Our results confirm that, by using the data commonly available in health information systems, it is possible to develop a tool for the screening of factors associated with suicide risk among psychiatric patients that does not require psychometric testing. This would be of great help to develop strategies aimed at mitigating such risk. The question is particularly relevant in light of the increasingly widespread adoption of electronic health records, which might provide opportunities for practical application of precision medicine and the possibility of predicting risky suicidal behaviour [6, 24]. The score model obtained (RASSA) is robust, with high sensitivity and specificity, and it will allow to identify the potential risk factor for suicide in a given individual. According to our model, the strongest prediction factors for identifying risk to commit suicide were ‘not using antipsychotic medication’, ‘non-psychiatric comorbidity’ —mainly skeletal muscle and neurological disorders, but also gastrointestinal and oncological disorders—, and ‘a family history of suicide’.
Suicide behaviour is complex. Indeed, it has been shown that a variety of clinical features beyond mental health diagnoses appear among the top 100 predictors [24]. Numerous studies have identified pain as a risk factor for suicide, and it is estimated that up to 50% of patients with chronic pain present suicidal ideation [25]. Furthermore, pain can mask underlying depression [26]. The high-risk score of the family history of suicide variable agrees with evidence of the genetic influence on suicidal behaviour and its overlapping with major depression [22]. As expected, suicidal behaviour was associated with depression as the principal mental health diagnosis [27, 28,]. However, it is interesting to point out that RASSA suggests that suicide attempt risk can be high even in the absence of depression if other risk factors are present, and that depression alone could be not enough to explain a suicide attempt. In fact, if depression is the only risk factor observed in the patient (of the 13 factors considered), the risk obtained is low.
Case group subjects in our sample were more exposed to antidepressants than control subjects (74% vs. 65.2%), particularly to SSRIs (54% vs. 37%). Frequency of case patients was higher in those exposed to escitalopram, venlafaxine, paroxetine, sertraline, citalopram, and fluvoxamine, which is consistent with previous results [15]. Thus, SSRIs appeared as a significant predictor of increased suicide risk in the univariate analysis and in the adjusted model. There was also an association between suicide attempt and use of certain medications. The protective effect of opioids, which appears after adjustment, is consistent with their well-known anxiolytic and sedative effects. Although mediated by different routes, this may be a similarly real effect to that of ketamine [29]. More difficult to explain is the association of non-opioid analgesics with the risk of a suicide attempt. This should be interpreted not as these analgesics provoke suicidal ideation, but that they might be a marker for those patients in high risk. Taking pills or pharmaceutical overdose is a common method of suicide attempt. NSAIDs and acetaminophen are widely used analgesics in the prescription and non-prescription settings and the literature shows that access to methods of suicide may increase the risk of it [30]. We found a protective factor related with antipsychotic drug use, but the contribution of antipsychotic drugs to suicide risk remains unclear. Whereas some observations suggest that the side effects of antipsychotic medications may contribute to suicidality, lack of adherence to antipsychotic drugs may increase suicide risk [12, 16, 31].
Substance abuse was also associated with the risk of suicide attempt, since alcohol, cocaine, and amphetamine dependence were higher among case subjects. Alcohol dependence, alone or in combination with comorbid psychopathology or negative life events, is known to dramatically increase the risk of suicidal ideation, suicide attempts and completed suicides in the long term (see review in [16]). In explaining suicidal behaviour, one must account for the stimulus necessary to carry out the act, which could certainly be produced by cocaine and amphetamines. This explanation coincides with one that has been given to understand the possible action of SSRIs on suicidal behaviour [32], as SSRIs and cocaine share a similar mechanism in the post-ganglionic nerve termination, that is, the inhibition of neurotransmitter reuptake. Cannabis had a similar prevalence of use among case subjects and control subjects, but in the estimation of the adjusted risk, a higher risk of suicide attempt was found among those suffering from a cannabis addiction. This increased risk may be explained by the mood and personality deterioration associated with chronic use [33]. On the other hand, results about the relationship of tobacco or nicotine with suicidal behaviour are contradictory; while some have identified a positive association [34], independently of comorbid mental disorders and physical diseases [35], others have not found it [36, 37]. These discrepancies could be due to the type of samples studied or to other associated factors, as smoking is particularly frequent among psychiatric patients, and even more so among patients who are medicated with antipsychotics. If antipsychotics exert a protective action on suicidal behaviour and these are associated to a greater extent with smoking [38, 39], the distribution found of this medication between case subjects (21%) and control subjects (31%) in our study would be consistent with this fact.
Finally, we also found that the risk of suicide attempt was significantly greater for women and for unmarried subjects. Although suicide rates are known to be higher among men, this is known to result from the more lethal suicide methods chosen by males. Indeed, the suicide attempt worldwide is higher in women than in men. This is a complex and multifactorial phenomenon. There is a multitude of potential social-cultural reasons for why the suicide attempt rate is higher among women, like their grater longevity. Another factor might be that women are more prone to depression than men [40]. However, mental disorders such as depression and schizophrenia are identified with suicidal behaviour in both men and women. Eating disorders are also correlated with an increased risk of suicide in women. As we know, the existence of possible violence, child abuse and factors related to pregnancy have also been associated with an increased risk of suicide in women [41]. Another possible explanation is the vulnerability related to gender and certain psychiatric pathologies, more prevalent in the case of women, as well as the existence of psychosocial stressors [42]. Hormonal disturbances, such as changes in the oestradiol level that occur during the menstrual cycle, may also be related to the higher frequency of suicides among women [43]. Nevertheless, this question remains to be fully dilucidated. On the other hand, the greater risk of suicide attempt for people who were unmarried may be explained by the risk for depression caused by isolation and thus for potential suicidal behaviour, which agrees with our results. Similarly, it has been shown that for both men and women, “separated marital status” is associated with more than a fourfold risk of suicidal behaviour compared with married patients [24].
Like all observational studies, the present work has some obvious limitations. We cannot completely rule out the possible existence of biases or possible residual confounding factors due to variables that were not considered into evaluation. For instance, alcohol abuse is a risk factor for suicide and suicide attempt repeatedly noted in the literature [16]. In our study, alcohol abuse resulted as a significant variable for suicide attempt in the univariate analysis but turned up not enough significant in the multivariate logistic regression after controlling for other factors. The alcohol abuse/dependence variable was strongly associated with the rest of the abuse/dependence variables whose effects on suicide attempt risk are considered into score. As a matter of fact, the combined consumption of alcohol and tobacco has been reported higher risk of attempt of suicide than each substance separately [34]. For this reason, RASSA could underestimate the risk of suicide attempt in patients with no other diagnosis of abuse/dependency but alcohol. However, it must be said that it is not easy to gather as many cases as the ones presented in our study, but we need to accept the limitations of data collection that is done in routine medical care. The innovation provided by the application of RASSA is based on a few independent factors with clinical sense identified and easily recorded in health databases, combined in a risk score with high discriminatory capacity. Therefore, our RASSA score model needs to be validated with large data and health systems, in different populations and periods, in order to assure its reliability by external validation. This would be especially important considering that predicting suicide risk from data records relies largely on the clinical judgment and treatment decisions of clinicians, and do not typically reflect important social risk factors such as job loss and relationship disruption [7]. Nevertheless, our results showed the robustness, high specificity and sensitivity, and easy management of our RASSA model. Therefore, we can consider this study as a pilot of a further assessment score to evaluate the risk of suicide attempt that can be applied to different populations and situations.