Atorvastatin lowers serum calcium levels in lithium-users: results from a randomized controlled trial.

BACKGROUND: Although lithium is considered the gold-standard treatment for bipolar disorder (BD), it is associated with a variety of major endocrine and metabolic side effects, including parathyroid hormone (PTH) dependent hypercalcemia. Aside from surgery and medication discontinuation, there are limited treatments for hypercalcemia. This paper will assess data from a randomized controlled trial (RCT). METHODS: This is a secondary analysis of an RCT that explored the effects of atorvastatin (n = 27) versus placebo (n = 33) on lithium-induced nephrogenic diabetes insipidus (NDI) in patients with BD and major depressive disorder (MDD) using lithium (n = 60), over a 12-week period. This secondary analysis will explore serum calcium levels and thyroid stimulating hormone (TSH) measured at baseline, week 4, and week 12. RESULTS: At 12-weeks follow-up while adjusting results for baseline, linear regression analyses found that corrected serum calcium levels were significantly lower in the treatment group (mean (M) = 2.30 mmol/L, standard deviation (SD) = 0.07) compared to the placebo group (M = 2.33 mmol/L, SD = 0.07) (ß = - 0.03 (95% C.I.; - 0.0662, - 0.0035), p = 0.03) for lithium users. There were no significant changes in TSH. CONCLUSION: In lithium users with relatively normal calcium levels, receiving atorvastatin was associated with a decrease in serum calcium levels. Although exciting, this is a preliminary finding that needs further investigation with hypercalcemic patients. Future RCTs could examine whether atorvastatin can treat PTH dependent hypercalcemia due to lithium and other causes.

A double-blind, randomized, placebo-controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users.

OBJECTIVE: Lithium remains an important treatment for mood disorders but is associated with kidney disease. Nephrogenic diabetes insipidus (NDI) is associated with up to 3-fold risk of incident chronic kidney disease among lithium users. There are limited randomized controlled trials (RCT) for treatments of lithium-induced NDI, and existing therapies can be poorly tolerated. Therefore, novel treatments are needed for lithium-induced NDI. METHOD: We conducted a 12-week double-blind pilot RCT to assess the feasibility and efficacy of 20 mg/d atorvastatin vs placebo in the treatment of NDI in chronic lithium users. Patients, recruited between September 2017 and October 2018, were aged 18 to 85, currently on a stable dose of lithium, and determined to have NDI. RESULTS: Urinary osmolality (UOsm) at 12 weeks adjusted for baseline was not statistically different between groups (+39.6 mOsm/kg [95% CI, -35.3, 114.5] in atorvastatin compared to placebo groups). Secondary outcomes of fluid intake and aquaporin-2 excretions at 12 weeks adjusted for baseline were -0.13 L [95% CI, -0.54, 0.28] and 98.68 [95% CI, -190.34, 387.70], respectively. A moderate effect size was observed for improvements in baseline UOsm by ≥100 mOsm/kg at 12 weeks in patients who received atorvastatin compared to placebo (38.45% (10/26) vs 22.58% (7/31); Cohen's d = 0.66). CONCLUSION: Among lithium users with NDI, atorvastatin 20 mg/d did not significantly improve urinary osmolality compared to placebo over a 12-week period. Larger confirmatory trials with longer follow-up periods may help to further assess the effects of statins on NDI, especially within patients with more severe NDI.

Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial.

BACKGROUND: Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. However, clinicians are increasingly avoiding lithium largely due to fears of renal toxicity. Nephrogenic Diabetes Insipidus (NDI) occurs in 15-20% of lithium users and predicts a 2-3 times increased risk of chronic kidney disease (CKD). We recently found that use of statins is associated with lower NDI risk in a cross-sectional study. In this current paper, we describe the methodology of a randomized controlled trial (RCT) to treat lithium-induced NDI using atorvastatin. METHODS: We will conduct a 12-week, double-blind placebo-controlled RCT of atorvastatin for lithium-induced NDI at McGill University, Montreal, Canada. We will recruit 60 current lithium users, aged 18-85, who have indicators of NDI, which we defined as urine osmolality (UOsm) < 600 mOsm/kg after 10-h fluid restriction. We will randomize patients to atorvastatin (20 mg/day) or placebo for 12 weeks. We will examine whether this improves measures of NDI: UOsm and aquaporin (AQP2) excretion at 12-week follow-up, adjusted for baseline. RESULTS: Not applicable. CONCLUSION: The aim of this clinical trial is to provide preliminary data about the efficacy of atorvastatin in treating NDI. If successful, lithium could theoretically be used more safely in patients with a reduced subsequent risk of CKD, hypernatremia, and acute kidney injury (AKI). If future definitive trials confirm this, this could potentially allow more patients to benefit from lithium, while minimizing renal risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT02967653 . Registered in February 2017.

Psychotropic medication use pre and post-diagnosis of cluster B personality disorder: a Quebec's health services register cohort.

Background: Cluster B personality disorders (PDs) are considered some of the most severe mental health conditions. Scarce evidence exists about the real-world utilization of psychotropics for cluster B PD individuals. Objective: We aimed to uncover trends and patterns of psychotropic medication use among individuals diagnosed with cluster B PD in the year before and after their diagnosis and to identify factors associated with medication use in a large cohort of individuals newly diagnosed with cluster B PDs. Methods: We conducted a population-based observational study using Quebec's health services register. We identified Quebec residents aged ≥14 years and insured with the provincial drug plan with a first diagnosis of cluster B PD recorded between April 1, 2002, and March 31, 2019. Cluster B PD was defined with ICD-9/10 diagnostic codes. We retrieved all claims for the main psychotropic medication classes: antipsychotics, antidepressants, anxiolytics, mood stabilizers, and attention-deficit/hyperactivity disorder (ADHD) medications. We calculated the proportion of individuals exposed to these medication classes and analyzed trends over the years using robust Poisson regression models, adjusting for potential confounders. We used robust Poisson regression to identify factors associated with medication class use. Results: We identified 87,778 new cases of cluster B PD, with a mean age of 44.5 years; 57.5% were women. Most frequent psychiatric comorbidities in the five years before cluster B PD diagnosis were depression (50.9%), anxiety (49.7%), and psychotic disorders (37.5%). Most individuals (71.0%) received at least one psychotropic during the year before cluster B PD diagnosis, and 78.5% received at least one of these medications in the subsequent year. The proportion of users increased after the diagnosis for antidepressants (51.6-54.7%), antipsychotics (35.9-45.2%), mood stabilizers (14.8-17.0%), and ADHD medications (5.1-5.9%), and remained relatively stable for anxiolytics (41.4-41.7%). Trends over time showed statistically significant increased use of antipsychotics and ADHD medications, decreased use of anxiolytics and mood stabilizers, and a stable use of antidepressants. Conclusion: Psychotropic medication use is highly prevalent among cluster B PD individuals. We observed an increase in medication use in the months following the diagnosis, particularly for antipsychotics, antidepressants, and mood stabilizers.

Differential diagnosis of bipolar affective disorder type II and borderline personality disorder: analysis of the affective dimension.

BACKGROUND: Differential diagnosis between bipolar affective disorder type II and borderline personality disorder can be problematic yet a priority for effective treatment planning. Diagnosis is problematic when symptoms do not present enough intensity or duration to clear the issue but also when there is a relative overlap of criteria between both disorders. If for many patients, the diagnosis is more easily differentiated, confounding conditions are found in 20% of cases for which it becomes a significant issue. METHOD: A research with the key words affective instability, borderline personality disorder, and bipolar disorder on Medline and Psych-Info was done. Other references were found through this review in related articles. Comparison of data about the affective dimensions concerning bipolar disorder and borderline personality disorder was noted. RESULTS: Affective instability is a confounding factor: quality and intensity of affects, speed of fluctuations, affective response to social stress, and its modulation are core elements of affective instability that need to be analyzed to clarify a proper diagnosis. LIMITATIONS: There is further necessity for research about affective instability in the 2 diagnoses. CONCLUSIONS: Making a valid differential diagnosis has an important clinical value in order for the clinician to plan proper treatment. Analysis of the affective experience and its qualitative and quantitative facets can help establish it.

[Understanding dissociation in patients with borderline personality disorder]. / Comprendre la dissociation chez les patients avec un trouble de personnalité limite.

Dissociation is a disturbing psychiatric concept fraught with controversy. It is however encountered in clinical contexts and has to be understood by clinicians. This article based on a Pubmed/Ovid on line research with key words dissociation and borderline personality disorder and other references, describes the clinical aspects of the dissociative phenomena in patients with borderline personality disorder. Psychodynamic hypotheses and neurophysiological data are examined to explain dissociation. Neurophysiological and neuroanatomical variables provided by cerebral imagery controlled studies support hypotheses brought forward. The article concludes with a defence mechanism developed within a context of biological predisposition, deprived psychological development and in reaction to trauma. In conclusion, emerging psychotherapeutic solutions are summarized.

[Insecure/disorganized attachment and borderline personality disorder: overcoming therapeutic problems]. / Attachement insécure/désorganisé et trouble de personnalité limite: peut-on sortir de l'impasse thérapeutique?

In this article, the authors discuss the obstacles in the therapeutic relationship with patients with borderline personality disorder because of problematic transference. They present the case of a patient and describe a therapeutic impasse triggered by an exacerbated insecure/disorganized attachment. They discuss strategies to resolve the therapeutic deadlock elaborated according to the attachment theory formulation and the understanding of transference issues.

Utilization of Health Care Services by Patients With Cluster B Personality Disorders or Schizophrenia.

OBJECTIVE: The comparable severities of cluster B personality disorders and schizophrenia are increasingly recognized. The authors sought to compare the general medical and psychiatric comorbid conditions and use of medical services among individuals with one or both of these disorders. METHODS: Data were collected from the linked health administrative databases of Quebec's universal health plan in the Quebec Integrated Chronic Disease Surveillance System, which covers 99% of Quebec's population. The study cohort of 2016-2017 included almost 7.05 million people, and the study covered the 1996-2017 period. RESULTS: Comorbid conditions were extremely prevalent in the three groups studied-persons with cluster B personality disorders, schizophrenia, or both-compared with the general population. People having both disorders had the highest prevalence of comorbid conditions. Psychiatric services were used more frequently by individuals in all three groups than among those in the general population, and use was especially high among people with both disorders. Medical care service use was heterogeneous, with patients with cluster B personality disorders using more medical care services but fewer specialized outpatient treatments and psychotherapy than those with schizophrenia or with both disorders. CONCLUSIONS: The three cohorts had higher rates of comorbid conditions and health care service use than individuals in the general population. Patients with cluster B personality disorders used fewer psychiatric services than patients with schizophrenia or with both disorders. One explanation for this difference may be that people with cluster B personality disorders encounter more obstacles in accessing mental health care services.

Group Cognitive Behavioral Analysis System of Psychotherapy (CBASP): A Pilot Study for Bipolar Depression.

OBJECTIVES: Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is an individually administered treatment model designed specifically for Persistent Depression however bipolar patients have traditionally been excluded from CBASP studies. There is a perception that bipolar depression will be harder to treat and requires a unique psychological approach. This pilot study reports on the feasibility of administering the same 20-week manualized group CBASP therapy with bipolar patients currently in a depressive episode. METHODS: This non-randomized, single-arm prospective pilot study, reports on an a posteriori exploration of benefits to bipolar depressed patients (n=26) of the same 20-week group CBASP intervention administered to unipolar depressed patients (n=81). The clinical trial for the initial phase examining benefits of the manualized 20-week group CBASP intervention with unipolar patients was registered with the ISRCTN registry, study ID: ISRCTN95149444. Results reported here include mixed ANOVA analyses, across group treatment models and diagnostic categories. Changes over time in self-reported depressive symptoms (Inventory of Depressive Symptoms -IDS-SR), self-reported social functioning, interpersonal problems and interpersonal dispositions are documented for all patients. An exploratory longitudinal latent class analysis was used to examine patients' trajectories of improvement in depressive symptoms. Finally, the best predictors of change in reported depressive symptoms were explored with a logistic regression for all patients. RESULTS: Improvements in depressive symptoms and in social functioning over time were significant for all patients with bipolar patients trending towards a greater improvement in depressive symptoms after controlling for baseline differences. An exploratory Latent Class Analysis identified two different treatment trajectories for the entire sample: 1) moderate to severely depressed patients who improved significantly (49%) and 2) severely depressed patients who did not improve (51%). The best predictors of non-response to group therapy include high baseline problems in social functioning and low rates of self-reported Perceived Improvements in overall health. CONCLUSION: Bipolar patients in a depressive episode appear to benefit from the same 20-week group CBASP model designed originally for the treatment of Persistent Depressive Disorder. Bipolar patients seem more easily mobilized both during and outside of group therapy sessions and report more interpersonal confidence and more agency than unipolar depressed patients.

The effect of atorvastatin on cognition and mood in bipolar disorder and unipolar depression patients: A secondary analysis of a randomized controlled trial.

OBJECTIVES: Statins have recently been linked to having effects on cognition and mood in mood disorders, though results are mixed. In this paper, we use data from a recent randomized controlled trial (RCT) to examine the effect of statins on cognition and mood in patients with Bipolar Disorder (BD) and Major Depressive Disorder (MDD). METHODS: This is a secondary analysis of a randomized, double-blind, placebo-controlled clinical trial (n = 60) originally designed to examine the effect of atorvastatin (n = 27) versus placebo (n = 33) for lithium-induced diabetes insipidus in BD and MDD patients who were using lithium. For this analysis, the primary outcome was global cognition Z-score at 12-weeks adjusted for baseline. The secondary cognition outcomes were (1) Screen for Cognitive Impairment in Psychiatry (SCIP), and (2) executive function Z-score. The primary mood outcome (secondary outcome of this analysis) was depression relapse during 12-week follow-up (Mongomery Asberg Depression Rating Scale (MADRS) ≥10). The secondary mood outcomes were (1) relapse rate into a manic episode, and (2) relapse rate into any mood episode. RESULTS: After 12 weeks follow-up, atorvastatin and placebo groups did not differ in terms of global cognition Z-score (ß = -0.009287 (-0.1698,0.1512), p-value = 0.91). Similarly, composite Z-scores for SCIP and executive functions did not differ significantly. Depression relapse during 12-week follow-up was not significantly different between the groups (χ2 (1) = 0.148, p-value = 0.70). Similarly, there was no difference between groups regarding relapse into mania. CONCLUSION: In BD and MDD patients with lithium-induced nephrogenic diabetes insipidus randomized to atorvastatin or placebo, we found no significant differences in cognition and mood outcomes at 12-week follow-up.

[An exploratory study of adaptation of people with schizophrenia]. / Une étude exploratoire de l'adaptation de personnes souffrant de schizophrénie.

This exploratory study examines relations between socio-demographic, social, psychological, cognitive, variables and stressors, coping strategies and adaptation of individuals with schizophrenia. The study's design is correlational with two repeated measures (cross-sectional) with 153 subjects at a six-month interval. The variables of the model explain 49,3 % of adaptation at time 1, and 54,6 % of adaptation at time 2. Data show that five predictors are simultaneously significant at both times : work, social integration, long term memory, positive and negative symptoms. At time 2, variables of self-esteem and "changing the situation" are also significant.

[Crisis interventions with patients with borderline personality disorder. Part 1: Preventive and resolving approaches in individual psychodynamic therapy]. / Interventions de crise auprès des patients souffrant d'un trouble de personnalité limite. Partie 1: Approches préventives et résolutives en thérapie psychodynamique individuelle.

Patients suffering from borderline personality disorder have by definition a poorly functional personality which is readily reacting to changes and psychosocial stressors with recurrent crises. A personality disorder is necessarily fraught with interpersonal difficulties, and it is often within the individual psychotherapeutic encounter that such clashes develop. This article discusses basic principles offering clinicians ways to prevent or structure crisis intervention adapted to borderline personality disorder within the individual psychotherapy context. It thus reviews various clinical issues such as suicidal or homicidal threats, conflicts related to requests expressed by the patient, the absence of the therapist or attempts at breaking the therapeutic framework in order to offer intervention modalities for the resolution of these crises.

[Guidelines for the treatment of patients with borderline personality disorder]. / Guide de lignes directrices pour le traitement des patients atteints de trouble de personnalité limite.

The prevalence of patients with borderline personality disorder in outpatient psychiatric clinics, the severity of their presenting symptoms including potential mortality and the difficulty to treat these poorly collaborative healthseekers are sufficient arguments to justify the need for a practice guideline about their treatment. Supported by a strong experience in the creation of many practice guidelines, the American Psychiatric Association has produced a guide that answers quite well to the scientific criteria of a treatment guide and respects most of the specified requirements emitted by the Canadian Medical Association and the Advisory Committee to Public Health Services of the American Institute of Medicine. A review of the suggested recommendations on psychotherapeutic and pharmacological treatments and their scientific evidence is given followed by comments and a critical discussion.

Toward a definition of affective instability.

Affective instability is a psychophysiological symptom observed in some psychopathologies. It is a complex construct that encompasses (1) primary emotions, or affects, and secondary emotions, with each category having its own characteristics, amplitude, and duration, (2) rapid shifting from neutral or valenced affect to intense affect, and (3) dysfunctional modulation of emotions. Affective instability is often confused with mood lability, as in bipolar disorders, as well as with other terms. To clarify the concept, we searched databases for the term affective instability and read related articles on the topic. In this article we situate the term within the current affective nomenclature and human emotional experience, explore its psychophysiological features, and place it within the context of psychopathology. We explain why the term can potentially be confused with mood pathology and then define affective instability as an inherited temperamental trait modulated by developmental experience.