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A Brief Clinical Tool to Estimate Individual Patients’ Risk of Depressive Relapse Following Remission: Proof of Concept

Abstract

Objective:

The authors sought to determine whether symptoms experienced by formerly depressed patients after at least 8 weeks of remission can be used to identify their risk for relapse during the next 6 months.

Method:

The study included 188 patients with major depressive disorder from the National Institute of Mental Health Collaborative Depression Study who had at least one Symptom Checklist–90 (SCL-90) assessment after at least 8 weeks of full remission from a depressive episode (defined as a value of 1 on the weekly psychiatric rating scale for all depressive conditions, recorded on Longitudinal Follow-Up Evaluation interviews). Mixed logistic regression was used to identify a set of SCL-90 items that were most predictive of relapse compared with nonrelapse within the next 6 months.

Results:

Of 514 SCL-90 assessments completed after remission, 73 (14.2%) were followed by depressive relapse within 6 months. Seventeen SCL-90 items (including symptoms of depression, anxiety, and psychological vulnerability) significantly distinguished relapse from nonrelapse. Of these, a set of 12 symptoms maximally separated relapse from nonrelapse. Experiencing one or more of these symptoms had a sensitivity of 80.8% and a specificity of 51.2% for identifying a period in which a relapse occurred, with a positive predictive value of 21.5% and a negative predictive value of 94.2%. The relapse rate was 5.8% when none of the 12 symptoms were present, 16.4% when one to five symptoms were present, 34.1% when six to nine symptoms were present, and 72.7% when 10 or more symptoms were present.

Conclusions:

A brief symptom scale can be used to identify patients who, despite full remission from a depressive episode, are at substantial risk of relapse within the next 6 months, and this can be used to provide a basis for personalizing the intensity of follow-up visits.

The aim of depression treatment is sustained symptom remission and functional recovery (14). Full remission of all symptoms of a major depressive episode (as opposed to symptom improvement to a subsyndromal status) is far more likely to lead to a stable well period with good everyday functioning (5, 6) and a lower risk of depressive episode relapse (46). We previously reported (6) that among 197 patients in the National Institute of Mental Health Collaborative Depression Study who achieved full remission from a major depressive episode, the rate of relapse was 16% over the next 6 months and 26% over 1 year. Others have also noted a modest but meaningful rate of relapse among depressed patients who have achieved complete remission (7, 8).

We currently have no patient-level indicators with which to plan care for individual depressed patients who have reached remission. Current guidance recommends visits every 1 to 6 months based on clinical judgment. However, if we could develop a clinical tool for estimating the likelihood of relapse for a given patient after complete remission, we would be able to tailor the follow-up visit schedule individually. Patients more likely to relapse could be followed up more often, in person or by telephone, whereas those at lower risk of relapse could be seen less frequently. Care would be more efficient, and, if needed, interventions could be delivered in a more timely fashion to patients with impending or actual relapses.

Our aim in this study was to determine whether a limited number of symptoms could be combined to create a person-level metric for guiding clinical decision making with sufficient accuracy that it could be used to inform care planning for depressed patients who have achieved full remission. The Hopkins Symptom Checklist–90 (SCL-90) provides an ideal instrument for this purpose because it includes a wide range of mood, somatic, behavioral, and cognitive symptoms (9).

Method

Subjects were drawn from the National Institute of Mental Health Collaborative Depression Study of 955 patients seeking treatment for a major affective episode at five U.S. academic centers between 1978 and 1981 (10, 11). Intake diagnoses were made by Research Diagnostic Criteria (12) based on Schedule for Affective Disorders and Schizophrenia interviews (13). The study was a naturalistic, prospective, longitudinal study of illness course, in which patients were periodically and systematically followed for up to 31 years. Treatment was recorded, not controlled. Patients had to be white (to test genetic hypotheses), speak English, have an IQ ≥70, and have no organic brain syndrome or terminal medical illness. Written informed consent was obtained from each patient.

The resulting database includes detailed information on psychiatric history, index episode characteristics, and follow-up data on weekly clinical status, somatic treatment, and psychosocial functioning gathered from self-reports, family informants, medical and research records, and ratings by trained clinical interviewers.

The sample for the present study was drawn from 487 patients with no lifetime bipolar disorder, schizoaffective disorder, or schizophrenia who entered the Collaborative Depression Study in an active major depressive episode, defined by Research Diagnostic Criteria as ≥2 consecutive weeks with at least five depressive symptoms, including intense sadness or dysphoria.

Follow-Up

Trained professional raters completed the Longitudinal Interval Follow-Up Evaluation (14) every 6 months for the first 5 years and yearly thereafter, using semistructured interviews. The interviewers used chronological memory prompts (e.g., birthdays and holidays), supplemented by available medical and research records, to establish changes in weekly symptom severity for all disorders defined by the Research Diagnostic Criteria. Raters were rigorously trained, resulting in intraclass correlation coefficients of 0.92 for reliability of psychiatric symptom change points, 0.95 for recovery from affective episodes, and 0.88 for subsequent appearance of affective symptoms (14). Results were recorded on Longitudinal Follow-Up Evaluation interviews as weekly psychiatric status ratings, with scale values anchored to diagnostic thresholds defined by the Research Diagnostic Criteria (12).

Severity ratings for depressive conditions were combined for each week during follow-up and classified into one of four mutually exclusive categories: met diagnostic threshold for a major depressive episode, met diagnostic threshold for a minor depressive episode, had subsyndromal depressive symptoms below either diagnostic threshold, and asymptomatic status (no symptoms of the episode, return to usual self).

Periodic Symptom Self-Report

Subjects completed the SCL-90 self-report at intake and at either 6-month or yearly intervals thereafter for 5 years, during the same visit when Longitudinal Interval Follow-Up Evaluation interviews were conducted. On the SCL-90, respondents indicate the degree to which they have been “bothered or distressed” by each of 90 symptoms “during the past week or so” on a 5-point scale ranging from “not at all” to “extremely.” The SCL-90 is typically scored for nine symptom domains: somatization, obsession/compulsion, interpersonal sensitivity, depression, anxiety, anger-hostility, phobic anxiety, paranoid ideation, and psychoticism. Domain scores have been developed and validated for various clinical and nonclinical populations (15, 16).

Selection of SCL-90 Records During Full Remission From Depressive Episodes

For this study, we analyzed the SCL-90 records obtained when those patients with major depressive disorder were in remission—defined as having a psychiatric status rating of 1 (asymptomatic, returned to usual self with no symptoms of the episode)—from major depression, minor depression, dysthymia, intermittent depression, atypical depression (DSM-III code 296.82), or adjustment disorder with depressed mood (DSM-III code 309.00) during the SCL-90 week and the previous 8 weeks. Mean time asymptomatic was 86.2 weeks (SD=64.4, range=9–262). Because we sought to identify predictors of relapse that occurred within the next 6 months, we selected only those SCL-90 records that were followed by uninterrupted weekly psychiatric status rating data for at least 26 weeks. Depressive relapse was defined as 2 consecutive weeks of psychiatric status ratings at the threshold for defining an episode of major or minor/dysthymic depression.

Statistical Analysis

For analysis, we converted each SCL-90 symptom item response into a binary response. We defined clinically meaningful symptom levels a priori as those rated 2 (bothered moderately), 3 (quite a bit), or 4 (extremely). Items rated as 0 (not bothered at all) or 1 (only a little bit) were considered not clinically meaningful.

We first examined the overall rate of all clinically meaningful SCL-90 symptoms during full remission. We then compared these symptom ratings by whether or not relapse occurred within the subsequent 6 months, based on mixed-model logistic regression, taking into account within-subject correlations for those subjects with repeated assessments.

Seventeen SCL-90 items significantly distinguished relapse from nonrelapse. Forward and backward stepwise mixed-model logistic regression was performed to identify 12 of these 17 symptoms that, together, were maximally predictive of short-term depressive relapse. Reduction in the −2 log likelihood ratio test was used to determine improvement in prediction with inclusion or exclusion of each variable, since it is a fit statistic that does not include a penalty for the number of predictors in the model. A complete set of predictive statistics (sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio) was computed for each number of symptoms in the final set of 12 predictors.

Data analysis was performed using SAS (SAS Institute, Cary, N.C.) and the SuperMix mixed-effects regression models program package (Scientific Software International, Skokie, Ill.), which combines the functionality of MIXOR and other mixed-effects programs developed by Hedeker and Gibbons (17).

Results

Figure 1 illustrates the formation of the analytic sample, which consisted of 188 patients who provided 514 SCL-90s. Majorities of the sample were female (58.5%), had at least some college education (56.4%), and were married or living with a partner (56.4%); 15.0% were separated, divorced, or widowed, and 28.5% had never been married. The mean age was 37.8 years (SD=14.4, range=18–74). About one-third (34.0%) were in their first depressive episode at study intake, 43.6% had experienced one or two previous episodes, and the remaining 22.3% had three or more previous episodes. Most subjects (71.8%) were inpatients at intake. The mean Global Assessment Scale (18) score for the worst period in the intake episode prior to intake (on a scale of 1–100, with higher numbers indicating better function) was 39.4 (SD=10.0, range=5–65), reflecting major impairment in several areas of functioning, or some impairment in reality testing or communication, or one or more suicide attempts.

FIGURE 1.

FIGURE 1. Selection of Symptom Checklist–90 (SCL-90) Assessments for Subjects With Major Depression When They Were Fully Remitteda

a Self-report assessments were performed at yearly follow-ups from year 1 to year 5 for all subjects in the National Institute of Mental Health Collaborative Depression Study (NIMH-CDS), and at 6-month intervals for a subset of 21 subjects in the analysis sample. Remission was defined as having a Longitudinal Follow-Up Evaluation psychiatric status rating of 1 (no symptoms of the episode; return to usual self) for all depressive episodes or conditions in the week of the SCL-90 assessment and each of the preceding 8 weeks.

The analytic sample consisted of 514 SCL-90 records following fully remitted periods, including 73 records (14.2%) (in 58 subjects) that were followed by a depressive episode relapse within the next 6 months and 441 records (85.8%) (in 165 subjects) that were free of relapse for 6 months or longer (Figure 1). The number of SCL-90 records per subject varied; 62 subjects contributed one SCL-90 record to the analysis, and the remainder had from two to 10 assessments. Among the 188 subjects, 130 (69.2%) had SCL-90 assessments followed only by nonrelapse status, 23 (12.2%) only by relapse status, and 35 (18.6%) by a mixture of nonrelapse and relapse.

Depressive relapse within 6 months could not be ascribed to receiving less intensive antidepressant treatment. The level of composite antidepressant treatment (on a 0–4 scale based on imipramine equivalents) was significantly higher for SCL-90 assessments that were followed by relapse than for assessments that were not (mean=1.11 [SD=1.37] compared with mean=0.69 [SD=1.25]; p=0.01). More assessments followed by relapses were associated with receiving any antidepressant than those not followed by relapse (N=34 [46.6%] compared with N=120 [27.2%]; p<0.001).

To assess the clinical impact of these relapses, we looked at the 5-year course of illness after the SCL-90 assessments. The SCL-90s that were followed by relapses were associated with a worse course of illness over the next 5 years, as indicated by a significantly greater percentage of time spent at each level of severity of depressive symptoms and proportionately fewer asymptomatic weeks (Table 1).

TABLE 1. Depressive Illness Course During Next 5 Years After Symptom Checklist–90 (SCL-90) Assessments Followed by Relapse or No Relapse Within 6 Monthsa

Percentage of Weeks During Next 5 Years
Assessments With Relapse Within 6 Months (N=66)Assessments Without Relapse Within 6 Months (N=440)
Level of Depressive IllnessbMeanSDMeanSDp
Asymptomatic status52.831.685.721.8<0.001
Subsyndromal symptom level11.816.94.710.70.001
Minor depression/dysthymia threshold23.421.25.510.7<0.001
Major depressive episode threshold12.014.04.09.0<0.001
Any level of depressive symptoms47.231.614.321.8<0.001

aAssessments with at least 2 years (104 weeks) of weekly Longitudinal Follow-Up Evaluation psychiatric status ratings in the 5 years after the SCL-90 assessment (based on 66 of 73 assessments with relapse within 6 months, and 400 of 441 assessments without relapse within 6 months).

bLevel of depressive illness in a given week was determined based on psychiatric status ratings per week on all depressive conditions. Asymptomatic status indicates no depressive symptoms of the episode (return to usual self). Subsyndromal symptoms are those below the severity threshold used to diagnose a minor or major depressive episode. Minor/dysthymic and major episode thresholds are based on severity level of depressive symptoms, not duration. Collaborative Depression Study rules for recording weekly psychiatric status ratings did not allow recording of prodromal increases in depressive symptoms below the minor depression threshold after 8 consecutive weeks at the asymptomatic status; thus, the percentage of weeks at the asymptomatic status may be inflated and weeks at the subsyndromal symptom status may be less than actually experienced.

TABLE 1. Depressive Illness Course During Next 5 Years After Symptom Checklist–90 (SCL-90) Assessments Followed by Relapse or No Relapse Within 6 Monthsa

Enlarge table

Table 2 lists the rates of 19 SCL-90 symptoms that occurred at a clinically meaningful level in at least 15% of the SCL-90s during this period of remission. We have grouped symptoms into clinically related categories, independently of the standard SCL-90 scoring key. The most common symptoms were features of anxiety, depression, and anger-irritability. Sleep disturbance and somatic complaints also occurred in 15% or more of the SCL-90s.

TABLE 2. Symptom Checklist–90 (SCL-90) Symptoms Rated as at Least Moderately Severe in at Least 15% of 514 SCL-90 Assessments of 188 Subjects With Major Depression When They Were Fully Remitteda

Symptom (SCL-90 Item Number)% of Assessments (N=514)
Anxiety
Worrying too much about things (31)27.8
Feeling tense or keyed up (57)24.9
Feeling pushed to get things done (86)14.8b
Depression
Trouble remembering things (9)22.8
Feeling low in energy or slowed down (14)20.4
Overeating (60)20.4
Loss of sexual interest or pleasure (5)18.3b
Blaming yourself for things (26)16.9
Feeling blocked in getting things done (28)16.1
Feeling lonely (29)16.0
Anger-irritability
Feeling easily annoyed or irritated (11)21.8
Feeling critical of others (6)19.9b
Sleep disturbance
Awakening in the early morning (64)16.9
Trouble falling asleep (44)15.2
Sleep that is restless or disturbed (66)15.2b
Somatization
Pains in lower back (27)19.1
Soreness of muscles (42)16.3
Other
Worried about sloppiness or carelessness (10)16.3
Feelings being easily hurt (34)15.6b

aItems in bold significantly predicted relapse compared with nonrelapse within the next 6 months. Clinically meaningful symptom levels were defined a priori as those rated 2 (bothered moderately), 3 (quite a bit), or 4 (extremely). Self-report assessments were performed at yearly follow-ups from year 1 to year 5 for all subjects, and at 6-month intervals for a subset of 21 of 188 subjects in the analysis sample. Remission was defined as having a Longitudinal Follow-Up Evaluation psychiatric status rating of 1 (no symptoms of the episode; return to usual self) for all depressive episodes or conditions in the week of the SCL-90 assessment and each of the preceding 8 weeks.

bData missing for one SCL-90 assessment.

TABLE 2. Symptom Checklist–90 (SCL-90) Symptoms Rated as at Least Moderately Severe in at Least 15% of 514 SCL-90 Assessments of 188 Subjects With Major Depression When They Were Fully Remitteda

Enlarge table

The first step in developing a clinical scale to distinguish risk of relapse compared with nonrelapse in the next 6 months was to identify SCL-90 symptoms that, when rated as at least moderately severe during the past week, significantly differentiated relapse from nonrelapse. After a Bonferroni correction (19) based on seven of the nine SCL-90 subscales that were relatively independent, 17 SCL-90 items that differentiated relapse from nonrelapse at p<0.0071 were considered statistically significant. Beginning with these 17 symptoms, the 12 symptoms in boldface in Table 3 contributed to prediction of relapse within 6 months based on forward- and backward-stepping mixed-model logistic regression.

TABLE 3. Symptom Checklist–90 (SCL-90) Symptoms That Significantly Distinguished Depressive Relapse From Nonrelapse Within 6 Months After Assessments of Subjects With Major Depression When They Were Fully Remitteda

Prevalence (%)
Symptom (SCL-90 Item Number)Subjects With Relapse Within 6 Months (N=73)Subjects With No Relapse Within 6 Months (N=441)pOdds Ratio95% CI
Feeling blocked in getting things done (28)35.612.9<0.0014.642.22, 9.70
Feeling pushed to get things done (86)31.512.0b<0.0014.362.06, 9.24
Feeling tense or keyed up (57)43.820.0b<0.0013.561.79, 7.05
Having ideas/beliefs others do not share (68)17.85.7<0.0016.182.32, 16.47
Feeling inferior to others (41)24.77.9<0.0014.702.01, 10.99
Feelings of worthlessness (79)20.66.6b<0.0014.831.96, 11.90
Feeling low in energy or slowed down (14)37.017.7<0.0013.271.64, 6.52
Feeling blue (30)28.99.5<0.0013.891.76, 8.59
Feeling very self-conscious with others (69)27.49.8b0.0013.791.69, 8.48
Headaches (1)30.111.30.0023.581.63, 7.86
Feeling lonely (29)31.513.40.0023.271.57, 6.82
Crying easily (20)19.25.40.0024.331.70, 11.08
Feeling no interest in things (32)19.27.00.0034.171.64, 10.61
Feelings being easily hurt (34)30.6b13.20.0043.031.42, 6.45
Worrying too much about things (31)45.224.90.0052.631.34, 5.13
Trouble concentrating (55)26.011.30.0072.961.35, 6.51
Feeling everything is an effort (71)19.27.0b0.0073.521.41, 8.76

aItems in boldface are the 12 that contributed to prediction of 6-month relapse after forward- and backward-stepping mixed-model logistic regression of all 17 items listed in the table. Clinically meaningful symptom levels were defined a priori as those rated 2 (bothered moderately), 3 (quite a bit), or 4 (extremely). Self-report assessments were performed at yearly follow-ups from year 1 to year 5 for all subjects, and at 6-month intervals for a subset of 21 of 188 subjects in the analysis sample. Remission was defined as having a Longitudinal Follow-Up Evaluation psychiatric status rating of 1 (no symptoms of the episode; return to usual self) for all depressive episodes or conditions in the week of the SCL-90 assessment and each of the preceding 8 weeks.

bData missing for one SCL-90 assessment.

TABLE 3. Symptom Checklist–90 (SCL-90) Symptoms That Significantly Distinguished Depressive Relapse From Nonrelapse Within 6 Months After Assessments of Subjects With Major Depression When They Were Fully Remitteda

Enlarge table

We found that experiencing any one or more of the 12 symptoms most predictive of relapse at a moderate or worse level of severity in the past week resulted in a sensitivity of 80.8% for identifying relapse occurrences within the next 6 months and a specificity of 51.2% for identifying true nonrelapses (Table 4). The generally accepted level of 80.0% specificity in identifying true nonrelapse occurrences was met when four or more of the 12 symptoms were present. After at least 8 weeks of full remission, if one or more of the 12 SCL-90 symptoms was experienced at a moderate or worse level, most (80.8% sensitivity) of the actual relapses were detected, but only 21.5% of such assessments were actually followed by a relapse (positive predictive value). On the other hand, if none of the 12 symptoms were endorsed, about half of the actual nonrelapses were identified (51.2% specificity), but with a very high certainty of actually not having a depressive relapse (negative predictive value of 94.2%). Having none of the 12 symptoms was associated with a 5.8% rate of relapse within the next 6 months; the rate increased to 16.4% for one to five symptoms, 34.1% for six to nine symptoms, and 72.7% for 10–12 symptoms (Figure 2). Detailed counts for these ranges are provided in Table S1 in the data supplement that accompanies the online edition of this article.

TABLE 4. Predictive Statistics for Depressive Relapse Within 6 Months After Assessment of Subjects With Major Depression When They Were Fully Remitted, Based on the Number of 12 Predictive Symptom Checklist–90 Symptoms Rated as at Least Moderately Severe During the Past Week

Minimum Number of SymptomsSensitivitya (%)Specificityb (%)Positive Predictive Valuec (%)Negative Predictive Valued (%)Positive Likelihood RatioeNegative Likelihood Ratiof
180.851.221.594.21.6560.375
264.466.424.167.41.9170.536
361.675.725.239.92.5350.507
438.484.128.625.72.4150.732
534.289.134.215.93.1380.738
631.592.741.810.54.3150.739
723.394.340.56.84.0880.813
816.496.846.25.15.1250.864
913.798.255.62.87.6110.879
1011.099.372.71.615.7140.896
114.199.875.00.620.5000.961
121.4100.0100.00.20.986

aProportion of actual relapsers correctly identified by having this number of symptoms.

bProportion of actual nonrelapsers correctly identified by having less than this number of symptoms.

cProportion of subjects with this number of symptoms who actually did relapse.

dProportion of subjects with less than this number of symptoms who actually did not relapse.

eRatio of relapsers identified by having this number of symptoms, among actual relapsers versus nonrelapsers.

fRatio of nonrelapsers identified by having less than this number of symptoms, among actual relapsers versus nonrelapsers.

TABLE 4. Predictive Statistics for Depressive Relapse Within 6 Months After Assessment of Subjects With Major Depression When They Were Fully Remitted, Based on the Number of 12 Predictive Symptom Checklist–90 Symptoms Rated as at Least Moderately Severe During the Past Week

Enlarge table
FIGURE 2.

FIGURE 2. Rates of Relapse Within 6 Months Based on the Number of 12 Selected Symptom Checklist–90 (SCL-90) Items Self-Rated as at Least Moderately Severe by Subjects With Major Depression When They Were Fully Remitteda

a SCL-90 ratings assessed self-reported past-week symptoms. It was administered at yearly follow-ups from year 1 to year 5 for all subjects in the National Institute of Mental Health Collaborative Depression Study, and at 6-month intervals for a subset of 21 subjects in the analysis sample. Remission was defined as having a Longitudinal Follow-Up Evaluation psychiatric status rating of 1 (no symptoms of the episode; return to usual self) for all depressive episodes or conditions in the week of the SCL-90 assessment and each of the preceding 8 weeks.

Discussion

We found that in about 1 in 7 occasions when 188 remitted subjects completed the SCL-90 (73 of 514 assessments), relapse followed within the ensuing 6 months. This relapse rate is consistent with other reports (68). Relapses were associated with more, not less antidepressant treatment. Notably, these relapses were clinically meaningful because they were associated with a more severe and chronic depressive illness course over the next 5 years.

Among patients who had achieved remission from their previous depressive episode, we found a broad range of SCL-90 symptoms present at a moderate or worse level, including dysphoria (depression, anxiety, anger-irritability), sleep disturbances, somatization, and having one’s feelings easily hurt. The co-occurrence of anxious and depressive symptoms is common in major depressive episodes (20), and it also seems to be the case in periods of remission, albeit with less severity.

Nierenberg et al. (8), using a far less stringent definition of remission (a score <6 on the 16-item Quick Inventory of Depressive Symptomatology, Clinician-Rated [21] for 7 days), also reported the presence of some depressive symptoms in remission. With an empirically valid 8-week period of full remission (6), the present study showed that indeed some depressive but also other symptoms were observed in the period of apparent remission. These symptoms could have been either prodromal early expressions of the subsequent episode or residual symptoms of a prior episode or condition. In either case, our study indicates that they were useful for predicting depressive relapse over the ensuing 6 months.

Specific SCL-90 symptoms that most differentiated relapse from nonrelapse included symptoms of depression, anxiety, headaches (common in both anxiety and depressive disorders), and affective instability. These appear to reflect dysfunction in several CNS systems, including neurocognitive (feeling blocked in getting things done, trouble concentrating), psychomotor, and reward systems (feeling pushed to get things done, feeling low in energy or slowed down), the fear circuit (feeling tense or keyed up, worrying too much about things), and affective dysregulation or instability (crying easily, feelings being easily hurt). Despite having achieved full remission, patients who are more likely to relapse appear to remain in an unstable state that impairs the needed resilience to deal with the ups and downs of daily living. Consistent with the association between neurocognitive impairment and poorer acute treatment outcome (22, 23), this impairment also seems to predict a worse prognosis in remitted depressed patients who relapse within the next 6 months.

Our results suggest that the more brain functions (circuits) involved, the greater the risk of relapse, which expands on the study of Nierenberg et al. (8), who found that a greater number of residual depressive symptom domains after remission was associated with a greater likelihood of relapse within the next year.

Of greatest importance in this study is that we demonstrated, as a proof of concept, that it is possible to construct a brief self-report scale that can be used to ascertain an estimated risk of relapse for the individual patient. Such a person-level indicator can be used to tailor the follow-up schedule for each remitted patient based on his or her individually identified risk of relapse and potentially to initiate interventions in a more timely fashion when needed.

A simple count of the number of symptoms (0–12) self-reported at a moderate or worse level of severity during the past week created a score that was highly related to the risk of relapse. A score of 0 was associated with a low (5.8%) risk for depressive relapse in the next 6 months, suggesting that these patients may be managed by, for example, telephone visits at 3 and 6 months. Patients with a score of 6–9 had a 34.1% risk of relapse, and those with a score of 10–12 had a 72.7% risk of relapse; for these patients, more frequent follow-up contacts would be warranted to intervene at the first sign of symptom worsening. Thus, this 12-item scale appears to provide clinically actionable guidance for over half of the sample, which would seem to have cost efficiencies as well as therapeutic advantages.

This study has several limitations. First, the clinical decision tool that we devised must be viewed as hypothesis-generating. Replication in other samples is essential. Second, we did not include all possible sociodemographic and clinical variables that might affect relapse. We limited ourselves to the symptoms in the SCL-90 in order to explore the possibility of constructing a simple and feasible clinical tool that can possibly even be administered as a self-report assessment. Whether prediction from this tool could be enhanced by adding other easily acquired patient-level variables would be of interest. Third, generalizability may be affected by lack of heterogeneity in the all-white study sample, by the requirement that the analytic sample have no missing weekly depression severity ratings for 6 consecutive months following the SCL-90, and by changes in both the care systems and antidepressant medications since the study period (1978–1987).

In summary, about 1 in 7 fully remitted, formerly depressed patients experienced clinically meaningful depressive relapses over the next 6 months. These relapses were associated with a far worse course of depression over the ensuing 5 years. As a proof of concept, we have demonstrated that a brief 12-item symptom-based tool can provide an estimate of the risk of relapse for individual patients. Such simple, clinically based indicators can provide a platform onto which laboratory-based measures could be added to further personalize patient care.

From the Department of Psychiatry, University of California, San Diego, La Jolla; and the Department of Psychiatry, Duke–National University of Singapore, Singapore.
Address correspondence to Dr. Judd ().

Supported by the Department of Psychiatry, University of California, San Diego (Dr. Schettler).

Dr. Rush has received consulting fees from the American Psychiatric Association, Brain Resource, Duke–National University of Singapore, Eli Lilly, Emmes Corporation, LivaNova, Lundbeck, MedAvante, Montana State University, NIDA, Santium, Stanford University, Takeda, University of Colorado, University of Texas Southwestern Medical Center; speaking fees from the American Society for Clinical Psychopharmacology, Hershey Penn State Medical Center, New York State Psychiatric Institute, Stanford Medical School, SingHealth–National University of Singapore, and the University of California, San Diego; royalties from Guilford Publications and the University of Texas Southwestern Medical Center; a travel grant from CINP; and research support from Duke–National University of Singapore; through the University of Texas Southwestern Medical Center, he has a potential financial interest in the Inventory of Depressive Symptomatology and several variations of it. Drs. Judd and Schettler report no financial relationships with commercial interests.

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