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

Results

We included 96 studies with 80488 participants in our analysis. Figure 1 shows the study selection process. Quality of studies and characteristics of included studies are described in supplementary table 2.

Suicide—Categorical Risk Factors

For the categorical risk factors, poor adherence to treatment (P < .0001), history of attempted suicide (P < .0001), worthlessness (P < .0001), hopelessness (P < .0001), being male (P = .0005), being white (P = .0105), history of tobacco use (P = .0169), and history of alcohol use (P = .0378) were significantly associated with patients with schizophrenia who committed suicide (Table 1). Family history of alcohol use (P = .0590), sleep disturbance (P = .0662), and history of depression (P = .0968) trended toward significance. Table 1 shows study heterogeneity and supplementary figures 1–8 show the forest plots of significant categorical risk factors for suicide.

Egger's test revealed a publication bias for history of attempted suicide (P = . 0.0168), and being white (P = .0036). It could not be calculated for worthlessness because only 2 studies reported these variables.[24,25] Duval and Tweedie's trim and fill method was performed on history of attempted suicide (OR = 2.73; CI: 1.96–3.81; P < .0001 with 5 studies estimated on the left side) and was still determined to be significant. It was performed on being white (OR = 2.98; CI: 0.87–10.23; P = .0822 with 2 studies on the left) and was no longer significant.

The significance of the effect size remained robust when leave-one-out models were used for poor compliance, history of attempted suicide, hopelessness, and being male. Significance testing revealed the effect size to be nonsignificant after removing 1 study history of tobacco use (supplementary table 5), any of 6 studies for history of alcohol use (supplementary table 6), 1 study for worthlessness (supplementary table 7), and 1 study for being white (supplementary table 8).

Suicide—Continuous Variables

For the continuous risk factors, IQ was higher (P < .0001) in patients with schizophrenia who committed suicide, illness length was shorter (P = .0069), and patients were younger (P = .0266) (Table 1). Table 1 also shows study heterogeneity and supplementary figures 9–11 show the forest plots.

Egger's test revealed a potential publication bias for illness length (P = .0304). It could not be calculated for IQ because only 2 studies reported this variable.[26,27] Duval and Tweedie's trim and fill method results did not change the parameter estimates for illness length.

The significance of the effect size remained robust when leave-one-out models were used for IQ and illness length. Significance testing revealed the effect size to be nonsignificant after removing 1 study for age (supplementary table 9).

Suicide—Meta-regression Analysis

In our investigation of sources of heterogeneity using univariate meta-regression analyses, we found that for male gender as a risk factor, NOQAS score, region, and mean age of the total sample accounted for heterogeneity. For being male, NOQAS score negatively correlated (b = −0.1294, P = .0197), studies conducted in Asia were less associated (b = −0.7589, P = .0131), and a higher mean age of the total sample positively correlated (b = 0.0230, P = .0257) with the increased risk of suicide (supplementary table 3). The multivariate meta-regression of these moderators accounted for 100% (pseudo-R 2) of the heterogeneity (F = 15.6286, P = .0036, k = 16), but none of the moderators retained a significant effect on the association by themselves (supplementary table 4). Univariate meta-regression did not reveal a significant moderator effect on any other risk factor.

Attempted Suicide—Categorical Variables

For categorical risk factors, physical comorbidity (P < .0001), history of depression (P < .0001), family history of psychiatric illness (P < .0001), family history of suicide (P < .0001), history of attempted suicide (P < .0001), hopelessness (P = .0001), history of alcohol use (P = .0001), history of drug use (P = .0024), history of tobacco use (P = .0034), and being white (P = .0022) were associated with patients with schizophrenia who attempted suicide (Table 2). Being male (P = .0417) and living alone (P = .0338) were found to have a reduced risk of attempted suicide (Table 2). Table 2 also shows study heterogeneity and supplementary figures 12–23 show the forest plots.

Egger's test revealed a potential publication bias for history of attempted suicide (P = .0009). Duval and Tweedie's trim and fill method results did not change the parameter estimates for history of attempted suicide.

By using leave-one-out models, significance testing revealed the effect size to be nonsignificant after removing one study for hopelessness (supplementary table 10), either of 2 studies for living alone (supplementary table 11) and 18 studies for being male (supplementary table 12). The significance of the effect size remained robust when leave-one-out models were used for the other risk factors.

Attempted Suicide—Continuous Variables

For continuous risk factors, number of psychiatric hospitalizations (P < .0001) and BDI score (P < .0001) were higher in patients with schizophrenia who attempted suicide, while age of onset (P = .0397) was lower (Table 2). PANSS positive score trended toward significance (P = .0967). Table 2 also shows study heterogeneity and supplementary figures 24–26 show the forest plots.

Egger's test revealed a potential publication bias for number of psychiatric hospitalizations (P = .0227) and age of onset (P = .0304). Duval and Tweedie's trim and fill method results did not change the parameter estimates for number of psychiatric hospitalizations or age of onset.

In leave-one-out models, significance testing revealed the effect size to be nonsignificant after removing any of the 3 studies for age of onset (supplementary table 13). The significance of the effect size remained robust when leave-one-out model was applied for other 2 continuous factors.

Attempted Suicide—Meta-regression Analysis

In our investigation of sources of heterogeneity using univariate meta-regression analyses, we found that for physical comorbidity, the mean age of the total sample was positively associated (b = 0.1977; P = .0474) with an increased risk for suicide attempt. For family history of psychiatric disorders, studies conducted in Africa were less associated (b = −0.8841; P = .0102) and studies conducted in Oceania were more associated (b = 0.5017; P = .0477) with an increased risk of suicide attempt. For history of drug use, NOQAS score was positively associated (b = 0.1271; P = .0239) with the risk of suicide attempt. For history of tobacco use, NOQAS score was positively associated (b = 0.1328; P = .0153) with the risk of suicide attempt. For being male, studies conducted at the lower latitudes were associated (b = −0.0074; P = .0022) with an increased risk of suicide attempt (supplementary table 3). Univariate meta-regression did not reveal a significant moderator effect on any other risk factor. Multivariate meta-regression was not performed since no risk factor had more than one moderator with a significant effect.

Suicide Ideation

For the categorical risk factors, no variable was significantly associated with suicidal ideation (Table 3). For the continuous risk factors, HAM-D score (P < .0001), BDI score (P < .0001), PANSS general score (P < .0001), and number of psychiatric hospitalizations (P < .0001) were higher in schizophrenic patients with suicidal ideation (Table 3). A higher PANSS positive score (0.0668) trended toward significance. Table 3 also shows study heterogeneity and supplementary figures 27 and 28 show the forest plots.

Egger's test did not reveal publication bias for any risk factor.

The significance of the effect size remained robust when leave-one-out models were used for each of these variables. Univariate meta-regression did not reveal a significant moderator effect on any risk factor.

Supplemental Analysis: Meta-analysis of Cohort Studies

As cross-sectional or case-control studies only delineate the association of variables with suicidality, we further performed a supplemental meta-analysis including only cohort studies to explore potential causality. We included 6 cohort studies for attempted suicide, and 9 studies for suicide (supplementary table 14). The analyses showed that being male (P = .0003), history of suicide attempts (P = .0034), history of tobacco use (P = .0401), younger age of onset (P = .0404), shorter disease length (P = .0058), younger age (P = .0014) are predictive for suicide (supplementary table 15). For suicide attempts, predictive factors include history of attempted suicide (P < .0001), history of alcohol use (P = .0052), and family history of psychiatric illness (P = .0007) and younger age of onset (P = .0063) (supplementary table 16). Supplementary figures 29–34 show the forest plots for suicide, supplementary figures 35–38 show forest plots for suicide attempt.

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