Assessing Mental Pain as a Predictive Factor of Suicide Risk in a Clinical Sample of Patients with Psychiatric Disorders

According to contemporary suicidology, mental pain represents one of the main suicide risk factors, along with more traditional constructs such as depression, anxiety and hopelessness. This work aims to investigate the relationship between the levels of mental pain and the risk to carry out suicide or suicide attempt in the short term in order to understand if a measurement of mental pain can be used as a screening tool for prevention. For this purpose, 105 outpatients with psychiatric diagnosis were recruited at the university hospital of Varese during a check-up visit and were assessed by using psychometric scales of mental pain levels, hopelessness, anxiety and depression. Clinical and sociodemographic variables of the sample were also collected. A period of 18 months following the recruitment was observed to evaluate any suicides or attempted suicides. Subjects numbering 11 out of 105 committed an attempted suicide. From statistical analyses, high values of the Beck Depression Inventory (BDI-II), Mental Pain Questionnaire (OMMP) and Hamilton Rating Scale for Depression (HAM-D) scales showed a significant association with the risk of carrying out a suicide attempt and, among these, OMMP and BDI-II showed characteristics of good applicability and predictivity proving suitable to be used as potential tools for screening and primary prevention of suicidal behavior

Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trial.

BACKGROUND Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. METHODS We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). FINDINGS The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01-2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. INTERPRETATION As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. FUNDING The study was funded by the Italian Medicines Agency within the "2016 Call for Independent Drug Research"

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

Towards personalized medicine: the role of pharmacogenetics in the treatment of bipolar disorder

Abstract Background Bipolar disorder (BD) is a severe psychiatric disease characterized by mood swings between mania and depression, with a life-time prevalence of approximately 2.4%. Patients suffering from BD frequently present several problems due to drug-resistance and drug-drug interactions, rapid-cycling, and cognitive decline. Pharmacogenetic tests (PGTs) have been proposed as a method to determine the most efficacious treatment with the lowest side effects, recognizing individual variability in genetics as a key component of drug response. Nevertheless, PGTs have been occasionally used in clinical practice up to now and their clinical utility is an empirical question that has remained largely untested. This research project aims to evaluate the utility of PGT in routine clinical practice for the treatment of BD in terms of efficacy and cost saving; evaluate the attitude of psychiatrists towards the PGT use in clinical practice; review the literature dealing with lithium, the most common mood stabilizer used, to find any correlation among genes and tolerability/efficacy. Materials and methods The first phase of study evaluated 30 patients affected by BD type I or II who underwent the PGT Neurofarmagen\uae between March 2016 and March 2017. Second phase compares 12 months before the execution of the PGT versus 12 months after, in terms of number and days of hospitalization and accesses to emergency services. Secondarily, it gives an economic value to the data based on the diagnosis-related group (DRG). The third part of the study evaluates psychiatrists\u2019 attitude towards the use of PGx into clinical practice; the last phase of study reviews the literature about lithium salts. Results In phase I At T0, 4 patients (13%) had an optimal therapy in line with the PGT suggestions. At 3-month followup, 13 patients (40%) had received a change of therapy consistent to the test, showing a significant statistical improvement in CGI-S score over time compared to those not having changes consistent with the test. Regarding AEs, at baseline 9 out of 10 (90%) of the patients who received a therapy modification according to the test presented AEs, and a significant within-group reduction was observed after 3 months (p = 0.031). At 12 months follow-up (T3) 93% of patients (n=28) received a therapy concordant to the test; the others (7%, n=2) had a therapy discordant to the test Phase II showed statistically significant differences in all the comparisons (p < 0.0001). Important cost saving emerged after the use of PGT (\u20ac148,920 the first year versus \u20ac39,048 the following year). Phase III showed a positive attitude of the 45 psychiatrists interviewed towards the use of PGX. All respondents 100% (N = 45) believe that pharmacogenetics can help in making decisions about psychopharmacological treatment. All respondents 100% (N = 45) believe that pharmacogenetics can help in setting up therapy, particularly regarding drug interactions. There were no significant differences between those who already had experience with PGTs and those who did not. Phase IV showed that the pharmacogenetics of Lithium appears to be a field still in its infancy, even though the advent of genome-wide association studies holds particular promise for future studies. Conclusion Despite the small sample size and lack of a control group this study shows promising data about the usefulness of PGT to support clinicians in reaching a more effective and tolerated treatment in the routine approach and the potential role of PGT in cost saving for the treatment of bipolar disorder. Also the attitude of clinicians seemed to be positive towards the use of PGT as a helpful tool into clinical practice. To confirm this result, larger and clinical trials are neede

Assessing Mental Pain as a Predictive Factor of Suicide Risk in a Clinical Sample of Patients with Psychiatric Disorders

According to contemporary suicidology, mental pain represents one of the main suicide risk factors, along with more traditional constructs such as depression, anxiety and hopelessness. This work aims to investigate the relationship between the levels of mental pain and the risk to carry out suicide or suicide attempt in the short term in order to understand if a measurement of mental pain can be used as a screening tool for prevention. For this purpose, 105 outpatients with psychiatric diagnosis were recruited at the university hospital of Varese during a check-up visit and were assessed by using psychometric scales of mental pain levels, hopelessness, anxiety and depression. Clinical and sociodemographic variables of the sample were also collected. A period of 18 months following the recruitment was observed to evaluate any suicides or attempted suicides. Subjects numbering 11 out of 105 committed an attempted suicide. From statistical analyses, high values of the Beck Depression Inventory (BDI-II), Mental Pain Questionnaire (OMMP) and Hamilton Rating Scale for Depression (HAM-D) scales showed a significant association with the risk of carrying out a suicide attempt and, among these, OMMP and BDI-II showed characteristics of good applicability and predictivity proving suitable to be used as potential tools for screening and primary prevention of suicidal behavior

Efficacy of short-term psychodynamic psychotherapy (STPP) in depressive disorders: A systematic review and meta-analysis

Introduction: Depression is a common illness worldwide and can severely interfere with daily and work functioning. Both pharmacological and psychotherapeutics interventions are used for adult depression. The aim of the review is to evaluate the efficacy of short-term psychodynamic psychotherapy (STPP) comparing with different types of intervention. Materials and methods: A systematic review with meta-analysis on the efficacy of STPP in depressive disorders was conducted. Results: Meta-analysis results confirm the superiority of STPP versus no interventions. The average effect size of depressive symptoms severity at the end of the treatment is -0.91 (95 % CI: -1.49 - -0.33) in favor of STPP, while for clinical improvement of depressive symptoms is -0.78 (95 % CI: -1.56 - 0.01). Results confirm a net superiority of STPP to usual treatments unstructured. A mild superiority of efficacy of STPP on support psychotherapy emerged. Comparison of the efficacy of STPP vs cognitive-behavioral psychotherapy (CBT) shows little superior in case of STPP. No substantial differences in efficacy in case of STPP than control interventions emerged. Antidepressant pharmacotherapy is resulted to be slightly more effective to STPP. Discussion: While all the other results confirm current literature, this review shows no superiority of combined treatment than STPP only. Limitations: The review has some limitations such as the lack of moderation analysis and the high heterogenicity of the type of the studies. Conclusions: The results confirm the efficacy of STPP in depressive disorders endorsing the guidelines of National Institute for Health and Clinical Excellence

Pharmacogenetic Tests in Reducing Accesses to Emergency Services and Days of Hospitalization in Bipolar Disorder: A 2-Year Mirror Analysis

Despite the enormous costs associated to mood disorders\u2019, few studies evaluate potential cost saving from the use of pharmacogenetic tests (PGT). This study compares 12 months before the execution of the PGT versus 12 months after, in terms of number and days of hospitalization and accesses to emergency services, in a sample of 30 patients affected by bipolar disorder. Secondarily, the study gives an economic value to the data based on the diagnosis-related group (DRG). Patients included in the study were required to be aged 6518 years, sign an informed consent, have a score of Clinical Global Impression item Severity (CGIs) 653, and have a discordant therapy compared to the PGT in the 12 months preceding it and a therapy consistent with it for the following 12 months. Cost saving has been evaluated by paired t-tests in a mirror analysis. Statistically significant differences in all the comparisons (p < 0.0001) emerged. Important cost saving emerged after the use of PGT (\u20ac148,920 the first year versus \u20ac39,048 the following year). Despite the small sample size and lack of a control group in this study, the potential role of PGT in cost saving for the treatment of bipolar disorder treatment emerged. To confirm this result, larger and clinical trials are needed

A case of reversible splenial lesion syndrome (Resles) related to neuroleptic malignant syndrome in a schizophrenic patient

Objective: Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological condition characterized by a transient lesion in the splenium of the corpus callosum. Method: A systematic search of the literature has highlighted a possible correlation between this rare condition and neuroleptic malignant syndrome (NMS) despite only few cases have been reported. Results: This paper reports a case of RESLES syndrome in a 36-years old male patient with NMS who was undergoing psychiatric treatment for schizophrenia. Conclusions: The reported clinical case highlights the possibility of including NMS as one of the differential diagnosis in RESLES syndrome