Acute Depressive Episode Research Articles

Wearable biosensors have the potential to monitor physiological changes associated with opioid overdose among people who use drugs: A proof-of-concept study in a real-world setting

IntroductionWearable biosensors have the potential to monitor physiological change associated with opioid overdose among people who use drugs. MethodsWe enrolled 16 individuals who reported ≥ 4 daily opioid use events within the previous 30 day. Each was assigned a wearable biosensor that measured respiratory rate (RR) and actigraphy every 15 s for 5 days and also completed a daily interview assessing drug use. We describe the volume of RR data collected, how it varied by participant characteristics and drug use over time using repeated measures one-way ANOVA, episodes of acute respiratory depression (≤5 breaths/minute), and self-reported overdose experiences. ResultsWe captured 1626.4 h of RR data, an average of 21.7 daily hours/participant over follow-up. Individuals with longer injection careers and those engaging in polydrug use captured significantly fewer total hours of respiratory data over follow-up compared to those with shorter injections careers (94.7 vs. 119.9 h, p = 0.04) and injecting fentanyl exclusively (98.7 vs. 119.5 h, p = 0.008), respectively. There were 385 drug use events reported over follow-up. There were no episodes of acute respiratory depression which corresponded with participant reports of overdose experiences. DiscussionOur preliminary findings suggest that using a wearable biosensor to monitor physiological changes associated with opioid use was feasible. However, more sensitive biosensors that facilitate triangulation of multiple physiological data points and larger studies of longer duration are needed.

Ketamine and other glutamate receptor modulators for depression in adults with bipolar disorder.

Ketamine and other glutamate receptor modulators for depression in adults with bipolar disorder.

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials.

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

Symptoms and Characteristics of Youth Hospitalized for Depression: Subthreshold Manic Symptoms Can Help Differentiate Bipolar from Unipolar Depression.

Background: Most people who have major depressive disorder (MDD) or bipolar disorder (BD) will have their first episode of depression in adolescence. However, in the absence of significant [hypo]manic symptoms, there are no clear guidelines for distinguishing bipolar from unipolar depression, which can lead to misdiagnosis and ineffective/harmful treatment. We aimed to compare phenomenological differences among youth with MDD or BD hospitalized for an acute episode of depression. Methods: A retrospective electronic chart review of adolescents hospitalized in an acute care inpatient unit who had a discharge diagnosis of MDD, MDD with mixed or psychotic features (MDD+), BD-I-current episode depressed, or BD-II-current episode depressed, was performed. Results: Altogether, 598 patients (mean age = 15.1 ± 1.5 years, female = 71%, and White = 46%) met study inclusion criteria, i.e., BD-I: n = 39, BD-II: n = 84, MDD: n = 422, and MDD+: n = 53 patients. The admission Hamilton Depression Rating Scale (HAMD) total score was significantly higher in the BD-I (29.3 ± 9.1) and MDD+ (31.2 ± 9.3) groups versus the MDD group (24.3 ± 9.7) (p < 0.05). Although there were some group differences in the severity of individual depression symptoms, these did not line up neatly across BD and MDD groups. At admission, Young Mania Rating Scale (YMRS) total scores were significantly higher in the BD-I (14.4 ± 7.4), BD-II (13.8 ± 6.5), and MDD+ groups (14.3 ± 6.6) versus the MDD group (8.2 ± 4.6, p < 0.05). Additionally, 9 of 11 and 4 of 11 YMRS items scored significantly higher in the BD-II and BD-I groups versus the MDD group, respectively. The motor activity and hypersexuality items, in particular, were scored consistently higher in the BD groups than MDD groups. Limitations: All diagnoses were made based on a clinical interview and not a structured diagnostic interview, and some of the subgroup sample sizes were relatively modest, limiting the power for group comparisons. Conclusion: The presence of subsyndromal manic symptoms during an episode of MDD currently offers the clearest way by which to differentiate bipolar depression from unipolar depression.

Second-Generation Antipsychotics in Management of Acute Pediatric Bipolar Depression: A Systematic Review and Meta-analysis.

Objectives: To evaluate the efficacy in reduction of depressive symptoms, and safety and tolerability of second-generation antipsychotics (SGAs) to manage pediatric bipolar depression (PBD). Methods: We conducted a systematic review for randomized clinical trials (RCTs) for PBD in MEDLINE, Scopus, and EMBASE. Four (quetiapine: 2, lurasidone: 1, olanzapine-fluoxetine combination [OFC]: 1) out of 569 studies met the criteria for inclusion in meta-analysis. RevMan was used for statistical analysis, and the mean difference (MD) between mean children's depression rating scale-revised (CDRS-R) score was used to measure treatment difference between SGA and placebo. Results: Lurasidone displayed a significant reduction in depressive symptoms (MD -5.70, 95% confidence interval [CI] -8.67 to -2.73) in PBD, followed by OFC (MD -5.00, 95% CI -8.64 to -1.36) and quetiapine (MD -2.30, 95% CI -6.80 to 2.20; MD 1.00, 95% CI -9.88 to 11.88). The response was significantly higher for lurasidone (59.5% vs. 36.5%; p < 0.001) and OFC (78.2% vs. 59.2%, p = 0.003) compared with placebo. There was no statistically significant MD in treatment and response rates between quetiapine and placebo in all RCTs. The weighted mean CDRS-R total score difference was -4.58 (95% CI -6.59 to -2.56) and overall effect was significant (p < 0.00001). Importantly, the p value for heterogeneity was 0.46, which indicated that there was no heterogeneity between outcomes of the studies. The number needed to treat (NNT) for lurasidone was 4.3, followed by OFC (NNT = 5.3) and quetiapine (NNT = 12.5; NNT = 25). Conclusion: Our findings showed lurasidone and OFC were more efficacious than placebo for acute depressive episodes in PBD. RCTs of treatments for PBD remain scarce pressing the need for more research.

Baseline serum amino acid levels predict treatment response to augmentation with N-acetylcysteine (NAC) in a bipolar disorder randomised trial

N-acetylcysteine (NAC) acts on glutamatergic and redox systems, two systems implicated in the pathophysiology of bipolar disorder (BD). This has led to the investigation of NAC as a potential candidate for the treatment of BD. The aim of this study was to investigate metabolomic markers to identify predictors of NAC response in a cohort of BD participants. This study is a secondary analysis of a 16-week, multi-site, randomized, double-blinded, parallel-group, placebo-controlled trial in BD participants with a current acute depressive episode. This study included trial participants who received either NAC 2000 mg/day, or placebo. Participants (NAC: n = 31, placebo: n = 29) were assessed at baseline and week 16 using the Montgomery Åsberg Depression Rating Scale (MADRS) and were dichotomised into “responders” (MADRS at week 16 < 50% of MADRS at baseline) and “non-responders” (MADRS at week 16 > 50% at baseline). Untargeted gas chromatography–mass spectrometry analysis was performed to analyse baseline levels of 68 serum metabolites. Of the nine metabolites that differentiated placebo and NAC groups, five were amino acids with lower levels in the NAC responder group compared with the NAC non-responders. Further analysis generated a predictive model of MADRS improvement including glycine, norleucine, threonine, proline, phenylalanine, tyrosine, glutamic acid, lysine and leucine (R2 = 0.853; adjusted R2 = 0.733). This prediction model predicted 85% of the variance in MADRS outcome after adjunctive treatment with NAC. BD participants with lower serum levels of free amino acids at baseline may be more likely to respond to adjunctive treatment with NAC.

The Right to Choose

The Right to Choose

Coping strategies in an euthymic phase for major depressed patients

Background and objectivesThe present study aimed to explore for a better understanding of the dysfunctional coping styles in patients with major depression, making a comparison between an acute and an euthymic phase. MethodsA longitudinal study included 65 patients diagnosed with recurrent major depressive disorder who were twice evaluated, clinically and for coping mechanisms, for the first time during an acute depressive episode and for the second time after 6 months of euthymia. Coping mechanisms were assessed with the Brief COPE scale and the severity of depression was evaluated by the Hamilton Depression Rating Scale — 17 items. For both phases of the illness, depression and euthymia, the results were compared with 35 healthy controls. ResultsEuthymic patients, in comparison with healthy individuals, displayed significant statistical differences (p < 0.05) showing greater use of self-distraction, disengagement, and substance use coping styles. For most of the dysfunctional coping tests applied the scores were found similar for depressed patients and euthymic ones. Also, no significant statistical associations were found between the use of dysfunctional coping mechanisms for the two phases of the examination. ConclusionsEuthymic patients, when compared with healthy controls, showed significant statistical differences in the use of dysfunctional coping strategies. No statistically significant differences were found between the two phases of depression, the use of dysfunctional coping mechanisms being the same.

Serum cortisol as a predictor for posttraumatic stress disorder symptoms in post-myocardial infarction patients

BackgroundAfter an acute myocardial infarction (MI22MI: myocardial infarction), patients may develop posttraumatic stress disorder (PTSD33PTSD: posttraumatic stress disorder). There is evidence for alterations in the hypothalamic–pituitary–adrenal axis in PTSD. An association between patients` cortisol level after experiencing an MI and subsequent PTSD symptoms has not been investigated yet. Therefore, the aim of this study was to examine whether serum cortisol measured in patients admitted to hospital for acute coronary care after MI is predictive of PTSD symptoms at three and 12 months post-MI, respectively. MethodsPatients (N=106) with a verified MI and high risk for the development of MI-induced PTSD symptoms were included in the study within 48 hours of hospital admission for acute coronary intervention. Serum cortisol was measured from fasting venous blood samples the next morning. Hierarchical regression analysis was used to test for an independent contribution of cortisol levels from admission to the Clinician-Administered PTSD Scale sum score three and 12 months after discharge from the coronary care unit. ResultsHierarchical regression analysis showed that lower serum cortisol levels were significantly associated with more severe PTSD symptoms three months (B=-0.002, p=0.042) and 12 months (B=-0.002, p=0.043) post-MI. LimitationsThe generalizability of the findings is limited to patients with high acute peri-traumatic distress and without an acute severe depressive episode. The study does not provide any information about the diurnal cortisol pattern. ConclusionLower serum cortisol measured during MI hospitalization may predict more severe MI-induced PTSD symptoms three and 12 months after hospital discharge.

Efficacy of amisulpride for depressive symptoms in individuals with mental disorders: A systematic review and meta-analysis.

BackgroundDepressive symptoms occur in several psychiatric disorders, often in the absence of a formal diagnosis of depression. We aimed to evaluate the efficacy and the tolerability of amisulpride, both alone and as augmentation therapy, in the treatment of depressive symptoms in individuals with any major psychiatric disorder.MethodsWe searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey and ProQuest up to March 2020 for randomised controlled trials focussing on the treatment of an acute depressive episode in any major psychiatric disorder. A random‐effect meta‐analysis was performed to synthesize the findings on depressive symptoms (primary outcome), response rate and tolerability.ResultsWe retrieved 11 studies including 2065 patients with a diagnosis of dysthymia (eight studies), major depression (one study) or schizophrenia (two studies). Amisulpride 50 mg/day was associated with a larger reduction of depressive symptoms compared to placebo (standardised mean difference [SMD] = −0.70, CI 95% −0.92, −0.49; I 2 = 0.0%), and was found to be comparable to selective serotonin reuptake inhibitors (SSRIs; SMD = −0.08, CI 95% −0.23, 0.06, I 2 = 0.0%), amineptine, imipramine and amitriptyline in the treatment of dysthymia (three studies, not pooled). In individuals with schizophrenia, amisulpride administered at higher doses (>400 mg/day) was comparable to olanzapine and risperidone (two studies, not pooled). In terms of tolerability, amisulpride was superior to placebo for dysthymia (odds ratio [OR] = 3.94, CI 95% 1.07, 14.48; I 2 = 0.0) and comparable with SSRIs (OR = 0.94, CI 95% 0.55, 1.62; I 2 = 0.0%).ConclusionTreatment with amisulpride could be a valid choice for selected individuals with dysthymia or depressive symptoms in the context of schizophrenia. More studies on the efficacy and tolerability of amisulpride are needed to draw firm conclusions on its potential benefits in other psychiatric disorders.

Assessment and Treatment of a Young Adult with Congenital Heart Disease and ADHD.

Phillip is a young man born with hypoplastic left heart syndrome referred to your practice for a range of mental health concerns. He underwent palliation to an extracardiac Fontan in infancy and experienced multiple complications over the next decade including valvular regurgitation and arrhythmias necessitating a pacemaker. Phillip continued to have systolic heart failure with New York Heart Association class II symptoms, managed with 4 medications and anticoagulation.Despite this complex history, Phillip had intact cognitive abilities, achieved typical milestones, and performed well academically in secondary school. His first year of college proved to be more challenging, and Phillip presented to the outpatient psychiatry service with an acute depressive episode. His family history included depression, without known attention-deficit/hyperactivity disorder (ADHD). Treatment, including a selective serotonin reuptake inhibitor, cognitive behavioral therapy, and family support, led to near resolution of his symptoms of depression.In subsequent appointments, Phillip described a long history of inattention and disorganization with onset in childhood. This contributed to the decision to leave college, despite remission of symptoms of depression. Phillip was unable to study for any extended period without "perfect conditions," described as the absence of potential distractions except for background music. Despite attempts to maintain "perfect conditions," Phillip was often off task and "hyperfocusing" on irrelevant topics. Phillip struggled with planning and time management and would misplace items daily. Moreover, although the importance of self-care was well understood, Phillip often forgot to take his cardiac medication or to exercise, and he admitted to inconsistent sleep habits because of losing track of time.Based on a comprehensive psychiatric evaluation including retrospective report from a parent, Phillip was diagnosed with ADHD, coexisting with major depressive disorder, in remission. Significant ADHD symptoms were documented by interview, self-report, and administration of an abbreviated neuropsychological battery.Considering concerns regarding use of stimulants in a patient with congenital heart disease, including death, stroke, and myocardial infarction,1,2 how would you assess the risks-benefits of use of stimulants with Phillip? 1. Wilens TE, Prince JB, Spencer TJ, et al. Stimulants and sudden death: what is a physician to do? Pediatrics. 2006;118:1215-1219.2. Zito JM, Burcu M. Stimulants and pediatric cardiovascular risk. J Child Adolesc Psychopharmacol. 2017;27:538-545.

Clinical profile and outcome of bipolar disorder patients receiving electroconvulsive therapy

IntroductionBipolar disorder (BD) is a serious and extremely recurrent illness frequently associated with cognitive and functional deterioration that poses many treatment challenges. However, over the years, with the evolution of more and more mood stabilizers and neuroleptics, there were controversies surrounding the use of electroconvulsive therapy (ECT).Objectives The present study was an attempt at studying the clinical profile of BD patients who receive ECT and to study its effectiveness.MethodsRetrospective data were collected from all bipolar patients submitted to acute ECT treatment, between June 2015 and June 2016, at the Department of Psychiatry of the University Hospital of Mahdia, Tunisia.ResultsDuring the study period, among all the patients who received ECT, 47% were diagnosed to have bipolar disorder. ECT was administered most commonly for mania with psychotic symptoms, followed by severe depression with psychotic symptoms. Most of patients showed more than 65% response (based on reduction in the standardized rating scales) with ECT. Few patients (18.7%) reported some kind of side effects.ConclusionsECT resulted very effective for all BD acute depressive and manic episodes not responding to conventional pharmacologic management.

Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression

Major depressive episodes in bipolar disorder are common and debilitating. Repetitive transcranial magnetic stimulation is well established in the treatment of major depressive disorder, and the intermittent theta burst stimulation (iTBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, iTBS has not been adequately studied in bipolar disorder and, therefore, its efficacy is uncertain. To determine whether iTBS to the left dorsolateral prefrontal cortex (LDLPFC) is safe and efficacious in the treatment of acute bipolar depression. This study was a double-blind, 4-week, randomized clinical trial of iTBS targeting the LDLPFC. Two Canadian academic centers recruited patients between 2016 and 2020. Adults with bipolar disorder type I or type II experiencing an acute major depressive episode were eligible if they had not benefited from a first-line treatment for acute bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments and were currently treated with a mood stabilizer, an atypical antipsychotic, or their combination. Seventy-one participants were assessed for eligibility, and 37 were randomized to daily sham iTBS or active iTBS using a random number sequence, stratified according to current pharmacotherapy. Data analysis was performed from April to September 2020. Four weeks of daily active iTBS (120% resting motor threshold) or sham iTBS to the LDLPFC. Nonresponders were eligible for 4 weeks of open-label iTBS. The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. Secondary outcomes included clinical response, remission, and treatment-emergent mania or hypomania. The trial was terminated for futility after 37 participants (23 women [62%]; mean [SD] age, 43.86 [13.87] years; age range, 20-68 years) were randomized, 19 to sham iTBS and 18 to active iTBS. There were no significant differences in Montgomery-Asberg Depression Rating Scale score changes (least squares mean difference between groups, -1.36 [95% CI, -8.92 to 6.19; P = .91] in favor of sham iTBS), and rates of clinical response were low in both the double-blind phase (3 of 19 participants [15.8%] in the sham iTBS group and 3 of 18 participants [16.7%] in the active iTBS group) and open-label phase (5 of 21 participants [23.8%]). One active iTBS participant had a treatment emergent hypomania, and a second episode occurred during open-label treatment. iTBS targeting the LDLPFC is not efficacious in the treatment of acute bipolar depression in patients receiving antimanic or mood stabilizing agents. Additional research is required to understand how transcranial magnetic stimulation treatment protocols differ in efficacy between unipolar and bipolar depression. ClinicalTrials.gov Identifier: NCT02749006.

Citalopram for Acute and Preventive Efficacy in Bipolar Depression (CAPE-BD): A Randomized, Double-Blind, Placebo-Controlled Trial.

To assess the efficacy and safety of citalopram in the acute and maintenance phases of bipolar depression in a randomized, double-blind, placebo-controlled trial. Between 2007 and 2014, 119 subjects with acute major depressive episodes diagnosed with DSM-IV bipolar disorder, type I or type II, were randomized blindly to citalopram or placebo, added to standard mood stabilizers. They were followed for 6 weeks for acute efficacy (primary outcome) and up to 1 year for maintenance efficacy (secondary outcome) using scores on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mania Rating Scale of the Schedule for Affective Disorders and Schizophrenia (MRS-SADS). The study was powered for a clinically meaningful effect size. Mean ± SD MADRS scores changed from a baseline value of 27.4 ± 9.1 to 13.1 ± 8.4 at the end of the acute phase for citalopram versus a change from 27.4 ± 7.3 to 15.2 ± 9.9 for placebo, a clinically and statistically nonsignificant difference. Maintenance efficacy also was not better with citalopram than with placebo. Acute manic/hypomanic episodes were similar in both groups, and subjects with type II illness did not have better outcomes than subjects with type I illness. In maintenance treatment, MRS-SADS scores were greater overall, especially in subjects with a rapid-cycling illness course, with citalopram versus placebo. Citalopram, added to standard mood stabilizers, did not have clinically meaningful benefit versus placebo for either acute or maintenance treatment of bipolar depression. Acute mania did not worsen with citalopram, but maintenance treatment led to worsened manic symptoms, especially in subjects with a rapid-cycling course. ClinicalTrials.gov identifier: NCT00562861.

Mobile App-Based Self-Report Questionnaires for the Assessment and Monitoring of Bipolar Disorder: Systematic Review.

BackgroundBipolar disorder is a chronic, progressive illness characterized by recurrent episodes of mania and depression. Self-report scales have historically played a significant role in the monitoring of bipolar symptoms. However, these tools rely on episodic memory, which can be unreliable and do not allow the clinician to monitor brief episodic symptoms or the course of symptoms over shorter periods of time. Mobile app–based questionnaires have been suggested as a tool to improve monitoring of patients with bipolar disorder.ObjectiveThis paper aims to determine the feasibility and validity of mobile app–based self-report questionnaires.MethodsWe performed a systematic review of the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, PsycInfo, Web of Science, Ovid MEDLINE, and EMBASE databases were searched for papers published in English that assessed adherence to and the validity of mobile app–based self-report questionnaires. Relevant studies published from database creation to May 22, 2020, were identified, and results examining the validity of and rates of adherence to app-based self-report questionnaires are reported.ResultsA total of 13 records were identified for inclusion in this review. Of these studies, 4 assessed the concurrent validity of mobile app–based self-report tools, with the majority of findings indicating significant associations between data collected using these tools and the Young Mania Rating Scale, Hamilton Depression Rating Scale-17, or Montgomery-Åsberg Depression Rating Scale (P<.001 to P=.24). Three studies comparing the variability or range of symptoms between patients with bipolar disorder and healthy controls suggested that these data are capable of differentiating between known groups. Two studies demonstrated statistically significant associations between data collected via mobile app–based self-report tools and instruments assessing other clinically important factors. Adherence rates varied across the studies examined. However, good adherence rates (>70%) were observed in all but 1 study using a once-daily assessment. There was a wide range of adherence rates observed in studies using twice-daily assessments (42%-95%).ConclusionsThese findings suggest that mobile app–based self-report tools are valid in the assessment of symptoms of mania and depression in euthymic patients with bipolar disorder. Data collected using these tools appear to differ between patients with bipolar disorder and healthy controls and are significantly associated with other clinically important measures. It is unclear at this time whether these tools can be used to detect acute episodes of mania or depression in patients with bipolar disorder. Adherence data indicate that patients with bipolar disorder show good adherence to self-report assessments administered daily for the duration of the study periods evaluated.

Lithium treatment - the state of the art for 2020.

The paper presents the current state of knowledge on lithium treatment. The history of the therapeutic application of lithium began in 1859 and its introduction to modern psychiatry took place 90 years later. Since the early 1960s, lithium became a precursor of mood-stabilizing drugs and nowadays is the drug of choice for the prevention of manic and depressive recurrences in mood disorders. It remains a valuable drug for the treatment of acute episodes of mania and depression, especially for the augmentation of antidepressant drugs in treatment resistant depression. The factors of prophylactic efficacy of lithium in the context of the so-called excellent lithium responders and the efficacy in affective episodes were discussed. Among mood-stabilizing drugs, lithium exerts the biggest effect on preventing suicidal behaviors. It also shows antiviral (mainly against herpes viruses) and immunomodulatory activity. The evidence has recently been gathered on neuroprotective and ‛antidementia' properties of lithium, which prompted its use in neurodegenerative disorders. The biochemical mechanism of lithium is associated mainly with the inhibition of glycogen synthase kinase-3 and an effect on intracellular signaling. The recommendations for managing lithium-induced adverse effects both in the early and late period of treatment as well as for lithium use in pregnancy and perinatal period were given. The necessity of overcoming negative perceptions of lithium was pointed out to increase the number of possible beneficiaries of lithium treatment. Both introduction of lithium into modern psychiatry and its therapeutic effects have been reflected in literature and art.

Evaluation of the capacity to consent to treatment among patients with bipolar disorder: Comparison between the acute psychopathological episode and the stable mood phase

• Treatment decision-making capacity (TDMC) is assessed with the MacCAT-T. • TDMC is different according to inpatient / outpatient status. • Inpatients are acutely ill, while outpatients are euthymic. • Outpatients score higher on MacCAT-T than inpatients. • Outpatients are more able to express consent for an alternative treatment. Treatment decision-making capacity (TDMC) is basic to therapeutic processes and can be measured with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T). TDMC may fluctuate in bipolar disorder (BD). We used the MacCAT-T to compare BD inpatients with an acute manic or depressive episode with euthymic BD outpatients on their TDMC. We used the MacCAT-T to cross-sectionally assessed from May 2018 through October 2019 the TDCM of adult BD patients with a Mini Mental State Examination score ≥18, a group of acutely ill hospitalized patients for a manic/hypomanic episode and another of euthymic outpatients during their regular visits at our outpatient clinic. Patients were assessed with other specific psychiatric rating scales. We also tested their TDCM to an alternative treatment. The inpatient group consisted of 53 patients and the outpatient of 47. Inpatients scored worse than outpatients on the MacCAT-T understanding, reasoning and expressing a choice subscale, but not on the appreciating scale. Outpatients were more capable in understanding the characteristics of an alternative advance treatment. MacCAT-T subscales correlated directly with mental state scores, and inversely with mania and psychopathology scores, while only the appreciating subscale correlated inversely with depression scores. The limitations include small sample size and cross-sectional design. TDCM is higher in BD patients at their euthymic state, hence this is the right time to obtain consent from a BD patient in view of possibly depositing psychiatric advance directives.

Depression and its Dilemma

Depression is a common mental disorder that presents with depressed mood, loss of interest or pleasure, decreased energy, feelings of guilt or low self-worth, disturbed sleep or appetite, and poor concentration. Depression shall become the second largest illness in terms of morbidity by another decade. 50-65% of patients respond to the first antidepressant. No particular antidepressant agent is superior to another in efficacy or time to response. Depression is less prevalent among older adults than among younger adults but can have serious consequences. Choice can be guided by matching patients’ symptoms to side effect profile, presence of medical and psychiatric co morbidity. The adequate treatment of residual symptoms following an acute depressive episode, including insomnia symptoms, may prevent relapse. In the near future, developments are likely to remain focused on monoamine neurotransmitters, with the aim of finding agents that are either more effective, better tolerated or that have a faster onset of action than existing options.

A Case of Lithium-Associated Hypocalciuric Hypercalcemia

Lithium is the treatment of choice for acute manic, mixed, and depressive episodes of bipolar disorder, along with long-term prophylaxis. A significant proportion of patients taking lithium develop lithium-associated hypercalcemia. Most cases are due to lithium-associated hyperparathyroidism with underlying parathyroid adenoma or hyperplasia. We present a 67-year-old woman who presented with increasing lethargy and loss of concentration and was found to have slightly raised serum calcium levels with inappropriately low urinary calcium excretion levels characteristic of hypocalciuric hypercalcemia. She had been on lithium therapy for over 15 years for bipolar disease. She had no other cause for these findings and had no family history to suggest familial hypocalciuric hypercalcemia. Neck imaging ruled out any parathyroid adenoma or hyperplasia. A diagnosis of lithium-associated hypocalciuric hypercalcemia was discussed with the patient, and she remains stable under surveillance.

Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study

A cross-diagnostic, post-hoc analysis of the BRIDGE-II-MIX study was performed to investigate how unipolar and bipolar patients suffering from an acute major depressive episode (MDE) cluster according to severity and duration. Duration of index episode, Clinical Global Impression-Bipolar Version-Depression (CGI-BP-D) and Global Assessment of Functioning (GAF) were used as clustering variables. MANOVA and post-hoc ANOVAs examined between-group differences in clustering variables. A stepwise backward regression model explored the relationship with the 56 clinical-demographic variables available. Agglomerative hierarchical clustering with two clusters was shown as the best fit and separated the study population (n = 2314) into 65.73% (Cluster 1 (C1)) and 34.26% (Cluster 2 (C2)). MANOVA showed a significant main effect for cluster group (p < 0.001) but ANOVA revealed that significant between-group differences were restricted to CGI-BP-D (p < 0.001) and GAF (p < 0.001), showing greater severity in C2. Psychotic features and a minimum of three DSM-5 criteria for mixed features (DSM-5-3C) had the strongest association with C2, that with greater disease burden, while non-mixed depression in bipolar disorder (BD) type II had negative association. Mixed affect defined as DSM-5-3C associates with greater acute severity and overall impairment, independently of the diagnosis of bipolar or unipolar depression. In this study a pure, non-mixed depression in BD type II significantly associates with lesser burden of clinical and functional severity. The lack of association for less restrictive, researched-based definitions of mixed features underlines DSM-5-3C specificity. If confirmed in further prospective studies, these findings would warrant major revisions of treatment algorithms for both unipolar and bipolar depression.