The 'STOP' suite of measures is a web-based tool, using the HealthTracker outcome monitoring system, which can be used to assess and monitor suicide risk, including increased risk associated with the side-effects of common medications for childhood mental health problems, asthma and respiratory allergies.
This online methodology has been validated and is being tested in 3 paediatric observational trials (Risperidone/Aripiprazole in children with severe psychopathology; Fluoxetine/cognitive behaviour therapy in depression; and Montelukast /other medications in bronchial asthma or respiratory allergy); and normal healthy controls. The tool is available in English, Spanish, French, German, Dutch and Italian languages.
Aims and objectives
The NICE Quality Standard on depression in children and young people (QS48) includes two statements which require a thorough and timely assessment of suicide risk in order to be achieved.
Quality Statement 3 states that: children and young people with suspected severe depression and at high risk of suicide are assessed by CAMHS (Child and Adolescent Mental Health Services) professionals within a maximum of 24 hours of referral.
Quality Statement 4 states that: children and young people with suspected severe depression but not at high risk of suicide are assessed by CAMHS (Child and Adolescent Mental Health Services) professionals within a maximum of 2 weeks of referral.
Our aim was to create a tool that could be used to assess and monitor suicide risk in children and adolescents who are taking medication for which side-effects may increase the risk of suicide.
- To develop a comprehensive assessment of suicide risk and its bio-psycho-social mediators (including medication characteristics, psychopathology, and biological, psychological and social risk and protective factors) in children and adolescents.
- To standardise the newly developed web-based assessment and monitoring measures (using the HealthTracker system) using data obtained in 3 observational clinical cohorts and a healthy non-clinical group.
- Address scientific questions about suicide risk and its bio-psycho-social mediators with a focus on medication-related suicide.
- To identify the rates of suicide reported in those taking different medication (antipsychotics, antidepressants, anti-asthmatics including Montelukast), those treated with CBT for depression and a non-clinical healthy group.
- Disseminate the knowledge acquired by these studies and make available the technology developed through this project to regulatory authorities, researchers, pharmaceutical companies, and medical and mental health professionals
Reasons for implementing your project
Suicide and suicide attempts by children and adolescents are a major public health problem and have long been a matter of great concern to modern society, particularly for clinicians who deal with mental health problems of children and adolescents. During the mid-adolescent years, the incidence of suicide attempts reaches a peak and mortality from suicide is the third leading cause of death.
The NICE Quality Standard on depression in children and young people states that children and young people with suspected severe depression should be are seen by a child and adolescent mental health service (CAMHS) professional within 2 weeks of referral, or within a maximum of 24 hours if at a high risk of suicide. Prompt access to services is essential if children and young people are to receive the right treatment at the right time. Arrangements should be in place so that children and young people referred to CAMHS with suspected severe depression and a high risk of suicide are kept in a safe place and seen as an emergency, within a maximum of 24 hours, to help prevent injury or worsening of symptoms.
The emergence of suicidal ideation and suicide related behaviour in patients receiving drug treatment is of concern because of the overall burden of these conditions and the possible link with completed suicide. The term 'Medication Related Suicidality' is a reported adverse event and is defined as any suicide related symptoms that are reported during the period of treatment with the drug. There is some evidence of an association between some medication use (e.g. serotonin-specific reuptake inhibitor (SSRIs) and other newer antidepressants, Atomoxetine, antiepileptics, Montelukast) and treatment-related suicidal ideation and suicide-related behaviour in children and adults.
We identified a need to develop and validate a suicidality measure that can define and explore the relationship between suicidal ideation, self-harm, and risk of suicide attempts and completed suicide in general populations and in populations known to be at elevated risk of suicide either due to psychopathology (for example, depression) or the use of psychoactive medication. Similarly, due to the possible importance of genetic factors as mediators of treatment response, biological sampling strategies are required that are appropriate and accurate when used in a paediatric population.
How did you implement the project
The starting point of the STOP project was to devise a methodology for generating signals of medication-associated suicide risk in children and young people from a pharmacovigilance database. Using data from the Vigibase database (maintained by the WHO Uppsala Monitoring Centre in Sweden), we designed a methodology to detect signals of suicide-related adverse events from large datasets. A systematic review was conducted based on the medications identified as having signals using the Vigibase database and we also identified side-effects reported alongside suicide-related adverse events.
Further to detecting suicide risk based on clinical and behavioural data it was important to establish a biological sampling methodology for the investigation of mediators of suicide in the paediatric population. This is necessary because, for a variety of reasons, it is difficult to collect blood samples from children with mental health problems. We therefore focussed on identifying what method of saliva collection would yield the best biological data, equivalent to that obtained through blood sampling. We identified the method and developed a standard operating procedure for this, allowing future researchers the possibility of collecting biological samples when doing research in this area.
Having now developed the STOP suite of measures we are now in the process of using them in 3 prospective observational studies in groups suggested to be at risk of suicide:
- Children and adolescents with depression treated with Fluoxetine (n=120) versus a psychological therapy comparison group (n=120),
- Children and adolescents with severe psychopathology which warrants treatment with an anti-psychotic medication (Aripiprazole or Risperidone) (n=400),
- Children and adolescents with asthma or another allergy with respiratory symptoms treated with Montelukast (n=100) or an alternative medication (n=100).
Finally, we are also using these measures to explore suicide risk in a large normative control sample without a history of psychiatric diagnoses. This will enable us to understand if and how suicide risk in clinical populations differs from what may be found in the general population.
The STOP project is still ongoing and these results are pending publication in peer reviewed journals. This study developed effective biological sampling strategies for children and adolescents. Although the yield from 2.5ml of saliva processed using Oragene.Dx kit in adults is approximately half that from a 5ml blood sample, the quality is good and 'fit for purpose', specifically, for a range of genomic applications, including single nucleotide polymorphism (SNP) analysis, variable number tandem repeat (VNTR) genotyping, long-range polymerase chain reaction (long-PCR), and genotyping using microarray technology. Furthermore, methylation assays are possible on saliva processed using Oragene.Dx kit with the caveat that there are tissue-specific differences in methylation. We have now developed specific extraction protocols for children less than 12 years that differ from that used in older children.
We developed and validated 3 self-report, internet-based questionnaires (using the HealthTracker system) for suicide risk in children and adolescents, specifically addressing the capture of possible influence of medication factors. The development of the instruments followed the Food and Drug Administration recommendations for Patient-Reported Outcome (PRO) instruments. The scales' items were based on information from previous literature, existing scales and experts' opinion and focus groups with adolescents and children were conducted to determine whether the concepts and items used were understood by patients.
The instruments developed were:
1) STOP Medication Side-effects Suicidality Scale (STOP-MS3),
2) STOP Suicidality Assessment Scale (STOP-SAS), and
3) STOP Risk and Resilience Scale (STOP-RRS).
Each questionnaire was designed with versions for children (8-11), adolescents (12-18), parents, and clinicians. The final questionnaires were administered to a sample of adolescents and children through a web-based monitoring system (using the HealthTracker system) to obtain data regarding test reliability and internal consistency.
To date, we have analysed data from 94 adolescents and 53 children with different diagnoses from several hospitals in Spain, Italy, France, Germany and the United Kingdom. Each of the 3 STOP scales achieved our expectations, showing a high internal consistency and good reliability.
Key learning points
- It is important to note that when attempting to use novel biological sampling techniques or clinical tests within a research protocol of an observational study, the study may be classified as a 'clinical trial'. This has implications from both an administrative and ethical perspective, and it is important for the researcher to take into account the extended time for study approvals that may result from this. In our experience, the Ethics Committee approvals from the various sites (across countries) were a prolonged process and took longer to achieve than anticipated, many required more convincing as we were exploring a sensitive topic.
- Recruiting a healthy non-clinical population was a challenge. It was difficult to get the support of local schools for research into child mental health issues, especially around self-harm. This highlights the importance of developing strong links with local schools. One approach could be to offer psycho-education to staff or to give assembly presentations to help build collaborations.
- Another important challenge was to fully engage with paediatricians about issues around mental health and suicide risk. We were surprised by the reluctance of non-mental health trained physicians to discuss the topic of suicide in the context of paediatric services. We discovered that many paediatricians found it difficult to give information about the STOP study because they found it difficult to discuss suicide and mental health difficulties with their patients, leading to fewer patients being enrolled. We overcame this in two ways: First, members of our research team were placed in outpatient clinics to discuss these issues with both clinicians and potential participants. Secondly, we provided psycho-education about suicide risk and related mental health conditions to the paediatric services. Our experience is that participants are often less sensitive about issues around suicide than the clinicians had expected.