bonar L, Perlman SB, Travis M, Gill MK, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Arnold LE, Fristad MA, Frazier TW, Youngstrom EA, Findling RL, Phillips ML
OBJECTIVE: Both bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task.
METHODS: We scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs. Our sample consisted of 22 youth with BPSD, 30 youth with ADHD/no BPSD, and 26 HCs. We used generalized psychophysiological interaction (gPPI) to calculate group differences to emerging emotional faces vs. morphing shapes in FxC between bilateral amygdala and ventral prefrontal cortex/anterior cingulate cortex.
RESULTS: FxC between amygdala and left ventrolateral prefrontal cortex (VLPFC) in response to emotions vs. shapes differed by group (p=.05): while BPSD showed positive FxC (emotions>shapes), HC and ADHD showed inverse FxC (emotions<shapes). A group x emotion interaction was found in amygdala-subgenual cingulate FxC (p=.025), explained by differences in FxC in response to negative emotions. While BPSD showed positive FxC, HC showed inverse FxC; ADHD were intermediate. Amygdala-subgenual FxC was also positively associated with depressive symptoms and stimulant medication.
LIMITATIONS: Co-morbidity and relatively small sample size.
CONCLUSIONS: Youth with BPSD showed abnormally positive FxC between amygdala and regions in the ventral prefrontal cortex during emotion processing. In particular, the amygdala-VLPFC finding was specific to BPSD, and not influenced by other diagnoses or medications.
PMID: 27756046 [PubMed - as supplied by publisher]
Evaluation of neuron-glia integrity by in vivo proton magnetic resonance spectroscopy: Implications for psychiatric disorders.
Neurosci Biobehav Rev. 2016 Oct 1;71:563-577
Authors: Xu H, Zhang H, Zhang J, Huang Q, Shen Z, Wu R
Proton magnetic resonance spectroscopy ((1)H-MRS) has been widely applied in human studies. There is now a large literature describing findings of brain MRS studies with mental disorder patients including schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorders. However, the findings are mixed and cannot be reconciled by any of the existing interpretations. Here we proposed the new theory of neuron-glia integrity to explain the findings of brain (1)H-MRS stuies. It proposed the neurochemical correlates of neuron-astrocyte integrity and axon-myelin integrity on the basis of update of neurobiological knowledge about neuron-glia communication and of experimental MRS evidence for impairments in neuron-glia integrity from the authors and the other investigators. Following the neuron-glia integrity theories, this review collected evidence showing that glutamate/glutamine change is a good marker for impaired neuron-astrocyte integrity and that changes in N-acetylaspartate and lipid precursors reflect impaired myelination. Moreover, this new theory enables us to explain the differences between MRS findings in neuropsychiatric and neurodegenerative disorders.
PMID: 27702600 [PubMed - as supplied by publisher]
[Search association between cannabis abuse and bipolar disorder: A study on a sample of patients hospitalized for bipolar disorder].
Encephale. 2016 Oct 10;:
Authors: Kazour F, Awaida C, Souaiby L, Richa S
INTRODUCTION: Cannabis use is very frequent in bipolar disorder and has been found to increase the duration and frequency of manic symptoms while decreasing those of depression. Bipolar patients who use cannabis were shown to have poorer compliance to treatment, more symptoms that are psychotic and a worse prognosis than patients who do not. In this study, we have evaluated the importance of cannabis use among bipolar patients admitted to the Psychiatric Hospital of the Cross, Lebanon (Hôpital Psychiatrique de la Croix [HPC]) as well as the clinical differences between cannabis users and non-users.
METHODS: Over a period of 13 months, we recruited the patients admitted to HPC for bipolar disorder according to the MINI DSM-IV criteria. These patients were screened for substance abuse/dependence and were accordingly divided into 2 groups: cannabis users and cannabis non-users. Both groups were interviewed by a medical student and asked to answer the following questionnaires: the MINI DSM-IV, the Young Mania Rating Scale (YMRS) for evaluating manic episodes, the Montgomery and Åsberg Depression Rating Scale (MADRS) for evaluating depressive episodes, the Scale for the Assessment of Positive Symptoms (SAPS) to assess psychotic symptoms associated to the bipolar disorder, and the Cannabis Abuse Screening Test (CAST) for evaluating the importance of cannabis consumption. The study's exclusion criteria were the following: diagnosis of a confusional state, schizophrenia and other psychotic disorders, dementia, age less than 18 years old or superior to 85 years old, and non-cooperation.
RESULTS: Among the 100 bipolar patients included in the study, 27 (27 %) were cannabis users. Eight of these 27 patients were first admitted to HPC for substance abuse and then included in the study after a bipolar disorder was diagnosed according to the MINI DSM-IV criteria. Cannabis use was found to be more prevalent in young males with a mean age of 20.3 years old at the first contact with the substance. Compared to non-users, cannabis users were found to be younger (33.6 vs. 43.0 years old), more commonly male (77.8 % vs. 49.3 %), and were symptomatic at a younger age (24.6 vs. 30.8 years old). Cannabis users had more hospital admissions in total (6.0 vs. 3.7), and per year (0.73 vs. 0.44) as well as higher socio-economical state. There was a linear relationship between the monthly income per household and cannabis consumption with an OR increasing with the monthly income. Consumers presented more often in a manic state (59.3 %) than in a depressed state (11.1 %). The respective scores of consumers and non-consumers were: YMRS (30.3 vs. 32.1), MADRS (38 vs. 39.5), SAPS (22.7 vs. 23.2). Among cannabis users, 55.6 % and 33.3 % represent the respective percentages of cannabis abuse and dependence. The mean CAST score in these patients was 13.4.
DISCUSSION: Compared to the results in the literature, cannabis use in bipolar disorder was found to be lower in our sample. Cannabis use was also associated with an earlier onset of the bipolar disorder as well as a higher number of hospitalizations per year. The age at the diagnosis of the bipolar disorder was 6.2 years lower among cannabis users. Cannabis users had scores of depression, mania and psychotic symptoms statistically similar to those of the non-consumers.
PMID: 27745717 [PubMed - as supplied by publisher]
[The Severe Chronic Irritability Concept: A clinical dimension to consider in child and adolescent].
Encephale. 2016 Oct 10;:
Authors: Fourneret P, Desombre H
INTRODUCTION: For a decade, the concept of irritability has known a renewed interest in infant and child psychopathology. Indeed, longitudinal follow-up studies clearly highlighted their predictive value - in the short, medium and long terms - of a broad field of behavioral disorders and emotion dysregulation. This dimensional and transnosographic approach of irritability, coupled with the latest neuroscience data, points out that irritability could be the equivalent of a psychopathological marker, covering both a neurobiological, cognitive and emotional component. It is a major challenge today to better understand the developmental sequence of severe chronic irritability and its predictive influence on the etiology of mental disorders from childhood to adulthood.
METHOD: We briefly review here the latest current data on this topic.
RESULTS: The important point is that chronic and non-episodic irritability in children, associated with strong emotional sensitivity to negative events and frequent access of anger, could have a predictive value for progression to anxiety disorder or severe mood disorder but not to bipolar disorder as it was believed until now. The risk of developing a bipolar disorder would be more frequently correlated with the notion of transient and episodic irritability in a context of previous family history of bipolar disorder.
CONCLUSION: Further studies are expected to narrow the discriminative validity of this notion of severe irritability and confirm or not its relevance as a major clinical criterion of Severe Mood Disorders in children and adolescents introduced in the last version of DSM (DSM-5).
PMID: 27745722 [PubMed - as supplied by publisher]
Personalized Medicine: Prediction of Disease Vulnerability in Mood Disorders.
Neurosci Lett. 2016 Oct 13;:
Authors: Prendes-Alvarez S, Nemeroff CB
Personalized or precision medicine is a medical discipline that proposes tailoring health care to each individual by integrating data from their genetic makeup, epigenetic modifications, other biomarkers, clinical symptoms and environmental exposures. Currently, patients typically present for treatment of mood disorders relatively late in the disease course and this is of great concern both because delay in attaining remission reduces the success of subsequent treatment and depressive episodes have negative cumulative effects on the brain and body. In this article we will discuss progress in personalized medicine for predicting disease vulnerability for major depressive disorder and bipolar disorder. We will review non-biological risk factors, genetic factors, epigenetic factors, as well as the roll of neuroimaging and electroencephalograms. Putting together this information with poise psychiatrists to make biological, system-based evaluations for their patients.
PMID: 27746310 [PubMed - as supplied by publisher]
Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series.
Drug Saf Case Rep. 2016 Dec;3(1):1
Authors: Cham S, Koslik HJ, Golomb BA
Psychiatric adverse drug reactions (ADRs) have been reported with statin use, but the literature regarding statin-associated mood/behavioral changes remains limited. We sought to elicit information germane to natural history and characteristics of central nervous system/behavioral changes in apparent connection with statin and/or cholesterol-lowering drug use, and delineate mechanisms that may bear on an association. Participants (and/or proxies) self-referred with behavioral and/or mood changes in apparent association with statins completed a survey eliciting cholesterol-lowering drug history, character and impact of behavioral/mood effect, time-course of onset and recovery in relation to drug use/modification, co-occurrence of recognized statin-associated ADRs, and factors relevant to ADR causality determination. Naranjo presumptive ADR causality criteria were assessed. Participants (n = 12) reported mood/behavior change that commenced following statin initiation and persisted or progressed with continued use. Reported problems included violent ideation, irritability, depression, and suicide. Problems resolved with drug discontinuation and recurred with rechallenge where attempted. Eight met presumptive criteria for "probable" or "definite" causality; others had additional factors not considered in Naranjo criteria that bear on casual likelihood. (1) Simvastatin 80 mg was followed in 5 days by irritability/depression culminating in suicide in a man in his 40s (Naranjo criteria: possible causality). (2) Simvastatin 10 mg was followed within 2 weeks by depression in a woman in her 50s (probable causality). (3) Atorvastatin 20 mg was followed in ~1 month by depression and irritability/aggression in a male in his 50s (probable causality). (4) Atorvastatin 10 mg was followed in several months by aggression/irritability and depression culminating in suicide in a man in his 40s (possible causality). (5) Fenofibrate + rosuvastatin (unknown dose), later combined with atorvastatin were followed in 1 month by aggression/irritability in a male in his 30s (probable causality). (6) Lovastatin (unknown dose and time-course to reaction) was followed by depression, dyscontrol of bipolar disorder, and suicide attempts in a male in his 40s (possible causality). (7) Atorvastatin 20 mg was followed within 2 weeks by cognitive compromise, and nightmares, depression, and anxiety culminating in suicide in a man in his teens (definite causality). (8) Simvastatin 10 mg was followed (time-course not recalled) by depression, aggression/irritability culminating in suicide in a man in his 60s (possible causality). (9) Simvastatin 20 mg then atorvastatin 10 mg were followed (time-course not provided) by irritability/aggression in a man in his 60s (definite causality). (10) Atorvastatin 10 then 20 then 40 mg were followed shortly after the dose increase by violent ideation and anxiety in a man in his 30s (probable causality). (11) Atorvastatin 20 mg and then simvastatin 20 mg were followed in 2 weeks by aggression/irritability in a man in his 50s (definite causality). (12) Lovastatin, rosuvastatin, atorvastatin, and simvastatin at varying doses were followed as quickly as 1 day by aggression, irritability, and violent ideation in a man in his 40s (definite causality). Most had risk factors for statin ADRs, and co-occurrence of other, recognized statin ADRs. ADRs had implications for marriages, careers, and safety of self and others. These observations support the potential for adverse mood and behavioral change in some individuals with statin use, extend the limited literature on such effects, and provide impetus for further investigation into these presumptive ADRs. Potential mechanisms are reviewed, including hypothesized mechanisms related to oxidative stress and bioenergetics.
PMID: 27747681 [PubMed - in process]