Enrollment occurred from April through November of 1999. Of 601 patients who provided informed consent and who were randomized to treatment, 573 completed the baseline telephone assessment. The 28 prebaseline dropouts were demographically similar to the 573 patients who completed the baseline assessment, but had slightly less severe depression (mean PHQ-9 score of 12.5 vs 14.3). Patients had a mean age of 46 years, with the majority being women (79%) and white (84%). Major depression was present in 74% of subjects, dysthymia alone in 18%, and minor depression in 8%. Approximately one third of the study participants reported a past history of treatment for depression. In the month preceding enrollment, 35% of the patients had experienced an anxiety attack and 45% had reported some use of alcohol. Follow-up interviews were successfully completed in 94% of patients at 1 month, 87% at 3 months, 84% at 6 months, and 79% at 9 months.
summarizes the prevalence of specific symptoms in this population of depressed patients at baseline, 1, 3, 6, and 9 months after randomization to an SSRI treatment group. All physical symptoms were quite prevalent—both the 2 symptoms that constitute actual DSM-IV criteria for depressive disorders (fatigue and sleep complaints) as well as the 12 symptoms not part of the explicit criteria for depression. In fact, most symptoms were present in at least a third to half of the patients and, when present, were severe in 10% to 20% or more of patients.
Prevalence of Physical Symptoms in Depressed Patients at Baseline and During 9 Months of Antidepressant Therapy
Incident symptoms were uncommon in this group of depressed patients being treated with an antidepressant. In other words, relatively few patients reported being “bothered a lot” by a particular physical symptom at follow-up if they had not reported being “bothered a lot” with that symptom at baseline. For most symptoms, the proportion of patients with an incident severe symptom at any of the four follow-up interviews was less than 5% to 10%, except back pain (13%), limb pain (12%), fatigue (12%), and sleep problems (11%).
The change in prevalence over the 9-month time period for five representative symptoms is displayed in . Focusing on these symptoms—fatigue, sleep, stomach problems, headaches, and palpitations—the baseline prevalence of a severe symptom (“bothered a lot”) ranged from 12% for palpitations to 69% for fatigue. Prevalence dropped substantially during the initial 4 weeks of SSRI therapy. Thereafter it plateaued, with only minimal improvement during the remaining 8 months of the trial. This time course was similar for the other 9 physical symptoms not shown in the graph.
FIGURE 1 Change in prevalence over the 9-month time period for five representative symptoms: fatigue, sleep, stomach problems, headaches, and palpitations. Illustrated is the baseline prevalence of a severe symptom (i.e., “bothered a lot”). This (more ...)
The proportion of variance in different domains of HRQoL attributable to physical symptoms and depression is summarized in . The variance estimates are adjusted for age, gender, race, anxiety, and comorbid disease. Physical symptoms accounted for the greatest proportion of variance in bodily pain (17% to 18%), role functioning due to physical health (11% to 14%), general health perceptions (13% to 15%), and physical functioning (13%), while depression had the greatest impact on mental health (26% to 45%), social functioning (14% to 32%), work functioning (9% to 32%), and multiple other domains of HRQoL. The possibility of an interaction between physical symptoms and depression was examined. While achieving statistical significance for a few HRQoL domains, adding the interaction term to the model produced only a slight change in the variance.
Percent of Variance in Various Domains of Health Status Attributable to Physical Symptom and Depressive Symptom Severity
Among demographic factors, age had the greatest effect. In particular, it accounted for a moderate proportion of the variance in the SF-36 physical functioning (17%), MOS sleep (3% to 7%), and general health perceptions (3%). Gender and race had a smaller impact accounting for less variance in fewer domains. These two demographic characteristics did not account for more than 1% to 3% of the variance in any HRQoL domain, except bodily pain (gender, 2% to 6%).
Additionally, anxiety and comorbid medical diseases were adjusted for within the analysis. Medical comorbidity did not account for any of the variance in the HRQoL domains, except role functioning due to physical health (0% to 1%), general health (2%), and physical functioning (1%). Anxiety affected the domains of mental health (7% to 10%) and work (5%) to the greatest extent. In the other HRQoL domains, anxiety accounted for 0% to 3% of the variance.
shows the time course for improvement for the nonpain (9 items) and pain (5 items) somatic symptom subscales of the PHQ compared to core depressive symptoms and positive well-being. Improvement in the latter two domains reflects a decrease in “negative” affective symptoms and an increase in “positive” affective symptoms, respectively. To standardize comparisons among these four domains, change was measured in effect size, which is the mean change divided by the pooled standard deviation for a measure. For core depressive symptoms and positive well-being, there was a rapid improvement as reflected by the steep curve in the first month, followed by more gradual improvement in the following months of the trial. In contrast, both pain and nonpain somatic symptoms showed a similar steep improvement in the first month of SSRI treatment but then plateau thereafter. Pain symptoms, in particular, showed the least improvement in terms of effect size.
FIGURE 2 Time course for improvement for the nonpain (9 items) and pain (5 items) somatic symptom subscales of the PHQ compared to core depressive symptoms and positive well-being. To standardize comparisons among these four domains, change was measured in effect (more ...)
shows the degree of physical symptom improvement according to the three levels of depression response at 3 months, classified as remission, response, and nonresponse.30
Remitters and partial responders had significantly more change (P
< .001) than nonresponders in both pain and nonpain physical symptoms at both 1 and 3 months. The magnitude of physical symptom improvement in remitters and partial responders ranged from an effect size of 0.6 to 1.0, compared to 0.3 to 0.5 for nonresponders. In contrast, remitters and partial responders did not differ significantly from one another in the degree of improvement in either their pain or nonpain physical symptoms at 1 or 3 months.
Physical Symptom Improvement According to the Level of Depression Response