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Section 8
Major Depression with Comorbid Anxiety

Question 8 | Test | Table of Contents

Several studies have focused on the impact of comorbid anxiety on suicidality in patients with major depression. Comorbid anxiety is a common clinical scenario, occurring in 40% to 77% of patients with major depression. Fawcett and others reported that among patients with major affective disorders, panic attacks were present in 62% of those who committed suicide within 1 year of assessment, compared with a significantly lower rate of 28% among patients who did not commit suicide. Others have found higher rates of suicide attempts in patients whose depression involved a comorbid anxiety disorder. In contrast, a retrospective study by Barraclough and others found similar rates of anxiety among patients with major depression who committed suicide versus those who did not commit suicide. Therefore, although most studies conclude that comorbid anxiety is a risk factor for suicidality among patients with depression, not all studies agree, and the magnitude of effect remains in question. Another factor for consideration is that patients with anxious depression are generally more severely ill than those with nonanxious depression. This raises the question whether comorbid anxiety increases the degree of suicidality among patients with depression independently of severity of depression.

Only one study of which we are aware simultaneously assessed the impact of comorbid anxiety and sex on suicidality in patients with major depression. Isometsa and others completed psychological autopsies on 71 suicide victims in Finland who had diagnosis of major depression. They found that 17% had a comorbid anxiety disorder and that there was no significant effect of sex, with 18% of males and 15% of females having comorbid anxiety. However, this study involved a small number of cases and could not evaluate the impact of severity of depression on suicide.
This study examines a large group of patients with major depression and evaluates comprehensively the effects of sex and anxiety on suicidal ideation in this population. The aim is to understand the impact sex and comorbid anxiety have on suicidal ideation in patients with major depression and to identify whether the effects of sex and anxiety interact or act independently. in addition, if sex and anxiety are found to affect suicidality, is this effect independent of the severity of depression?

This study retrospectively reviewed a database of patients with major depression seen at the Depression Clinic of the Centre for Addiction and Mental Health (the former Clarke Institute), a university-affiliated tertiary care psychiatric facility. Complete data were available for 533 patients (190 men, 343 women). In each case a diagnosis of major depressive disorder had been made clinically and then confirmed using either the Structured Clinical Interview for DSM-IV (SCID-IV) or the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-LV). We obtained informed consent for all patients included in our database.

Demographic data and illness history were obtained for each of the patients. A current diagnosis or lifetime diagnosis (including those with a current episode) of an anxiety disorder was identified using the SCID-IV or SADS-LV. The following anxiety disorders were assessed: panic disorder, agoraphobia without history of panic disorder, obsessive-compulsive disorder (OCD), social phobia, specific phobia, posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). To assess current mood symptoms, the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used.

For this study, suicidal ideation was considered to be present if a subject scored more than 0 on the suicide items of both the HDRS and the BDI. That is, the subject must have endorsed "I have thoughts of killing myself, but I would not carry them out" or a more severe symptom on the BDI, and a rater must have assessed that the subject "feels life is not worth living," or a more severe symptom on the HDRS. Degree of suicidal ideation was determined by taking into account the suicide items on both the HDRS (objective) and BDI (subjective) as follows: a score of 0 for degree of suicidal ideation signified no suicidal ideation; a score of 1 signified passive suicidal ideation (that is, "I have thoughts of killing myself, but I would not carry them out" or "feels life is not worth living"); a score of 2 signified active suicidal ideation (that is, "I would like to kill myself" or "wishes he were dead or any thought of possible death to self"); a score of 3 signified active suicidal ideation with intent (that is, "I would kill myself if I had the chance" or "suicidal ideas or gestures"); and a score of 4 signified a suicide attempt (that is, "attempts at suicide")

To identify differences in demographic variables and baseline scores between women and men and between patients with or without a comorbid anxiety disorder, t-tests were used. We examined the effects of sex and comorbid anxiety on the presence of suicidal ideation using a logistic regression with presence or absence of suicidal ideation as the dependent variable and with sex and the presence or absence of a comorbid anxiety disorder as independent variables. The effects of sex and comorbid anxiety on the degree of suicidal ideation was examined using an analysis of covariance (ANCOVA) with current age and score on the "depressed mood" item of the HDRS as covariates.

A total of 533 patients were included in the study--190 men (35.6%) and 343 women (64.4%). The mean age was 38.1 years (SD10.8), with an average of 2.7 (SD 2.4) lifetime depressive episodes and a mean age at first depressive episode of 26.8 years (SD 11.7). The mean score on the 17-item HDRS was 20.5 (SD 4.3).

Women were significantly younger, with a mean current age of 37.3 (SD 10.5) versus 39.6 years (SD 11.1) years for men (P = 0.02). Women also had a significantly younger mean age at first depression, 25.8 years (SD 11.4), versus 28.6 years (SD 12.2) for men (P = 0.01). There was no significant sex difference in HDRS scores or number of depressive episodes. The mean current age did not differ according to presence or absence of a current or lifetime anxiety disorder. Patients with a current anxiety disorder were, however, younger when they developed their first depression (25.0 years [SD 10.8] versus 27.6 years [SD 12.0]) (P = 0.03) and had a higher HDRS score (21.2 [SD 4.6] versus 20.3 [SD 4.1]) (P = 0.03) than those without a current anxiety disorder. Results were similar for patients with and without a lifetime anxiety disorder.

Among all patients, 28.7% had a current anxiety disorder and 43.2% had a lifetime anxiety disorder. Women had higher rates of both current (female 29.7%, male 26.8%) and lifetime (female 45.8%, male 38.4%) anxiety; however, these differences were not significant. Women (21.6%) did, however, have a significantly higher rate of lifetime panic disorder than did men (11.6%) (x[sup2] = 8.27, df 1, P < 0.005). There were no other significant differences in rates of individual current or lifetime anxiety disorders based on sex.  Using the previously described definition, suicidal ideation was observed in 57.8% of all patients: 12.0% had passive suicidal ideation, 24.6% had active suicidal ideation, 20.3% had active suicidal ideation with a plan, and 0.9% had made a suicide attempt within the past 2 weeks.

Patients with a lifetime anxiety disorder were more likely to have suicidal ideation than were patients with no lifetime anxiety disorder (63.0% versus 53.8%; x[sup2] = 8.63, df 1, P = 0.01). Patients with a lifetime anxiety disorder also had a significantly higher mean score on degree of suicidal ideation (F = 6.89, df 1, P = 0.01). The greater degree of suicidal ideation remained significant when current age and severity of depression (as determined by the score on the HDRS "depressed mood item") were entered as covariates (F = 5.78, df 1, P = 0.02). There were no significant differences between subjects with or without a current anxiety disorder in terms of the proportion who endorsed suicidal ideation or the mean score on the degree of suicidal ideation.

Table 2 displays the frequency and severity of suicidal ideation according to sex as well as the presence or absence of a comorbid lifetime anxiety disorder. To assess for a possible interaction between sex and lifetime anxiety, the interaction term for sex and lifetime anxiety was forced into the logistic regression model first, followed by sex and lifetime anxiety separately. The interaction term was not significant, with the presence or absence of suicidal ideation as the dependent variable (x[sup2] = 0.02, df 2, P = 0.99).

Being female and having a lifetime anxiety disorder independently increase the frequency and degree of suicidal ideation among patients with a current major depression. Since there was no interaction between biological sex and anxiety, we conclude that these factors may have an independent impact on suicidal ideation. Of importance, the effects of sex and anxiety remained significant when severity of depression and age were accounted for. Thus, being female and having a lifetime anxiety disorder not only are markers of more severe depression but also appear to be independent factors that increase the frequency and extent of suicidal ideation in patients with depression.

Our results are consistent with much of the available literature that examines the impact of sex and anxiety on suicidality. Other authors have found that the presence of comorbid anxiety increases suicidality in patients with major depression, and Joffe and others showed that patients with comorbid anxiety have more severe depression. Our results support these findings but also provide new evidence that the effects of comorbid anxiety on severity of depression as well as suicidality are independent phenomena. These effects were seen only among patients with a lifetime anxiety disorder (that is, current or past), since patients with only a current anxiety disorder did not have higher rates of suicidality. Other researchers have also noted that trait, but not state, anxiety increases suicidality, and it has been suggested that trait but not state anxiety may effect suicidality independently of depression. Although we focused exclusively on patients with major depression, this hypothesis warrants further study. One possible interpretation of these results is that rates of lifetime anxiety disorders may be overestimated in patients with suicidal ideation if their recall of past symptoms is influenced by their current mental state, leading to a false-positive finding that lifetime anxiety increases suicidality. Another possibility is that patients who develop an anxiety disorder prior to the onset of depression, or early in the course of their depressive illness, may be more prone to experiencing suicidal ideation. If this were true, there may be enduring biological and psychological factors involved. For example, serotonergic dysfunction has been linked to both anxiety disorders and suicidality, and early adverse experiences have also been independently linked with both anxiety and suicide. One further explanation may be that there were too few subjects with a current anxiety disorder, resulting in a Type I error.

An important clinical issue arising from our results is the high frequency of suicidal ideation among patients with major depression. Overall, 57.8% of patients were subjectively and objectively found to have suicidal thoughts. Even among men with no comorbid anxiety--the group of patients who had the lowest risk of suicidal ideation--47.9% experienced suicidal thoughts. Among women with comorbid anxiety--the highest risk group--65.6% experienced suicidal ideation as part of their current depression. Despite the finding that being female and having comorbid anxiety increase suicidality, from a clinical perspective, clearly any patient with major depression is at significant risk of experiencing suicidal ideation.

Table 2. Frequency and degree of suicidal ideation acording to sex and lifetime anxiety
Legend for chart:  A1=Number of subjects with suicidal ideation[supa] (%) 
A2=Mean severity of suicidal ideation[supb] (SD)  A3=Anxiety (n = 30)  A4=No anxiety (n = 303) A5=Anxiety (n = 73)  A6=No anxiety (n = 117)  A7=Anxiety (n = 157)  A8=No anxiety (n = 186) A9=103 (65.6)  B1=107 (57.5)  B2=2.24 (0.72)   B3=2.21 (0.74)

              All patients                           Male                                Female
            A3                 A4             A5               A6                A7               A8
A1   145 (63.0)    163 (53.8)     42 (57.5)      56 (47.9)       A9               B1
A2   2.23 (0.71)   2.10 (0.76)   2.19 (0.71)   1.87 (0.76)     B2               B3
[supa] Patients with a lifetime anxiety disorder were more likely to experience suicidal ideation (x[sup2] = 8.63, df 1, P = 0.01) 
[supb] patients with a lifetime anxiety disorder had a significantly greater degree of suicidal ideation (F = 6.89, df 1, P = 0.01)
GRAPH: Figure 1. Rates of lifetime anxiety disorders based on sex. [sup*]P = 0.004.
- Schaffer, Ayal, Levitt, Anthony J, Bagby, R Michael, Kennedy, Sidney H, Levitan, Robert D, Joffe, Russell T, Canadian Journal of Psychiatry, 07067437, Nov2000

Suicidal Ideation and Risk Factors in Primary Care Patients
with Anxiety Disorders

- Bomyea, J., Lang, A. J., Craske, M. G., Chavira, D., Sherbourne, C. D., Rose, R. D., ..., and Stein, M. B. Suicidal Ideation and Risk Factors in Primary Care Patients with Anxiety Disorders. Psychiatry Res, Aug 2013, 209(1). p 60-65. doi:10.1016/j.psychres.2013.03.017

Personal Reflection Exercise Explanation
The Goal of this Home Study Course is to create a learning experience that enhances your clinical skills. We encourage you to discuss the Personal Reflection Journaling Activities, found at the end of each Section, with your colleagues. Thus, you are provided with an opportunity for a Group Discussion experience. Case Study examples might include: family background, socio-economic status, education, occupation, social/emotional issues, legal/financial issues, death/dying/health, home management, parenting, etc. as you deem appropriate. A Case Study is to be approximately 225 words in length. However, since the content of these "Personal Reflection" Journaling Exercises is intended for your future reference, they may contain confidential information and are to be applied as a "work in progress." You will not be required to provide us with these Journaling Activities.
The article above contains foundational information. Articles below contain optional updates.

Personal Reflection Exercise #1
The preceding section contained information about suicidal ideation in major depression with comorbid anxiety.  Write three case study examples regarding how you might use the content of this section in your practice.

Peer-Reviewed Journal Article References:
Barrenger, S. L., Maurer, K., Moore, K. L., & Hong, I. (2020). Mental health recovery: Peer specialists with mental health and incarceration experiences. American Journal of Orthopsychiatry, 90(4), 479–488.

Chan, K. K. S., & Lam, C. B. (2018). The impact of familial expressed emotion on clinical and personal recovery among patients with psychiatric disorders: The mediating roles of self-stigma content and process. American Journal of Orthopsychiatry, 88(6), 626–635.

Nelson, B. D., Sarapas, C., Robison-Andrew, E. J., Altman, S. E., Campbell, M. L., & Shankman, S. A. (2012). Frontal brain asymmetry in depression with comorbid anxiety: A neuropsychological investigation. Journal of Abnormal Psychology, 121(3), 579–591.

Salemink, E., Rinck, M., Becker, E., Wiers, R. W., & Lindenmeyer, J. (2021). Does comorbid anxiety or depression moderate effects of approach bias modification in the treatment of alcohol use disorders? Psychology of Addictive Behaviors. Advance online publication.

Yoon, K. L., & Joormann, J. (2012). Stress reactivity in social anxiety disorder with and without comorbid depression. Journal of Abnormal Psychology, 121(1), 250–255.

According to Schaffer, what two factors that independently increase the frequency and degree of suicidal ideation among patients with a current major depression? To select and enter your answer go to Test.

Section 9
Table of Contents