The association between depression and suicidal thoughts and behaviour is well established (e.g. Chesney et al., 2014; De Beurs et al., 2019). Suicide ideation is also one of the symptoms of depression according to the DSM criteria, and often an item in depression scales that are used as primary outcomes in trials (Kroenke et al., 2001). Therefore, it seems logical to assume that effective treatments of depression also have a significant effect on suicidality. However, contemporary theories of suicidal behaviour, such as the Integrated Motivational Volitional model state that suicidal behaviour is not just a symptom of depression, but rather the results of a process on its own (O’Connor & Kirtley, 2018).

Recent years, therefore, saw the introduction of therapies such as the collaborative assessment and management of suicidality (CAMS) (Jobes et al., 2016), that directly target suicidality. Nevertheless, in daily clinical practice, depressed patients, who often also report suicidal ideation, are most likely to receive a psychological intervention such as cognitive behavioural therapy that specifically focuses on depression and not directly on suicidality. Importantly, suicidality is often an exclusion criterion for psychological intervention trials.

Thus, the empirical question remains: how large the effect of psychological interventions aimed at depression is on suicidal ideation and behaviours given the current available RCTs? A recent meta-analysis titled “Assessment of Suicide Risk in Psychological Interventions for Depression” by Miguel and colleagues (2024) aimed to answer this question by systematically investigating any reported effects on suicidality within trials of psychological interventions for depression.

Methods

The study utilised the Metapsy database, a “living analytic database” which includes randomised controlled trials of psychological treatments for depression. The analysis included trials with an inactive control group that reported suicide-related outcomes either as an adverse event or as part of the safety monitoring. The authors selected randomised controlled trials that aimed to test the effects of psychological interventions for depression. They included a wide range of suicide-related factors, including suicide ideation (thoughts, intents and/or plans), suicidal risk (chance of (non)fatal suicide attempts) and behaviours (attempts and severe self-harm). The authors only included studies that used established instruments.

Results

• 469 RCTs were identified in which a psychological intervention for depression was compared to an inactive control.
• In the majority of studies (54%), participants were excluded because of a risk for suicide.
• For the meta-analysis on the effectiveness of a psychological intervention of depression on suicidal ideation, only 12 trials were selected.
• These were quite different trials, one in pregnant people, one in incarnated, three among participants with a general medical condition.
• The therapies were CBT, mindfulness and behavioural activation.
• Overall, there was a small effect on suicidal ideation of psychological interventions for depression.
• When excluding trials where suicide outcomes only relied on a single item, no significant differences were found.
• Furthermore, no significant longitudinal effects were found.
• Also, an increase in levels of suicidality was found in 25 trials.
• Heterogeneity was high in all studies.

Conclusions

• Suicidal thoughts and behaviours are rarely reported in trials studying the effect of psychological interventions on depression.
• Perhaps even more importantly, in more than half of the studies (54%), suicidal patients were excluded.
• The meta-analysis of 12 trials showed a small effect of the interventions on suicide ideation, but the authors state these are mainly driven by 2 studies focussing on suicide. When these were omitted, no significant results were found.
• No long-term effects were found.
• In 25 studies, an increase in suicidality was found during the study.

Strengths and limitations

The strength of this study is that it provides an updated view on the reporting of suicide risk factors within clinical trials, and an overview of the rate of exclusion of suicidal patients within studies of depression. The team is an excellent expert group on meta-analyses, so the quality of the search and the analysis is beyond doubt.

As far as I can tell, the main limitation is that due to the limited number of the studies and their heterogeneity, the data does not per se tell us much about the effectiveness of psychological interventions for depression on suicide ideation. The information is just not there.

Also, the studies that did report suicide ideation often relied on single items from existing depression scales. We know from different studies that single items tend to present a biased insight in the level of suicidality (Millner et al., 2015). Relatedly, we know from ecological momentary assessment studies that suicidality fluctuates heavily even within periods of an hour (Kleiman & Nock, 2018). Given this general small effect, one wonders if an individual patient data meta-analysis (IPDMA) would not have resulted in a more fine-grained insight into the relationship between psychological interventions for depression and suicidality.

Also, a head-to-head comparison of interventions that indirectly target suicidality (such as psychological intervention for depression) and interventions that directly target suicidality, such as CAMS, would be interesting.

Importantly, but also frustratingly, as even in interventions that directly target suicidality, the effect size remains small. One wonders if we will ever be able to get a definitive scientific answer to the question: how to best treat suicidality from RCTs or meta-analysis (Fox et al., 2020).

Implications for practice

It remains staggering that the patients that might need psychological therapy the most, i.e. patients with high risk for suicidality remain excluded from most of the trials. This limits the insights into the effectiveness of most common offered interventions in daily clinical practice on suicidality. This is a topic often addressed, but must be put higher on the agenda of researchers and ethical committees.

The insight that the indirect effects of the interventions are small is in line with many other interventions aimed at the reduction of suicidality (Fox et al., 2020). Clinicians will have experience that when treating depression, in many patients the suicidality also decreases, but it’s good to not take the effect of psychological interventions on depression on suicidality for granted.

Clinicians should be aware that although it is likely that suicidal risk decreased when the depression treatment is effective, it might be that for some patients, suicidal risk remains present. Therefore, clinicians should frequently monitor suicidal ideation, and at the end of treatment explicitly discuss any residual risk for suicidality. Risk factors specific for suicidality, such as feelings of entrapment or perceived burdensomeness might also help clinicians to better assess the risk for suicidality (De Beurs et al., 2018; De Beurs et al., 2020).

Also, once someone has been suicidal, the differential activation hypothesis states that patients are more likely to again become suicidal after another experience of stress or entrapment (Lau et al., 2004). Therefore, offering a form of psychoeducation or safety planning about how to recognise a novel crisis might better protect people from relapse (Nuij et al., 2021).

For researchers, it should be fairly simple to report on the scores on suicide ideation or risk outcomes in papers, making an update of this study in 10 year’s time easier and more informative. Ideally, within studies, risk for suicidality should be assessed with dedicated scales such as the Suicidal Ideation attributes scale (SIDAS) (van Spijker et al., 2014).

If anything, suicidal behaviour is complex and the result of many interacting variables, and a relevant question is whether any study or meta-analysis will ever be able to provide definite answers to what works best for whom (De Beurs et al., 2020). Other designs, such as IPDMA, or qualitative interviews might offer the required clinically useful insights. Different perspectives, such as the network perspective, or a complexity perspective might also help us further entangle the complexity at the individual level (De Beurs et al., 2020). Until then, clinicians should always be aware of risk for suicidality within depressed patients, and actively pay attention to it during any form of psychological or pharmacological treatment.

Statement of interests

Derek de Beurs is member of the Dutch guideline for suicidal behaviour. He knows three of the authors (PC, EK and WB).

Links

Primary paper

Miguel, C., Cecconi, J., Harrer, M., Van Ballegooijen, W., Bhattacharya, S., Karyotaki, E., Cuijpers, P., Gentili, C., & Cristea, I. A. (2024). Assessment of suicidality in trials of psychological interventions for depression: A meta-analysis. The Lancet Psychiatry, 11(4), 252–261. https://doi.org/10.1016/S2215-0366(24)00027-0

Other references

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De Beurs, D., Cleare, S., Wetherall, K., Eschle-Byrne, S., Ferguson, E., B O’Connor, D., & C O’Connor, R. (2020). Entrapment and suicide risk: The development of the 4-item Entrapment Scale Short-Form (E-SF). Psychiatry Research, 284. https://doi.org/10.1016/j.psychres.2020.112765

de Beurs, D., Fried, E., Wetheral, K., Cleare, S., O’ Connor, D., Ferguson, E., O’ Carroll, R., & O’ Connor, R. (2018). Exploring the psychology of suicidal ideation: A theory driven network analysis. Preprint. https://doi.org/10.1016/j.brat.2019.103419 

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