Sleep Quality After Quetiapine Augmentation in Patients With Treatment-Resistant Depression and Personality Disorders.

PURPOSE/BACKGROUND: Quetiapine is a first-line augmenting agent for treatment-resistant depression (TRD) and is used off-label in insomnia. Quetiapine and its active metabolite norquetiapine act mostly on 5-HT2A, 5-HT2C, H1, and D2 as antagonists and on 5-HT1A as partial agonists. Patients with TRD often have comorbid personality disorder (PD), and evidence suggests an association between sleep disturbance and recovery among patients with PD. Here, we aimed to evaluate the effects of quetiapine on sleep in TRD patients with and without PD (PD+/PD-). METHODS/PROCEDURES: We reviewed health records of 38 patients with TRD (20 TRD/PD+) who had been treated with a pharmacotherapy regimen including quetiapine. Clinical outcomes were determined by comparing changes in sleep items of the Hamilton Depression Rating Scale at the beginning (T0) and after 3 months of an unchanged treatment (T3). FINDINGS/RESULTS: Patients with TRD/PD+ and TRD/PD- taking quetiapine showed significant improvement in sleep items from T0 to T3 (P < 0.001, ηp2 ≥ 0.19). There was a significant personality × time interaction for sleep-maintenance insomnia (P = 0.006, ηp2 = 0.23), with TRD/PD+ showing a greater improvement at T3 compared with TRD/PD- (P = 0.01). While exploring other sleep items, no personality × time interaction was found. In the TRD/PD- group, improvement in sleep items was associated with an overall improvement in depressive symptoms (r = 0.55, P = 0.02). IMPLICATIONS/CONCLUSIONS: Quetiapine induced greater improvements in sleep-maintenance insomnia among TRD/PD+ patients than TRD/PD-. These findings suggest quetiapine could have a therapeutic role for insomnia in PD underscoring a distinct underlying neurobiological mechanism of sleep disturbance in people living with PD.

Examining the Therapeutic Effect of Ceremonial Ayahuasca on Narcissistic Personality and Antagonistic Externalizing in Adults.

Changes in narcissistic traits (e.g., entitlement) following the ceremonial use of ayahuasca were examined across three timepoints (baseline, postretreat, 3-month follow-up) in a sample of 314 adults using self- and informant-report (N = 110) measures. Following ceremonial use of ayahuasca, self-reported changes in narcissism were observed (i.e., decreases in Narcissistic Personality Inventory [NPI] Entitlement-Exploitativeness, increases in NPI Leadership Authority, decreases in a proxy measure of narcissistic personality disorder [NPD]). However, effect size changes were small, results were somewhat mixed across convergent measures, and no significant changes were observed by informants. The present study provides modest and qualified support for adaptive change in narcissistic antagonism up to 3 months following ceremony experiences, suggesting some potential for treatment efficacy. However, meaningful changes in narcissism were not observed. More research would be needed to adequately evaluate the relevance of psychedelic-assisted therapy for narcissistic traits, particularly studies examining individuals with higher antagonism and involving antagonism-focused therapeutic approaches.

Antidepressant and anti-suicidal effects of ketamine in treatment-resistant depression associated with psychiatric and personality comorbidities: A double-blind randomized trial.

OBJECTIVE: To evaluate the effects of ketamine treatment on depression and suicidal ideation in treatment resistant depression (TRD) and to determine whether they are influenced by other psychiatric and personality comorbidities. METHODS: A randomized double-blind parallel-arm controlled study on 36 patients with TRD. Patients were divided into two treatment groups: ketamine (K group) and placebo (P group). Patients in the K and P groups received one infusion of medicine per week for two weeks. All participants were assessed using the Structured Interview for the Five-Factor Personality Model (SIFFM), Hamilton Depression Rating Scale (HDRS), Suicide Probability Scale (SPS), and Symptom Checklist 90 (SCL 90). RESULTS: After treatment, there was a significant decrease in the total HDRS and SPS scores in the K group compared to the P group, but the magnitude of response was not influenced by the presence of other psychiatric symptoms. Regression model, only receive ketamine treatment was significant factor for improve suicide and depression scores. LIMITATIONS: lack of data on other outcomes that are important to patients (e.g., quality of life, cognition) and need for a larger sample size. CONCLUSIONS: Ketamine infusions in TRD reduce suicidal ideation and depression despite the presence other psychiatric and personality disorders.

Ayahuasca's therapeutic potential: What we know - and what not.

The therapeutic potential of the psychedelic brew ayahuasca has been investigated in preclinical and clinical studies. Currently, the most consistent evidence refers to depression. However, various studies suggest that ayahuasca may comprise therapeutic benefits in other health conditions. This narrative review provides a comprehensive, up-to-date overview of ayahuasca's therapeutic effects in diverse clinical conditions in human (clinical, cross-sectional, observational, and qualitative) and preclinical (animal and in vitro) studies. In addition to summarizing and discussing the most commonly studied conditions, such as depression, anxiety, and substance use disorders (SUD), we also examine less frequently studied psychiatric, neurological, and physical conditions. Moreover, we discuss evidence from epidemiological studies on the impact of regular, long-term ayahuasca use on health and psychosocial outcomes. Overall, evidence for depression and SUD is more consistent, with numerous and diverse studies. However, a growing body of evidence suggests that other conditions equally relevant to public health might be promising targets for ayahuasca's therapeutic effects. This includes preliminary studies indicating potential for grief, eating disorders, posttraumatic stress disorder, personality disorders, Parkinson's and Alzheimer's disease, and severe physical illnesses (e.g., cancer, chronic conditions). Moreover, preliminary evidence in long-term ayahuasca users does not suggest detrimental effects but possible benefits for individual and collective health. In light of the emerging evidence of psychedelic drugs as therapeutic agents, it is essential to further investigate in rigorous designs the therapeutic potential of ayahuasca in conditions other than depression.

Association between quetiapine use and self-harm outcomes among people with recorded personality disorder in UK primary care: A self-controlled case series analysis.

BACKGROUND: Quetiapine is frequently prescribed to people with personality disorder diagnoses, but this is not supported by evidence or treatment guidelines. AIMS: To examine associations between periods of quetiapine prescribing and self-harm events in people with personality disorder. METHOD: Self-controlled case series using linked primary care and hospital records covering the period 2007-2017. We calculated incidence rates and incidence rate ratios (IRRs) for self-harm events during periods when people were prescribed (exposed to) quetiapine, as well as periods when they were unexposed or pre-exposed to quetiapine. RESULTS: We analysed data from 1,082 individuals with established personality disorder diagnoses, all of whom had at least one period of quetiapine prescribing and at least one self-harm episode. Their baseline rate of self-harm (greater than 12 months before quetiapine treatment) was 0.52 episodes per year. Self-harm rates were elevated compared to the baseline rate in the month after quetiapine treatment was commenced (IRR 1.85; 95% confidence interval (CI) 1.46-2.34) and remained raised throughout the year after quetiapine treatment was started. However, self-harm rates were highest in the month prior to quetiapine initiation (IRR 3.59; 95% CI 2.83-4.55) and were elevated from 4 months before quetiapine initiation, compared to baseline. CONCLUSION: Self-harm rates were elevated throughout the first year of quetiapine prescribing, compared to the baseline rate. However, rates of self-harm reduced in the month after patients commenced quetiapine, compared to the month before quetiapine was initiated. Self-harm rates gradually dropped over a year of quetiapine treatment. Quetiapine may acutely reduce self-harm. Longer-term use and any potential benefits need to be balanced with the risk of adverse events.

Personality dysfunction in opiate addicts on opioid substitution treatment and the risk of HCV infection.

Background: Impulsivity, affective instability, and neglect of oneself and other people's safety as symptoms of personality dysfunction are associated with risky behaviors regarding the transmission of infectious diseases either sexually or by intravenous drug abuse. Objective: The aim of this study was to analyze the association between hepatitis C virus (HCV) infection and personality dysfunction in opiate addicts on opioid substitution treatment. Methods: This was a cross-sectional, observational investigation of patients over 18 years of age who were actively participating in opioid substitution treatment at five centers in Bosnia and Herzegovina. The occurrence of HCV infection was the primary study outcome, and personality functioning, the main independent variable, was assessed using the Severity Indices of Personality Problems (SIPP-118) questionnaire. The association between scores of personality functioning domains items and HCV infection status was determined by binary logistic regression analysis. Results: Patients on opioid substitution therapy with HCV infection more frequently had personality disorders (OR 2.168, 95% CI 1.161-4.05) and were treated longer than patients without HCV infection (OR 1.076, 95% CI 1.015-1.14). HCV infection was associated with lower self-respect (OR 0.946, 95% CI 0.906-0.988), decreased capacity to have enduring relationships with other people (OR 0.878, 95% CI 0.797-0.966), and lower capability to cooperate with others (OR 0.933, 95%CI 0.888-0.98). On the other hand, except for self-respect, other elements of the Identity Integration domain (enjoyment, purposefulness, stable self-image, and self-reflexive functioning), when more functional, increased the risk of HCV infection. Conclusions: Our study demonstrates that opiate addicts on opioid substitution treatment have a higher risk of HCV infection if their personality is dysfunctional, especially in the aspects of self-respect, enduring relationships, and cooperativity. The risk is even higher in addicts who have an established diagnosis of any kind of personality disorder.

Commentary: Bringing together lived experience, clinical and research expertise - a commentary on the May 2022 debate (should CAMH professionals be diagnosing personality disorder in adolescence?).

BACKGROUND: There is a wealth of evidence to suggest that the Borderline Personality Disorder (BPD, or similar Emotionally Unstable Personality Disorder, EUPD) construct is harmful. We provide a commentary on the ideas expressed in the May Debate issue, highlighting both concerns and alternatives. METHOD: We bring together lived experience, clinical and research expertise. This commentary was written collaboratively drawing on all these sources of evidence. RESULTS: We outline evidence that the BPD construct is invalid, harmful, not necessary for effective treatment and a potential block to the development and evaluation of alternatives. CONCLUSIONS: We ask readers to consider these concerns, perspectives and ideas.

Prescribing of antipsychotics among people with recorded personality disorder in primary care: a retrospective nationwide cohort study using The Health Improvement Network primary care database.

OBJECTIVES: To investigate the extent of antipsychotic prescribing to people with recorded personality disorder (PD) in UK primary care and factors associated with such prescribing. DESIGN: Retrospective cohort study. SETTING: General practices contributing to The Health Improvement Network UK-wide primary care database, 1 January 2000-31 December 2016. PARTICIPANTS: 46 210 people registered with participating general practices who had a record of PD in their general practice notes. 1358 (2.9%) people with missing deprivation information were excluded from regression analyses; no other missing data. MAIN OUTCOME MEASURES: Prescriptions for antipsychotics in general practice records and length of time in receipt of antipsychotic prescriptions. RESULTS: Of 46 210 people with recorded PD, 15 562 (34%) were ever prescribed antipsychotics. Among the subgroup of 36 875 people with recorded PD, but no recorded severe mental illness (SMI), 9208 (25%) were prescribed antipsychotics; prescribing was lower in less deprived areas (adjusted rate ratio (aRR) comparing least to most deprived quintile: 0.56, 95% CI 0.48 to 0.66, p<0.001), was higher in females (aRR:1.25, 95% CI 1.16 to 1.34, p<0.001) and with a history of adverse childhood experiences (aRR:1.44, 95% CI 1.28 to 1.56, p<0.001). Median time prescribed antipsychotics was 605 days (IQR 197-1639 days). Prescribing frequency has increased over time. CONCLUSIONS: Contrary to current UK guidelines, antipsychotics are frequently and increasingly prescribed for extended periods to people with recorded PD, but with no history of SMI. An urgent review of clinical practice is warranted, including the effectiveness of such prescribing and the need to monitor for adverse effects, including metabolic complications.

Differences in antipsychotic treatment between depressive patients with and without a suicide attempt.

BACKGROUND: Depressed suicide attempters are, according to some earlier studies, treated more often with antipsychotics than depressive non-suicide attempters. Cluster B personality disorders, especially borderline personality disorder, are associated with a high suicide risk, and antipsychotics are commonly used for the reduction of symptoms. However, no previous study has taken comorbid personality disorders into account when assessing the use of antipsychotics in patients with unipolar depression. Therefore, the aim of this study was to investigate the clinical selection of pharmacotherapy in unipolar depression with and without a previous suicide attempt, taking into account potential confounders such as cluster B personality disorders. METHODS: The study sample consisted of 247 patients with unipolar depression. The study was approved by the Regional Ethical Review Board in Lund, Sweden. Study participants were recruited from 4 different secondary psychiatric care clinics in Sweden and were diagnosed according to the DSM-IV-TR with the MINI and SCID II. Previous and ongoing psychiatric treatments were investigated in detail and medical records were assessed. RESULTS: Thirty percent of the patients had made previous suicide attempts. Depressed suicide attempters underwent both lifetime treatment with antipsychotics and an ongoing antipsychotic treatment significantly more often than non-attempters. Significances remained after a regression analysis, adjusting for cluster B personality disorders, symptom severity, age at the onset of depression, and lifetime psychotic symptoms. CONCLUSIONS: This is the first study to consider the effect of comorbidity with cluster B personality disorders when comparing treatment of depressive suicide and non-suicide attempters. Our findings suggest that suicide attempters are more frequently treated with antipsychotics compared to non-suicide attempters, regardless of cluster B personality disorder comorbidity. These findings are important for clinicians to consider and would also be relevant to future studies evaluating reduction of suicide risk with antipsychotics in patients with psychiatric comorbidity and a history of attempted suicide.

Efficacy of Polyunsaturated Fatty Acids (PUFAs) on Impulsive Behaviours and Aggressiveness in Psychiatric Disorders.

It is the focus of increasing interest to investigate the effects of long-chain n-3 and long-chain n-6 polyunsaturated fatty acids (LC n-3 PUFAs; LC n-6 PUFAs) on psychiatric symptoms in a transdiagnostic perspective. There is some evidence that low levels of LC n-3 PUFAs and a higher ratio of LC n-6 to LC n-3 PUFAs in plasma and blood cells are associated with aggressive and impulsive behaviours. Therefore, implementation of LC n-3 PUFAs may produce positive effects on hostility, aggression, and impulsivity in both psychiatric and non-psychiatric samples across different stages of life. A possible mechanism of action of LC n-3 PUFAs in conditions characterized by a high level of impulsivity and aggression is due to the effect of these compounds on the serotonin system and membrane stability. Studies that evaluated the effects of LC n-3 PUFAs on impulsivity and aggressiveness indicated that addition of rather low doses of these agents to antipsychotic treatment might reduce agitation and violent behaviours in psychosis, attention deficit hyperactivity disorder, personality disorders, and impulsive control and conduct disorders. The present review is aimed at examining and discussing available data from recent trials on this topic.

Clozapine for Treatment-Refractory Aggressive Behavior.

Emergency psychiatry has the main role of resolving suicidal behavior and aggression. These severe psychiatric symptoms can be found in many psychiatric disorders such as schizophrenia, bipolar disorder, major depression, personality disorders, cognitive disorders, intellectual disability and substance abuse. Although indications for the use of antipsychotics are limited to a specific group of diseases, they are frequently used as rescue medication in high-risk or nonresponsive cases. Clozapine, the gold standard for TRS (treatment resistant schizophrenia) is effective in controlling aggression. The aim of the research was to identify the use of clozapine for treatment-refractory aggressive behavior in psychiatric emergency. A retrospective study based on the paper files of patients admitted between 2010 and 2019 in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania. Were included all the patients admitted as a psychiatric emergency and treated with clozapine for aggressive behavior. The hospital is an academic institution with 150 beds for acute patients, serving an area of over 600,000 inhabitants. It is the main public institution where patients with psychiatric emergencies are hospitalized. Off 19,000 patients admitted during the study period, 504 patients (2,4%) with a diagnosis other than schizophrenia or schizoaffective disorder received clozapine for aggressiveness (89.5%). The first four diagnoses identified were bipolar disorder (n = 172), intellectual disability (n = 128), cognitive impairment (n = 112), and personality disorder (n = 92). Other disorders identified but with a smaller number of cases were major depressive disorder (n = 3), adjustment disorders (n = 2), delusional disorder (n = 2), obsessive compulsive disorder (n = 2) and postpartum psychosis (n = 1). Clozapine was used as 3rd or 4th choice. The dose was greater for manic patients (350.29 ± 98.01 mg/day) compared with all the other diagnoses. Clozapine was effective and safe in cases of patients with treatment-refractory aggressive behavior.

Systematic review and meta-analysis of the role of personality disorder in randomised controlled trials of pharmacological interventions for adults with mood disorders.

BACKGROUND: Personality disorder (PD) may affect the efficacy of pharmacological interventions for mood disorders, but the extent to which this occurs is uncertain. We aimed to examine the available published evidence concerning the role of PD in pharmacological treatment outcomes of randomised controlled trials (RCTs) for adults with mood disorders (i.e. depressive and bipolar spectrum disorders). METHODS: A systematic search of Cochrane Central Register of Controlled Clinical Trials, PubMed, EMBASE, PsycINFO, CINAHL Complete, and Google Scholar databases was undertaken to identify studies of interest. Data were independently extracted by two reviewers. The Cochrane Risk of Bias tool was used to assess methodological quality and risk of bias. A random effects model was utilised and statistical heterogeneity was assessed using the I2 statistic. This systematic review was registered with PROSPERO (CRD42018089279) and the protocol is published. RESULTS: The search yielded 11,640 studies. Subsequent to removing duplicates, 9657 studies were screened at title and abstract stage and 1456 were assessed at full-text stage. Eighteen studies met criteria for inclusion in this review. Meta-analysis did not reveal a significant difference between groups for treatment outcome (standardised mean difference 0.22 [-0.09, 0.54]; I2: 69%, p=0.17) and remission (risk ratio 0.84 [0.64, 1.11]; I2: 51%, p=0.22). LIMITATIONS: This review was limited by lack of studies on bipolar disorder. CONCLUSION: PD comorbidity does not appear to affect treatment efficacy of pharmacological interventions for adults with mood disorders.

Prescribing in personality disorder: patients' perspectives on their encounters with GPs and psychiatrists.

OBJECTIVE: The purpose of this study was to explore the views of patients with personality disorder on their experiences of prescribing practices by general practitioners (GPs) and psychiatrists, and their expectations of primary and secondary mental health services. DESIGN: This was a qualitative study involving two focus groups. Discussion in the focus groups was recorded, transcribed verbatim and then analysed by a thematic analysis process to generate the key themes. SETTING: The study took place at a specialist outpatient personality disorder service in the UK. PARTICIPANTS: A total of seven participants took part in the study. They were purposively sampled from an NHS specialist outpatient personality disorder service. All participants had a primary diagnosis of emotionally unstable personality disorder and their age ranged from 20 to 52 years. RESULTS: Five key themes emerged. Participants felt that medication has a powerful impact on their mind and body but expressed confusion and uncertainty on how it is affecting them. Participants had a need for a good relationship with their doctors (GPs or psychiatrists). They described a feeling of being dismissed and not believed, expressing a desire to confront the 'powerful' position of their doctors by showing anger. The nature of the doctor-patient relationship was seen to moderate positively or negatively the experience of doctors' prescribing. Finally, there were key expectations of the primary-secondary care interface, including continuity of care, diagnostic clarity and a desire for different healthcare professionals to communicate with one another. CONCLUSION: The doctor-patient relationship is an important medium for providing validation and seeking negotiation of therapeutic treatment strategies in patients with personality disorder. Given that personality disorder is associated with high rates of physical and mental health comorbidity, it is therefore vital for clinical guidelines and training packages to take more account of the relational aspects of prescribing in consultations for this patient group with a view to improve outcomes.

Psychotropic medication use among personality disordered young adults. A follow-up study among former adolescent psychiatric inpatients.

OBJECTIVE: To analyze the use of prescribed psychotropic medication in subjects with personality disorder (PD) diagnosed in early adulthood. METHODS: The study population consisted of former adolescent psychiatric inpatients (N=508). 63 had a diagnosis of PD, including with borderline PD (BPD) (N=38) and other PD (OPD) (N=25). DSM IV-based psychiatric diagnoses in adolescence were based on the Schedule for Affective Disorder and Schizophrenia for School-Age Children Present and Lifetime (K-SADS-PL). The information on in-or outpatient hospital treatments until the end of 2016 were extracted from the National Care Register for Health Care. Lifetime data on purchases of physician-prescribed psychotropic medications was obtained from the Social Insurance Institution of Finland. RESULTS: 98.4% (N=62) of subjects with PD had purchased at least one type of psychotropic medication during the follow-up period. The use of non-opioid analgesics and antipyretics was over twice as common among subjects with BPD than subjects with OPD (57.9% vs.28.0%, p=0.020). Anxiolytic use was 1.5 times more common among subjects with BPD than subjects with OPD (65.8% vs. 40.0%, p=0.044) CONCLUSIONS: Psychotropic medication use was common among subjects with PD. The use of non-opioid analgesics, antipyretics and anxiolytics was more common among subjects with BPD.

Effects of Omega 3 Fatty Acids on Main Dimensions of Psychopathology.

The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying their benefic properties are still partially unknown. These agents seem to express their action on the membrane phospholipid composition and permeability and modulation of second messenger cascades. In psychiatry, the efficacy and tolerability of omega-3 fatty acids were investigated in several psychiatric disorders, including major depression, bipolar disorder, personality disorders, high-risk conditions to develop psychosis, attention-deficit hyperactivity disorder, and autism spectrum disorders. Initial findings in this field are promising, and some relevant questions need to be addressed. In particular, the effects of these agents on the main symptom dimensions have to be investigated in a trans-diagnostic perspective. The present systematic review is aimed to examine the available data on the efficacy of omega-3 fatty acids on domains of psychotic symptoms, affective symptoms, impulsivity, and aggressiveness, and harmful behaviors, and suicide risk.

[Features of positive personality phenomena in patients with mild cognitive impairment and asthenic syndrome treated with recognan (citicoline)]. / Vliianie primeneniia preparata Rekognan (tsitikolin) na proiavleniia pozitivnykh lichnostnykh kachestv u patsientov s astenicheskim sindromom i legkimi kognitivnymi narusheniiami.

AIM: To assess the formation of positive personality phenomena in patients with mild cognitive impairment and asthenic syndrome during the treatment with recognan (citicoline). MATERIAL AND METHODS: Thirty-eight patients (17 men and 21 women), aged 18 to 45 years (mean age 27.8±12.1 years), with asthenic syndrome with mild cognitive impairment (ICD-10 F06.7) were examined. Patients were divided into two groups: 20 people in the main group and 18 people in the comparison group. The main group received recognan (orally, in solution, 100 mg in 1 ml) for 30 days, the daily dosage of the drug was 0.5 g (5 ml solution). The comparison group did not receive any medications. Adapted methods of positive personality psychology were used: the Fordyce Emotions Questionnaire, the Subjective Happiness Scale (SHS), the Adult Hope Scale (AHS), the Satisfaction with Life Scale (SWLS), M. Atkinson's Scale of Emotional Maturity, the projective technique 'Map of experiences'. The follow-up period was 30 days. All subjects were examined three times (at baseline, 15 and 30 days after treatment). RESULTS AND CONCLUSION: After a month of treatment with recognan, there was an improvement of positive personality traits and a significant decrease in negative experiences, indicating the positive impact of the drug on the formation of positive personality manifestations and compensation for emotional disorders in patients with mild cognitive impairment and asthenic syndrome.

Comorbid personality disorders in manic bipolar I disorder patients is associated with increased use of long-acting injectable antipsychotic treatment and higher rates of rehospitalization.

Personality disorder comorbidity is considered a poor prognostic factor among bipolar disorder patients. However, an evidence-based pharmacological treatment for this sub-population is lacking, and only few studies investigated the impact of personality disorder on bipolar disorder-I course. Here, we studied the effect of comorbid personality disorder on the administrated psychopharmacotherapy and rehospitalization risk among manic bipolar disorder-I patients. A sample of 340 patients with bipolar disorder-I, who were hospitalized with acute manic episode between 2005 and 2013, were retrospectively followed for a mean duration of 1129 days. Drug treatment at discharge and rehospitalization rates during follow-up time were compared between bipolar disorder-I patients with (n = 55) or without (n = 285) personality disorder comorbidity. Multivariate survival analyses adjusted for covariates were conducted. During the study period, 39.4% of bipolar disorder-I patients were rehospitalized due to a mood episode. Comorbid personality disorder was significantly associated with higher rates of long-acting injectable antipsychotics administration at discharge from hospitalization (adjusted odds ratio 2.66, 95% confidence interval: 1.19-5.94, P = 0.017). Comorbid personality disorder significantly increased the adjusted risk of rehospitalization due to a mood episode (hazard ratio = 2.04, 95% confidence interval: 1.29-3.23, P = 0.002). In conclusion, comorbid personality disorder in manic bipolar disorder-I patients is associated with increased use of long-acting injectable antipsychotics and higher rates of rehospitalization.

An Integrative Model of Personality Disorder: Part 3: Mechanism-Based Approach to the Pharmacotherapy of Personality Disorder: An Emerging Concept.

Temperament traits of Novelty Seeking, Harm Avoidance, Reward Dependence, and Persistence, are well defined in terms of their neural circuitry, neurochemical modulators, and patterns of associative learning. When heritably excessive, each of these traits may become a mechanistically fundamental biogenetic trait vulnerability for personality disorder. The other main risk factor for personality disorder is environmental, notably abuse, neglect, and psychological trauma. The emerging concept of mechanism-based pharmacotherapy aims to activate the brain's homeostasis as the only available delivery system to re-calibrate complex neurophysiological participants in each of the temperament traits. In a positive feedback, a homeostasis-driven improvement of excessive temperament is expected to facilitate maturation of neocortical networks of cognition, most reliably in expert psychotherapy (Part I of this paper) and, ultimately, thereby improve top-down cortical control of subcortical affect reactivity. As an emerging concept informed by neuroscience and clinical research, mechanism-based pharmacotherapy has the potential to be superior to traditional symptom-based treatments. Such mechanism-based approach illustrates what the pharmacological treatment of Research Domain Criteria (RDoC) might look like.

Role of personality disorder in randomised controlled trials of pharmacological interventions for adults with mood disorders: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Remission rates for mood disorders, including depressive and bipolar disorders, remain relatively low despite available treatments, and many patients fail to respond adequately to these interventions. Evidence suggests that personality disorder may play a role in poor outcomes. Although personality disorders are common in patients with mood disorders, it remains unknown whether personality disorder affects treatment outcomes in mood disorders. We aim to review currently available evidence regarding the role of personality disorder on pharmacological interventions in randomised controlled trials for adults with mood disorders. METHODS AND ANALYSIS: A systematic search of Cochrane Central Register of Controlled Clinical Trials (CENTRAL) via cochranelibrary.com, PubMed via PubMed, EMBASE via embase.com, PsycINFO via Ebsco and CINAHL Complete via Ebsco databases will be conducted to identify randomised controlled trials that have investigated pharmacological interventions in participants aged 18 years or older for mood disorders (ie, depressive disorders and bipolar spectrum disorders) and have also included assessment of personality disorder. One reviewer will screen studies against the predetermined eligibility criteria, and a second reviewer will confirm eligible studies. Data will be extracted by two independent reviewers. Methodological quality and risk of bias will be assessed using the Cochrane Risk of Bias tool. A systematic review, and if sufficient evidence is identified, a meta-analysis will be completed. Meta-analysis will be conducted using the standardised mean difference approach and reported with 95% CIs. A random effects model will be employed and statistical heterogeneity will be evaluated using the I2 statistic. Prespecified subgroup analyses will be completed. ETHICS AND DISSEMINATION: As this systematic review will use published data, ethics permission will not be required. The outcomes of this systematic review will be published in a relevant scientific journal and presented at a research conference. TRIAL REGISTRATION NUMBER: CRD42018089279.