Mixed states in bipolar and major depressive disorders: systematic review and quality appraisal of guidelines.

OBJECTIVE: This systematic review provided a critical synthesis and a comprehensive overview of guidelines on the treatment of mixed states. METHOD: The MEDLINE/PubMed and EMBASE databases were systematically searched from inception to March 21st, 2018. International guidelines covering the treatment of mixed episodes, manic/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II. RESULTS: The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood-stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo/manic/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The AGREE II overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines. CONCLUSION: The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.

Aggressiveness in depression: a neglected symptom possibly associated with bipolarity and mixed features.

OBJECTIVE: To evaluate aggressiveness during a major depressive episode (MDE) and its relationship with bipolar disorder (BD) in a post hoc analysis of the BRIDGE-II-MIX study. METHOD: A total of 2811 individuals were enrolled in this multicenter cross-sectional study. MDE patients with (MDE-A, n = 399) and without aggressiveness (MDE-N, n = 2412) were compared through chi-square test or Student's t-test. A stepwise backward logistic regression model was performed. RESULTS: MDE-A group was more frequently associated with BD (P < 0.001), while aggressiveness was negatively correlated with unipolar depression (P < 0.001). At the logistic regression, aggressiveness was associated with the age at first depressive episode (P < 0.001); the severity of mania (P = 0.03); the diagnosis of BD (P = 0.001); comorbid borderline personality disorder (BPD) (P < 0.001) but not substance abuse (P = 0.63); no current psychiatric treatment (P < 0.001); psychotic symptoms (P = 0.007); the marked social/occupational impairment (P = 0.002). The variable most significantly associated with aggressiveness was the presence of DSM-5 mixed features (P < 0.001, OR = 3.815). After the exclusion of BPD, the variable of lifetime suicide attempts became significant (P = 0.013, OR = 1.405). CONCLUSION: Aggressiveness seems to be significantly associated with bipolar spectrum disorders, independently from BPD and substance abuse. Aggressiveness should be considered as a diagnostic criterion for the mixed features specifier and a target of tailored treatment strategy.

Unravelling potential severe psychiatric repercussions on healthcare professionals during the COVID-19 crisis.

The coronavirus disease 2019 (COVID-19) outbreak is putting healthcare professionals, especially those in the frontline, under extreme pressures, with a high risk of experiencing physical exhaustion, psychological disturbances, stigmatization, insomnia, depression and anxiety. We report the case of a general practitioner, without relevant somatic or psychiatric history that experienced a "brief reactive psychosis (298.8)" under stressful circumstances derived from COVID-19. She presented with delusional ideas of catastrophe regarding the current pandemic situation, delusions of self-reference, surveillance and persecution, with high affective and behavioural involvement. Physical examination and all further additional investigations did not reveal any secondary causes. She was administered olanzapine 10 mg with significant psychopathological improvement being later discharged with indications to maintain the treatment. To our knowledge this is the first reported case of severe mental illness in a healthcare professional without previous psychiatric history due to COVID-19 outbreak. Around 85% of patients presenting a brief psychotic disorder will develop a potentially disabling serious psychotic illness in the long-term. This case represents the potentially serious mental health consequences on healthcare professionals throughout the COVID-19 crisis and emphasizes the need to implement urgent measures to maintain staff mental health during the current pandemic.

Lithium and suicide prevention in mood disorders and in the general population: A systematic review.

Suicide contributes to 1-4 % of deaths worldwide every year. We conducted a systematic review aimed at summarizing evidence on the use of lithium for the prevention of suicide risk both in mood disorders and in the general population. We followed the PRISMA methodology (keywords: "lithium", "suicide" AND "suicidal" on Pubmed, Cochrane CENTRAL, Clinicaltrial.gov, other databases). Inclusion criteria: lithium therapy in mood disorder or found in drinking water or scalp in the general population. Exclusion criteria: no lithium administration. From 918 screened references, 18 prospective (number of participants: 153786), 10 retrospective (number of participants: 61088) and 16 ecological studies (total sample: 2062) were included. Most of the observational studies reported a reduction in suicide in patients with mood disorders. All studies about lithium treatment's duration reported that long-term lithium give more benefits than short-term lithium in suicide risk The evidence seems to attribute an intrinsic anti-suicidal property of lithium, independent of its proven efficacy as a mood stabilizer.

A systematic review on sleep alterations anticipating the onset of bipolar disorder.

BACKGROUND: Sleep alterations are frequent occurrence in Bipolar Disorder (BD), both in acute and interepisodic phases. Sleep alterations have been also described both long before BD onset, as aspecific risk syndromes, or as immediate prodromes of BD onset. The aim of the present study is to systematically review the relationship between sleep alterations anticipating for the full-blown onset of BD, both in general and according to specific polarities of onset. METHODS: A systematic literature research according to PRISMA statement and considering: 1. prospective studies about BD patients' offspring with sleep alterations who later developed BD. 2. prospective studies assessing patients with sleep disorders who later developed BD. 3. retrospective studies on BD patients where sleep alterations before BD onset of the disease were reported. RESULTS: A total of 16 studies were included in this review. Sleep disturbances may frequently appear 1 year before the onset of BD or more, often during childhood or adolescence. A decreased need for sleep may precede the onset of the illness, specially a manic episode, while insomnia appears to anticipate either a manic or a depressive episode. Hypersomnia seems to precede bipolar depressive episodes. CONCLUSIONS: Sleep alterations frequently appear long before the onset of BD, and appear to be related specifically to the polarity of the index episode. The detection and treatment of sleep alterations in special high risk populations may help achieving an earlier detection of the illness.

The implications of hypersomnia in the context of major depression: Results from a large, international, observational study.

According to the DSM-5, "reduction in the need for sleep" is the only sleep-related criteria for mixed features in depressive episodes. We aimed at studying the prevalence, clinical correlates and the role of hypersomnia in a sample of acutely depressed patients. Secondarily, we factors significantly increasing the odds of hypersomnia were studied. We conducted a post-hoc analysis of the BRIDGE-II-Mix study. Variables were compared between patients with hypersomnia (SLEEP+) and with insomnia (SLEEP-) with standard bivariate tests. A stepwise backward logistic regression model was performed with SLEEP+ as dependent variable. A total of 2514 subjects were dichotomized into SLEEP+ (n = 423, 16.8%) and SLEEP- (n = 2091, 83.2%). SLEEP+ had significant higher rates of obese BMI (p < 0.001), BD diagnosis (p = 0.027), severe BD (p < 0.001), lifetime suicide attempts (p < 0.001), lower age at first depression (p = 0.004) than SLEEP-. Also, SLEEP+ had significantly poorer response to antidepressants (AD) such as (hypo)manic switches, AD resistance, affective lability, or irritability (all 0<0.005). Moreover, SLEEP+ had significantly higher rates of mixed-state specifiers than SLEEP- (all 0 < 0.006). A significant contribution to hypersomnia in our regression model was driven by metabolic-related features, such as "current bulimia" (OR = 4.21) and "overweight/obese BMI (OR = 1.42)". Globally, hypersomnia is associated with poor outcome in acute depression. Hypersomnia is strongly associated with mixed features and bipolarity. Metabolic aspects could influence the expression of hypersomnia, worsening the overall clinical outcome. Along with commonly used screening tools, detection of hypersomnia has potential, costless discriminative validity in the differential diagnosis unipolar and bipolar depression.

The aggressor at the mirror: Psychiatric correlates of deliberate self-harm in male prison inmates.

BACKGROUND: Deliberate self-harm (DSH) causes important concern in prison inmates as it worsens morbidity and increases the risk for suicide. The aim of the present study is to investigate the prevalence and correlates of DSH in a large sample of male prisoners. METHODS: A cross-sectional study evaluated male prisoners aged 18+ years. Current and lifetime psychiatric diagnoses were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders - DSM-IV Axis I and Axis II Disorders and with the Addiction Severity Index-Expanded Version. DSH was assessed with The Deliberate Self-Harm Inventory. Multivariable logistic regression models were used to identify independent correlates of lifetime DSH. RESULTS: Ninety-three of 526 inmates (17.7%) reported at least 1 lifetime DSH behavior, and 58/93 (62.4%) of those reported a DSH act while in prison. After multivariable adjustment (sensitivity 41.9%, specificity 96.1%, area under the curve=0.854, 95% confidence interval CI=0.811-0.897, P<0.001), DSH was significantly associated with lifetime psychotic disorders (adjusted Odds Ratio aOR=6.227, 95% CI=2.183-17.762, P=0.001), borderline personality disorder (aOR=6.004, 95% CI=3.305-10.907, P<0.001), affective disorders (aOR=2.856, 95% CI=1.350-6.039, P=0.006) and misuse of multiple substances (aOR=2.024, 95% CI=1.111-3.687, P=0.021). CONCLUSIONS: Borderline personality disorder and misuse of multiple substances are established risk factors of DSH, but psychotic and affective disorders were also associated with DSH in male prison inmates. This points to possible DSH-related clinical sub-groups, that bear specific treatment needs.