Childhood sexual abuse and suicide attempts in patients with substance use disorders: The mediating role of emotion dysregulation.

BACKGROUND: Suicide attempts (SA) are a public health concern because of increasing prevalence and clinical implications. Childhood trauma (CT) and emotion dysregulation (ED) have been proposed as predictors of SA, but few data are available in patients with Substance Use Disorder (SUD). OBJECTIVE: Our study aims to investigate the association of sociodemographic/clinical variables, CT typologies, and ED features with SA in SUD patients. PARTICIPANTS AND SETTING: Subjects with SUD were screened in an outpatient setting. The final sample consisted of 226 patients, subdivided according to the presence of lifetime SA (SUD, n = 163 vs. SUD-SA, n = 63). METHODS: Participants were compared for sociodemographic and clinical information. CT and ED were assessed through the Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Difficulties in Emotion Regulation Scale (DERS), respectively. We performed a mediation analysis to test the effect of CT and ED on SA. RESULTS: Patients with a history of SA (27.9 %) displayed more psychiatric comorbidities (p = 0.002) and hospitalizations (p < 0.001), higher scores at CTQ-SF sexual abuse (p < 0.001) and DERS 'impulse' (p = 0.002), 'goals', 'non-acceptance', 'strategies' (p < 0.001) subscales. The relationship between CTQ-SF sexual abuse and SA was significantly mediated by DERS 'strategies' (p = 0.04; bootstrapped 95 % LLCI-ULCI = 0.004-0.024). CONCLUSIONS: CT and different dimensions of ED were associated with SA in SUD patients. In our sample, the effects of childhood sexual abuse on SA were mediated by limited access to emotion regulation strategies. SUD patients are burdened with higher all-cause mortality, and CT and lifetime SA can worsen clinical outcomes. Clarifying the reciprocal interactions of psychopathological dimensions may help deliver targeted interventions and reduce suicide risk in specific populations.

Reduction in Cognitive Symptoms Following Intranasal Esketamine Administration in Patients With Chronic Treatment-resistant Depression: A 12-Week Case Series.

BACKGROUND: Cognitive symptoms are a core feature of depressive disorders, interfere with full functional recovery and are prominent in patients with treatment-resistant depression (TRD), particularly in severe chronic cases. Intranasal (IN) esketamine was recently approved for the treatment of TRD; however, its effects on cognitive symptoms are unclear. In this article, we describe cognitive changes in 8 patients with chronic TRD who were treated with IN administration of esketamine. METHODS: Eight outpatients with chronic TRD received IN esketamine over 3 months and were assessed at baseline and after 4, 8, and 12 weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Digit Symbol Substitution Test (DSST), the Trail Making Test-B (TMT-B), the Patient Deficits Questionnaire for Depression 5-item (PDQ-D5), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impressions Scale (CGI). FINDINGS: We observed reductions in cognitive symptoms according to DSST, TMT-B, and PDQ-D5 scores within the first 2 months of treatment with IN esketamine. These improvements were observed before patients achieved clinical response (≥50% decrease in baseline MADRS scores), and they also occurred earlier than reductions in HARS scores. CONCLUSIONS: A clinical response to IN esketamine was detected in severely ill patients with chronic TRD after 3 months of treatment. Interestingly, improvements on measures of cognitive symptoms were observed before patients achieved antidepressant response. These preliminary observations suggest an additional value to the antidepressant properties of IN esketamine. Clinical studies specifically investigating cognition as a primary outcome measure of IN esketamine in TRD are warranted.

The Patient's Perspective on the Effects of Intranasal Esketamine in Treatment-Resistant Depression.

The effectiveness of the esketamine nasal spray (ESK-NS) for treatment-resistant depression (TRD) has been confirmed by real-world studies. Available evidence derived from clinician-rated assessments might differ from patients' perceptions about the helpfulness of treatments. We aimed to verify the effect of ESK-NS from patients' view in 25 TRD patients (56% males, 55.1 ± 10.9 years) treated with ESK-NS (mean dose: 78.4 ± 11.43 mg) for three months and evaluated at different time-points through clinician-rated and self-administered scales, assessing changes in depression, anhedonia, sleep, cognition, suicidality, and anxiety. We observed an overall early improvement that lasted over time (endpoint total score reduction in Montgomery-Åsberg Depression Rating Scale, p < 0.001, Beck Depression Inventory, p = 0.003). Patients reported a significant self-rated decrease in anhedonia at two months (Snaith-Hamilton Pleasure Scale, p = 0.04) and in suicide ideation at endpoint (BDI subitem 9, p = 0.039) vs. earlier improvements detected by clinicians (one-month reduction in MADRS subitem 8, p = 0.005, and subitem 10, p = 0.007). These findings confirm the effectiveness of a three-month treatment with ESK-NS in TRD patients, highlighting an overall overlapping response from patients' and clinicians' perspectives, although with some differential effects on specific symptoms at given time-points. Including patients' viewpoints in routine assessments could inform clinical practice, ensuring a better characterization of clinical phenotypes to deliver personalized interventions.