Abstract
Objective:
Symptoms which commonly remain after treatment for major depression increase the risk of relapse and recurrence in medically well patients. The same symptoms predict major adverse cardiac events in observational studies of patients with coronary heart disease (CHD). The purpose of this study was to determine the prevalence and predictors of residual depression symptoms in depressed patients with CHD-.
Methods:
Beck Depression Inventory-II data from two randomized clinical trials and an uncontrolled treatment study of depression in patients with CHD were combined to determine the prevalence and predictors of residual symptoms.
Results:
Loss of energy, loss of pleasure, loss of interest, fatigue, and difficulty concentrating were the five most common residual symptoms in all three studies. They are also among the most common residual symptoms in medically well patients who are treated for depression. The severity of pre-treatment anxiety predicted the post- treatment persistence of all these symptoms except for loss of energy.
Conclusions:
The most common post-treatment residual symptoms found in this study of patients with coronary heart disease and comorbid major depression are the same as those that have been reported in previous studies of medically-well depressed patients. This suggests that they may be resistant to standard depression treatments across diverse patient populations. More effective treatments for these symptoms are needed.
Keywords: Antidepressive agents, Cognitive behavior therapy, Coronary heart disease, Depressive disorders, Depression
1. Introduction
In randomized controlled trials (RCTs) of treatments for depression, remission is often defined in ways that do not require the patient to be completely free of symptoms. Consequently, many “successfully treated” patients are left with residual symptoms. In medically well patients with major depression, fatigue, loss of energy, anhedonia (i.e., loss of interest or pleasure in usual activities), and sleep disturbances are common symptoms before treatment, and they often persist after otherwise successful treatment. [1–5] Unfortunately, patients with these residual symptoms are at high risk of relapse and recurrent depressive episodes. [6–9]
There has been little research on residual depression symptoms in patients with coronary heart disease (CHD). It is not known whether the same symptoms that often persist after treatment in medically-well patients also persist in patients with CHD. If they do, their clinical importance would extend beyond the risk of relapse and recurrence because sleep problems, fatigue, and anhedonia also increase the risk of major adverse cardiac events in patients with CHD, regardless of whether other symptoms of depression are present. [10–14] If treatment of comorbid major depression in patients with CHD tends to leave the same residual symptoms as have been found in treatment studies of depressed but otherwise medically-well psychiatric patients, this may help to explain why it has been difficult to show that treatment of depression in CHD can decrease cardiac morbidity and mortality. We recently found fatigue, loss of energy, and loss of interest to be the most common depression residual symptoms after treatment with cognitive behavior therapy (CBT) and sertraline. [15] Unfortunately, this study included only 125 participants and lacked adequate statistical power for more in-depth analyses.
The purpose of the present study was to determine whether residual sleep problems, fatigue, and anhedonia are consistently common after treatment of depression in patients with CHD, and to identify pre- treatment predictors of residual symptoms. The present analysis combined data from three studies previously conducted by the authors. Two of these studies were designed to determine the efficacy of two omega-3 formulations when combined with sertraline. Studies of omega-3 supplements in medically well depressed patients have produced mixed results, but there have been very few studies in patients with heart disease. Sertraline alone has been shown to be effective in treating depression in patients with CHD [16], but adding omega-3 supplement did not improve depression outcome in either trial. The purpose of the third study was to identify clinical predictors of depression treatment outcome in patients with CHD. The patients in this study were treated with CBT, augmented with sertraline as needed.
2. Methods
2.1. Procedure
Participants in two RCTs and an uncontrolled treatment study were recruited from outpatient cardiology practices at Washington University Medical Center between May 2005 and June 2018. The protocols were approved by the Washington University School of Medicine Human Studies Committee, and informed consent was obtained from all participants. Details of the three studies are available elsewhere. [17–19] Medically stable outpatients with CHD who met the study’s eligibility criteria were scheduled for a structured clinical interview. Those who scored ≥14 on the Beck Depression Inventory II (BDI-II) [20] and met the DSM-5 criteria for major depression without other major psychiatric diagnoses except for anxiety disorders, were enrolled. The first study compared the combination of 50 mg/day of sertraline plus a supplement containing 930 mg/day EPA and 750 mg/day DHA, to sertraline and a placebo capsule [17]. The second study randomized patients to receive either 50 mg/day of sertraline and two grams/day of EPA, or sertraline and a placebo capsule [18]. In the third study, participants received up to 12 weekly sessions of individual CBT. Those who were not taking an antidepressant at enrollment and whose BDI-II score did not improve by 30% or more by the 5th week of treatment, or by 50% or more by the 8th week, were prescribed 50 mgs of sertraline which could be adjusted up to a maximum dose of 100 mg at the discretion of the prescribing psychiatrist. The BDI-II was readministered after 10 weeks in the first two studies [17,18], and after an average of 12 weeks in the third study [19]. The Beck Anxiety Inventory (BAI) [21] was also administered at baseline in all three studies.
Symptoms that were reported both at baseline and at post-treatment (BDI-II item ≥1) were classified as residual symptoms in each of the three studies. Symptoms that were reported at baseline but not at post- treatment were classified as successfully treated. Symptoms that were reported at baseline but not pre-treatment, and ones that were not reported on either occasion, were also documented.
2.2. Statistical analysis
Common data elements were combined across the three studies to produce a single dataset with 423 participants for the present analysis. Symptom data that were plausibly missing at random were imputed. <8% of the data for any analysis variable were missing. Proc MI Procedure in SAS version 9.4 (SAS Institute, Cary, NC) was used to create the multiple imputation models, and SAS Proc MIANALYZE was used to fit the statistical models to the imputed data. Each single imputation dataset included outcomes, predictors, and covariates chosen a priori for the statistical models, as well as any auxiliary variables that were moderately correlated (r ≥ 0.30) with each outcome of interest. Final imputation estimates were based on the creation of m = 100 single imputation datasets and then combined across the datasets to support valid statistical inference.
The five most common residual symptoms were identified, as were the five symptoms that were most likely to remit. For each of these symptoms, subgroups of patients who were treated successfully (absent) or unsuccessfully (residual) were formed. These subgroups were then compared with respect to baseline demographic and medical variables and the pre-treatment severity of depression and anxiety.using Chi-square tests and analysis of variance models
All statistical hypothesis tests were two-tailed with a Type I experiment-wise error rate set to 0.01 to control for multiple comparisons associated with each of the top five most common residual symptoms that were considered for analysis.
3. Results
The participants ranged in age from 31 to 82 years (mean, 59.3 ± 9.0 years), and 159 (37.6%) were women. Depression outcomes did not differ between the omega-3 and placebo arms in either clinical trial (Table 1).
Table 1.
Baseline and posttreatment BDI-II scores by study.
| Omega-3 A (16) | Sertaline + Placebo (N = 60) | Sertaline + Omega-3 (N = 62) | |
| Baseline BDI-II | 29.0 (9.2) | 28.1 (8.7) | 0.59 |
| Posttreatment (10 weeks) | 14.8 (9.7) | 16.1 (10.2) | 0.44 |
| Omega-3 B (17) | Sertaline + Placebo (N = 73) | Sertaline + Omega-3 (N = 71) | |
| Baseline BDI-II | 29.1 (8.8) | 28.1 (9.0) | 0.59 |
| Posttreatment (10 weeks) | 9.1 (7.7) | 11.0 (9.9) | 0.20 |
| Uncontrolled Study (18) | CBT + Sertraline (N = 152) | ||
| Baseline BDI-II | 30.0 (8.6) | ||
| Posttreatment (12 weeks) | 8.3 (7.5) |
The number of patients reporting a symptom as either present (≥1) or absent (<1) at both baseline and at post-treatment is presented in Table 2 for each the 21 symptoms from the BDI-II. The five most common symptoms reported at both baseline and post treatment (residual symptoms) in descending order were loss of energy (reported by 74.5%), loss of pleasure (66.2%), fatigue (64.5%), loss of interest (59.1%), and difficulty concentrating (51.5%). These were the five most common residual symptoms in all three studies, although the proportion of patients reporting each symptom varied slightly across studies. Thirty percent of the patients reported insomnia at both baseline and post- treatment, and 30% reported it baseline but not post-treatment. The five most common symptoms reported at baseline but not at post- treatment (successfully treated) were sadness (reported by 58.6%), self-dislike (51.5%), irritability (55.1%), guilty feelings (48.7%), pessimism (48.2).
Table 2.
BDI-II symptoms present (≥1) or absent at baseline and posttreatment.
| Symptom | Present/Present N (%) | Present/Absent N (%) | Absent/Present N (%) | Absent/Absent N (%) |
|---|---|---|---|---|
| BDI-II Items (21) | ||||
| Sadness | 142 (33.6) | 248 (58.6) | 2 (0.5) | 31 (7.3) |
| Pessimism | 195 (46.1) | 204 (48.2) | 3 (0.7) | 21 (5.0) |
| Previous Failure | 207 (48.9) | 168 (39.7) | 12 (2.8) | 36 (8.5) |
| Loss of Pleasure | 280 (66.2) | 139 (32.9) | 1 (0.2) | 3 (0.7) |
| Guilty Feelings | 158 (37.4) | 206 (48.7) | 5 (1.2) | 54 (12.8) |
| Punishment Feelings | 88 (20.8) | 134 (31.7) | 8 (1.9) | 193 (45.6) |
| Self-Dislike | 155 (36.6) | 218 (51.5) | 4 (1.0) | 46 (10.9) |
| Self-Criticalness | 181 (42.8) | 203 (48.1) | 11 (2.6) | 28 (6.6) |
| Suicidal Thoughts | 22 (5.2) | 107 (25.3) | 2 (0.5) | 292 (69.0) |
| Crying | 103 (24.4) | 190 (44.9) | 19 (4.5) | 111 (26.2) |
| Agitation | 147 (34.8) | 203 (48.0) | 15 (3.6) | 58 (13.7) |
| Loss of Interest | 250 (59.1) | 159 (37.6) | 6 (1.4) | 8 (1.9) |
| Indecisiveness | 171 (40.4) | 199 (47.0) | 7 (1.7) | 46 (10.9) |
| Worthlessness | 153 (36.2) | 200 (47.3) | 12 (2.8) | 58 (13.7) |
| Loss of Energy | 315 (74.5) | 103 (24.4) | 2 (0.5) | 3 (0.7) |
| Insomnia | 127 (30.0) | 128 (30.3) | 37 (8.8) | 131 (31.0) |
| Hypersomnia | 66 (15.6) | 87 (20.6) | 50 (11.8) | 220 (52.0) |
| Irritability | 125 (29.6) | 233 (55.1) | 8 (1.9) | 57 (13.5) |
| Decreased Appetite | 97 (22.9) | 99 (23.4) | 51 (12.1) | 176 (41.6) |
| Increased Appetite | 58 (13.7) | 110 (26.0) | 37 (8.8) | 218 (51.5) |
| Concentration difficulty | 218 (51.5) | 181 (42.8) | 5 (1.2) | 19 (4.5) |
| Tiredness or fatigue | 273 (64.5) | 137 (32.4) | 1 (0.2) | 12 (2.8) |
| Loss of interest in sex | 175 (41.4) | 174 (41.1) | 15 (3.6) | 59 (14.0) |
Tables 3A, 3B, and 3C compare the demographic characteristics, baseline medical characteristics, and pre-treatment -BDI-II and BAI scores of patients with residual symptoms vs. patients with successfully treated symptoms. These variables were chosen a priori as potential ` predictors of residual symptoms and were the only variables considered for analysis.
Table 3A.
Baseline medical and demographic characteristics of continued presence vs. absence of the most common BDI-II residual symptoms at post-treatment.
| Characteristic | BDI-II residual symptom | |||||
|---|---|---|---|---|---|---|
|
|
||||||
| Loss of energy | Tiredness or fatigue | |||||
|
|
|
|
||||
| Pres./Pres. (n = 315) | Pres./ Abs. (n = 103) | P | Pres./Pres. (n = 273) | Pres./Abs. (n = 137) | P | |
| Demographics | ||||||
| Age | 59.6 ± 9.2 | 59.2 ± 8.2 | 0.67 | 59.4 ± 9.3 | 59.3 ± 8.2 | 0.86 |
| Female | 111 (35.2) | 45 (43.7) | 0.13 | 102 (37.4) | 53 (38.7) | 0.79 |
| Caucasian | 239 (75.9) | 76 (73.8) | 0.67 | 203 (74.4) | 105 (76.6) | 0.61 |
| Education (≤ 12y) | 100 (31.7) | 30 (29.1) | 0.62 | 90 (33.0) | 37 (27.0) | 0.22 |
| Medical | ||||||
| History of MI | 184 (58.4) | 49 (47.6) | 0.07 | 159 (58.2) | 71 (51.8) | 0.22 |
| History of CHF | 103 (32.7) | 22 (21.4) | 0.03 | 87 (31.9) | 35 (25.5) | 0.19 |
| Diabetes | 137 (43.5) | 39 (37.9) | 0.32 | 115 (42.1) | 60 (43.8) | 0.75 |
| Hypertension | 264 (83.8) | 88 (85.4) | 0.69 | 226 (82.8) | 119 (86.9) | 0.29 |
| Revascularization | 254 (80.6) | 85 (80.6) | 0.67 | 224 (82.1) | 107 (78.1) | 0.34 |
| BMI (kg/m2) | 33.5 ± 7.3 | 32.8 ± 7.6 | 0.42 | 33.2 ± 7.3 | 33.4 ± 7.0 | 0.81 |
| Current smoker | 67 (21.3) | 24 (23.3) | 0.66 | 59 (21.6) | 32 (23.4) | 0.69 |
| Medications | ||||||
| Beta blockers | 255 (81.0) | 80 (77.7) | 0.47 | 226 (82.8) | 104 (75.9) | 0.10 |
| Statins | 260 (82.5) | 87 (84.5) | 0.65 | 229 (83.9) | 111 (81.0) | 0.47 |
| Anxiolytics | 59 (18.7) | 19 (18.4) | 0.95 | 49 (17.9) | 26 (19.0) | 0.80 |
| Medical events during TX | ||||||
| Any hospitalization(s) | 42 (13.3) | 12 (11.7) | 0.70 | 35 (12.8) | 16 (11.7) | 0.78 |
| Any ED visit(s) | 55 (17.4) | 18 (17.5) | 0.91 | 49 (17.9) | 20 (14.6) | 0.41 |
| Depression/anxiety severity | ||||||
| BDI-II Item Score | 1.83 ± 0.61 | 1.67 ± 0.63 | 0.03 | 1.95 ± 0.73 | 1.85 ± 0.83 | 0.22 |
| BDI-II total score | 29.7 ± 8.7 | 28.9 ± 9.0 | 0.42 | 30.0 ± 8.7 | 29.2 ± 8.6 | 0.38 |
| BAI total score | 14.5 ± 9.8 | 13.4 ± 8.2 | 0.28 | 15.1 ± 10.0 | 12.6 ± 7.9 | 0.01 |
Table 3B.
Baseline medical and demographic characteristics of continued presence vs. absence of the most common BDI-II residual symptoms following treatment.
| Characteristic | BDI-2 Residual symptom | |||||
|---|---|---|---|---|---|---|
|
|
||||||
| Loss of pleasure | Loss of interest | |||||
|
|
|
|
||||
| Pres./Pres. (n = 280) | Pres./Abs. (n = 139) | P | Pres./Pres. (n = 250) | Pres./Abs. (n = 159) | P | |
| Demographic | ||||||
| Age | 59.3 ± 9.2 | 59.7 ± 8.7 | 0.65 | 59.1 ± 9.1 | 59.9 ± 8.7 | 0.43 |
| Female | 91 (32.5) | 66 (47.5) | 0.003 | 89 (35.6) | 65 (40.9) | 0.28 |
| Caucasian | 203 (72.5) | 111 (79.9) | 0.10 | 187 (74.8) | 123 (77.4) | 0.56 |
| Education (≤12y) | 88 (31.4) | 44 (31.7) | 0.96 | 75 (30.0) | 52 (32.7) | 0.56 |
| Medical | ||||||
| History of MI | 157 (56.1) | 77 (55.4) | 0.90 | 135 (54.0) | 94 (59.1) | 0.31 |
| History of CHF | 96 (34.3) | 28 (20.1) | 0.003 | 78 (31.2) | 41 (25.8) | 0.24 |
| Diabetes | 123 (43.9) | 53 (38.1) | 0.26 | 101 (40.4) | 68 (42.8) | 0.64 |
| Hypertension | 234 (83.6) | 119 (85.6) | 0.59 | 205 (82.0) | 139 (87.4) | 0.14 |
| Revascularization | 228 (81.4) | 112 (80.6) | 0.83 | 201 (80.4) | 132 (83.0) | 0.51 |
| BMI (kg/m2) | 33.4 ± 7.2 | 33.3 ± 7.7 | 0.95 | 33.3 ± 7.2 | 33.2 ± 7.4 | 0.89 |
| Current smoker | 61 (21.8) | 30 (21.6) | 0.96 | 58 (23.2) | 31 (19.5) | 0.38 |
| Medications | ||||||
| Beta blockers | 228 (81.4) | 107 (77.0) | 0.28 | 202 (80.8) | 128 (80.5) | 0.94 |
| Statins | 234 (83.6) | 115 (82.7) | 0.83 | 205 (82.0) | 134 (84.3) | 0.55 |
| Anxiolytics | 47 (16.8) | 30 (21.6) | 0.23 | 44 (17.6) | 30 (18.9) | 0.75 |
| Medical events during TX | ||||||
| Any hospitalization(s) | 30 (10.7) | 23 (16.5) | 0.09 | 30 (12.0) | 21 (13.2) | 0.71 |
| Any ED visit(s) | 48 (17.1) | 24 (17.3) | 0.93 | 47 (18.8) | 25 (15.7) | 0.46 |
| Depression/Anxiety severity | ||||||
| BDI-II Item score | 1.75 ± 0.64 | 1.64 ± 0.63 | 0.09 | 1.85 ± 0.70 | 1.60 ± 0.70 | 0.001 |
| BDI-II total score | 30.0 ± 8.6 | 28.7 ± 9.1 | 0.15 | 30.3 ± 8.6 | 28.9 ± 9.0 | 0.11 |
| BAI total score | 14.9 ± 9.6 | 12.9 ± 9.0 | 0.05 | 15.7 ± 10.0 | 11.7 ± 7.8 | <0.0001 |
Table 3C.
Baseline medical and demographic characteristics of continued presence vs. absence of the most common BDI-II residual symptoms following treatment.
| Characteristic | BDI-2 Residual Symptom | ||
|---|---|---|---|
|
|
|||
| Concentration | |||
|
|
|
||
| Pres./Pres. (n = 220) | Pres./Abs. (n = 179) | P | |
| Demographic | |||
| Age | 59.0 ± 9.1 | 59.4 ± 8.8 | 0.69 |
| Female | 73 (33.2) | 78 (43.6) | 0.03 |
| Caucasian | 159 (72.3) | 140 (78.2) | 0.17 |
| Education (≤ 12y) | 75 (34.1) | 50 (27.9) | 0.19 |
| Medical | |||
| History of MI | 128 (58.2) | 94 (52.5) | 0.26 |
| History of CHF | 77 (35.0) | 46 (25.7) | 0.04 |
| Diabetes | 87 (39.5) | 80 (44.7) | 0.30 |
| Hypertension | 181 (82.3) | 158 (88.3) | 0.10 |
| Revascularization | 178 (80.9) | 143 (79.9) | 0.80 |
| BMI (kg/m2) | 32.8 ± 7.1 | 34.1 ± 7.7 | 0.08 |
| Current smoker | 50 (22.7) | 34 (19.0) | 0.36 |
| Medications | |||
| Beta blockers | 183 (83.2) | 139 (77.7) | 0.16 |
| Statins | 184 (83.6) | 147 (82.1) | 0.69 |
| Anxiolytics | 41 (18.6) | 35 (19.6) | 0.82 |
| Medical events during TX | |||
| Any hospitalization(s) | 26 (11.8) | 25 (14.0) | 0.54 |
| Any ED visit(s) | 36 (16.4) | 32 (17.9) | 0.67 |
| Depression/Anxiety severity | |||
| BDI-II Item score | 1.71 ± 0.60 | 1.55 ± 0.59 | 0.003 |
| BDI-II total score | 30.6 ± 8.6 | 29.2 ± 8.9 | 0.10 |
| BAI total score | 15.7 ± 10.1 | 13.0 ± 8.5 | 0.005 |
There were no differences in BDI-II total scores between any of the subgroups, but pre-treatment BAI scores were higher in patients with residual fatigue, loss of pleasure, loss of interest, or poor concentration than they were in patients whose symptoms remitted.
The mean pre-treatment BDI-II item scores for poor concentration (1.71 ± 0.60 vs. 1.55 ± 0.59; p = 0.003), loss of interest (1.85 ± 0.70 vs.1.60 ± 0.70; p = 0.001), and loss of energy (1.83 ± 0.61 vs. 1.67 ± 0.63; p = 0.03) were higher in the subgroups that were unsuccessfully treated for these symptoms than in the subgroups that were successfully treated. Men and patients with a history of heart failure (HF) were more likely to have residual loss of pleasure than were women and patients without HF.
4. Discussion
The five most common residual symptoms after treatment for depression (loss of energy, loss of pleasure, fatigue, loss of interest, and difficulty concentrating) in our study of patients with CHD have previously been shown to be among the most common residual symptoms following depression treatment in medically-well psychiatric patients. [1–5] This suggests that these symptoms are often resistant to standard depression treatments across diverse patient populations. Therefore, their persistence in patients with CHD is unlikely to be attributable solely to heart disease.
The five symptoms that were most likely to remit after treatment were sadness, self-dislike, irritability, guilt, and pessimism. The next five were self-criticalness, agitation, feeling worthless, indecisive, and crying. Thus, the symptoms of depression that are the most responsive to treatment in patients with CHD are cognitive and affective symptoms.
Secondary analyses of the major depression treatment trials in patients with CHD have found inadequate response to depression treatment to be a significant risk factor for mortality and cardiac morbidity. [22] Unfortunately, the trial reports did not disclose remission rates for individual depression symptoms. There is evidence that somatic symptoms of depression are more strongly predictive of cardiac morbidity and mortality in patients with CHD than are cognitive symptoms [23]. Also, improvement in somatic symptoms has been associated with improved survival, but improvement in cognitive symptoms generally has not. [24] Most residual symptoms are somatic, so this may help to explain why it is difficult to improve survival in patients who are treated for depression.
Surprisingly, insomnia was not one of the most common residual depression symptoms in this study. Furthermore, change in insomnia was not highly correlated with change in either loss of energy (r = 0.13) or tiredness/fatigue (r = 0.18). Thus, improvement in fatigue or in energy loss was only weakly related to improvement in insomnia, leaving open the question of what might explain the presence of these symptoms following treatment.
Patients who were highly anxious at baseline were more likely to report residual fatigue, loss of pleasure, loss of interest, or poor concentration following treatment. Consistent with this finding, anxiety has been found to predict treatment outcome in studies of medically well patients with major depressive disorder [25].
Hospitalizations and emergency department visits during the 12–16 weeks of treatment did not differ between subgroups with residual vs. successfully treated symptoms. This suggests that the intercurrent medical events do not explain why some patients have residual symptoms after treatment while others do not.
Most efforts to identify predictors of responses to specific antidepressants have met with limited success. [26–30] However, a recent meta-analysis of 87 randomized placebo controlled clinical trials of antidepressants found significantly more variability in response to antidepressants than to placebo [31], suggesting that some treatments might be better than placebo at improving some depression symptoms. Unfortunately, the effects of the treatments on specific symptoms are not reported in most trials. With few exceptions e.g. [32], there is little evidence that any specific antidepressant medication or specific type of psychotherapy has a greater effect than any other on specific depression symptoms. [33–36]. However, a recent meta-analysis of 17 trials comparing antidepressants to CBT for depression found a slight difference favoring antidepressants over CBT for improvement in depressed mood, guilt, suicidal thoughts, psychic anxiety, and “general somatic symptoms”, which includes “heaviness in limbs, back or head, backaches, headaches, muscle aches,” and “loss of energy.” [37] Unfortunately, it is unclear how much of the modest difference between CBT and antidepressants for “general somatic symptoms” is related to loss of energy. The other somatic symptoms are not considered to be primary symptoms of depression.
In conclusion, loss of energy, anhedonia (loss of pleasure or loss of interest in usual activities), fatigue, and difficulty concentrating are the most common post-treatment residual symptoms in patients with CHD and comorbid major depression. These are among the same symptoms that are least likely to remit following treatment in studies of medically well depressed patients. This suggests that they are often resistant to standard depression treatments across diverse patient populations, and that their resistance to treatment is unlikely to be attributable solely to the presence of heart disease. Highly anxious patients are more likely to have residual symptoms after treatment, which suggests that anxiety should be a secondary target when major depression is treated in patients with CHD.
Sertraline is a popular SSRI antidepressant and is widely used in patients with CHD in part because of its safety profile. Nevertheless, research is needed to determine the most common residual symptoms after treatment with non-SSRI antidepressants, as well as after psychotherapeutic interventions other than CBT. This could perhaps be accomplished in secondary analyses of completed clinical trials when symptom data are available.
Acknowledgements
The authors thank Patricia Herzing, RN and Jessica Winker MPH, for their contributions to the study.
Funding
This research study was supported by Grant Number 5 R01 HL147862-03 from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, Maryland. The funding agency was not directly involved in the study design, the collection, analysis, and interpretation of data, or the writing of the manuscript.
Footnotes
Declaration of Competing Interest
Dr. Carney or a member of his family owns stock in Pfizer, Inc. The other authors report no relevant conflicts of interest.
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