Affiliations : John Hopkins Hospital, Baltimore, USA
Journal reference: doi: 10.1002/da.22964.
Summary: Anxiety and depression are often comorbid disorders. This article examines whether depressed patients who also suffer from anxiety, still benefit from positive outcomes from antidepressant treatment.
Anxiety and depression frequently go hand in hand. When they co-exist, a term coined anxious depression is used; we also say that anxiety is “comorbid” with depression.
Anxiety disorders can be grouped into two main symptom categories: worry/distress disorders (often chronic apprehension about a distal source of worry) and fear disorders, like panic (state of acute intense hyperarousal). Although both can be associated with depression, fear disorders tend to decline with age while worry may become more common in older depressed individuals.
Up to 65% of elderly patients with depression also have symptoms of anxiety. Depression with comorbid anxiety is particularly important to address in older adults as it is associated with more severe depression, greater memory decline, greater impairment in social/physical functioning and more somatic complaints. There have also been some reports of increased all-cause mortality associated with elderly anxious depression and, importantly, suicidality and suicide attempts are seen more frequently in this population as well.
It is an on-going area of research to figure out whether people with anxious depression are different from those with depression alone, and whether this has any implication on treatment. While regular antidepressant treatments include but are not restricted to selective serotonin reuptake inhibitors (SSRIs- first line option), selective serotonin and norepinephrine reuptake inhibitors (SNRIs- usually second line option) and tricyclic antidepressants and monoamine oxidase inhibitors (less frequently used), several studies had investigated the effect of comorbid anxiety on antidepressant treatment response in depressed older adults; and, despite some reports showing the contrary, many studies concluded that the presence of comorbid anxiety (mostly the worry type) predicted a poorer response to antidepressant treatment and a quicker relapse into depression. However, all these studies analyzed a rather small number of patients or assessed anxiety in an indirect way.
This prompted our group to address this question by measuring anxiety directly, in a large population of depressed older adults.
Goals of our study
- Our first goal was to examine the influence of comorbid anxiety symptoms on something called ‘remission’ of depression and time to ‘remission’. Remission is either the reduction or resolution of the signs and symptoms of a disease.
- Our second goal was to study the relationship between comorbid anxiety symptoms and the presence of suicidal ideation, both at baseline and over the course of treatment.
Population and treatment
The population was gathered from 372 patients with Major Depressive Disorder, aged 60 years or older, presenting at 3 large university hospitals in St. Louis (USA), Pittsburgh (USA) and Toronto (Canada) – between July 2009 and January 2014. Older depressed patients who also had comorbid anxiety were allowed to participate in the study. They were enrolled in a multi-phase trial. During the first phase, they were all given the same medication: venlafaxine (it is an SNRI). They were aware of the treatment being given, so we call this phase: ‘open label’. Study patients were given extended-release venlafaxine for a total of 12 to 14 weeks. The dose was initiated at 37.5 mg daily and gradually increased to a maximum of 300 mg daily based on efficacy and tolerability.
How did we assess anxiety?
We used clinical validated scales :
- Anxiety Sensitivity Index (ASI) – it is a self report questionnaire that assesses the patient’s predisposition to anxiety and, more particularly, to panic
- Brief Symptom Inventory (BSI) – it is a self report questionnaire that assesses general nervousness and fear/panic
- Penn State Worry Questionnaire (PSWQ) – it is a self report questionnaire that assesses worrying types of anxiety
Patients were also asked to complete a Scale for Suicide Ideation (which assesses suicidality) and remission of depression was tracked by clinical measures of depression.
All those scales were evaluated every 1 to 2 weeks.
What did we find?
Of the 372 older depressed patients: 191 patients had remission of their depressive symptoms and 181 patients did not achieve remission.
Non remitters (patients who continued to be depressed) were patients who had more severe depression at the beginning.
The average dose of venlafaxine at the end of the study was of around 228.4 mg for non-remitters and of around 165.2 mg for remitters.
Did baseline anxiety play a role?
Having comorbid anxiety at baseline did not predict how patients were going to respond to their antidepressant treatment on venlafaxine. In this older patient population, patients with anxiety and patients without anxiety were just as likely to have improvement in their depression once treated with an optimal dose of venlafaxine.
As patients became less depressed, both worry and fear/panic symptoms improved.
What about suicidality?
The presence of suicidality at baseline was associated with more severe depression, worry, and fear/panic.
What were some major limitations of this study?
Although this was the largest prospective study to assess anxiety in older depressed individuals with validated anxiety measures, it did have two main limitations:
- It was an ‘open label’ study meaning that both patients and the study team knew what treatments the patients were getting. There was no comparison group getting placebo.
- Some patients were allowed to continue taking anxiolytics.
Take home message
Older depressed patients who also struggled with anxiety may have more severe depression. Yet, this did not significantly impact the outcome of their antidepressant treatment, if on an optimal dose of medication.