The Ketamine Trial for Acute Suicidality (KETA): Study Protocol of a Double‐Blind Randomized Placebo‐Controlled Superiority Trial on Intranasal Racemic Ketamine Compared to the Active Placebo Intranasal Midazolam as Treatment for Acute Suicidality

Single fixed-dose intranasal racemic ketamine treatment for the treatment of acute suicidality in a transdiagnostic patient population: Results of a pilot study.

Suicidal ideation declines with improvement in the subjective symptoms of major depression

3447 Effects of intranasal ketamine on uncontrolled cancer related pain

Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine's acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior. Symptomatic patients with treatment-resistant unipolar major depression (inadequate response to ≥3 antidepressants) were assessed using a composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation, Montgomery-Asberg Rating Scale suicide item, Quick Inventory of Depressive Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected for its similar, rapid anesthetic effects. Twenty four hours postinfusion, explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group. Fifty three percent of ketamine-treated patients scored zero on all three explicit suicide measures at 24 hr, compared with 24% of the midazolam group (χ(2) = 4.6; P = .03). Implicit associations between self- and escape-related words were reduced following ketamine (P = .01; d = .58) but not midazolam (P = .68; d = .09). Ketamine-specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline, and were mediated by decreases in nonsuicide-related depressive symptoms. Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo. Further study is warranted to test ketamine's antisuicidal effects in higher-risk samples.

ObjectivesAccumulating evidence supports a role for vascular endothelial growth factor (VEGF) in the pathogenesis of depression, but its relationship with the antisuicidal effects of ketamine is not clear. Our objective was to determine whether there was an association between the plasma VEGF (pVEGF) concentrations and the antisuicidal response to serial ketamine infusions.MethodsSix ketamine infusions (0.5 mg/kg) over a 12-day period were administered to sixty depressed individuals suffering from suicidal ideation. The Hamilton Depression Rating Scale (HAMD) suicide item, the Montgomery-Åsberg Depression Rating Scale (MADRS) suicide item, and the Beck Scale for Suicide Ideation (SSI-part I) were used to assess suicidal ideation at baseline, 1 day after the first infusion (day 1), 1 day following the last infusion (day 13), and again 2 weeks post-infusion (day 26). For this purpose, plasma was obtained at baseline, day 13 and 26.ResultsThe rates of antisuicidal response to ketamine were 61.7% (37/60), 81.7% (49/60), and 73.3% (44/60) at days 1, 13, and 26, respectively. The linear mixed model revealed significant time effects on suicidal ideation and pVEGF concentrations over time (all Ps < 0.05). Antisuicidal responders did not have significantly altered pVEGF concentrations compared with non-responders on day 13 and day 26 (all Ps > 0.05). No significant correlation was found between the baseline pVEGF concentration and suicidal ideation as measured by the SSI part 1, HAMD suicide item and MADRS suicide item on days 1, 13, and 26 (all ps > 0.05).ConclusionThis preliminary finding does not support a role for VEGF in the antisuicidal effects of serial ketamine treatments in individuals with depression and suicidal ideation. Further research is needed to confirm and expand these findings.

Recently, low-dose ketamine has been proposed as a rapid-acting treatment option for suicidality. The majority of studies to date have utilised intravenous (IV) ketamine, however, this route of administration has limitations. On the other hand, oral ketamine can be administered in a range of settings, which is important in treating suicidality, although studies as to safety and feasibility are lacking. n = 32 adults (aged 22–72 years; 53% female) with chronic suicidal thoughts participated in the Oral Ketamine Trial on Suicidality (OKTOS), an open-label trial of sub-anaesthetic doses of oral ketamine over 6 weeks. Participants commenced with 0.5 mg/kg of ketamine, which was titrated to a maximum 3.0 mg/kg. Follow-up assessments occurred at 4 weeks after the final dose. The primary outcome measure was the Beck Scale for Suicide Ideation (BSS) and secondary measures included scales for suicidality and depressive symptoms, and measures of functioning and well-being. Mean BSS scores significantly reduced from a high level of suicidal ideation at the pre-ketamine (week 0) timepoint to below the clinical threshold at the post-ketamine (week 6) timepoint. The proportion of participants that achieved clinical improvement within the first 6 weeks was 69%, whereas 50% achieved a significant improvement by the follow-up (week 10) timepoint. Six weeks of oral ketamine treatment in participants with chronic suicidality led to significant reduction in suicidal ideation. The response observed in this study is consistent with IV ketamine trials, suggesting that oral administration is a feasible and tolerable alternative treatment for chronic suicidality.

National surveys indicate high rates of suicidal ideation in youth, especially among females. Coping skill training programs hold promise as a potential intervention that can help young people better manage stress and not consider suicide as a solution to life's problems. To assess the promise of this strategy, the present research examined which coping strategies (if any) predicted reduction in youth suicidal ideation over a 1-year follow-up, and explored the potential pathways through which their influence was channeled. Two waves of panel data from a nationally representative sample of youth, assessed 1 year apart (N = 710; Mean age = 18 years) were analyzed separately by gender using multiple group path analytic procedures. Four coping strategies, namely problem solving, emotional regulation, support seeking and acceptance were found to predict reduction in suicidal ideation among both males and females. However, the influence of these strategies (at baseline) was channeled through distinct pathways. The effect of emotional regulation (and acceptance) was channeled through its use at follow-up and was mediated by reductions in perceived stress and depressive symptoms, leading to reduction in suicidal ideation. The influence of support seeking was also channeled through its more recent use at follow-up, but directly predicted reduction in suicidal ideation, with no effect on perceived stress or depressive symptoms. The effect of problem solving on suicidal ideation was mediated by reduction in depressive symptoms, but was not channeled through its use at follow-up, suggesting a longer time course for the protective influence of this strategy. Finally, acceptance had a direct risk-enhancing effect on suicidal ideation. Coping strategies commonly used by youth can be effective in reducing suicidal ideation and therefore universal training in the effective use of these strategies should be considered. An understanding of the distinct pathways through which their effect on suicidal ideation is transmitted can better inform the design of youth suicide prevention interventions.

Negative Emotions and Suicidal Ideation during Psychosocial Treatments in Older Adults with Major Depression and Cognitive Impairment

Acute Suicidal Ideation in the Context of Esketamine Maintenance Therapy

Data suggests that the available therapeutic tools are still insufficient to deal with suicidality. Non-Invasive Brain Stimulation techniques (NIBS) have entered the recognized guidelines for therapies in psychiatry due to the advantages related to safety and tolerability. The purpose of this review and meta-analysis is to assess if and how NIBS techniques are used and could be effective in the treatment of suicidal ideation. The search included the Scopus, Pubmed, and Web of Science databases. The word “suicide” was combined with “NIBS”, “transcranial magnetic stimulation” (TMS), “deep TMS” and “transcranial direct current stimulation”. Nine studies met the inclusion criteria and were included in the review. High frequency repetitive TMS (rTMS) protocols were associated with a significant reduction in suicidal ideation, with individual studies reporting improvements ranging from 20% to over 35% on scales such as the scale for suicide ideation (SSI) and the Beck scale of suicide ideation (BSI) (p < 0.01; p < 0.01; p < 0.001). The meta-analysis showed that active rTMS significantly reduced suicidal ideation compared to sham control conditions (Z = 16.79, p < 0.0001). Heterogeneity was high (I² = 99%, chi-square = 473.22, df = 3, p < 0.0001). High frequency rTMS protocols appeared most effective; deep TMS (dTMS) showed mixed results, and only one study utilized transcranial direct current stimulation (tDCS). Due to limited data, no meta-analysis was conducted on dTMS or tDCS studies. Although preliminary findings suggest a potential for NIBS techniques to reduce suicidal ideation, the current evidence is limited by the small number of high-quality studies and heterogeneity in the protocols and outcomes. Therefore, conclusions regarding clinical efficacy should be considered tentative.

ABSTRACTBackground: Grief involves a set of emotions, thoughts and behaviors that people experience when faced with a lack or threat of loss. This study was conducted to evaluate the suicidal ideation among women with experience of the death of a young person and assessed the predictive role of individualism-collectivism, social support, and resilience in suicidal ideation.Methods:This cross-sectional study was conducted from March to August 2016 through recruitment of 146 breaved women from Gilan-e gharb (the west part of Iran). Data gathering instruments included Individualism-Collectivism Questionnaire, Multidimensional Scale of Perceived Social Support (MSPSS), Connor-Davidson Resilience scale (CD-RISC), and Beck Scale for Suicidal Ideation. Collected data were analyzed using SPSS-22.Results: The findings showed that among women, 48 percent had suicidal ideation (scores above 6). The results of Pearson correlation showed that there were significant negative relationships between suicidal ideation (P<0.05) and factors such as collectivism (r=-0.286), family support (r=-0.558), support from friends (r=-0.307), support from significant others (r=-0.617), social support (r=-0.561), and resilience (r=-0.457). The results showed that individualism - collectivism, social support, and resilience correctly predicted 73.5% of women with suicidal ideation and 83.3% of women without suicidal ideation.Conclusion:We concluded that higher collectivism, social support, and resilience in the bereaved women can lead to a reduction in suicidal ideation. Therefore, psychologists and counselors can provide the necessary background to strengthen supportive issues and the use of resilience-based interventions among bereaved women.

ObjectiveThis study aimed to evaluate the efficacy of a single infusion of ketamine in inducing rapid remission of severe suicidal ideation, compared to Midazolam, in a population with acute suicidal thoughts. In a double-blind randomized controlled trial conducted in Tehran, Iran, from January to July 2022 (IRCT20220118053756N1), 36 inpatients with acute severe suicidal ideation were enrolled. Participants were randomly assigned to receive either a single dose of ketamine (0.5 mg/kg) or Midazolam (0.02 mg/kg). Suicidality was assessed using the Beck Scale for Suicide Ideation (BSSI) and the Suicide-Visual Analog Scale (S-VAS) before the intervention and at 12 and 24 h post-administration.ResultsAt baseline, the Midazolam group exhibited significantly higher BSSI scores and a higher rate of borderline personality disorder than the Ketamine group. Mean BSSI and S-VAS scores at 12 and 24 h after the treatment decreased significantly compared to baseline in both groups. Despite these observations, no statistically significant differences were found between the groups in terms of BSSI and S-VAS scores.Trial registrationThe protocol for this RCT was registered at the Iranian Registry of Clinical Trials (IRCT). The trial registration details are as follows: IRCT registration number IRCT20220118053756N1, with the registration date being June 12, 2022 (1401/03/22). It is important to note that this trial was retrospectively registered.

Bipolar depression poses an overwhelming suicide risk. We aimed to examine the efficacy and safety of transcranial direct current stimulation (tDCS) combined with quetiapine in bipolar patients as a suicidal intervention. In a single-center, double-blind, treatment-naive bipolar depression patients with suicidal ideation were randomly assigned to quetiapine in combination with either active (n = 16) or sham (n = 15) tDCS over the left dorsolateral prefrontal cortex for three consecutive weeks. The 30-min, 2-mA tDCS was conducted twice a day on the weekday of the first week and then once a day on the weekdays of the two following weeks. Primary efficacy outcome measure was the change in the Beck Scale for Suicidal Ideation (BSSI). Secondary outcomes included changes on the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Outcome was evaluated on Day 3 and weekend. Safety outcome was based on the reported adverse reactions. Active tDCS was superior to sham tDCS on the BSSI at Day 3 and tended to sustain every weekend during the treatment process, compared to baseline. However, no difference between active and sham in HDRS-17 and MADRS was found. Response and remission rate also supported the antisuicide effect of tDCS, with higher response and remission rate in BSSI, but no antidepressant effect, compared to sham, over time. Regarding safety, active tDCS was well tolerated and all the adverse reactions reported were mild and limited to transient scalp discomfort. The tDCS was effective as an antisuicide treatment for acute bipolar depression patients with suicidal ideation, with minimal side effects reported.

BACKGROUND Despite their prevalence, access to effective treatment remains limited due to financial, geographic, and social barriers. Online self-help groups offer a promising and scalable form of peer-based support beyond traditional clinical settings. Integrating Cognitive Behavioral Therapy (CBT) techniques such as cognitive restructuring and behavioral activation into self-help groups may enhance their effectiveness. OBJECTIVE This study evaluated the efficacy of a CBT-based Online Self-help group (COS), which integrates structured CBT techniques with peer-led group support, as a low-intensity intervention for individuals with depressive symptoms. A randomized controlled trial and a separately recruited waitlist control group were used to examine the efficacy of the COS. METHODS Participants were recruited online. After eligibility screening via a structured clinical interview, participants were randomly assigned to a COS group (n = 79) or an CBT-based mobile application group (n = 39). An additional waitlist control group (n = 48) was recruited separately during the second phase of the study. The COS intervention involved seven videoconferencing sessions that incorporated peer-led group discussions, sharing lived experiences, and core CBT techniques such as cognitive restructuring. The primary outcome measure was depressive symptoms, assessed using the Beck Depression Inventory-II, and the secondary outcome was suicidal ideation, estimated using the Beck Scale for Suicide Ideation, measured at baseline, post-intervention, and 3-month follow-up. Linear mixed models were used to evaluate group × time interaction effects. Reliable change indices were also calculated to assess clinical significance. RESULTS Among participants assigned to the COS group, 56.5% completed all seven sessions, and 81.2% attended five or more sessions. A significant Time × Group interaction was observed for depressive symptoms (F4, 288.47 = 7.23, P &lt; .001). The COS group exhibited a substantial reduction in depressive symptoms from baseline to post-intervention (t285.76 = 10.77, P &lt; .001), with a large within-group effect size (d = 1.38); this improvement was maintained at the 3-month follow-up. Suicidal ideation also significantly decreased in the COS group (t277.11 = 4.55, P &lt; .001), with sustained effects at follow-up. Clinically meaningful improvement in depressive symptoms, as defined by the Reliable Change Index, was observed in 74.7% of COS participants. While both the COS and app-based CBT groups achieved comparable reductions in depressive symptoms, only the COS group demonstrated a significant reduction in suicidal ideation. CONCLUSIONS Our RCT findings provide novel evidence for the efficacy of a structured, CBT-informed online self-help group intervention in reducing depressive symptoms and suicidal ideation. The COS program offers a scalable, accessible alternative to traditional therapy, particularly in settings with limited access to mental health professionals. CLINICALTRIAL Clinical Research Information Service (CRIS) KCT0007673 (One of the primary registries of the WHO International Clinical Trials Registry Platform).

Objective: The majority of individuals with suicidal ideation do not receive help, and every year close to 800,000 people die by suicide. This study aimed to investigate the effectiveness of a guided internet-based self-help program compared to a waiting list control group in reducing suicidal ideation.Methods: In a randomized controlled trial, 402 individuals with suicidal ideation were assigned to a guided internet-based self-help program or a waiting list control group from September 13, 2016, to September 2, 2018. The primary outcome was suicidal ideation measured with the Beck Scale for Suicide Ideation at postintervention (6 weeks after baseline).Results: Participants assigned to the internet-based self-help program experienced at postintervention a significant reduction on the primary outcome of suicidal ideation (mean difference: 2.91; 95% CI, 1.28 to 4.54; P = .0005, Cohen's d = 0.25) compared to the waiting list control group and on the secondary outcomes of hopelessness (mean difference: 1.98; 95% CI, 0.97 to 3.99) and worrying (mean difference: 5.19; 95% CI, 2.36 to 8.10). Six months later (follow-up), the difference between the groups remained significant for suicidal ideation, hopelessness, and worrying. A total of 28 (16.8%) of the participants in the intervention group reported negative effects from the internet-based self-help program.Conclusions: Internet-based self-help therapy was associated with a reduction in suicidal ideation at postintervention and 6-month follow-up. Some participants found it challenging to work with the therapeutic exercises, and we recommend that internet-based self-help therapy be implemented in mental health clinics or crisis lines, where support or online counseling is available.Trial Registration: ClinicalTrials.gov identifier: NCT02872610.