Risk Factors for Suicide and Suicide Attempts Among Patients With Treatment-Resistant Depression: Nested Case-Control Study

Abstract

The risk of suicide is elevated among patients with treatment-resistant depression (TRD). Risk factors for suicide and suicide attempts among cases and controls with TRD were investigated using data from nationwide Swedish registers. Among 119,407 antidepressant initiators with a diagnosis of depression, 15,631 patients who started a third sequential treatment trial during the same depressive episode were classified with TRD. A nested casecontrol study compared cases with suicide and suicide attempts with up to three closely matched controls. Sociodemographic and clinical risk factors were assessed using conditional logistic regression analyses. In all, 178 patients died by suicide and 1,242 experienced a suicide attempt during follow-up. History of suicide attempts, especially if <1 year after the attempt, was a significant independent risk factor for suicide (adjusted odds ratio [aOR], 8.9; 95% confidence interval [CI], 5.1-15.7) as were 10 to 12 years of education compared to lower education (aOR, 1.69; 95% CI, 1.02-2.81). For attempted suicide, the strongest independent risk factors were history of suicide attempts (<1 year aOR, 5.1; 95% CI, 4.0-6.5), substance abuse (aOR, 2.6; 95% CI, 2.2-3.1), personality disorders (aOR, 1.9; 95% CI, 1.5-2.3), and somatic comorbidity (aOR, 2.0; 95% CI, 1.04-3.9). Suicide attempts, especially if recent, are strong risk factors for completed suicide among patients with TRD. Established risk factors for suicide attempts were confirmed for patients with TRD.

Clinical characteristics of treatment-resistant depression in adults in Hungary: Real-world evidence from a 7-year-long retrospective data analysis

“…However, it appears that the adequate treatment of at least some somatic comorbidities, such as hypothyroidism, results in the dissipation of the difference in AD responses between patients with and without the given somatic comorbidity [38]. Some features of an MDD episode may also be associated with treatment resistance; for example, greater symptom severity, psychotic symptoms, suicidality and longer duration of the current episode are predictors of treatment resistance [8,11,37]. In the STAR � D trial, remission rates were highest in the first two AD trials and dropped significantly in subsequent AD trials, and even for the small number of patients with TRD that do achieve remission, 60% relapsed within 6 months [39,40].…”

“…However, the vast majority of studies show not only overt, but also 'subthreshold', bipolarity (marked by, for example, agitated/mixed depressive episodes, early onset, depressive episodes with psychotic/atypical/anxious features, family history of bipolar disorder, highly recurrent [i.e. more than three] depressive episodes), may be associated with poorer response to AD treatment [8,11,29,30,32,[41][42][43][44][45][46][47][48].…”

“…Pharmacotherapy-resistant depression (denoted as TRD in the following) is a term used to describe a subpopulation of MDD with a suboptimal response to an adequate dose and duration of antidepressants (ADs); however, there is not yet a standardised definition for TRD and existing definitions have key differences. For example, the number of unsuccessful AD trials in which patients experience a lack of response/remission, along with whether or not the subsequent AD should belong to a different AD class than the previous one, differs across TRD definitions [2,4,8,[11][12][13][14][15], although most current definitions require the failure of at least two AD monotherapy trials [13,14]. The European Medicines Agency (EMA) defines TRD as a lack of clinically meaningful improvement despite the use of adequate doses of at least two AD agents belonging to the group(s) of commonly used first-line treatments prescribed for an adequate duration with adequate affirmation of treatment adherence [16].…”

A prospective, multi-center randomized, controlled, blinded trial of vagus nerve stimulation for difficult to treat depression: A novel design for a novel treatment

“…MDD is associated with significant adverse consequences for the patient, their family, and society, including impairments in daily functioning, social relationships, and work/school productivity [16,28]. MDD carries considerable mortality from suicide, and increased morbidity due to concomitant medical conditions [22,39].…”

Reply to letter to the editor

“…In summary, the accumulated literature suggests that for the vast majority of practical cases, the risks are minimal and rTMS treatment may be safely applied. Given the known and quite significant risks of suicide [6] and disability [7] resulting from treatment resistant depression, and weighing these established risks against the theoretical risks of rTMS in patients with non-ferromagnetic aneurysm clips, (all of which should be discussed with each patient in the informed consent process) we stand by our conclusion that "an absolute contraindication to TMS for all aneurysm clip patients is inappropriate and could deprive treatment-resistant depressed aneurysm patients access to this potentially efficacious therapy." Yet, we agree with the need for systematic ex vivo and in vivo experiments in order to produce a catalog of TMS-safe implants to help enable many potential patients to benefit from TMS.…”