Cariprazine Augmentation in Treatment-Resistant Bipolar Depression: Data from a Retrospective Observational Study.

BACKGROUND: Treatment-resistant bipolar depression is one of the leading problems in psychiatry with serious consequences on patients functioning, quality of life and resource utilization. Despite this, there is a lack of consensus on diagnostic criteria and treatment algorithms. OBJECTIVE: The objective of the present study is to assess the acute effectiveness and tolerability of cariprazine in the management of treatment resistant bipolar depression. METHODS: This is a four weeks retrospective multicentric observational study on patients with treatment resistant bipolar depression receiving cariprazine in augmentation to the current treatment. Cariprazine dosage changed during the follow-up period according to clinical judgment. Since data followed a non-normal distribution, non-parametric tests were used to pursue the analysis. The effectiveness of cariprazine was assessed through the mean change in Hamilton Depression rating scale (HAM-D) scores from baseline to endpoint. For missing values, a "Last Observation Carried Forward" approach was applied. RESULTS: Fifty-one patients were enrolled. Four patients (7.8%) discontinued cariprazine mainly due to adverse events. Mean cariprazine dose was 1.7 mg/day. The mean HAM-D score decreased significantly from baseline (T0) to week 4 (T4) at each evaluation point. Fourty-five.one per cent of the patients benefited of cariprazine add-on strategy: 23.5% achieved a clinical response and 21.6% were remitters. Among the completers, 70.6% experienced at least one adverse event. All side effects were mild to moderate. CONCLUSION: Cariprazine seems to be an effective and well tolerated option in the management of patients with treatment resistant bipolar depression.

Differential diagnosis of unipolar versus bipolar depression by GSK3 levels in peripheral blood: a pilot experimental study.

BACKGROUND: The differential diagnosis of patients presenting for the first time with a depressive episode into unipolar disorder versus bipolar disorder is crucial to establish the correct pharmacological therapy (antidepressants vs mood stabilizers), but no biological markers are currently available. Several lines of evidence indicate an involvement of Glycogen Synthase Kinase-3 (GSK3) in the pathophysiology of depression. However, previous reports about GSK3 in peripheral blood were incomplete or inconsistent, so a specific marker is not yet available. The aim was to search for consistent differences in GSK3α and GSK3ß or of their phosphorylated forms in samples of peripheral blood from patients with unipolar and bipolar depression. METHODS: Mononucleate peripheral blood cells (PBMCs) of samples from patients presenting with a depressive episode were analyzed with the western blot technique. RESULTS: The total amount of GSK3ß in PBMCs was significantly lower in patients with bipolar disorder than in patients with unipolar depression. The sensitivity based on GSK3ß was 85%. GSK3α was not significantly different but allowed a correct detection of 57% of BD patients. The combination in series of GSK3ß and GSK3α yields a sensitivity of about 100%, but with 26.7% false negatives. CONCLUSIONS: Our results suggest that PBMC GSK3ß could be a candidate biomarker for the differential diagnosis of bipolar disorder versus unipolar depression. This finding may help in implementing the still limited panel of peripheral biomarkers for differential diagnosis between unipolar and bipolar disorder in patients presenting with a depressive episode.

Assessing Adult ADHD Through Objective Neuropsychological Measures: A Critical Overview.

OBJECTIVE: This review examines the role of neuropsychological tests in the diagnostic assessment of adult ADHD, focusing on their ability to discriminate individuals with ADHD from those with other psychiatric conditions. METHOD: PubMed, Embase, and PsycINFO were searched for eligible peer-reviewed studies from inception to September 2022. RESULTS: Ten studies were included. Among the objective measures analyzed, Continuous Performance Tests were the only capable to reliably distinguish individuals with ADHD from other psychiatric patients, in a combined approach with clinical interview instruments. The other objective tests showed mixed and inconsistent results. CONCLUSION: This finding suggest that further studies are needed to develop objective measures more tailored to the core symptoms of ADHD, in order to improve the discriminatory ability of the tests and help the clinicians in the complex differential diagnosis between ADHD and other psychiatric disorders.

A Psychoanalytic-Derived Brief Psychotherapeutic Approach in the Treatment of Major Depression: Monotherapy Studies.

Over the years, short term psychodynamic therapy (STPP) has been broadly researched in order to evaluate its efficacy in the treatment of major psychiatric disorders. In particular, a consistent number of studies focused on assessing clinical outcomes of the principal psychodynamic techniques in treating depressive disorders. We conducted a narrative review in which we aimed to evaluate the efficacy of STPP in monotherapy in major depressive disorder and to assess possible features that may correlate with its clinical use. Databases searched were PubMed, Ovid, Scopus, PsycINFO and Cochrane Libraries from inception to July 2022. Our research underlined that STPP in monotherapy is particularly effective in moderately severe depression and in preventing depressive relapses. Moreover, a case-by-case evaluation of its efficacy should be performed when considering STPP for the treatment of major depression with other comorbid psychiatric conditions. Although such key points emerged from scientific evidence, STPP should be better studied in the long-term perspective; further research is needed to define the clinical scenarios in which STPP can be considered a first-line approach as monotherapy in major depressive disorder compared to medications or other types of psychotherapy.

Manic-Depressive Cycles in Bipolar Disorder: Clinical and Treatment Implications.

INTRODUCTION: Cycle patterns of bipolar disorders (BDs) have been previously shown to be associated with clinical characteristics and response to lithium salts. Here, we evaluated the distribution of different types of manic-depressive cycles in a large sample of patients with BD. The associations between a mania-depression-interval (MDI) course and depression-mania-interval (DMI) course with sociodemographic/clinical factors were also assessed in order to define specific clinical profiles. METHODS: In this cross-sectional study, 806 patients with BD admitted to the Psychiatric Unit of San Luigi Gonzaga Hospital in Orbassano and Molinette Hospital in Turin, Italy, were recruited. Patients were grouped according to the following course patterns: MDI, DMI, continuous cycling (CC, <4 episodes/year without intervals), rapid cycling (RC, ≥4 episodes/year), and irregular (IRR) cycling. We compared several sociodemographic and clinical variables in an MDI versus DMI course by means of ANOVA and Pearson χ2 with Bonferroni correction. RESULTS: Bipolar cycles were distributed as follows: 50.2% IRR course, 31.5% MDI course, 16% DMI course, 1.2% CC, and 1% RC. Compared to DMI course, patients with an MDI course were more often men, younger, with an earlier onset, a manic polarity onset, and more lifetime compulsory admissions. They were more frequently treated with lithium and antipsychotics. Patients with a DMI course had older age at diagnosis and at first mood-stabilizer treatment and were more often misdiagnosed with a major depressive disorder. These patients were more commonly treated with anticonvulsants, and they had more frequently failed treatment trials with lithium salts in the past. CONCLUSION: This study supports the utility of classifying BD according to their course patterns. This classification holds prognostic as well as therapeutic implications.

Aripiprazole Augmentation to Mood Stabilizers for Obsessive-Compulsive Symptoms in Bipolar Disorder.

Background and objectives: Aripiprazole is a first-line agent in the treatment of bipolar disorder (BD) and available data demonstrates its efficacy on clinical symptoms in serotonin reuptake inhibitors-resistant obsessive-compulsive disorder (OCD) patients. Therefore, aripiprazole augmentation to mood stabilizers could represent a promising treatment in BD patients with comorbid OCD. The study examined the efficacy and safety of aripiprazole added to lithium or valproate for the treatment of obsessive-compulsive (OC) symptoms in euthymic BD patients with comorbid OCD. Materials and methods: This is a 12-week prospective observational study. The efficacy of aripiprazole on OC symptoms was assessed through the mean change of Yale-Brown Obsessive-Compulsive (YBOCS) total score. Tolerability was assessed with the Utvalg for Kliniske Undersogelser (UKU) side effect scale and by reporting adverse events. Results: A total of 70 patients were included in the analyses. The withdrawal rate was 21.4%, mainly due to adverse events. Mean ± SD final aripiprazole dose was 15.2 ± 5.3 in the completer sample (N = 55). The Y-BOCS mean score decreased from 24.0 ± 4.1 at baseline to 17.1 ± 4.3 at 12 weeks. Treatment response rate (Y-BOCS reduction ≥ 35%) was 41.8%, while partial response rate (Y-BOCS reduction greater than 25% but less than 35% from baseline) accounted for the other 18.2% of patients. Overall, 91.4% of completers had at least 1 adverse effect (tremor, tension/inner unrest, reduced duration of sleep, akathisia). No significant differences emerged comparing aripiprazole efficacy and tolerability between patients treated with lithium or valproate. Conclusion: Our findings show that aripiprazole addition to lithium or valproate can reduce OC symptoms in real-world BD euthymic patients.