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.

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.

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.

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.

[Pharmacotherapy in older adults with personality disorders: a new area of attention]. / Farmacotherapie bij ouderen met persoonlijk­heids­stoornissen: een nieuw aandachtsgebied.

BACKGROUND: Pharmacotherapy in older adults with personality disorders (PD) is a new and important area of attention. Nowadays, symptom based pharmacotherapy in older adults with PD is based on multidisciplinary guidelines, which are constructed on research performed in patients up to 50 years of age. There is no specific guideline for older adults with PD. GOAL: Providing a description of patient characteristics: number of comorbid psychiatric disorders, use of medication, including polypharmacy, in older adults (≥ 65 years) with personality disorders. METHOD: A retrospective cross-sectional patient file study (n = 50) in a clinical center of excellence for older adults with personality disorders (outpatient setting). RESULTS: . From the file study, it appears that 1) the unspecified/other specified personality disorder and the borderline personality disorder (BPD) occur most frequently, 2) there is a trend (no significant difference) that older adults with BPS use most medication (somatic medication and psychotropics) and 3) there is a trend (no significant difference) that polypharmacy is the most prevalent amongst older adults with BPD. CONCLUSION: The use of medication in certain subgroups of older adults with PD tends to be high. Further research is necessary to optimize pharmacotherapy in older adults with PD.

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.

An Integrative Model and Dynamic Nosology of Personality Disorder: Part 2: Symptom-based pharmacotherapy.

This paper presents an integrative model of personality and personality disorder which incorporates psychoanalytic concepts with modern neuroscience. In addition, a dynamic, personalized, and context - and time-sensitive diagnosis of personality disorder is introduced. The authors cogently argue that all clinical variants of personality disorder share the same common deficit: fragmented basic units of experience at the nonconscious core of the mind (aka "partial object relations"). The fragmentation propagates through mental faculties (thought, motivation, emotion), as they self-organize into subsystems of personality, e.g., one's sense of self, identity, character, moral values, rendering them polarized into extreme and thus adaptively suboptimal. The syndrome of personality disorder arises as a nonconscious compensatory maneuver of the fragmented mind to organize itself through a defensive but unrealistic self-image (e.g., narcissistic, schizoid, antisocial, etc.), giving rise to a host of unique symptoms. Symptomatic pharmacotherapy of personality disorder is best organized around four empirically derived domains of symptoms, shared by all variants to a variable degree: i) mood and anxiety dysregulation; ii) impulsivity, aggression, and behavior dyscontrol; iii) emotional disinterest and detachment; and iv) cognitive distortions and brief reactive psychoses. Pharmacotherapy targeting the above domains is nonspecific, as medications affect multiple domains simultaneously. Modest empirical evidence and considerable clinical benefits continue to support the use of medications in the overall symptomatic treatment of personality disorder.

A cross-validation Delphi method approach to the diagnosis and treatment of personality disorders in older adults.

INTRODUCTION: The Delphi method is a consensus-building technique using expert opinion to formulate a shared framework for understanding a topic with limited empirical support. This cross-validation study replicates one completed in the Netherlands and Belgium, and explores US experts' views on the diagnosis and treatment of older adults with personality disorders (PD). METHODS: Twenty-one geriatric PD experts participated in a Delphi survey addressing diagnosis and treatment of older adults with PD. The European survey was translated and administered electronically. RESULTS: First-round consensus was reached for 16 out of 18 items relevant to diagnosis and specific mental health programs for personality disorders in older adults. Experts agreed on the usefulness of establishing criteria for specific types of treatments. The majority of psychologists did not initially agree on the usefulness of pharmacotherapy. Expert consensus was reached following two subsequent rounds after clarification addressing medication use. CONCLUSIONS: Study results suggest consensus among regarding psychosocial treatments. Limited acceptance amongst US psychologists about the suitability of pharmacotherapy for late-life PDs contrasted with the views expressed by experts surveyed in Netherlands and Belgium studies.

[Sustained upgaze in a patient who ingested high doses of bupropion. Report of one case]. / Supraversión de la mirada en intoxicación mortal por bupropión.

Upgaze or sustained elevation of the eyes, is an alteration of ocular motility initially described in hypoxic coma. We report a 65-year-old woman admitted with hypotension and alteration of sensorium due to the ingestion of 9.5 g of Bupropion. She presented two seizures of short duration, without epileptic activity on the EEG. She had a persistent asynchronous myoclonus in extremities, tachycardia and prolonged Q-t. She suffered a cardiac arrest caused by asystole, which recovered quickly in five minutes. At that moment, upgaze appeared, associated with a persistent ocular opening, which persisted for days, but finally disappeared, without remission of coma. A magnetic resonance imaging done at the eighth day, showed hyperintensity of the oval center and corpus callosum which disappeared in a new imaging study done 30 days later, where images of hypoxia in the basal nuclei and cortex appeared. The patient died forty seven days after admission. Up-gaze is an ominous oculomotor alteration linked to an important but incomplete damage in the cerebral cortex, a condition that perverts some sequences of the ocular opening, reversing the Bell phenomenon and producing eyelid retraction.

[Time for cluster C personality disorders: state of the art]. / Tijd voor cluster C-persoonlijkheids-stoornissen: state of the art.

BACKGROUND: Compared to cluster B personality disorders, the assessment and treatment of people with obsessive-compulsive, dependent, and avoidant personality disorders (cluster C) is given little attention in the field of research and clinical practice. AIM: Presenting the current state of affairs in regard to cluster C personality disorders. METHOD: A systematic literature search was conducted using the main data bases. RESULTS: Cluster C personality disorders are present in approximately 3-9% of the general population. In about half of the cases of mood, anxiety, and eating disorders, there is co-morbid cluster C pathology. This has a major influence on the progression of symptoms, treatment effectiveness and potential relapse. There are barely any well conducted randomized studies on the treatment of cluster-C in existence. Open cohort studies, however, show strong, lasting treatment effects. CONCLUSION: Given the frequent occurrence of cluster C personality disorders, the burden of disease, associated societal costs and the prognostic implications in case of a co-morbid cluster C personality disorder, early detection and treatment of these disorders is warranted.

Association between personality traits and Escitalopram treatment efficacy in panic disorder.

BACKGROUND: There is strong evidence to suggest that personality factors may interact with the development and clinical expression of panic disorder (PD). A greater understanding of these relationships may have important implications for clinical practice and implications for searching reliable predictors of treatment outcome. AIMS: The study aimed to examine the effect of escitalopram treatment on personality traits in PD patients, and to identify whether the treatment outcome could be predicted by any personality trait. METHOD: A study sample consisting of 110 outpatients with PD treated with 10-20 mg/day of escitalopram for 12 weeks. The personality traits were evaluated before and after 12 weeks of medication by using the Swedish universities Scales of Personality (SSP). RESULTS: Although almost all personality traits on the SSP measurement were improved after 12 weeks of medication in comparison with the baseline scores, none of these changes reached a statistically significant level. Only higher impulsivity at baseline SSP predicted non-remission to 12-weeks treatment with escitalopram; however, this association did not withstand the Bonferroni correction in multiple comparisons. LIMITATIONS: All patients were treated in a naturalistic way using an open-label drug, so placebo responses cannot be excluded. The sample size can still be considered not large enough to reveal statistically significant findings. CONCLUSIONS: Maladaptive personality disposition in patients with PD seems to have a trait character and shows little trend toward normalization after 12-weeks treatment with the antidepressant, while the association between impulsivity and treatment response needs further investigation.

Predictors of Length of Stay in an Inpatient Psychiatric Unit of a General Hospital in Perugia, Italy.

The aim of this study was to understand which of a number of factors are most associated with psychiatric inpatient length of stay (LoS). We hypothesized that a longer LoS would be predicted by: older age, male gender, unmarried marital status, foreign nationality, more than one hospitalization, being hospitalized involuntarily, psychotic symptoms and behavioral dyscontrol at admission, discharge diagnosis of psychotic and personality disorders, not having a substance use disorder, treatment with more than one class of medications, and being discharged to a community residential facility. All admissions to the Psychiatric Inpatient Unit of Santa Maria della Misericordia, Perugia Hospital, Umbria, Italy, from June 2011 to June 2014, were included in a medical record review. Bivariate analyses were performed and a multiple linear regression model was built using variables that were associated (p < .05) with LoS in bivariate tests. The study sample included 1236 patients. In the final, most parsimonious regression model, five variables independently explained 18 % of variance in LoS: being admitted involuntarily, being admitted for thought disorders, not having a substance-related disorder, having had more than one hospitalization, and being discharged to a community residential facility. LoS on this inpatient psychiatric unit in Umbria was associated with a number of sociodemographic and clinical characteristics. Knowledge of these and other predictors of LoS will be increasingly important to, when possible, reduce the length of restrictive, costly hospitalizations and embrace community-based services.

Psychotropic prescribing in seriously violent men with schizophrenia or personality disorder in a UK high security hospital.

OBJECTIVES: To analyze antipsychotic prescribing patterns in a UK high security hospital (HSH) that treats seriously violent men with either schizophrenia or personality disorder and examine how different groups consented to treatment and prescribing for metabolic conditions. We hypothesized that there would be high prevalence of antipsychotic polypharmacy, and high-dose antipsychotic and clozapine prescribing. BACKGROUND: HSHs treat seriously violent, mentally disordered offenders, and the extant literature on prescribing patterns in forensic settings is sparse. METHODS: Prescribing and clinical data on all 189 patients in a UK HSH were collected from the hospital's databases. Data were analyzed using SPSS. RESULTS: The population was split into the following groups: schizophrenia spectrum disorder (SSD-only), personality disorder (PD-only), and comorbid schizophrenia spectrum disorder and PD. The majority (93.7%) of all patients were prescribed at least one antipsychotic, and (27.5%) were on clozapine. Polypharmacy was prevalent in 22.2% and high-dose antipsychotic in 27.5%. Patients on clozapine were more likely to be prescribed antidiabetic, statins, or antihypertensive medication. Patients in the PD-only group were more likely to be deemed to have the capacity to consent to treatment and be prescribed clozapine in contrast to the SSD-only group. CONCLUSIONS: Rates of clozapine and high-dose antipsychotic prescribing were higher than in other psychiatric settings, while polypharmacy prescribing rates were lower. Higher clozapine prescribing rates may be a function of a treatment-resistant and aggressive population. A higher proportion of PD-only patients consented to treatment and received clozapine compared with in-house SSD-only as well as other psychiatric settings. Implications of the findings are discussed.

Relating DSM-5 section II and section III personality disorder diagnostic classification systems to treatment planning.

BACKGROUND: Beginning with DSM-III, the inclusion of a "personality" axis was designed to encourage awareness of personality disorders and the treatment-related implications of individual differences, but since that time there is little accumulated evidence that the personality disorder categories provide substantial treatment-related guidance. The DSM-5 Personality and Personality Disorders Work Group sought to develop an Alternative Model for personality disorder, and this study examined whether this model is more closely related to clinicians' decision-making processes than the traditional categorical personality disorder diagnoses. PROCEDURES: A national sample of 337 clinicians provided complete personality disorder diagnostic information and several treatment-related clinical judgments about one of their patients. FINDINGS: The dimensional concepts of the DSM-5 Alternative Model for personality disorders demonstrated stronger relationships than categorical DSM-IV/DSM-5 Section II diagnoses to 10 of 11 clinical judgments regarding differential treatment planning, optimal treatment intensity, and long-term prognosis. CONCLUSIONS: The constructs of the DSM-5 Alternative Model for personality disorders may provide more clinically useful information for treatment planning than the official categorical personality disorder diagnostic system retained in DSM-5 Section II.

Personality Disorder in Adult Attention-Deficit/Hyperactivity Disorder: Attrition and Change During Long-term Treatment.

Personality disorders (PDs) are commonly found in adults with attention-deficit/hyperactivity disorder (ADHD) and are associated with increased ADHD symptoms and psychosocial impairment. To assess the impact of PDs or personality traits on retention rates in ADHD trials and whether treating ADHD affects the expression of PD, data were analyzed from 2 methylphenidate trials. Assessment of PDs and personality traits included using the Wisconsin Personality Disorders Inventory IV and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Personality Disorders. Attention-deficit/hyperactivity disorder symptoms were evaluated using the Wender-Reimherr Adult Attention Deficit Disorder Scale. Major findings were that subjects with cluster A, cluster B, passive-aggressive, or more than 1 PD showed more attrition. Subjects dropping out also had more schizoid and narcissistic traits. Attention-deficit/hyperactivity disorder symptoms (p < 0.001) and all personality traits (range, p = 0.03 to p = 0.001) improved, but there was almost no correlation between changes on these 2 measures. Conversely, of 11 Wisconsin Personality Disorders Inventory IV items that improved most, 8 resembled ADHD or oppositional defiant disorder symptoms.

Non-psychotic mental disorders in the perinatal period.

Mental disorders are among the most common morbidities of pregnancy and the postnatal period, and can have adverse effects on the mother, her child, and family. This Series paper summarises the evidence about epidemiology, risk factors, identification, and interventions for non-psychotic mental disorders. Although the phenomenology and risk factors for perinatal mental disorders are largely similar to those for the disorders at other times, treatment considerations differ during pregnancy and breastfeeding. Most randomised controlled trials have examined psychosocial and psychological interventions for postnatal depression, with evidence for effectiveness in treating and preventing the disorder. Few high-quality studies exist on the effectiveness or safety of pharmacological treatments in the perinatal period, despite quite high prescription rates. General principles of prescribing of drugs in the perinatal period are provided, but individual risk-benefit analyses are needed for decisions about treatment.

The Association Between Benzodiazepine Use and Depression Outcomes in Older Veterans.

Benzodiazepines (BZDs) are commonly prescribed to older adults with depression, but it is unknown whether they improve antidepressant (AD) adherence or depressive symptoms. We followed 297 older veterans diagnosed with depression and provided a new AD medication prospectively for 4 months. Data include validated self-report measures and VA pharmacy records. At initial assessment, 20.5% of participants were prescribed a BZD. Those with a BZD prescription at baseline were significantly more likely than those without to have a personality disorder, schizophrenia spectrum disorder, or other anxiety disorder, and higher depressive symptom and anxiety symptom scale scores on average. In adjusted regressions, BZD use was not significantly associated with AD adherence, any improvement in depressive symptoms, or a 50% reduction in depressive symptoms. Our results suggest BZD use concurrent with AD treatment does not significantly improve depressive outcomes in older veterans.

Psychodynamics and psychopharmacotherapy in the treatment of difficult patients with personality and eating disorders.

The complex inter-relationship between external and internal reality, a source of interest and controversy in psychiatry, has come to the foreground more prominently in the context of more integrative understanding of psychopharmacotherapy. This paper discusses the meaning and clinical applications of the psychodynamic related to psychopharmacotherapy for difficult personality and eating disorders patients. The one of the psychodynamic explanations for patients' being difficult is related to their perceived lack of mentalizing (reflective) capacities. Lack of mentalizing capacity implies disturbed view of psychopharmacotherapy. Therapeutic relationship and optimal alliance offers the frame for acceptance of psychiatric drugs as positive and useful for personality and eating disorder patients. Mentalization and intersubjectivity theories have direct implications for clinical practice, and that the notion of the third is particularly useful in understanding what happens in the patient-doctor relationship.