Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550

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

Emotional stress, psychosocial variables and coping associated with hepatitis C virus and human immunodeficiency virus infections in intravenous drug users

BACKGROUND: The increasing health problem of hepatitis C virus (HCV) infection has only recently attracted the attention of psychosocial research, especially among subjects at higher risk (e.g. intravenous drug users; IDUs). The aim of the present study was to compare emotional stress symptoms, psychosocial variables (i.e. social support, external locus of control and emotional repression) and coping strategies in HCV-seropositive, human immunodeficiency virus (HIV)-seropositive and HCV/HIV-noninfected IDUs. METHODS: IDUs followed by the Infectious Diseases Outpatient clinic were enrolled in the study over a period of 1 year. HCV-positive (n = 62) and HIV-positive (n = 76) IDUs and HCV/HIV-seronegative IDUs (n = 152) completed the Brief Symptom Inventory, the Social Provision Scale, the Locus of Control scale and the affective inhibition scale of the Illness Behavior Questionnaire. Coping with illness among HCV-positive and HIV-positive subjects was assessed through a modified version of the Mental Adjustment to Cancer Scale. RESULTS: No significant differences were found between the samples with respect to individual and interpersonal variables. HCV-positive subjects showed higher scores on several psychological stress dimensions (i.e. obsessive-compulsive, phobic anxiety, paranoid ideation, psychoticism) and lower scores on fighting spirit, hopelessness and anxious preoccupation towards illness than HIV-positive patients. HCV-positive and HCV/HIV-seronegative IDUs reported comparable scores on most of the psychological measures. CONCLUSIONS: The findings indicate that routine assessment of psychosocial variables and coping mechanisms should be integrated into all HCV and HIV services, especially those dedicated to treatment of patients with substance abuse, as a vulnerable segment of the population at risk for life-threatening physical illness such as HCV and HIV infections

Factors related to admission of psychiatric patients to medical wards from the General Hospital Emergency Department: A 3-year study of urgent psychiatric consultations

none8Objective - Emergency Department (ED) in General Hospitals has a significant role in providing for psychiatric evaluation. The aims of the present study were to examine the decision-making process of consultation psychiatry at the GH-ED and to analyze the differences between psychiatric patients admitted to a medical ward with those admitted to the psychiatry unit and those who are discharged from the ED. Method - Psychiatric consultations requested by ED physicians over a period of three years were recorded by using a form to describe epidemiological and clinical data on the consultation. Results - Of 1,962 consultations, most regarded subjects who had had previous psychiatric contacts (76.2%) and at least one psychiatric admission (53.6%), and were currently cared for by the Mental Health Services (51.1%). Neurotic disorders (27.98%), schizophrenia (27.67%), and personality disorders (21.81%) were the most frequent ICD-10 diagnoses. The psychiatrist’s disposal was to discharge the patient in 49.9% cases, to admit him/her to medical wards of the General Hospital (26.9%) (GH) or to the Acute Inpatient Psychiatric Unit (23.1%) (AIPU). GH group statistically differed from AIPU group for being female (p<0.01), older (p < 0.01), having an ICD-10 diagnosis of neurosis and related syndromes (p<0.01) or organic mental disorder (p<0.01), and less likely having a diagnosis f schizophrenia (p<0.01), being in charge of the Mental Health Services (p<0.01) and having had previous psychiatric admissions (p <0.01). These results were confirmed by logistic regression analysis. Conclusions - The study shows that the medical wards of the General Hospital are a significant entry-point for providing psychiatric care of patients with ICD-10 organic mental syndromes and neurotic and stress-related syndromes.noneBIANCOSINO B.; MARMAI L.; ZOTOS S.; PERON L.; MARANGONI C.; VANNI A.; MAGRI V.; GRASSI L.Biancosino, Bruno; Marmai, Luciana; Zotos, Spyridon; Peron, L.; Marangoni, C.; Vanni, Adello; Magri, Vanessa; Grassi, Luig

Dimensions and predictors of clinical and personal recovery in first‐episode psychoses: Results from a cross‐sectional study

Introduction: First episode psychosis (FEP) services ensure higher recovery rates compared to usual care. The aim of this study was to investigate the different dimensions of recovery and its predictors. Methods: This cross-sectional study recruited within those admitted to the Ferrara FEP service since 2012 that at the time of analysis were still receiving psychiatric care. At admission, demographic, social and clinical information were collected. In September 2022, patients were assessed with the Health of the Nation Outcome Scale to evaluate clinical/functional recovery, the Recovery Assessment Scale to evaluate personal recovery, and the G12 item of the Positive and Negative Syndrome Scale to evaluate insight. Patients in recovery were compared to those not in recovery by bivariate analyses. Adjusted logistic regressions were performed to investigate predictors of recovery. Results: Within 141 admitted, and 105 still receiving care, 54 patients completed the assessment. Most (51.9%) were in clinical/functional, 61.1% in personal recovery, and 38.8% both. Psychiatric hospitalization positively predicted clinical/functional recovery, whereas being prescribed oral antipsychotics was a negative predictor. Personal recovery was predicted by male sex and showed a negative association with overall severity of symptomatology. Those in personal recovery were more likely to have been prescribed long-acting antipsychotics, but this was not significant in the multivariable analysis. Poor insight negatively predicted clinical/functional recovery but had no impact on personal recovery. Conclusion: Our findings confirm that clinical/functional and personal recovery are semi-independent dimensions and not always overlap. Further research is needed to promote interventions targeted at all recovery dimensions

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550