The sample of 366 patients were mostly White (86%) and female (66%), and had a mean age of 69 years. Approximately 56% of the patients were taking an antidepressant at the time of study enrollment and these depression assessments. A total of 33% had no history of antidepressant use at enrollment.
Profiles of Depressive Symptoms in the CES-D
Complete CES-D data were available for 336 of the 366 patients in the analysis sample. The symptoms most frequently endorsed at some level were feeling depressed, sad, and everything was an effort. Feeling that people were unfriendly and people disliked (me) were the symptoms least likely to be endorsed. The symptoms that were most likely to be experienced most or all of the time included feeling depressed, feeling sad, having difficulty concentrating, feeling everything was an effort and sleep was restless. The mean scores for each of the 20 symptoms are shown in .
Mean symptom scores across instruments
Using the BIC statistic, we concluded a four-cluster model fit the data best. The classification error was estimated to be 8.3% for our final model. Cluster numbers are assigned by size. A total of 36% of the participants had the highest probability of being in Cluster 1, 34% in Cluster 2, 22% in Cluster 3 and 8% in Cluster 4. The symptom profiles for each cluster are shown in where CES-D symptoms are ordered within the four factors: negative affect (7 symptoms), positive affect (4 symptoms), somatic symptoms (7 symptoms), and interpersonal relationships (2 symptoms) previously identified. The profiles suggest the clusters differ primarily in severity. Patients in Cluster 1 appear to have moderate symptoms across most categories with the exception of the interpersonal symptoms. Those in Cluster 2 appear to have less severe symptoms on average compared with Cluster 1 but a similar response to talking less than usual and restless sleep. Patients in Cluster 3 appeared on average to have more severe symptoms compared with the other patients. Finally, those in Cluster 4 appeared to have few depressive symptoms overall as measured by the CES-D.
Profiles of depressive symptoms at enrollment by cluster for the CES-D.
As shown in , perceived stress and subjective social support were significantly associated with cluster membership defined through responses to the CES-D items. Cluster 3 had the highest proportion of patients with impaired subjective social support, while Cluster 4 had the lowest proportion. Similarly, patients in Cluster 3 had the highest levels of perceived stress, while those in Cluster 4 had the lowest levels. These data also suggested those in Cluster 3 were more likely to have one or more IADL limitations compared with those in other clusters, particularly Cluster 4 which had the lowest percentage of patients with IADL impairment. The clusters did not appear to differ by demographic variables or depression history.
Baseline sample characteristics by cluster across instruments
We also explored cluster membership by history of antidepressant use at enrollment based on our STAGED variable (Steffens et al., 2002
) and found significant differences by cluster (χ2
=42.8, p<.0001). Clusters 2 and 4 had a higher proportion of patients without a history of antidepressant use compared with Clusters 1 and 3. In addition, 19% of the patients received electroconvulsive therapy (ECT) during the course of the study, and we observed differences by cluster (χ2
=23.1, p<.0001), with 38% of the patients in Cluster 3 receiving ECT compared with 8% in Cluster 2. We had a significant amount of data missing for both the STAGED and ECT variables, so these results must be interpreted with caution.
Profiles of Depressive Symptoms in the HAM-D
Complete HAM-D data were available for 363 patients. The symptoms most frequently observed at some level were depressed mood, anxiety-psychic symptoms, and reduced work and interest. The symptoms that were least likely to be observed were loss of insight and loss of weight. The symptoms with the highest proportion of patients coded as more severe (a code 3 or 4 on a 0–4 scale) were depressed mood and reduced work and interest. The symptoms coded 0–2 with the highest proportion of patients with a code of 2 were middle insomnia and general somatic symptoms. The mean scores for each symptom are presented in .
Using the BIC statistic, we determined a three-cluster model fit these data best. The classification error was estimated to be 7.5% for our final model. The symptom profiles for each cluster are shown in . Patients appeared to differ primarily in terms of severity. Patients in Cluster 1 (60%) had the lowest mean scores across all symptoms, while those in Cluster 3 (8%) generally had the highest mean scores. Patients in Cluster 2 (32%) had mean scores that for the most part fell between the mean scores for the other clusters. Patients in Cluster 2 showed similar mean values for delayed insomnia and general somatic symptoms when compared with patients in Cluster 3. It is important to remember that all the HAM-D items do not have the same scale of measurement. For example, a mean score of 3.5 for reduced work and interest (item range 0–4) for Cluster 3 may not be significantly more severe than a mean score of 1.5 for loss of weight (item range 0–2).
Profiles of depressive symptoms at enrollment by cluster for the HAM-D.
As shown in , several variables were differentially associated with cluster membership. Patients in Cluster 3 with the highest mean scores across all symptoms were older, were less educated, had a later age of onset of depression, had lower MMSE scores, and were more likely to have impairments in basic ADLs and IADLs compared with the patients in the other two clusters. Patients in Clusters 2 and 3 had higher levels of perceived stress compared with patients in Cluster 1. Levels of subjective social support and demographic variables other than age were not significantly different across clusters.
History of antidepressant use was significantly associated with cluster membership χ2=65.9, p<.0001. Forty two percent of patients in Cluster 1 did not have a history of antidepressant use compared with 33% of patients in Cluster 2, and 4% in Cluster 3. Similarly, ECT during the duration of the study was associated with cluster membership χ2=79.8, p<.0001. A total of 82.1% of the patients in Cluster 3 had ECT at some point during the study compared with less than ten percent for patients in Cluster 1 and 22.0% of those in Cluster 2, χ2 =79.8, p<.0001. Again, there was considerable missing data for these variables, so the findings must be interpreted with caution.
Profiles of Depressive Symptoms Using the Major Depression Module of the DIS
Complete information for all of the DIS items was available for 331 of the 366 patients. The most frequently reported symptoms were feeling depressed, having trouble falling asleep, feeling tired all the time, having trouble concentrating, and losing interest and pleasure. The least frequently reported symptoms were attempting suicide, not being able to sit still, and gaining weight. The means for each symptom are presented in .
A comparison of the BIC statistics across the DIS models suggested a four-cluster model provided the best fit. The classification error in the final model was 9.3%. The symptom profiles, shown in , reflect a complex pattern of symptom endorsement that appears to differ in ways other than severity. Over one-third of the patients (35%) had the highest probability of being in Cluster 1, 24% of being in Cluster 2, 21% of being in Cluster 3, and 20% of being in Cluster 4. As we saw with the other two measures, one cluster had the lowest mean scores across all symptoms, in this case Cluster 3. Unlike the CES-D and the HAM-D, there was not a group that had consistently highest mean scores across the symptoms. Patients in Clusters 2, 3 and 4 shared similar profiles with the exception of losing appetite and weight and thoughts of death, wanting to die and suicidal thoughts. We did not detect one cluster specifically associated with reporting two years of feeling depressed with loss of interest, which would have suggested a cluster of patients with major depression perhaps superimposed upon underlying dysthymia.
Profiles of depressive symptoms at enrollment by cluster for the DIS.
Overall, as shown in , a number of variables were differentially distributed across the clusters as defined by the items in the DIS. The mean age was highest for patients in Cluster 4 and lowest for Cluster 1. Cluster 4 had the highest proportion of patients with 12 or less years of education while Clusters 1 and 3 had the lowest. Cluster 2 had the highest proportion of patients who were not married while Cluster 3 had the lowest. The proportion of patients with lower MMSE scores was significantly higher in Cluster 4 compared with the other three clusters. Like observed with the CES-D and the HAM-D, levels of perceived stress in the previous six months also differed across clusters, with Cluster 2 reporting the highest mean score and Cluster 3 the lowest. Similarly, patients in Cluster 2 also had the highest proportion of patients reporting low levels of subjective social support. Clusters 2 and 4 had a higher proportion of patients reporting limitations in both basic as well as instrumental ADLs compared with Clusters 1 and 3.
History of antidepressant use was associated with cluster membership (χ2 =27.0, p=0.0078). A total of 69% of the patients in Cluster 4 and 62% of the patients in Cluster 2 were taking an antidepressant at the time of study enrollment, compared with 42% of the patients in Cluster 1 and 36% of the patients in Cluster 3. Only 21% of the patients in Cluster 4 had never taken an antidepressant, compared with 35% in Cluster 2, 44% in Cluster 1 and 56% in Cluster 3. Similarly, 30% of the patients in Cluster 4 and 26% of the patients in Cluster 2 received ECT at some point during the course of the study compared with 10% in Cluster 3 and 7% in Cluster 1 (χ2 =17.0, p=0.0007).
We have chosen to include only patients with complete data for all items in the LCA given the uncertainty of missing at random and to be consistent with our earlier work. We reran the cluster models for the CES-D and the DIS including an option to impute data when missing for the indicators and the results were essentially unchanged. The number of clusters was the same and the characteristics continued to be differentially distributed across clusters (analyses available upon request).
Profiles of Depressive Symptoms Using Set of Representative Symptoms
A total of 308 patients had complete data for the combined analyses. We identified 17 symptom dimensions from our 66 items. One item, attempted suicide from the DIS, was dropped from the VARCLUS procedure because no patients had endorsed this item. lists the symptoms within each dimension as well as the identified representative symptom from that cluster. We noted some potential overlap among the clusters. There were four inter-cluster correlations greater than 0.60: Clusters 1 and 5, Clusters 1 and 9, Clusters 3 and 13 and Clusters 5 and 11.
Summary of Symptoms Identified from the VARCLUS Procedure (*** Representative Symptom)
We then used the 17 representative symptoms as the (standardized) parameters for the final model. A three-cluster model provided the best fit to the data. Four local dependencies were included as direct effects: DIS3 and DIS6, MADRS4 and DIS6, DIS3 and HAMD12 and MADRS4 and DIS8. The classification error in the final model was 10.3%. A total of 43.7% of the patients were in Cluster 1, 34.1% were assigned to Cluster 2 and 22.1% were in Cluster 3. The average probabilities of class membership for each latent class were as follows: Cluster 1=0.897 (range 0.393–0.999), Cluster 2=0.896 (range 0.575–0.999) and Cluster 3=0.899 (range 0.352–0.999). For 14 of the 17 indicators, knowledge of that parameter significantly contributed toward discriminating between the clusters. The three symptoms which didn’t appear to vary across classes were lost appetite, people were unfriendly, and felt like you wanted to die. Across the covariates added to the model, sex, marital status, education and age contributed toward differentiating the clusters. Older patients and those with fewer years of education were less likely to be in Cluster 2, while those who were unmarried were more likely. Women, patients with more education, and unmarried patients were more likely to be in Cluster 3. The contributions of MMSE score and race were not significant. shows the symptom profiles for each cluster. We noted that these groups appear to differ in ways other than severity. That is, the profiles were not parallel. While the mean scores for patients in Cluster 1 were all below zero, there was considerable variation between symptom means for patients in Cluster 2 and 3, particularly for apparent sadness, lost appetite, reduced sleep, gastrointestinal symptoms, anxiety-somatic symptoms, and dysthymia.
Profiles of depressive symptoms at enrollment by cluster using representative symptoms (n=308)
With the exception of race and number of lifetime depression spells, the clusters differed by the variables of interest. That is, the identified clusters of patients differed by demographic variables, age of onset, MMSE score, functional limitations and social variables including stress and social support.
As a check, we also allowed the covariates to define the number of classes and the results were essentially unchanged (analyses available upon request).