A Naturalistic, European Multi-Center Clinical Study of Electrodermal Reactivity and Suicide Risk Among Patients With Depression

Background: Electrodermal hyporeactivity has been proposed as a marker of suicidal risk. The EUDOR-A study investigated the prevalence of electrodermal hyporeactivity among patients with depression and its association with attempted and completed suicide.Methods: Between August 2014 and March 2016, 1,573 in- and outpatients with a primary diagnosis of depression (active or remission phase) were recruited at 15 European psychiatric centers. Each patient was followed-up for 1 year. Electrodermal activity was assessed at baseline with the ElectroDermal Orienting Reactivity Test. Data on the sociodemographic characteristics, clinical diagnoses, and treatment of the subjects were also collected. The severity of the depressive symptoms was assessed through the Montgomery–Asberg Depression Rating Scale. Information regarding number, time, and method of suicide attempts was gathered at baseline and at the end of the 1-year follow-up. The same data were collected in case of completed suicide.Results: Hyporeactive patients were shown to be significantly more at risk of suicide attempt compared to reactive patients, both at baseline and follow-up. A sensitivity of 29.86% and a positive predictive value (PPV) of 46.77% were found for attempted suicide at baseline, while a sensitivity of 35.36% and a PPV of 8.92% were found for attempted suicide at follow-up. The sensitivity and PPV for completed suicide were 25.00 and 0.61%, respectively. However, when controlled for suicide attempt at baseline, the association between hyporeactivity and follow-up suicide attempt was no longer significant. The low number of completed suicides did not allow any analysis.

“Hard to Say, Hard to Understand, Hard to Live”: Possible Associations between Neurologic Language Impairments and Suicide Risk

In clinical practice, patients with language impairments often exhibit suicidal ideation (SI) and suicidal behavior (SB, covering the entire range from suicide attempts, SA, to completed suicides). However, only few studies exist regarding this subject. We conducted a mini-review on the possible associations between neurologic language impairment (on the motor, comprehension, and semantic sides) and SI/SB. Based on the literature review, we hypothesized that language impairments exacerbate psychiatric comorbidities, which, in turn, aggravate language impairments. Patients trapped in this vicious cycle can develop SI/SB. The so-called “affective prosody” provides some relevant insights concerning the interaction between the different language levels and the world of emotions. This hypothesis is illustrated in a clinical case that we reported, consisting of the case of a 74-year old woman who was admitted to a psychiatric emergency department (ED) after a failed SA. Having suffered an ischemic stroke two years earlier, she suffered from incomplete Broca’s aphasia and dysprosody. She also presented with generalized anxiety and depressive symptoms. We observed that her language impairments were both aggravated by the exacerbations of her anxiety and depressive symptoms. In this patient, who had deficits on the motor side, these exacerbations were triggered by her inability to express herself, her emotional status, and suffering. SI was fluctuant, and—one year after the SA—she completed suicide. Further studies are needed to ascertain possible reciprocal and interacting associations between language impairments, psychiatric comorbidities, and SI/SB. They could enable clinicians to better understand their patient’s specific suffering, as brought on by language impairment, and contribute to the refining of suicide risk detection in this sub-group of affected patients.

Mental Health Among Patients with Non-Hodgkin Lymphoma: A Danish Nationwide Study of Psychotropic Drug Use in 7,201 Patients and 36,005 Matched Comparators

Introduction: A cancer diagnosis is associated with profound psychological distress that potentially can lead to mental health problems such as depression and anxiety. Non-Hodgkin lymphomas (NHLs) are a heterogenous group of indolent and aggressive cancer diseases with high variability in treatment selections and patient outcomes. Some patients are chronically ill with recurrent need for mild chemotherapy whereas others face immediately life-threatening, yet curable disease. To gain valuable insights into the psychological distress associated with NHLs, the present study investigated the incident psychotropic drug (PD - antidepressants, anxiolytics, and antipsychotics) use, contact patterns to psychiatric departments, and intentional self-harm (including suicide) in Danish NHL patients relative to sex- and age matched individuals from the background population. Methods: The study was carried out as a nationwide population-based matched cohort study based on prospectively collected data from several Danish registries. All adult NHL patients (≥18 years) diagnosed between 2005 and 2015 were identified in the Danish Lymphoma Registry and included if they had not been treated with any kind of PD within the last 10 years prior to date of NHL diagnosis (index date). NHL patients were matched on age and sex with five random comparators from the Danish background population on the index date. Comparators had to be alive and without PD use 10 years prior to the index date. Incident PD use was defined as first redeemed prescription of PD after index date. Prescriptions were captured in the National Prescription Registry and described by cumulative incidences using the Aalen-Johansen estimator with death and NHL relapse as competing risk. Contacts with psychiatric departments and registration of intentional self-harm or completed suicide were captured in the Danish National Patient Registry. Patients were subcategorized according to type of lymphoma (Table 1). Results: In total, 7,201 NHL patients and 36,005 matched comparators were included (median follow-up 7.1 years). Follicular lymphoma (FL, 44.4%) and diffuse large B-cell lymphoma (DLBCL, 41.0%) were the most common subtypes (Table 2). Two-year cumulative incidence of PD use was higher in NHL patients overall (16.2%, 95%CI 15.4-17.0%) compared to matched comparators (5.7%, 95%CI 5.5-5.9%). Patients with aggressive NHL subtypes tended to have the highest incidence of PD use (Figure 1). Antidepressants (two-year cumulative incidence, 9.0%, 95%CI 8.4-9.6) and anxiolytics (8.2%, 95%CI 7.6-8.8) were the most used PDs in all NHL subtypes. The risk of PD use was higher in the first years following diagnosis, but except for patients with indolent NHL subtypes, the risk of PD use normalized over time to that of the background population. As for the risk of any psychiatric department contacts, there was no difference in two-year cumulative incidences between NHL patients (range 0.6-0.9%) and the matched comparators (range 0.6%-0.9%), whereas the two-year cumulative incidence of intentional self-harm and suicide was slightly higher for NHL patients (0.3%) compared to the matched comparators (0.2%, p=0.01). Conclusion: This study suggests that NHL patients have a significantly higher risk of mental health problems compared to the Danish background population, (when) using PD prescriptions as a proxy measure. The risk of intentional self-harm and completed suicide was also higher, but numerical differences were very small. Overall, the results emphasize the need for directing clinical attention on mental health in newly diagnosed NHL patients and screening for relevant symptoms during follow-up to provide best possible support to patients suffering from anxiety and depression. Figure 1 Figure 1. Disclosures Øvlisen: Abbvie: Other: Travel expenses. Kragholm: Novartis: Honoraria. Nielsen: Lundbeck: Honoraria, Other: Investigator, Research Funding; Otsuka Pharmaceuticals: Honoraria, Other: Prior Advisor, Research Funding; Bristol-Myers Squibb: Honoraria; Astra Zeneca: Honoraria, Other: Prior advisor; Janssen & Cilag: Honoraria, Other: Investigator; Servier: Honoraria; Teva A/S: Honoraria; Eli Lilly: Honoraria, Other: Prior Advisor; Takeda: Other: Prior advisor; Medivir: Other; Boehringer: Other: Investigator. Brown: BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartys: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Dahl-Soerensen: Takeda: Other: Travel grant. Frederiksen: Novartis: Research Funding; Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding. Mannering: Novartis: Research Funding; Swedish Orphan Biovitrum (SOBI): Membership on an entity's Board of Directors or advisory committees. Jørgensen: Gilead: Consultancy; Roche: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Clausen: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expences ASH 2019; Gilead: Consultancy, Other: Travel expences 15th ICML . El-Galaly: ROCHE Ltd: Ended employment in the past 24 months; Abbvie: Other: Speakers fee.

Offspring's risk for suicidal behaviour in relation to parental death by suicide: systematic review and meta-analysis and a model for familial transmission of suicide

Background Exposure to parental suicide has been associated with increased risk for suicide and suicide attempts, although the strength of this association is unclear as evidence remains inconsistent. Aims To quantify this risk using meta-analysis and identify potential effect modifiers. Method A systematic search in PubMed, PsycInfo and Embase databases to 2020 netted 3614 articles. Inclusion criteria were: observation of history of parental death by suicide, comparison with non-exposed populations and definition of suicide and suicide attempt according to standardised criteria. We focused on population-based studies. The primary outcome was the pooled relative risk (RR) for incidence of suicide attempt and suicide in offspring of a parent who died by suicide compared with offspring of two living parents. Additionally, we compared the RR for attempted and completed suicide after parental suicide with the RR for attempted and completed suicide after parental death by other causes. Results Twenty studies met our inclusion criteria. Offspring exposed to parental suicide were more likely to die by suicide (RR = 2.97, 95% CI 2.50–3.53) and attempt suicide (RR = 1.76, 95% CI 1.58–1.96) than offspring of two living parents. Furthermore, their risk of dying by or attempting suicide was significantly higher compared with offspring bereaved by other causes of death. Conclusions The experience of losing a parent to suicide is a strong and independent risk factor for suicidal behaviour in offspring. Our findings highlight the need for prevention strategies, outreach programmes and support interventions that target suicide-related outcomes in the exposed population.

Prevalence of Suicidality in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Comparative Studies

Background: Suicidality is common in major depressive disorder (MDD), but there has been no systematic review published about all aspects of suicidality. This meta-analysis and systematic review compared the prevalence of the whole range of suicidality comprising suicidal ideation (SI), suicide plan (SP), suicide attempt (SA), and completed suicide (CS), between patients with MDD and non-MDD controls.Methods: Major international (PubMed, PsycINFO, Web of Science, EMBASE) and Chinese (Chinese Nation Knowledge Infrastructure and WANFANG) databases were systematically and independently searched from their inception until January 12, 2021.Results: Fifteen studies covering 85,768 patients (12,668 in the MDD group and 73,100 in the non-MDD group) were included in the analyses. Compared to non-MDD controls, the odds ratios (ORs) for lifetime, past month, past year, and 2-week prevalence of SI in MDD were 2.88 [95% confidence interval (CI) = 0.30–27.22, p = 0.36], 49.88 (95% CI = 2–8.63, p < 0.001), 13.97 (95% CI = 12.67–15.41, p < 0.001), and 24.81 (95% CI = 15.70–39.22, p < 0.001), respectively. Compared to non-MDD controls, the OR for lifetime SP in MDD was 9.51 (95% CI = 7.62–11.88, p < 0.001). Compared to non-MDD controls, the ORs of lifetime and past-year prevalence of SA were 3.45 (95% CI = 1.58–7.52, p = 0.002), and 7.34 (95% CI = 2.14–25.16, p = 0.002), respectively, in MDD patients. No difference in the prevalence of CS between MDD and controls was found (OR = 0.69, 95% CI = 0.23–2.02, p = 0.50).Conclusions: MDD patients are at a higher risk of suicidality, compared to non-MDD controls. Routine screening for a range of suicidality should be included in the management of MDD, followed by timely treatment for suicidal patients.Systematic Review Registration: Identifier [INPLASY202120078].

1066Increased Risk of Suicide among Cancer Survivors Who Developed a Second Primary Malignancy

Background Cancer diagnosis entails substantial psychological distress and is associated with dramatically increased risks of suicide and psychiatric disorders. However, little is known about the suicide risk among cancer survivors who developed a second primary malignancy (PCa-2). Methods Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study, including 7,169,704 patients with first primary malignancy (PCa-1) and 686,174 PCa-2 patients diagnosed from January 1, 1975, through December 31, 2016. Compared with patients with PCa-1, we measured the hazard ratios (HRs) of completed suicide after receiving a PCa-2 diagnosis, using Cox proportional hazard models. Results 10,938 and 937 completed suicides were identified among PCa-1 and PCa-2 patients, respectively. The HR of suicide deaths was 1.24 [95% confidence interval (CI), 1.15-1.32] after a PCa-2 diagnosis, compared with PCa-1 patients (adjusted for demographic factors, state, and tumor characteristic). The risk elevation was most pronounced when PCa-2 was prostate cancer (HR 1.37, 95% CI 1.18-1.60); and PCa-2 patients diagnosed between 60 to 75 years old had highest increased relative risk of suicide (HR 1.35, 95% CI 1.23-1.49). Conclusions Compared with patients with first primary cancer, cancer survivors receiving a PCa-2 diagnosis, particularly of prostate cancer or at age 60-75, are at increased risk of suicide. These findings emphasize the need to support and carefully monitor cancer survivors for PCa-2. Key messages Patients with PCa-2 are at a higher risk of suicide compared with patients with PCa-1, especially for PCa-2 diagnosed at age 60 to 75 or PCa-2 of prostate.

Incidence of completed suicide and suicide attempts in a global prospective study of Huntington's disease

Background Risk of death from suicide in Huntington's disease is notably elevated relative to that in the general population, although the incidence within HD populations has not been precisely defined. Robust incidence estimates of suicidal behavior can serve as references for HD therapeutic research and post-marketing surveillance to help evaluate the suicidality risk of novel therapeutics. Aims To estimate the incidence rate of completed suicide and suicide attempt in the global, prospective HD cohort study Enroll-HD that records these events per protocol. Method A total of 20 912 participants were available for analysis (HD gene-expansion carriers (HDGECs) n = 15 924; non-HDGECs n = 4988) representing a collective observation period of 53 390 participant-years. Each observed event was subject to clinical review and evaluation. We generated incidence rates (events per 100 000 person-years) for suicides and suicide attempts using all available data, as well as by year of study and geographical region. Proportionate mortality statistics for suicide and respective 95% confidence intervals were also generated. Results The overall incidence rate of suicide in HDGECs was 72 per 100 000 person-years, and 8 per 100 000 person-years in non-HDGECs. Proportionate mortality attributable to suicide in HDGECs was 4.6%. For suicide attempts, the global overall incidence rate observed in HDGECs was 306–375 per 100 000 person-years, and 23–38 per 100 000 person-years in non-HDGECs. Conclusions The incidence estimates calculated here can be used as a reference to help evaluate drug safety and may also be useful in assessing progress in clinical care for HDGECs once therapeutic interventions become widely available.