Why are patients with active suicidal ideation excluded from early phase clinical trials?

From the Guidelines

Patients with active suicidal ideation are excluded from early phase clinical trials primarily to protect their safety and well-being, as they require immediate psychiatric intervention rather than experimental treatments with unknown risks. This decision is guided by the need to prioritize the safety and well-being of vulnerable individuals, as highlighted in studies such as 1, which emphasizes the importance of considering the methodological limitations and ethical implications of including patients with active suicidal ideation in clinical trials.

Key Considerations

• The investigational drugs being tested in early phase trials may have unpredictable side effects, including potential neuropsychiatric effects that could worsen suicidal thoughts or behaviors 1.
• The research environment may not provide the comprehensive psychiatric support needed for suicidal patients, as research teams are often not equipped with the specialized mental health resources required for crisis intervention.
• There are also concerns about whether individuals experiencing suicidal thoughts can provide truly informed consent, as their decision-making capacity may be compromised by their psychological distress.

Ethical and Methodological Implications

The exclusion of patients with active suicidal ideation from early phase clinical trials is a complex issue that involves balancing the need to advance medical knowledge with the need to protect vulnerable individuals. As noted in 1, researchers should strive for the most rigorous design that is feasible, while also being mindful of the ethical implications of their study design. This may involve using alternative research and evaluation methods, such as rigorously designed quality improvement projects and practice-based research networks, to ensure that the needs of suicidal patients are addressed in a safe and effective manner.

Future Directions

Once a medication has progressed to later-phase trials with better established safety profiles, patients with managed suicidal ideation may be included with appropriate safeguards in place. This may involve using a higher threshold for exclusion, such as active suicidal intent or elevated suicide risk, as suggested in 1. Ultimately, the goal is to ensure that clinical trials are conducted in a way that prioritizes the safety and well-being of all participants, while also advancing our understanding of effective treatments for suicidal ideation and other mental health conditions.

From the Research

Exclusion of Patients with Active Suicidal Ideation from Early Phase Clinical Trials

• Patients with active suicidal ideation are often excluded from clinical trials of psychiatric medications and investigations using neurobiological techniques 2.
• The exclusion of these patients is due to concerns about their safety and the potential impact of their suicidal ideation on the trial outcomes.
• However, some studies suggest that research can be conducted in depressed patients with active suicidal ideation if such research coincides with careful observation 2.

Safety Features and Inclusion Criteria

• Some clinical trials have implemented safety features to include patients with suicidal ideation, such as careful consideration of inclusion and exclusion criteria and other safety features 3.
• These safety features can enable the safe conduct of randomized clinical trials in suicidal adult patients, including the inclusion of participants who have undergone a prescribed tapering off of psychotropic medications prior to baseline assessment 3.
• The use of suicidal ideation and behavior screening instruments can also help identify patients who may be at risk of suicide and exclude them from clinical trials if necessary 4.

Impact of Exclusion Criteria on Trial Outcomes

• The exclusion of patients with suicidal ideation from clinical trials may not significantly impact the effects observed in clinical trials 5.
• A meta-analysis of randomized controlled trials of PTSD psychotherapies found that the difference in effect sizes between trials that excluded and did not exclude suicidal ideation was not significant 5.
• However, other studies have found that patients with active suicidal ideation can benefit from treatment, such as esketamine nasal spray, which has been shown to rapidly reduce depressive symptoms in patients with major depressive disorder who have active suicidal ideation with intent 6.

Feasibility of Enrolling Patients with Suicidal Ideation in Clinical Trials

• Suicidality screening is feasible in people with epilepsy, and the proportion of patients who may be excluded from clinical trials based on worrisome suicidal ideation or suicide attempt is small 4.
• This suggests that it is possible to enroll most eligible individuals in clinical trials, even if they have suicidal ideation, as long as appropriate safety features and screening instruments are used 4.