Risk Factors for Suicidality in Patients With Schizophrenia

A Systematic Review, Meta-analysis, and Meta-regression of 96 Studies

Ryan Michael Cassidy; Fang Yang; Flávio Kapczinski; Ives Cavalcante Passos

Disclosures

Schizophr Bull. 2018;44(4):787-797. 

In This Article

Discussion

This is the first meta-analysis and meta-regression analysis of risk factors associated to suicide ideation and suicide attempts in patients with schizophrenia. It is also the first meta-analysis and meta-regression analysis of continuous risk factors associated to suicide in schizophrenia. Furthermore, we also updated a previous meta-analysis published in 2005 that assessed only categorical risk factors for suicide in patients with schizophrenia.[12] For the first time, we used strategies to explore heterogeneity and bias, namely: meta-regression, leave-one-out, Egger's test, and trim and fill and performed a separate analysis only with cohort studies.

Suicidal Ideation and Attempt

Our meta-analysis showed that some symptoms scales were associated with suicidality in patients with schizophrenia. Depressive symptoms as assessed by BDI and HAM-D scores were associated with both suicide ideation and suicide attempt. The PANSS general scale was also associated with suicide ideation. Future studies may identify more specific subscales for predicting suicide. Finally, a greater number of psychiatric hospitalizations was strongly associated with both ideation and attempts; this likely represents a more severe course of illness.

Suicide Attempt

Besides hopelessness, history of depression, history of attempted suicide, family history of psychiatric illness, family history of suicide, and being white, we found that history of alcohol, drug, and tobacco use were all associated with increased risk of suicide attempts. Tobacco use is particularly common in patients with schizophrenia, and it was reported that smoking cessation reduces depression and suicidality in patients with psychosis.[28] Two protective factors were identified for suicide attempts: living alone and being male. Living alone was usually dichotomized against a group-living or long-term care facility, so it may represent a greater functional capacity and reduced disease burden. Male as a protective factor is consistent with the "gender paradox" phenomena in suicidology, where men are less likely to attempt suicide, but more likely to use lethal suicide means.[29,30] Univariate models accounted for heterogeneity in several risk factors for suicide attempts (see "Results" section). For instance, for history of drug use and tobacco use, studies with high quality as assessed by NOQAS were more associated with an increased risk of suicide attempt.

Suicide

Three continuous risk factors, shorter illness length, younger age, and higher IQ were noted in our study to be associated with increased suicide; the first two were also significant in the cohort study. We also identified that history of tobacco use and history of alcohol use as significant risk factors for suicide, while these factors were either not tested or not significant in the prior meta-analysis for suicide.[12] We confirmed some results of the previous meta-analysis:[12] being male, history of attempted suicide, worthlessness, hopelessness, poor treatment adherence are significant risk factors of suicide in patients with schizophrenia. The first two remained significant in our cohort meta-analysis. A model composed of 3 variables (NOQAS score, region of study, and mean age of the samples) was able to explain all the heterogeneity for being male.

Most articles included in this analysis did not employ suicide risk assessment scales; when they did, often they were unique to that study and not used in any other, preventing their inclusion in our analysis. This reflects the lack of consensus on how one assesses suicidality in schizophrenia. A similar statement can be made about assessment tools for symptomatology; while we included scoring for schizophrenic symptoms, depression, and anxiety, many other scales were excluded because they were reported only within one article.

The 3 categories of suicidality described in this article had largely similar risk factors, with some notable differences. There are several reasons why this may be the case. First, there is a difference in the information available to collect in the case of suicide and suicide attempt, as most suicide studies were post-mortem psychological autopsies and things such as symptomatology scales could not be evaluated. Another reason is that these categories do seem to represent different phenomena; eg, it is well-established that women are more likely to attempt suicide, but men are more likely to commit suicide, indicating that being female is a risk factor for suicide attempt, and being male is a risk factor for suicide. One goal of our study was to highlight these differences in risk factors for each category.

Strengths and Limitations

While we cannot infer causality from this pooling and analysis of observational studies, the results of this meta-analysis have significantly strengthened and grounded the evidence for the existence of these risk factors for suicidality in schizophrenia and provides an opportunity for clinicians to employ the typical strategies targeting reduction of these risk factors with the additional benefit of reducing suicide risk. An important strength of our systematic review was the search strategy, since we have made an exhaustive effort to acquire data by contacting the authors. Thus, we were able to include a large number of papers, providing a more accurate estimate of the influence of these risk factors. In addition, we were able to perform a supplemental analysis only with cohort studies. Our study has some limitations. For the significant risk factors, high levels of between-study heterogeneity (I 2 > 50%) were recorded for illness length, history of attempted suicide and age for suicide, and for history of attempted suicide, history of drug use, history of alcohol use, and number of psychiatric hospitalizations for suicide attempt. However, univariate meta-regression analysis showed that quality of the included studies assessed by NOQAS explained a large amount of heterogeneity for history of drug use. Unexplained heterogeneity could be related to genetics, presence of different subgroups, or methodological variability. For instance, evaluation of potential risk factors often took place a long time before death or attempt occurred, and these factors might have changed in the intervening period. We were also unable to examine treatments in this meta-analysis, because medication was often referred to in general terms, such as "antipsychotics" or chlorpromazine dose equivalence. However, our meta-analysis showed that suicide risk is considerably increased in patients who adhere poorly to treatment. In addition, we could not exclude the effect of publication bias in the effect size of the following variables: illness length for suicide and history of attempted suicide and number of psychiatric hospitalizations for suicide attempt. Finally, a small number of studies may have driven the effect size observed, as the leave-one-out method demonstrated in some variables as reported in results section. Therefore, additional studies are needed for a definitive conclusion on these variables.

processing....