Recurrence of Major Depressive Disorder in Hospitalized Children and Adolescents

Recurrence of Major Depressive Disorder in Hospitalized Children and Adolescents GRAHAM J. EMSLIE, M.D., A. JOHN RUSH, M.D., WARREN A. WEINBERG, M.D., CHRISTINA M. GULLION, PH.D., JEANNE RINTELMANN, B.S., AND CARROLL W. HUGHES, PH.D.

ABSTRACT Objective: To evaluate the outcome of a sample of children and adolescents hospitalized with major depressive disorder (MDD) and to assess different duration and severity criteria to define recovery and recurrence. Method: Fifty-nine of 70 children and adolescents were reevaluated 1 to 5 years later, and the intervening course of depression and other disorders was assessed using the Kiddie-Longitudinal Interval Follow-up Evaluation (K-LIFE). Results: Ninety-eight percent of subjects had recovered from their index MDD episode within 1 year of their initial evaluation, but 61% had at least one recurrence during the follow-up period. Of those with recurrences, 47.2% had a recurrence within 1 year and 69.4% by 2 years from the offset of the index episode. Changing the criteria for recovery by increasing the length of time required to define recovery resulted in decreases in the number of episodes of recurrence reported. Conclusion: MDD in children and adolescents is often an episodic disorder. Differences in definitions of recovery and recurrence affect the data reported. Consistent definitions of remission, recovery, relapse, and recurrence are needed. These data suggest that recovery may be defined after two consecutive months without symptoms and that episodes of MDD may be briefer, but more frequent, in children and adolescents than in adults. J. Am. Acad. Child Adolesc. Psychiatry, 1997, 36(6):785-792. Key Words: depression, recurrence, child, adolescent, course of illness.

Major depressive disorder (MDD) in children and adolescents is recognized as causing significant morbidity and mortality (Cannvell, 1992; Fleming and Offord, 1990). Depression is a major factor in suicide in adolescents (Brent, 1987; Kovacs et al., 1993; Pfeffer

Accepted December I I , 1996. Drs. Emslie, Rush, Gullion, and Ms. Rintelmann are with the Department of Psychiaty, and Dr. Weinberg is with the Departments of Neurology and Pediatrics, University of Texas Southwestern Medical Center at Dallas and Childreni Medical Center of Dallas. Dr. Hughes is with the Terrell State Hospital. This work was supported by grants fiom the NIMH (MH 39188, Dr. Emslie;MH41115, the Mental Health ClinicalResearch Center), the Mdrthur Depression Network, Caleb C. and Julia W Dula Education and Charitable Foundation, Mr. and Mrs. Woody Hunt, Mr. and Mrs. Morton Mtyerson, and the Awulay Fami4 (Or. Weinberd. The authors acknowledgethe administrative support of Kenneth Z. Altshuler, M.D., Stanton Sharp Distinguished Chair, Profissor, and Chairman, Department of Psychiatry; statistical consultation fiom Tom Carmody, Ph.D.; the clinical assistance of the staff of the Child and Adolescent Psychiatry Unit, Children j Medical Center of Dallas; and the secretarial support of Melody Brummett. Reprint requests to Dr. Emslie, Department of Psychiaty, UTSWMC, 5323 Harry Hines Blvd., Dallas, 7X 75235. 0890-8567/97/3606-0785$03.00/0O1997 by the American Academy of Child and Adolescent Psychiatty.

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et al., 1991; Rao et al., 1993) and a common cause of school failure and school dropout (Weinberg et al., 1973). While the phenomenology, genetics, and biology of depression in children and adolescents appear to be similar to those of adult depression (Cantwell, 1992; McCracken, 1992), numerous questions remain about the course and outcome of depression in children and adolescents. Earlier studies assessed outcome primarily crosssectionally. When reevaluated 6 to 7 years later, depression remained a problem in 40% to 50% of clinical patients (Asarnow et al., 1988; Eastgate and Gilmour, 1984; Goodyer et al., 1991; Poznanski et al., 1976) and in approximately 25% of patients in nonreferred community samples (Fleming et al., 1993; McGee and Williams, 1988). Depression is an episodic disorder. Therefore, of interest is not only the overall outcome, but also the course of depressive symptoms during the intervening periods. Recovery from an index episode of major depression is remarkably consistent across samples, with more than 90% of depressed child and adolescent

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outpatients (Kovacs et al., 1984a; McCauley et al., 1993), adolescent inpatients (Strober et al., 1993), and nonreferred adolescents (Keller et al., 1988) having recovered from an episode of MDD within 1 to 2 years. In two of these samples (Keller et al., 1991; Kovacs et al., 1984a), recovery occurred with minimal treatment in the majority of subjects. Once recovered, however, depressed children and adolescents have a high rate of recurrence of their depression. Recurrence (new episode of depression) is reported in 54% to 72% of depressed children and adolescents followed for 3 to 8 years, with similar rates in inpatients (Garber et al., 1988) and outpatients (Kovacs et al., 1984b; McCauley et al., 1993; Rao et al., 1995). In a 5-year prospective follow-up of 431 adult subjects, Keller et al. (1992) found 88% had recovered by 5 years. Fifty percent of the subjects recovered within the first 6 months, and after 6 months the rate of recovery declined markedly. Similarly, Coryell et al. (1994) noted recovery occurring in 60% by 6 months and 80% by 1 year. However, Shea et al. (1992) reported that in an 18-month naturalistic follow-up of adult outpatients with M D D , only 19% to 30% entered remission and remained well over an 18-month post-acute phase treatment period. Keller et al. (1982) reported on recurrences in 75 adults with MDD who had recovered from their index episode. Within 1 year, 16 (21%) met Research Diagnostic Criteria for a subsequent major depressive episode. Factors predicting relapse and recurrence in adults include three or more previous episodes (Keller et al., 1982; Maj et al., 1992), severity of index episode (Gonzales et al., 1985), psychotic features (Copeland, 1983; Schatzberg and Rothschild, 1992), psychosocial factors, early age at onset of illness, and double depression (Gonzales et al.,, 1985; Keller et al., 1983). “Double depression” is defined as MDD superimposed on dysthymic disorder. Prophylactic drug treatment reduces the risk of relapse and recurrence compared with no treatment (Frank et al., 1990). Furthermore, continued treatment appears to reduce the severity of subsequent episodes (Maj et al., 1992). On e factor limiting such studies in adults, as well as in children and adolescents, is the lack of uniform definitions for relapse or recurrence of illness (Frank et al., 1991). The rationale for having uniform definitions includes the ability to compare data across studies,

786

to examine predictors of clinical course, and to improve guidelines for evaluation of clinical efficacy of drugs by regulatory agencies, as well as development of improved treatment guidelines and empirically based revision of diagnostic criteria. Frank et al. (1991) proposed that definitions for remission, recovery, relapse, and recurrence be based on observable phenomena, i.e., symptoms, and specifically be independent of treatment, e.g., while the term “recovery” with or without medication might have different meanings depending on the orientation of the observer, it would have an unambiguous phenomenological meaning. It was recommended that the terms be defined on the basis of severity of observable symptoms, either number or intensity, and duration of symptoms. The initial basis for these definitions requires defining an episode of depression, usually meeting full syndromal criteria for a defined number of days, e.g., DSM-IV criteria for MDD for 14 days. An episode does not end until a patient reaches recovery. Remission is a relatively brief period during which an individual is asymptomatic or has minimal symptoms independent of treatment. A remission that lasts for a defined number of days or longer is defined as a recovery and refers to recovery from an episode but not necessarily the illness. A relapse is a return of symptoms satisfying syndrome criteria for an episode during a period of remission but before recovery. Recurrence is the development of a new episode of MDD occurring by definition after recovery. These definitional differences are important because identifying patients who are prone to recurrence has implications for long-term treatment. However, if the time frame to declare recovery is too long, the recurrent nature of the condition will be obscured in patients with frequent cycles of depression (e.g., twice a year). These subjects will be included with subjects who do not cycle but rather do not recover from the index episode. However, if the time to declare recovery is too short, then maintenance treatment may be initiated prematurely. Also, in determining clinical predictors of recurrence, it is important to separate subjects who recover but have recurrences from those who do not recover from an episode of M D D . Finally, uniform definitions are required to assess differences across the life span (Kovacs, 1996). Our study undertook to examine retrospectively the course of MDD in 70 children and adolescents who

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were hospitalized at their index episode with MDD. These subjects had participated in previous studies of sleep polysomnography and major depression (Emslie et al., 1990, 1994), which were conducted over a 3-year period. The present study took place over a 1-year period. It included all subjects who had been evaluated at least 1 year previously for the initial polysomnographic studies. This report attempts to (1) add to the available literature on course of MDD in a well-studied population of child and adolescent inpatients and (2) assess the impact of different duration and severity criteria on definitions of recovery and recurrence. METHOD Clinical Evaluation T h e initial clinical evaluation methods have been published (Emslie et al., 1990). Briefly, all subjects were admitted to the Psychiatry Unit at Children’s Medical Center in Dallas. All met DSM-III-R criteria for M D D (American Psychiatric Association, 1987) and were 8 to 1 7 years old. No patients were included who were not in good general medical health, as documented by medical review of systems, physical, neurological, and routine laboratory evaluations (SMA-20, thyroid panel, complete blood cell count, and urinalysis). Subjects whose IQ was less than 80, as measured by WISC-R, were excluded. Recent history of alcohol or substance abuse and of anorexia or bulimia were also exclusion criteria. After initial screening, written informed consent was obtained from one or both parents, and verbal assent was obtained from each patient. Initially, patients and parents were interviewed separately by a trained, experienced research assistant, using a DSM-Ill-R-based semistructured interview, the Diagnostic Interview for Children and Adolescents (DICA) (Herjanic and Reich, 1982; Reich et al., 1982). Parents were additionally interviewed for family history using family history Research Diagnostic Criteria (Andreasen et al., 1977, 1986). Patients completed a self-report scale for depression, the Weinberg Screening Affective Scale (WSAS) (Weinberg and Emslie, 1988). Parents completed the Bellevue Index ofnepression Parent Form (BID-P) (Petri, 1985). Patients and parents were then interviewed separately by two experienced clinicians. These interviews were usually separated by 3 to 5 days. During these interviews, the DICA and the family and medical histories were reviewed. T h e Bellevue Index of Depression (BID), a clinicianrated measure of depression severity, was completed. Detailed information was also obtained about episode history, length of illness, and number of episodes. This diagnostic process took approximately 2 weeks. Information was obtained from school, relatives, and clinical observations on the unit. T h e structured interviews, two independent clinical interviews, self-report measures, and clinical data were systematically reviewed in a research diagnostic conference, at which time a consensus DSM-III diagnosis was established. Current and lifetime psychiatric diagnoses in addition to M D D were also specified. These data were recorded o n the diagnostic summary. A consensus BID was used as a severity index of depression. All subjects were initially inpatients.

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Treatment After the above initial evaluation, all patients were treated. Fiftyseven (8 1.4%) of 70 received antidepressant medications, with dose and type of medication dictated by clinician choice. All patients received individual, group, family, and milieu therapy while in the hospital. T h e average time in the hospital after the evaluation was 33 days (SD = 18.3, range = 1 to 107). After discharge, patients either returned to their psychiatrist or other physician for continued management, or they continued treatment with faculty. T h e clinical management was uncontrolled and left to the discretion of the physician and patient. Thus, this report is a naturalistic follow-up study of the course of illness of M D D after hospitalization for the index episode.

Follow-up Evaluations T h e follow-up interviews were conducted during a 12-month period. T h e time from initial diagnosis (is., within 2 weeks of the index hospitalization) to the follow-up interview ranged from 1.0 to 5.8 years. T h e data collected were retrospective in nature and depended o n the recall of patients and parents. Whenever possible, however, medical records were obtained and treating professionals were contacted. Of 70 subjects initially diagnosed, 59 were located. Of these 53, 42 agreed to face-to-face interviews, of which 71.4% included the parents. T h e remaining 17 gave follow-up information by telephone contact with the former patient and parent. T h e follow-up interviews were conducted using a modified Kiddie-Longitudinal Interval Follow-up Evaluation (K-LIFE) (Keller et al., 1984). The K-LIFE is designed for follow-up at 6-month intervals. In this study, K-LIFE-elicited information was obtained by recalling both school grade and seasons, spring, summer, fall, and winter. In addition to the diagnosis of depression, the K-LIFE also assesses the presence of other diagnoses. If, for example, a child had been initially seen during the fall of the sixth grade and was seen for follow-up in the spring of the ninth grade, then each period was “screened” for continued levels of depressive symptoms and other disorders. However, when changes in status were identified, they were coded by using dates. This date was the midpoint of the period remembered as being the change point, e.g., if the child had another episode meeting criteria for M D D starting just after school started, the date coded might be September 15. Episode length, time to recovery, etc., were all calculated in days. T h e severity of M D D during the follow-up period was coded using the criteria in the K-LIFE (6 = severe, 5 = definite criteria, 4 = marked symptoms, 3 = partial remission, 2 = residual symptoms, 1 = usual self). W e used the terms proposed by Frank et al. (1391). T h e level of symptom rating was the MDD criteria from the K-LIFE. Initially, a subsequent episode of depression was examined using an M D D K-LIFE rating of 5 or greater for 14 days. Remrssion was defined as asymptomatic ( M D D K-LIFE rating of 1 or 2) for at least 14 days. Recovery was defined as an asymptomatic period ( M D D K-LIFE rating of 1 or 2) of at least 60 days. Relapse was an episode of depression after remission (at least 14 days) but before recovery. Recurrence was defined as an episode of depression after recovery.

Statistical Analysis Differences between subjects who had follow-up and those lost to follow-up and between those who had recurrences and those

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xZ

who did not were tested with t tests or tests as appropriate. T i m e to recurrence was estimated using the Kaplan-Meier (Kaplan and Meier, 1958) survival curve. Cox proportional-hazards regression was used to identify important predictors of recurrence status (Collett, 1994). A Cox model was done using each possible predictor variable by itself, and any predictor variable with a p value less than .15 was included in the multivariate variable-selection procedure. T h e all-possible-subsets procedure was used to select the important predictors. T h e n the model was checked for the validity of the proportional-hazards assumption, outliers, and needed transformations and interaction terms.

RESULTS

i

'61 0.0 -

0

Of the initial 70 subjects, 59 participated in the follow-up and 1 1 were not located. There were no significant differences between these groups on any demographic or clinical variables, except the 1 1 not located did have a lower socioeconomic status ( t = 2.5, df10,58, p = .01) ( p < .05). Given the large number of variables compared, this is not statistically significant. All seven subjects with an initial diagnosis of psychotic depression were recontacted. The length of the follow-up varied. Ten were followed for between 1 and 2 years, 15 between 2 and 3 years, 15 between 3 and 4 years, and 19 for 4 or more years. Of the 1 1 subjects not found, 5 (45%) would have been within 3 years of their initial evaluations. Therefore, those lost to follow-up were not weighted toward the longer follow-up group. Using the above definitions for remission, recovery, relapse, and recurrence, the average time to remission of MDD (symptom severity 1 2 for 14 days) from the initial evaluation was 59.5 days (SD = 50.9, range = 14 to 246 days). Using the definition for recovery as asymptomatic for at least 60 days, then 98% of subjects recovered within 1 year of initial evaluation. There was, however, a high rate of recurrence. A new episode was initially set at a K-LIFE of 5 or greater for 2 weeks. Only 23 (39%)of 59 subjects had no recurrence during the follow-up period. Of those nonrecurring, 56.5% had been followed for less than 3 years and 43.5% for more than 3 years. Of the 36 subjects (61%) who had a recurrence, 47.2% ( n = 17) did so within the first year of follow-up, and 69.4% ( n = 25) by 2 years. A Kaplan-Meier survival curve was computed for time to first recurrence (Fig. 1 ) . Based on this curve, the percent of subjects without a recurrence was estimated to be as follows: 1 year, 62.7%; 2 years, 56.9%; 3 years, 44.8%; 4 years, 28.6%; and 5 years, 788

c, ~

12

~ ~-

24

~

s Months

~

48

~

m

_

72

Fig. 1 Survival analysis plot of the number of months until the first recurrence of major depressive disorder in children and adolescents.

23.8%. Fifteen subjects (42%) had one recurrence during their follow-up period and 21 (58%) had two or more recurrences. The mean length of follow-up of those having one recurrence was 3.6 years, which was the same in the 21 individuals with at least two or more recurrences. Table 1 presents the clinical characteristics at initial evaluation of those who had a definite recurrence compared with those who did not, using the above criteria (i.e., K-LIFE at MDD 2 5 for 14 days after 60 days asymptomatic). There were no demographic differences between the two groups. Clinician-rated (BID) ( t = 3.02, 55 dJ p = .004) and self-reported (WSAS) ( t =3.10, 53 dJp = .003) severity of depressive symptoms were both significantly higher at initial assessment for those with a later recurrence. Furthermore, those with recurrences were more likely to have had some suicidal behaviors = 4.94, df = 1, p < .026). This would not be statistically significant when the Bonferroni correction (Altman, 199 1 ) for multiple comparisons was done. Notable was that six of seven subjects with psychotic depression evidenced a recurrence during the follow-up period. While comorbid diagnoses were common at initial evaluation, no particular diagnostic groupings were more likely to have a recurrence. Cox proportional-hazards regression (Collett, 1994) was done to find predictors of time to recurrence. Potential predictor variables were all those listed in Table 1. A Cox model was done using each predictor variable by itself, and any predictor variable with a p value less than .15 was included in the multivariate

(x2

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_

I

RECURRENCE OF M D D

TABLE 1 Clinical and Demographic Characteristics at Index Episode (Those With Recurrence Versus Those With No Recurrence)

Variables

Recurrence

No Recurrence

( n = 36)

( n = 23)

Demographic 13.0 (1.9) Age: years (SD) Yo Female 47.2 Yo Caucasian 88.9 Clinical Severity of depression: mean (SD) BID 73.3 (11.0) 21.5 (11.1) WSAS Parent BID 49.8 (20.3) 44.9 (4.2) CGAS Positive family history (Yo) 58.3 No. of episodes (SD) 1.9 (1.1) Duration of episode: weeks (SD) 19.1 (17.3) Length of illness: months (SD) 19.5 (21.7) Age of onset: years (SD) 11.4 (2.4) Suicidal behavior: n (Yo) None 5 (13.9) Death wishes 4 (11.1) Suicidal thoughts/plans 18 (50.0) Attempts 9 (25.0) Concurrent diagnosis: n (Yo) None 7 (19.4) Melancholic 15 (41.7) Psychotic 6 (16.7) Dis thymic 13 (36.1) 11 (30.6) ODD/conduct Anxiety disorder 7 (19.4) ADHD 14 (38.9)

12.1 (2.9) 43.5 95.7 62.3 12.9 33.4 46.9 56.5 1.6 24.9 23.4 10.3

(16.7)** (8.2)** (14.7) (6.1) (0.7) (23.1) (32.3) (4.0)

9 1 8 5

(39.1)’ (4.3) (34.7) (21.7)

5 9 1 14 7 8 9

(21.7) (39.1) (4.3) (60.9) (30.4) (34.8) (39.1)

Note: BID = Bellevue Index of Depression; WSAS = Weinberg Screening Affective Scale; CGAS = Children’s Global Assessment Scale; O D D = oDDositionaI defiant disorder; ADHD = attentiondeficit hyperactivity disorder. * p < .05; * * p < .01. I

I

variable-selection procedure. The all-possible-subsets procedure was used to select the important predictors. Then, the model was checked for the validity of the proportional-hazards assumptions, outliers, and needed transformations and interaction terms. Table 2 presents the final model. Clinician-rated (BID), parent-rated (BID-P), and self-rated (WSAS) depression severity, race, older age, and psychotic subtype all increased the risk for recurrence. Only 51 subjects were used for the above analyses because of missing data for parent BID and WSAS. Of these 51 subjects, only 3 had psychotic subtype. T o show that loss of the sample did not distort the results, psychotic subtype was examined separately. For psychotic subtype ( n = 59) the risk ratio was 4.22 ( p = .003). The risk ratio of 4.2 for

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psychotic subtype with all 59 (7/59)subjects is similar to the 4.34 risk ratio obtained with 51 subjects. The other variables also have similar risk ratios. Although treatment was not controlled, information was obtained on whether or not subjects were treated with antidepressant medication. Thirty-five (59.3%) of 59 were in no treatment at the time they were contacted for follow-up. Of the 36 subjects who experienced a recurrence, 33 (91.7%)were taking antidepressant medications at hospital discharge, but only 16 (44%) were taking antidepressants at the time of their recurrence. Of the 23 subjects without a recurrence, 17 (74%) were taking medication at discharge and 11 (48%) were taking medication at the time of reevaluation. Thus, recurrences occurred both with and without medication. T o examine the impact of different criteria for how long a patient must be asymptomatic to declare recovery, we defined recovery as after a period of remission of 30, 60, 90, 120, and 180 days. A subsequent episode was defined as MDD 1 5 for 14 days. Table 3 lists the number of subjects who recovered, the number of subjects who had a recurrence and the number of recurrence episodes, and the number of relapses (episodes before recovery). Increasing the time in remission to define recovery progressively decreased the total number of new episodes (recurrences) reported in follow-up, with 62 dejinite episodes in 36 subjects if a 60-day criterion was used to 38 episodes in 28 subjects if 180 days was used. Conversely, the number of relapses increased from 3 to 27. The biggest impact was on the number of episodes in subjects with multiple episodes. Only eight additional subjects are defined as having no recurrence if a longer duration is required to consider the person recovered. In addition, we assessed possible episodes and increasing the duration criteria for an episode from 14 to 30 days. Adding possible (subsyndromal) episodes (i.e., MDD = 4 ) had little impact. While subjects had distinct episodes that were felt to be below criteria, only four subjects had only a below-criteria episode after 60 days of remission. Only 2 of 65 episodes had a duration of less than 30 days. DISCUSSION

This retrospective follow-up of children and adolescents hospitalized for MDD revealed that while all

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TABLE 2 Variables Increasing the Risk of Recurrence Variable

Rxk Ratio

95% CI

p Value

Interpretation

Clinician BID (10 units)

1.49

1.11-2.02

,0086

Parent BID (10 units)

1.36

1.10-1.68

,004 1

WSAS (10 units)

1.51

1.08-2.13

.O 169

Psychotic subtype

4.34

1.12-16.80

,0333

Age at onset

1.25

1.03-1.53

.0259

Race

5.19

0.97-27.9

.0546

For each 10-unit increase in the clinician BID, risk of recurrence increases by a factor of 1.5, or about 50% For each 10-unit increase in parent BID, risk of recurrence increases by a factor of 1.36, or about one third For each 10-unit increase in WSAS, the risk of recurrence increases by 1.51 times, or about 50% Those with psychotic subtype have about 4 times the risk of recurrence as those without psychotic subtype For each year of increase in age at onset, the risk of recurrence increases by a factor of 1.25, or 25% Nonwhite subjects have about 5 times more risk of recurrence than white subjects

Note: CI

=

confidence interval: BID

=

Bellevue Index of Depression; WSAS

subjects have remission of their symptoms, depression is often an episodic disorder. Sixty-one percent suffered a recurrence of a definite episode of MDD after at least a 60-day period of remission, and an additional 7% (4/59) had a possible recurrence (episode below criteria). Most of these major recurrences occurred within 2 years of the index episode. The risk of recurrence was highest in the first year after recovery. Forty-seven percent of those with a recurrence had their recurrence within the first year, 22% had it in the second year, and for 31% of the subjects the recurrence followed at least 2 years of recovery/ remission. Higher clinician, parent, and self-report of depressive symptoms, older age, race, and psychotic subtype increased the risk of recurrence. Nearly all (6/7) who TABLE 3 Impact of Changes in Definitions for RecoverylRecurrenceIRelapse

Time to Recovery

Recovery: No. of Subjects

Recurrence: No. of Subjects

Recurrence: No. of Episodes

30 days 60 days 90 days 120 days 180 days

59 59 58 57 57

36 36 33 29 28

65 62 50 47 38

Relapse: No. of Episodes ~

0 3

15 18 27

Note: An episode is defined as at least 14 days with major depressive disorder 25 (definite episode).

790

=

Weinberg Screening Affective Scale.

had psychotic symptoms had a recurrence. There was no difference between the groups with regard to positive family history, which was defined as any first-degree relative with affective disorder treated with medication or hospitalization. It has been suggested that a family history of recurrent depression is more likely to be predictive of recurrences in the proband. Why comorbid dysthymic disorder did not predict recurrence in this population, as has been previously reported (Kovacs, 1984b), is not clear. The clinical implications of these findings and previous studies are evident. The treatment of MDD goes beyond the treatment of the acute episodes in many patients. It is important that patients be followed closely, especially over the first year or two after an episode. Research is needed on continuation treatment (how long to treat an episode) and maintenance treatment (how to prevent recurrence) (Agency for Health Care Policy and Research, 1993). Treatment is important as there is an increased risk of suicide and suicide attempts (Kovacs et al., 1993; Rao et al., 1993) over time, and depression and dysfunction can continue into adulthood (Harrington et al., 1990; Kandel and Davies, 1986). Definitions used for recovery substantially affect the way the course of depression is characterized in these children and adolescents with M D D . Take, for example, the definition of relapse versus recurrences. When recovery required 180 days asymptomatic as opposed

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to 60 days, almost 50% of subsequent episodes of depression were defined as relapses and not recurrences. Potentially, the well intervals used to define remission and recovery are not as prolonged in children and adolescents as would be expected from adult followup studies. Requiring a longer period of asymptomatic status to define recovery would obscure the recurrent nature of the episodes. As mentioned previously, recovery in this context refers to recovery from the episode and not the illness, as has been proposed by Frank et al. (1991). There are several problems with interpreting these data because of the retrospective nature of the assessment. All subjects were rigorously assessed during the index episode, and 71% of those followed a face-toface structured interview at follow-up. It is expected that the impact of retrospective data would be to miss episodes of recurrence, especially if at more remote times from the reevaluation. As would be expected, the 11 subjects who were not located on follow-up tended to come from more unstable or disadvantaged family environments. The outcome of these 11 subjects is at least as likely to be as problematic as subjects who were located, and the data from this sample are conservative estimates of recurrence rates. Another limitation of this study is that it is a naturalistic follow-up (i.e., treatment was not controlled). This population was treated aggressively, with 84.7% discharged on antidepressant medication and 18% on multiple medications. However, many had discontinued treatment at the time of follow-up. Another limitation of this report is that follow-up was measured at only one time point, and results may not be generalizable to other patients (e.g., outpatients) with MDD. However, the results are similar to those of other studies in this age group. This study does show the impact of different duration and severity criteria for remission, recovery, relapse, and recurrence. The results suggest that the presence of 60 days of remission (K-LIFE 1 or 2) with a new episode (K-LIFE rating of 5 or 6 for at least 14 days) is a good definition for recovery and recurrence from episodes of depression. A consistency in definitions of remission, relapse, recovery, and recurrence would assist in comparisons of data across different populations.

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