Efficacy and suitability of adding short-term psychodynamic psychotherapy (STPP) to pharmacotherapy in patients with depressive disorders: a systematic review.

INTRODUCTION: Recent guidelines on depressive disorders suggest a combination of antidepressants and psychotherapy in case of moderate to severe symptomatology. While cognitive behavioral therapy and interpersonal therapy are the most investigated interventions, psychodynamic psychotherapies have been less explored. OBJECTIVE: The aim of this paper is to systematically review literature data on the efficacy of shortterm psychodynamic psychotherapy (STPP) in combination with antidepressants in the treatment of depressive disorders, focusing both on short and on long-term results and on potential moderators that could influence its effectiveness. METHODS: The systematic review was conducted using the PRISMA guidelines. Databases searched were PubMed, Ovid, Scopus, and Cochrane Library, from inception to August 2023. RESULTS: Adding STPP to medications in the first six months of treatment didn't influence remission rates, but improved acceptability, work adjustment, interpersonal relationships, social role functioning, hospitalization rates and cost-effectiveness. After 12 months, a significant difference in remission rates arised, favouring combined therapy. In a long-term perspective, adding STPP to pharmacotherapy reduced the recurrence rate by almost 50%. STPP has proven to be more effective in longer depressive episodes, in more severe depressions and in patients with a childhood abuse history. Instead, STPP had no impact on major depressive disorder with comorbid Obsessive-Compulsive Disorder (OCD). CONCLUSIONS: Combining STPP with antidepressants appeared to be helpful both in a short-term and in a long-term perspective. Still, there are few rigorous studies with large samples and further research is needed to identify which subgroups of patients may benefit more from STPP.

The interplay between mentalization, personality traits and burnout in psychiatry training: Results from a large multicenter controlled study.

BACKGROUND: A better characterization of educational processes during psychiatry training is needed, both to foster personal resilience and occupational proficiency. METHODS: An adequate coverage of medical residents at the national level was reached (41.86% of the total reference population, 29 out of 36 training centers-80.55%). Controls were recruited among residents in other medical specialties. All participants were assessed by questionnaires to evaluate early life experiences, attachment style, personality traits, coping strategies, emotional competencies. A Structural Equation Model (SEM) framework was employed to investigate the interplay between individual factors. RESULTS: A total sample of 936 people was recruited (87.9% response-rate; 645 residents in psychiatry, 291 other medical residents). Psychiatry trainees reported a higher prevalence of adverse childhood experiences (emotional abuse, emotional neglect, physical neglect), greater attachment insecurity (anxious or avoidant) in comparison to other medical trainees. Psychiatry residents also reported higher social support-seeking as a coping strategy, lower problem-orientation, and lower transcendence. Lower neuroticism, higher openness to experience, and higher emotional awareness were also observed in psychiatry trainees. Psychiatry training was associated with a redefinition of conflict management skills as a function of seniority. The SEM model provided support for an interplay between early traumatic experiences, mentalization skills (coping strategies, emotion regulation), interpersonal competencies and occupational distress. CONCLUSIONS: The findings of the present study supported a theoretical model based on mentalization theory for the interactions between personal and relational competencies in psychiatry training, thus providing potential target of remodulation and redefinition of this specific process of education.

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.

Risk Factors for Suicide Reattempt among Adolescents and Young Adults: The Role of Psychiatric Disorders.

Suicidal behaviour among young people is a serious public health concern. Each suicide attempt is related to further suicide attempts and completed suicide. This study aims to explore risk factors associated with repeated suicide attempt among adolescents and young adults. The cohort included 510 patients aged 12-29 years residing in Piedmont Region in North-Western Italy, who had been admitted to hospital or emergency department with a diagnosis of suicide attempt between 2010 and 2020. Cox regression models were used to evaluate potential risk factors for repeated suicide attempt. During the 11-years follow-up, 20.6% of adolescents and young adults repeated suicide attempt, 24.8% of females and 12.3% of males. Nearly 90% of youth who attempted suicide had a diagnosis of psychiatric disorder. After adjustment, younger age of onset of suicidal behaviour, and diagnosis of schizophrenia, bipolar disorder, depressive disorder, anorexia nervosa and personality disorder were significantly associated with repeated suicide attempt. The early identification of patients at higher risk of repetition of suicidal behaviour is of crucial importance. Better understanding of risk factors and effective treatment of mental disorders could help suicide prevention to reduce the burden of the problem among young people. Special attention should be paid during the initial months following discharge from hospital or emergency department, when suicide reattempt risk is very high.

Prevalence and Correlates of Serotonin Syndrome in Real-World Inpatients.

BACKGROUND: Serotonin syndrome (SS) is a potentially life-threatening adverse drug reaction due to an increased central and peripheral serotonin activity, which usually presents as a triad of behavioral changes, neuromuscular excitability, and autonomic instability. Probably SS is often misdiagnosed, and its symptoms are mistaken for psychiatric symptoms or general medical issues: the true incidence of SS is not clear, and literature concerning potential risk factors is scarce. Our aims were to examine the prevalence of SS in a naturalistic sample of hospitalized patients and to evaluate potential factors related to the risk of developing the condition. METHODS: The sample included 133 patients being treated with serotonergic medications admitted to the psychiatric inpatient unit of the San Luigi Gonzaga Hospital. All patients received a medical examination (including a neurological examination) within 24 hours of admission. Serotonin syndrome was diagnosed according to Hunter Criteria. RESULTS: Sixteen patients (12%) were diagnosed with SS. In the subgroup of subjects with SS, we found a higher rate of male patients when compared with subjects with no SS (62.5% vs 33.3%, P = 0.023). CONCLUSIONS: SS probably is an underestimated condition, which should be carefully assessed in patients on serotonergic medications. Male gender was the only factor found to be significantly related to a higher risk of developing SS. Further studies on larger samples are needed, to gain more information on possible risk factors and to identify subjects more prone to developing SS, given the potential risk for patients' health.

The rapid antidepressant effectiveness of repeated dose of intravenous ketamine and intranasal esketamine: A post-hoc analysis of pooled real-world data.

INTRODUCTION: Intravenous ketamine (KET-IV) and intranasal esketamine (ESK-NS) are effective in the acute treatment of Treatment-Resistant Depression (TRD). Studies comparing KET-IV and ESK-NS concerning their action, safety, and tolerability are currently lacking. MATERIALS AND METHODS: We combined patients' data from two unipolar TRD cohorts that received KET-IV (n = 171) at the Canadian Rapid Treatment Center of Excellence in Toronto, Canada, or ESK-NS (n = 140) at several TRD clinics in Italy. The Quick Inventory for Depression Symptomatology-Self-Report-16/QIDS-SR16 in the KET-IV group and Montgomery-Åsberg Depression Rating Scale/MADRS in the ESK-NS group measured depressive symptoms at baseline (T0) and after the acute treatment phase (T1) (i.e., four infusions of KET-IV and eight administrations of ESK-NS). As different scales were used, the primary outcome was to compare the improvement in depression severity in the two cohorts by measuring effect sizes, response and remission rates. Finally, we compare side effects and discontinuation rates. RESULTS: At T1, KET-IV and ESK-NS significantly reduced depressive symptoms (respectively: QIDS-SR16 mean reduction = 5.65, p < 0.001; MADRS mean reduction = 11.41, p = 0.025). KET-IV showed larger effect sizes compared to ESK-NS (1.666 vs. 1.244). KET-IV had higher response rates (36 % vs. 25 %; p = 0.042) but not superior remission rates (13 % vs. 12 %; p = 0.845) than ESK-NS at T1. Despite more reported side effects, KET-IV did not cause more discontinuations for adverse events (4.6 % vs. 2.12 %; p = 0.228) than ESK-NS. CONCLUSION: KET-IV showed a higher short-term antidepressant effect, whereas ESK-NS exhibited lower side effects. Both were generally well tolerated. Future head-to-head studies should consider the long-term efficacy of these treatments.

Facts and myths about the use of lithium for bipolar disorder in routine clinical practice: an expert consensus paper.

BACKGROUND: Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a 'forgotten drug' and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common "misconceptions" and "stereotypes" associated with lithium treatment; we also provide a list of "good reasons" for using lithium in ordinary clinical practice to overcome those false myths. MAIN TEXT: A narrative search of the available literature has been performed entering the following keywords: "bipolar disorder", "lithium", "myth", "mythology", "pharmacological treatment", and "misunderstanding". The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients' groups suffering from bipolar disorder; (3) Drug-drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. CONCLUSIONS: In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

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.

Routine treatment pathways in a cohort of patients with major depression and suicidality in Italy: the ARIANNA observational study.

BACKGROUND: Major Depressive Disorder (MDD) with suicidal ideation, intent, or behavior is a psychiatric emergency with controversial care management. Our study describes the comprehensive treatment pathways of this population in Italian routine clinical practice. METHODS: ARIANNA [NCT04463108] is an observational prospective and retrospective cohort study involving both primary data collection and secondary data extract. A total of 137 adult MDD patients with suicidality were enrolled from 24 Italian care sites and followed for 90 days. Other than the description of treatment patterns, the impact of treatment on depressive symptoms and suicidality, the burden on the patient's and caregiver's quality of life, healthcare resource utilization and costs were described. RESULTS: Of the 133 eligible patients, 68.4% were female, and the median age was 47. Approximately half of the study population had a current severe major depressive episode. Treatment strategies at the time of active suicidal ideation with intent definition/confirmation (t0) were heterogeneous, increasing in complexity during observation. According to the MADRS, patients with remission at t0+1 day were 2.6%, with the mean total score decreasing from 37.2 at t0 to 32.3. LIMITATIONS: The study sites were not randomly selected. CONCLUSIONS: To the best of our knowledge, this is the first cohort study that prospectively describes the characteristics of patients with MDD and suicide risk in Italy, and how they are treated in clinical practice. The study confirms this is a difficult-to-treat population. In addition, a lack of rapid, effective treatment for reducing depressive symptoms and suicidality is observed.

Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING).

Treatment-resistant depression (TRD) represents a severe clinical condition with high social and economic costs. Esketamine Nasal Spray (ESK-NS) has recently been approved for TRD by EMA and FDA, but data about predictors of response are still lacking. Thus, a tool that can predict the individual patients' probability of response to ESK-NS is needed. This study investigates sociodemographic and clinical features predicting responses to ESK-NS in TRD patients using machine learning techniques. In a retrospective, multicentric, real-world study involving 149 TRD subjects, psychometric data (Montgomery-Asberg-Depression-Rating-Scale/MADRS, Brief-Psychiatric-Rating-Scale/BPRS, Hamilton-Anxiety-Rating-Scale/HAM-A, Hamilton-Depression-Rating-Scale/HAMD-17) were collected at baseline and at one month/T1 and three months/T2 post-treatment initiation. We trained three different random forest classifiers, able to predict responses to ESK-NS with accuracies of 68.53% at T1 and 66.26% at T2 and remission at T2 with 68.60% of accuracy. Features like severe anhedonia, anxious distress, mixed symptoms as well as bipolarity were found to positively predict response and remission. At the same time, benzodiazepine usage and depression severity were linked to delayed responses. Despite some limitations (i.e., retrospective study, lack of biomarkers, lack of a correct interrater-reliability across the different centers), these findings suggest the potential of machine learning in personalized intervention for TRD.

Risk factors for mortality after hospitalization for suicide attempt: results of 11-year follow-up study in Piedmont Region, Italy.

PURPOSE: Suicide attempters are at high risk of premature death, both for suicide and for non-suicidal causes. The aim of this study is to investigate risk factors and temporal span for mortality in a cohort of cases admitted to hospital for suicide attempt. METHODS: The cohort included 1489 patients resident in Piedmont Region, North West of Italy, who had been admitted to hospital or emergency department for suicide attempt between 2010 and 2020. Cox regression models were used to identify risk factors for death. The final multivariate model included gender, age, area deprivation index, family composition, psychiatric disorders, malignant neoplasms, neurological disorders, diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease, and intracranial injury or skull fracture. RESULTS: During the observation period, 7.3% of patients died. The highest mortality was observed within the first 12 months after suicide attempt, and remained elevated for many years afterwards. Male gender, older age, high deprivation index of the census area, single-parent family, mood disorders, malignant neoplasms, diabetes mellitus and intracranial injuries or skull fracture were independent predictors of death. Risk factors for natural and unnatural causes of death were also identified. CONCLUSIONS: The mortality risk of suicide attempters is very high, both in the months immediately following the attempt and afterwards. The identification of high-risk groups can help to plan outpatient care following the hospital discharge. Our findings urge the need to design strategies for the assistance and care of these patients at long term in order to reduce the unfavourable outcomes.

The pharmacological bases for repurposing statins in depression: a review of mechanistic studies.

Statins are commonly prescribed medications widely investigated for their potential actions on the brain and mental health. Pre-clinical and clinical evidence suggests that statins may play a role in the treatment of depressive disorders, but only the latter has been systematically assessed. Thus, the physiopathological mechanisms underlying statins' putative antidepressant or depressogenic effects have not been established. This review aims to gather available evidence from mechanistic studies to strengthen the pharmacological basis for repurposing statins in depression. We used a broad, well-validated search strategy over three major databases (Pubmed/MEDLINE, Embase, PsychINFO) to retrieve any mechanistic study investigating statins' effects on depression. The systematic search yielded 8068 records, which were narrowed down to 77 relevant papers. The selected studies (some dealing with more than one bodily system) described several neuropsychopharmacological (44 studies), endocrine-metabolic (17 studies), cardiovascular (6 studies) and immunological (15 studies) mechanisms potentially contributing to the effects of statins on mood. Numerous articles highlighted the beneficial effect of statins on depression, particularly through positive actions on serotonergic neurotransmission, neurogenesis and neuroplasticity, hypothalamic-pituitary axis regulation and modulation of inflammation. The role of other mechanisms, especially the association between statins, lipid metabolism and worsening of depressive symptoms, appears more controversial. Overall, most mechanistic evidence supports an antidepressant activity for statins, likely mediated by a variety of intertwined processes involving several bodily systems. Further research in this area can benefit from measuring relevant biomarkers to inform the selection of patients most likely to respond to statins' antidepressant effects while also improving our understanding of the physiopathological basis of depression.

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.

Efficacy and moderators of short-term psychodynamic psychotherapy for depression: A systematic review and meta-analysis of individual participant data.

BACKGROUND: Short-term psychodynamic psychotherapy (STPP) is frequently used to treat depression, but it is unclear which patients might benefit specifically. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses and identify patient-level moderators. This IPD meta-analysis examined the efficacy and moderators of STPP for depression compared to control conditions. METHODS: PubMed, PsycInfo, Embase, and Cochrane Library were searched September 1st, 2022, to identify randomized trials comparing STPP to control conditions for adults with depression. IPD were requested and analyzed using mixed-effects models. RESULTS: IPD were obtained from 11 of the 13 (84.6%) studies identified (n = 771/837, 92.1%; mean age = 40.8, SD = 13.3; 79.3% female). STPP resulted in significantly lower depressive symptom levels than control conditions at post-treatment (d = -0.62, 95%CI [-0.76, -0.47], p < .001). At post-treatment, STPP was more efficacious for participants with longer rather than shorter current depressive episode durations. CONCLUSIONS: These results support the evidence base of STPP for depression and indicate episode duration as an effect modifier. This moderator finding, however, is observational and requires prospective validation in future large-scale trials.

Paliperidone Palmitate: A Breakthrough Treatment for Schizophrenia? A Review on Patient Adherence Levels, Healthcare Resource Utilization and Costs.

International guidelines suggest long-term antipsychotic therapies for treating schizophrenia; however, medication compliance remains a critical issue in schizophrenia. Paliperidone palmitate (PP) is a second-generation antipsychotic long-acting injectable (SGA-LAI) approved for the treatment of schizophrenia. To date, the majority of studies on PP compliance patterns did not use specific instruments to assess medications' adherence, have been performed in not naturalistic samples and present partially overlapping populations. We conducted a systematic review in which we aimed to review the current knowledge on PP-LAI adherence levels and to describe healthcare resource utilisation and costs related to PP-LAI treatment. The evaluation has been conducted by searching in different databases (PubMed, Ovid, Scopus, and Cochrane Library) from inception to September 2022. Our findings suggest that paliperidone palmitate should be considered a good treatment strategy for patients affected by schizophrenia: PP showed both a good efficacy and tolerability and better adherence patterns and more favourable healthcare resource utilisation and costs, compared to OA.

Correlates of long duration of untreated illness (DUI) in patients with bipolar disorder: results of an observational study.

BACKGROUND: Despite a high number of studies investigating the correlation between long Duration of Untreated Illness (DUI) and poor course of Bipolar Disorder (BD), the results concerning the impact of DUI on some specific factors, such as suicidality and medical comorbidities, are still inconsistent. This cross-sectional observational study aimed at analyzing potential socio-demographic and clinical correlates of long DUI in a large cohort of real-world, well-characterized BD patients. METHODS: The socio-demographic and clinical characteristics of 897 patients with BD were collected. The sample was divided for analysis in two groups (short DUI vs long DUI) according to a DUI cutoff of 2 years. Comparisons were performed using χ2 tests for categorical variables and the Kruskal-Wallis test for continuous variables. Logistic regression (LogReg) was used to identify explanatory variables associated with DUI (dependent variable). RESULTS: Six-hundred and sixty patients (75.5%) presented long DUI (> 2 years) and mean DUI was 15.7 years. The LogReg analysis confirmed the association of long DUI with bipolar II disorder (p: 0.016), lower age at onset (p < 0.001), depressive predominant polarity (p: 0.018), depressive polarity onset (p < 0.001), longer duration of illness (p < 0.001), lifetime suicide attempts (p: 0.045) and current medical comorbidities (p: 0.019). CONCLUSIONS: The present study confirms the association between long DUI and higher risk of suicide attempts in patients with BD. Moreover, an association between long DUI and higher rates of medical conditions has been found.

Cause-specific mortality after hospital discharge for suicide attempt or suicidal ideation: A cohort study in Piedmont Region, Italy.

BACKGROUND: Suicide attempters are at higher risk of death than the general population. The present study aims to investigate the excess of all-cause mortality and cause-specific mortality in a cohort of patients who have attempted suicide or had suicidal ideation compared with the general population. METHOD: The cohort included 826 patients residing in the Piedmont Region of Northwest Italy who were admitted to a hospital or emergency department for suicide attempts or suicidal ideation between 2010 and 2016. Mortality excesses of the study population compared to the general population were estimated by applying indirect standardization. Standardized Mortality Ratios and 95% Confidence Intervals were calculated for all-cause, and cause-specific, natural, and unnatural causes of death by gender and age. RESULTS: During the 7 years of follow-up, 8.2% of the study sample died. The mortality of suicide attempters and ideators was significantly higher than that of the general population. Mortality was about twice than expected from natural causes, and 30 times than expected from unnatural causes. The mortality due to suicide was 85 times higher than that of the general population, with an excess of 126 times for females. The SMRs for all-cause mortality decreased with increasing age. CONCLUSIONS: Patients who access hospitals or emergency departments for suicide attempts or suicidal ideation are a frail group at high risk of dying from natural or unnatural causes. Clinicians should pay special attention to the care of these patients, and public health and prevention professionals should develop and implement appropriate interventions to timely identify individuals at higher risk for suicide attempts and suicidal ideation and provide standardized care and support services.

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression.

BACKGROUND: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD. OBJECTIVES: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch. METHODS: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. RESULTS: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch. CONCLUSIONS: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.

Which patients benefit from adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression? A systematic review and meta-analysis of individual participant data.

BACKGROUND: Adding short-term psychodynamic psychotherapy (STPP) to antidepressants increases treatment efficacy, but it is unclear which patients benefit specifically. This study examined efficacy moderators of combined treatment (STPP + antidepressants) v. antidepressants for adults with depression. METHODS: For this systematic review and meta-analysis (PROSPERO registration number: CRD42017056029), we searched PubMed, PsycINFO, Embase.com, and the Cochrane Library from inception to 1 January 2022. We included randomized clinical trials comparing combined treatment (antidepressants + individual outpatient STPP) v. antidepressants in the acute-phase treatment of depression in adults. Individual participant data were requested and analyzed combinedly using mixed-effects models (adding Cochrane risk of bias items as covariates) and an exploratory machine learning technique. The primary outcome was post-treatment depression symptom level. RESULTS: Data were obtained for all seven trials identified (100%, n = 482, combined: n = 238, antidepressants: n = 244). Adding STPP to antidepressants was more efficacious for patients with high rather than low baseline depression levels [B = -0.49, 95% confidence interval (CI) -0.61 to -0.37, p < 0.0001] and for patients with a depressive episode duration of >2 years rather than <1 year (B = -0.68, 95% CI -1.31 to -0.05, p = 0.03) and than 1-2 years (B = -0.86, 95% CI -1.66 to -0.06, p = 0.04). Heterogeneity was low. Effects were replicated in analyses controlling for risk of bias. CONCLUSIONS: To our knowledge, this is the first study that examines moderators across trials assessing the addition of STPP to antidepressants. These findings need validation but suggest that depression severity and episode duration are factors to consider when adding STPP to antidepressants and might contribute to personalizing treatment selection for depression.

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.