Status of minor depression or dysthymia in primary care following a randomized controlled treatment

General Hospital Psychiatry 23 (2001) 301–310

Psychiatry and Primary Care Recent epidemiologic studies have found that most patients with mental illness are seen exclusively in primary care medicine. These patients often present with medically unexplained somatic symptoms and utilize at least twice as many health care visits as controls. There has been an exponential growth in studies in this interface between primary care and psychiatry in the last 10 years. This special section, edited by Wayne J. Katon, M.D., will publish informative research articles that address primary care-psychiatric issues.

Status of minor depression or dysthymia in primary care following a randomized controlled treatment Thomas E. Oxman, M.D.a,*, James E. Barrett, M.D.b, Anjana Sengupta, Ph.D.c, Wayne Katon, M.D.d, John W. Williams, Jr., M.D., MHSe, Ellen Frank, Ph.D.f, Mark Hegel, Ph.D.a a

Departments of Psychiatry and Community & Family Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA Departments of Community & Family Medicine and Psychiatry, Dartmouth Medical School, Lebanon, NH 03756, USA c Department of Psychiatry, Dartmouth Medical School, Lebanon, NH 03756, USA d Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA e Health Services Research and Development Service, Department of Veterans Affairs Medical Center and Division of General Internal Medicine Division, Duke University Medical Center, Durham, NC, USA f Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA, USA b

Abstract This report describes the rates of recovery and remission from minor depression or dysthymia in primary care patients three months after completing a randomized controlled treatment trial. The subjects were primary care patients who received ⱖ4 treatment sessions with Problem-Solving Treatment, paroxetine, or placebo and who completed an independent assessment 3 months after the study (201 with minor depression, 229 with dysthymia). The 17-item Hamilton Rating Scale for Depression (HAMD), semistructured questions about postintervention depression treatments, and baseline medical comorbidity, neuroticism, and social function were the primary measures. For minor depression 76% and for dysthymia 68% of subjects who were in remission at the end of the 11-week treatment trial were recovered (HAMD ⱕ6) three months after the treatment trial. Of patients who were not in remission at 11 weeks, for minor depression 37% and for dysthymia 31% went on to achieve remission at 25 weeks. The majority of patients chose not to use antidepressants or psychotherapy after the trial. Patients with minor depression that had greater baseline social function and lower neuroticism scores were more likely to be recovered. For patients with minor depression, these findings suggest a need for some matching of continuation and maintenance treatment to patient characteristics rather than uniform, automatic treatment recommendations. Because of the chronic, relapsing nature of dysthymia, practical improvements in encouraging effective continuation and maintenance phases of treatment are indicated. © 2001 Elsevier Science Inc. All rights reserved. Keywords: Depression; Primary care; Antidepressants; Psychotherapy; Dysthymia; Minor depression

1. Introduction In a recent multi-site study of minor depression and dysthymia [1], we compared outcomes in primary care patients receiving a manualized behavioral treatment (Problem-Solving Treatment for Primary Care, PST-PC [2], par* Corresponding author. Tel.: ⫹1-603-650-6147; fax: ⫹1-603-6505842. E-mail address: [email protected] (T. Oxman).

oxetine, or placebo. There were six treatment visits that were scheduled for each intervention. Paroxetine showed moderate benefit compared to placebo for depressive symptoms and mental health function in patients with dysthymia and the more severely impaired subgroup of patients with minor depression [3,4]. PST-PC showed benefits that were smaller, and less consistent than paroxetine. One issue raised is that behavioral treatments such as PST-PC may have delayed and/or longer lasting effects than pharmacotherapy [5– 8]. More broadly, there is also a dearth of

0163-8343/01/$ – see front matter © 2001 Elsevier Science Inc. All rights reserved. PII: S 0 1 6 3 - 8 3 4 3 ( 0 1 ) 0 0 1 6 6 - 9

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research on post-treatment trial outcomes in dysthymia or minor depression, especially in primary care. Remission and recovery are almost exclusively examined in major depression. As initially proposed by Frank et al. [9], two characteristics define remission and recovery: severity and duration of symptoms. Both terms require a sufficient magnitude of symptom improvement. For example, using the 17-item Hamilton Depression Rating Scale (HAMD) [10], a symptom severity level for both remission and recovery is set as a score of six or less. The duration for remission is briefer than that for recovery, e.g., lasting greater than two weeks, and usually relates to the acute treatment phase. Remission implies that no increase in treatment frequency or dose or type is required. The duration for recovery is longer, e.g., six months and implies that treatment can be discontinued or, if continued, the aim is prevention of future episodes rather than treating the current episode. In major depression, adherence to antidepressants during the continuation and maintenance phases of treatment is notably low [11]. This is despite the frequent warning that continuation treatment reduces relapse by at least 50% during the first six months after remission [12–14] and that maintenance treatment, when indicated for recovered patients, also may reduce recurrent episodes by at least 50% [15,16]. Correlations of recovery could be useful to clinicians in allocating resources for more or less aggressive treatment follow-up plans. For example, rates are thought to be similar in older and younger patients [17] implying that age should not influence allocation. The NIMH Collaborative Study of Depression and Paykel et al. [18] both suggest that lesser severity of symptoms, such as in minor depression or dysthymia, is also related to greater probability of recovery. Other reported correlations of recovery include life events [19,20], comorbid anxiety [21], number of previous episodes [20]; and specific personality traits such as neuroticism [20,22]. In previous work [23,24], we examined patient predictors of 11-week remission response in the multi-site study of minor depression and dysthymia. For minor depression, we found that an 11-week remission response was associated with younger age, Caucasian ethnicity, and lower baseline severity of depression. For dysthymia, we found that an 11-week remission response was associated with a higher level of education, being a younger female, lower neuroticism, and less severe comorbid medical illness. The purpose of this study was to examine patient status after the 11-week research treatment trial for minor depression and dysthymia had ended. Unlike the previous work examining remission rates, this is a naturalistic follow-up in which patients decided whether or not to continue, discontinue, or switch the treatment to which they had been randomized. We asked four specific questions: 1) What are the rates of recovery at 25 weeks, following treatment in a randomized controlled trial (RCT)?; 2) What are the rates of remission at 25 weeks for those who were not remitted at

the end of the RCT?; 3) What is the frequency of continuation phase treatment after an acute treatment trial?; and 4) Are initial treatment or patient characteristics associated with recovery or subsequent remission?

2. Methods Our methods have been described in detail elsewhere [1] but are summarized here. The institutional review boards for each participating site approved the study. For patients meeting criteria, a complete description of the study was provided, and written informed consent was obtained. 2.1. Patients and setting Patients aged 18 and older were recruited through referral and screening in four cities (Lebanon, NH, Pittsburgh, PA, San Antonio TX, Seattle, WA) at community, Veterans-Affairs, and academic-affiliated primary care clinics. The four participating centers were chosen for geographic diversity and diversity of clinical populations. To be included, patients needed to have minor depression or dysthymia with three or four of the relevant DSM-IV symptoms of depression, one of which was depressed mood or anhedonia, as assessed by clinical interview and score ⱖ 10 on the 17-item Hamilton Depression Rating Scale [10,25,26]. Depression diagnoses were made by a research psychiatrist or psychologist using the PRIME-MD, a diagnostic instrument designed for use in primary care [25]. Exclusion criteria were the following: recent major depression, psychosis, schizophrenia or schizo-affective disorder, bipolar affective disorder, alcohol or other substance abuse within the past six months, antisocial personality disorder, borderline personality disorder, serious suicidal risk, moderate or severe cognitive impairment (Folstein Mini-Mental State score ⱕ 23) [27], or medical illness with a prognosis of less than six months to live. In addition, patients in current mental health treatment were excluded. A total of 656 patients were randomized. For the purposes of this report, only the 535 (82%) patients who received adequate treatment (ⱖ 4 sessions) were included. This adequate exposure group was used to give clinicians a better estimate of recovery rates for patients who do receive an adequate course of treatment. 2.2. Procedures Patients giving consent were randomly assigned to PSTPC, paroxetine, or placebo. All patients were scheduled for six treatment sessions occurring over eleven weeks. Treatment sessions took place in the general medical setting. For patients assigned to medication, visits occurred at weeks 1, 2, 4, 6, 8 and 11. For patients assigned to PST-PC, the final treatment visit was at 10 weeks instead of 11 to permit any effect of the last treatment session to be demonstrated at the

T. Oxman et al. / General Hospital Psychiatry 23 (2001) 301–310

final 11-week assessment. Medication therapists included general internists (n⫽5) and psychiatrists (n⫽6); visits consisted of medication dose titration, symptom assessment, a review of adverse effects, and general support. Visits were designed to last approximately 15 min. Specific psychological treatments were prohibited as was outside study psychotherapy. Paroxetine and placebo were given in a doubleblind manner. Paroxetine was initiated at 10 mg per day and, if well tolerated, increased at week two to the target dose of 20 mg. At week four or six, the dose could be further increased to 30 mg per day and at week six or eight to 40 mg if there had been limited clinical improvement. Placebo was titrated in an identical manner. Adherence was assessed by patient self-report of missed medication. PST-PC therapists were primarily Ph.D. psychologists (n⫽7) but also included three masters’ level social workers and two masters’ level psychologists. All therapists received training consisting of a two-day course with theory, role-playing in clinical scenarios, and a training videotape. Subsequently, therapists treated at least four training patients for six sessions each, under supervision. Supervision was done by trainer review (Mynors-Wallis or Hegel) of two audiotapes of sessions from each case followed by telephone feedback and discussion. A follow-up one-day course occurred consisting of group reviews of videotaped patient sessions by the therapists. Prior to seeing a study patient, therapists had to be certified as competent in the technique. Certification involved review by Mynors-Wallis of two audiotaped sessions using a competency check-list [28]. PST-PC is based on cognitive-behavioral principles and includes three main steps. First, the patient’s symptoms are linked with their problems in living; second, the problems are defined and clarified; and third, an attempt is made to solve the problems in a structured way [2]. Sessions lasted approximately one hour for the first visit, and 30 min for each subsequent visit. Antidepressant medication and outside study psychotherapy were prohibited. At the end of the treatment trial, patients in the medication arm were told which treatment they had been receiving. Patients who remitted with paroxetine were advised to continue it for six months. Patients desiring to continue paroxetine were given a limited supply to last until their next PCP appointment. Patients who remitted with placebo were informed of the positive nature of their ability to respond and no additional treatment was recommended. Patients who remitted with PST-PC were encouraged to continue using the skills they learned and no further treatment was recommended. PST-PC was not available in the study communities except as part of the treatment trial. Patients who remitted with placebo or PST-PC who still desired to start antidepressants or a different psychotherapy were referred back to their PCP to further discuss these options. Patients who did not remit with any of the three treatments were encouraged to discuss starting a different treatment with their PCP. For all patients, a letter was sent to their PCP

303

describing the diagnosis, response to treatment, and recommendations made for future treatment. 2.3. Measures A modified PRIME-MD [29] was used to make diagnoses. This is a semistructured, interview-administered instrument that provides DSM-IV psychiatric diagnoses in five areas, three of which were used in this study (mood, anxiety, alcohol), modified by additional eligibility questions. Outcome measurements included self-report and interviewer-rated instruments; the latter were completed blind to the patient’s treatment assignment. The primary outcome measure for this study was the 17-item Hamilton Depression Rating Scale (a measure of severity) measured at baseline, 11 and 25 weeks [10]. Sociodemographic and clinical information was collected at baseline. Neuroticism was assessed using the NEO [30]. The NEO Neuroticism Scale consists of 12 self-report items used to assess neuroticism as a personality trait. In previous primary care studies, this scale has predicted persistence of depressive symptoms [31]. Social functioning was assessed using a scale from the Medical Outcomes Short Form 36 (SF-36) [32]. The SF-36 is a multidimensional measure of function developed by the RAND Corporation from the Health Insurance Experiment. This instrument consists of eight scales. The scale scores are converted to a scale from 0 to 100 with 0 representing worst function and 100 best function. The Social Functioning scale consists of two Likert scaled items asking about interference in normal social activities with family, friends, neighbors, or groups. Coexisting medical illness was evaluated by chart review using the Duke Severity of Illness Index (DUSOI) [33]. This index ranges from 0 to 100 with higher scores indicating greater morbidity. The use of psychosocial and psychopharmacologic treatments during the naturalistic follow-up period was assessed using the Care as Usual Treatment form, a 20-item, “yes/ no” self-report questionnaire developed for the treatment trial to determine use of psychosocial and psychotropic treatments for depression and anxiety. For this study, two categorical variables were used: 1) one or more prescriptions for any antidepressant drug between weeks 11 and 25; 2) one or more visits with a psychiatrist or counselor for individual therapy between weeks 11 and 25. The small number of patients who were using both were counted in the antidepressant group. 2.4. Data analysis Treatment outcome was based on a categorization of the HAMD rating scale and duration. Patients were initially classified as remitters (score ⱕ6) or nonremitters at Week 11 [9]. Recovery was then defined as a combination of

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T. Oxman et al. / General Hospital Psychiatry 23 (2001) 301–310

Table 1 25-Week Status (HAMDⱕ6) for 428 subjects with adequate treatment trial exposure and completed 25 wk assessments, separated by diagnosis and 11week remission status (HAMDⱕ6) Minor depression

Treatment groups

11 Week remission status

Placebo

Paroxetine

Remitted n⫽40 Status @ 25 Wks Recovered n % Remitted n %

Non-remitted n⫽28

29 73%

Remitted n⫽38

PST-PC Non-remitted n⫽26

32 84% 11 39% ␹2⫽7.50 p⫽.006

Dysthymia

Treatment groups

11 Week remission status

Placebo Non-remitted n⫽42

22 69%

11 42% ␹2⫽12.29 p⫽.001

Non-remitted n⫽33

Remitted n⫽113

Non-remitted n⫽87

86 76% 10 30% ␹2⫽11.50 p⫽.001

32 37% ␹2⫽31.42 p⫽.001 Total

Remitted n⫽46

PST-PC Non-remitted n⫽28

30 65% 12 29% ␹2⫽11.81 p⫽.001

Remitted n⫽35

25 71%

Paroxetine

Remitted n⫽32 Status @ 25 Wks Recovered n % Remitted n %

Total

Remitted n⫽44

Non-remitted n⫽36

31 70% 8 29% ␹2⫽9.36 p⫽.002

symptom severity (HAMD ⱕ6) and duration (status at Week 25). Analyses were performed based on an adequate treatment exposure subgroup, defined as completing at least four treatment sessions. Initially, 25-week recovery was examined as an effect of remission status at Week 11, stratified by diagnosis and randomized treatment assignment. We then examined the naturalistic use of depression treatments after the end of the 11-week treatment trial, stratified by the same categories. Because this was a naturalistic study, we then examined HAMD status at the end of six months, regardless of remission status at the end of the treatment trial. Bivariate relationships were tested between 25-week HAMD status (HAMD ⱕ 6 versus ⬎ 6) and design variables (site, treatment, age group), moderating variables (demographics, medical comorbidity, social function, neuroticism), and mediating variables (post trial use of antidepressants or psychotherapy). ␹2 analyses with corrections for continuity were used for categorical predictors of treatment assignment, site, age cohort, gender, education, income, ethnicity, antidepressant use, and psychotherapy use. T-tests were used for the DUSOI, NEO neuroticism scale, and baseline SF-36 Social function scale. Variables with bivariate relationships to 25-week status of Pⱕ.10 were included in two separate logistic regression models (one for each diagnosis)

Remitted n⫽122

Non-remitted n⫽106

83 68% 13 36% ␹2⫽944 p⫽.002

33 31% ␹2⫽30.90 p⫽.001

as predictors of 25-week status. Because of the design of the study, three design terms were entered into the models regardless of statistical significance: site (dummy coded into three variables with the Lebanon, NH cite as the reference group, age cohort (18 –59 vs. 60⫹), and treatment group (two dummy coded variables with placebo as the reference group). 3. Results The adequate treatment sample consisted of 430 patients, 201 patients with minor depression and 229 patients with dysthymia. A total of 105 patients were not used in the analyses because of missing Week 25 Hamilton Depression ratings. Patients who were included in the analyses were compared to those not included on study design variables, demographic variables and clinical variables. There was only one significant difference. Patients with dysthymia who were excluded had a lower mean DUSOI score (less medical comorbidity) than those included (t⫽2.01, df 60,218, P⫽.05). Table 1 shows the rates of 25-week recovery separated by treatment group and 11-week remission status for each diagnostic group. Two patients were missing 11-week HAMD scores and had to be excluded from this cross-

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305

Table 2 25-Week status (HAMDⱕ6) for 428 adequate exposure treatment trial subjects & naturalistic use of depression treatments after the trial during 14 week follow-up Minor depression

Treatment groups

11 Week status

Placebo Remitted n⫽40

F/U treatments & 25-week status Antidepressant Recovered Remitted Psychotherapy only Recovered Remitted None Recovered Remitted

7 5 (71%) 3 1 (33%) 30 23 (77%)

Paroxetine Non-remitted n⫽28

Remitted n⫽38

11

11 11 (100%)

6 (55%) 3 0 (0%) 14

0 0 (0%) 27 21 (78%)

5 (36%)

Dysthymia

Treatment groups

11 Week status

Placebo Remitted n⫽32

F/U treatments & 25 week status Antidepressant Recovered Remitted Psychotherapy only Recovered Remitted None Recovered Remitted

Total

2 2 (100%) 3 2 (67%) 27 18 (67%)

PST-PC Non-remitted n⫽26 3 3 (100%) 3 1 (33%) 20

2 1 (50%) 28 21 (75%)

Non-remitted n⫽33

Remitted n⫽113

Non-remitted n⫽87

10

23 19 (83%)

24

3 (30%) 2 1 (50%) 21

5 2 (40%) 85 65 (76%)

6 (29%)

12 (50%) 8 2 (25%) 55 18 (33%)

Total

Non-remitted n⫽42

Remitted n⫽46

12

19 14 (74%)

1 (50%) 28

5 3 (60%)

7 (35%)

Paroxetine

3 (25%) 2

Remitted n⫽35

0 0 (0%) 27 16 (59%)

8 (29%)

tabulation. The majority of patients who were in remission at the end of the 11-week treatment trial were also recovered at 25 weeks. This relationship between 11-week remission status and 25-week recovery was significant and similar for each of the three treatment groups across both diagnoses (ranging from 71% to 84% for minor depression and 65% to 70% for dysthymia). At the same time, a substantial minority of subjects who were not in remission at the end of the 11-week treatment trial went on to achieve remission at 25 weeks (ranging from 30% to 42% for minor depression and 29% to 36% for dysthymia). Without knowing what treatments were naturalistically used after the treatment trial, it is not possible to attribute 25-week status to the randomized treatment assignment during the trial. Table 2 shows the use of reported treatments following the treatment trial. A minority of patients who were not remitted at 11 weeks chose active treatment during the follow-up period (32/87 or 37% for minor depression and 29/106 or 27% for dysthymia). Similarly, a relatively low number of patients who did remit at 11 weeks used antidepressants or saw a mental health professional during the follow-up period (28/113 or 25% for minor depression and 32/122 or 26% for dysthymia). Patients in all

PST-PC Non-remitted n⫽28 6 2 (33%) 0 0 (0%) 22 6 (27%)

Remitted n⫽44 4 4 (100%) 4 4 (100%) 36 23 (64%)

Non-remitted n⫽36 5 1 (20%) 4 2 (50%) 27 10 (37%)

Remitted n⫽122

Non-remitted n⫽106

25 20 (80%)

23

7 6 (86%) 90 57 (63%)

6 (26%) 6 3 (50%) 77 24 (31%)

groups who chose an active treatment during the follow-up period were more likely to receive an antidepressant than psychotherapy. For minor depression patients who were remitted at 11 weeks there appears to be little benefit of a follow-up treatment compared to no follow-up treatment for 25-week status. Although the numbers are small for dysthymic patients who were remitted at 11 weeks, there appears to be some advantage for engaging in an active treatment compared to none. Because treatment assignment was not significantly related to 25-week recovery, and because the use of active treatments during the follow-up period was low, we examined the relationship of patient characteristics to 25-week status. Table 3 shows the bivariate relationships. For minor depression, baseline characteristics of better SF-36 Social Function and lower NEO neuroticism were significantly associated with status at 25 weeks. In addition, there were a small number of patients engaged in psychotherapy (n⫽13), and among these a HAMD ⱕ 6 at 25 weeks was less likely. For dysthymia, there was a significant site effect with patients at one site (Lebanon, NH) having significantly higher rates of good 25-week status (HAMD ⱕ6). Design and demographic characteristics of younger age cohort, female

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Table 3 Bivariate relationship of design and patient characteristics to 25-week status (HAMDⱕ6) Minor depression

Treatment: Paroxetine PST-PC Placebo Site: Lebanon Pittsburgh San Antonio Seattle Age cohort: 18–59 years ⱖ60 years Gender: Female Male Education: Less than high school 0 High school or greater 1 Income: Lower 0 Higher 1 Ethnicity: Caucasian Non-caucasian Antidepressant after study Yes No Psychotherapy after study Yes No Duke severity of illness SF-36 social function Neuroticism

Dysthymia

HAMDⱕ6

HAMD⬎6

n

%

n

%

43 35 40

67% 51% 58%

21 33 29

33% 49% 42%

38 20 15 45

69% 54% 44% 60%

17 17 19 30

31% 46% 56% 40%

45 73

64% 56%

25 58

36% 44%

67 51

61% 55%

42 41

39% 45%

40 78

56% 60%

32 51

44% 40%

46 68

56% 60%

36 46

44% 40%

100 16

60% 48%

17 66

52% 40%

31 87

66% 56%

16 67

34% 44%

31% 61% SD 13.44 26.36 0.48

9 74 Mean 21.93 53.16 2.80

69% 39% SD 13.63 25.22 0.46

X2

3.383

5.84

1.379

0.749

0.459

0.247

1.565

1.33

4.45* 4 114 Mean 18.74 66.67 2.55

t-test 1.632 3.634 3.716

p(X2)

HAMDⱕ6

HAMD⬎6

n

n

%

0.184 38 44 34

51% 55% 46%

37 36 40

49% 45% 54%

44 13 21 38

72% 43% 35% 49%

17 17 39 40

28% 57% 65% 51%

50 66

61% 45%

32 81

39% 55%

63 53

57% 45%

47 66

43% 55%

45 71

47% 54%

51 61

53% 46%

55 59

46% 55%

64 49

54% 45%

102 14

55% 32%

83 30

45% 68%

26 90

54% 50%

22 91

46% 50%

0.121

0.240

0.387

0.498

0.619

0.211

0.249

0.043

p(t) 0.1044 0.0004 0.0003

9 107 Mean 18.68 61.74 2.77

69% 50% SD 12.95 25.02 0.46

4 108 Mean 25.39 57.21 2.80

X2

p(X2)

%

31% 50% SD 13.25 23.69 0.48

1.261

0.532

17.899

0.001

5.443

0.020

3.709

0.054

1.063

0.303

1.602

0.206

7.732

0.005

0.300

0.584

1.108

0.292

t-test 3.789 1.397 0.4711

p(t) 0.0002 0.1637 0.638

* Fisher’s exact test.

gender and Caucasian race were also associated with higher rates of good 25-week status in dysthymia. In addition, the baseline patient characteristics of lower medical comorbidity (DUSOI overall score) was significantly associated with 25-week status. Because of missing data, the logistic regression models were based on 193 patients with minor depression (Table 4) and 219 patients with dysthymia (Table 5). In the model for minor depression, because of the small number of subjects receiving psychotherapy after the treatment trial, this variable was not included and the overall results were not changed. Better baseline social function and lower neuroticism were associated with the 25-week status. In the final model for dysthymia only site was significantly associated with 25-week status, although there was a trend for lower severity of medical comorbidity to be associated with 25-week status. Age cohort, gender and ethnicity, which were all significant in bivariate analyses, were no longer significant.

4. Discussion In examination of recovery status at 25 weeks for those who were in remission at the end of the treatment trial, 76% of patients with minor depression and 68% of patients with dysthymia met recovery criteria. The strong relationship of 11-week remission to 25-week status is similar to what is reported for major depression [34] and for psychiatric patients with chronic depression (dysthymia or major depression) [35]. In combining patients regardless of remission status at the end of the treatment trial, we found that 59% of patients with minor depression and 51% with dysthymia had a good symptom response (HAMD ⱕ 6) at 25 weeks. These rates were quite similar to the 11-week remission rates at the end of the treatment trial, 54% and 52%, respectively. The similarity in 25-week status across treatment groups in each diagnosis suggests that, contrary to our expectation, there was not a difference in longer-term (three month) posttreatment effect of PST-PC compared to the other two

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Table 4 Minor depression (n⫽193) logistic regression for 25-week status (HAMDⱕ6) Variable Site* Pittsburgh San Antonio Seattle Treatment group** Paroxetine PST-PC Younger age group SF36 social function, baseline DUSOI, baseline NEO, baseline

B

Wald’s chi-square

df

p

Adjusted OR

95% CI

⫺0.465 ⫺0.774 ⫺0.338

0.698 1.846 0.547

1 1 1

0.403 0.174 0.460

0.628 0.461 0.713

0.211–1.870 0.151–1.409 0.291–1.747

⫺0.583 ⫺0.046 ⫺0.175 0.016 ⫺0.019 ⫺1.102

2.118 0.015 0.178 6.669 1.994 9.329

1 1 1 1 1 1

0.146 0.904 0.673 0.010 0.158 0.002

1.791 0.955 0.840 1.085 0.909 0.802

0.817–3.927 0.452–2.018 0.373–1.889 1.020–1.154 0.796–1.038 0.696–0.924

* Lebanon is the comparison group; ** Placebo is the comparison group.

treatments. Given that a very low proportion of primary care patients were motivated to continue or start antidepressants or psychotherapy after the treatment trial it is also possible that few patients were motivated to practice or use the skills they learned in PST-PC. 4.1. Treatment after trial The low rate of antidepressant treatment after the trial is disappointing. This rate is consistent with the low rates of antidepressant drug adherence generally in primary care. For example, Lin et al. [11] reported that 28% of patients stop taking antidepressants during the first month of therapy and 44% by the third month. Although the numbers are small, our results suggest this may be more important in dysthymia than in minor depression. By the definition of dysthymia, continuation and maintenance treatment should be particularly important to prevent relapse and recurrence. Devanand et al., [36] for example, found that in a small sample of responders to fluoxetine, 50% discontinued the antidepressant during a 24-week follow-up and half of these relapsed. Similarly, Hellerstein et al. [37] found that in

Table 5 Dysthymia (n⫽219) logistic regression for 25-week status (HAMDⱕ6) Variable Site* Pittsburgh San Antonio Seattle Treatment group** Paroxetine PST-PC Younger age group Caucasion Sex DUSOI, baseline

B

Wald’s df p chi-square

Adjusted 95% CI OR

⫺0.898 2.717 ⫺1.223 5.986 ⫺0.898 4.744

1 0.099 0.407 1 0.144 0.294 1 0.029 0.407

0.140–1.185 0.111–0.784 0.182–0.914

0.126 0.566 ⫺0.114 0.644 ⫺0.457 ⫺0.023

1 1 1 1 1 1

0.555–2.318 0.870–3.566 0.400–1.992 0.839–4.323 0.340–1.177 0.790–1.008

0.120 2.477 0.077 2.369 2.085 3.476

0.730 0.116 0.781 0.124 0.149 0.062

1.134 1.762 0.892 1.904 0.633 0.891

* Lebanon is the comparison group; ** Placebo is the comparison group.

patients with dysthymia who remained on antidepressants over a 40-week period, only 17.4% relapsed. During the RCT phase of the present study, with six scheduled visits and pill counts, patients reported taking 96% of scheduled doses [3]. At the end of the RCT, patients who responded to paroxetine were advised of the recommendation to continue the medication for six months but to consult with their primary care physician. They were given enough medication to last until an appointment could be scheduled. Patients who did not respond to a treatment were also strongly encouraged to consult with their primary care physician for an alternative treatment recommendation. These instructions were not followed or implemented. These findings suggest that research studies obtain better treatment initiation and adherence than usual care [38,39] and that relapse is more likely once participation in a research study is completed [40]. Continuing PST-PC is different than continuing pharmacotherapy. The goal of PST-PC is to give patients skills they can continue to use on their own. For successful PST-PC we would want there to be a lower rate of entering into any therapy after completing the initial course. The fact that there was no difference among the treatment arms in the use of any type of therapy after the treatment trial, suggests this marker of success was probably not met. 4.2. Predictors of recovery Of particular interest in this study are the smaller but similar proportions of patients that moved from remission at 11 weeks to nonrecovered at 25 weeks or that moved from nonremission at 11 weeks to remission at 25 weeks. The similar proportions across treatment groups in each diagnosis suggest that patient characteristics may be more important predictors of 25-week status in primary care patients with dysthymia or minor depression. Such predictors may prove helpful in cost-effective targeting of active maintenance and relapse prevention treatments. Of the predictors examined in this study, patient characteristics were signifi-

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cant only for minor depression. Better baseline social function and less neuroticism were associated with 25-week status for patients with minor depression but not dysthymia. In previous work with older patients, we found that higher levels of perceived adequacy of social support was associated with less frequent occurrence of depression [41, 42] and better outcomes for patients receiving placebo [43]. Social function is not the same construct as social support, but it is highly related. Impaired social functioning in minor depression is in large part due to depression and improves with depression treatment [44]. Among personality traits, neuroticism is the trait that has most consistently been associated with predicting new episodes of major depressive disorder [45– 47]. Thus it should not be surprising that low baseline neuroticism was associated with a better 25-week status for minor depression as well. Moreover, enduring personality traits, such as neuroticism may be associated with higher numbers of adverse life events, increased reactivity to those events, and relapse rates of depressive episodes [23]. Neuroticism can also lead to smaller, less supportive networks [48]. What is perhaps more surprising is the lack of association between neuroticism and dysthymia. It is possible that this was due to more homogeneity with higher neuroticism in the dysthymia group compared to the minor depression group (25.3 ⫾ 7.9 vs. 22.9 ⫾ 7.3, t⫽3.21, P⫽.001). There may be different groups of minor depression analogous to different groups of dysthymia and these two groups may have been better represented in the minor depressives than the dysthymic disorder group. One group may be more like early onset dysthymia with higher neuroticism and poorer social function, and thus copes less well to personal and social stressors. Another group, may have later onset, a different biological susceptibility to depression or be experiencing more severe stressors. In future research, greater attention to number of episodes and time of onset could be helpful. It is also possible that state effects differentially contaminate personality trait assessment in these two subtypes of depression [49,50]. Initially surprising was the negative relationship between post-trial participation in psychotherapy for minor depression and lower likelihood of 25-week HAMD ⱕ 6. This involves a relatively small number of subjects. Only 13 (6%) of the minor depressives were involved in psychotherapy after the study, similar to the 6% of dysthymics involved in psychotherapy after the trial. It is likely that the minor depressives in post-trial psychotherapy had more complex psychosocial stressors or comorbid psychiatric diagnoses. Patients with more refractory symptoms or comorbid psychiatric conditions may be the ones most likely to seek or use more treatment. In addition, we cannot verify the quality of the psychotherapy or counseling in this naturalistic study. At the least, however, this finding reinforces the absence of a delayed positive effect from ProblemSolving Treatment.

4.3. Limitations There are a variety of limitations to this study. Most important is that it was a naturalistic follow-up of an acute phase treatment trial and not a randomized maintenance trial. The follow-up was relatively short. Also there was a substantial drop out rate (24%) and persons without 11week remission were less likely to be seen in follow-up. Information regarding how frequent patients followed-up with their PCP and what happened during those interviews was not available. Nevertheless, this was the first multi-site, primary care treatment trial for these conditions and the naturalistic follow-up is helpful in planning future trials. 4.4. Implications The clinical conceptualization of recovery is to raise the possibility that treatment can be discontinued, or alternatively, the consequences of relapse if treatment is discontinued [9]. Overall, these results demonstrate that naturalistic treatment initiation and adherence are relatively poor after participation in a research project with its increased resources designed to achieve high adherence. Methods to improve treatment adherence or to change failed treatments in usual care are clearly indicated. Agreeing to treatment and adherence to it are influenced by multiple factors including intentional and sometimes justified decisions. These decisions are informed, or misinformed, by illness beliefs, side effects, treatment costs, symptom relevance, and culture [51]. Just imparting knowledge, such as informational pamphlets or a letter to the PCP about the importance of continuation treatment adherence, is an insufficient method to address these factors. Some interaction with the primary care provider or his/her surrogate is necessary [52]. Several studies that have integrated a nurse [53,54], case manager [55], or mental health specialist [56,57] into the care of depression in primary care have also shown improved treatment initiation and adherence in acute and continuation phases of treatment. For depression treatment in primary care to be truly effective, we need to learn how to transfer the techniques of clinical trials into usual care in a cost-effective manner. One component of applying these techniques in a cost-effective fashion is to identify consistent, easy to assess patient characteristics to help target increased mental health resources to patients most likely to benefit from these techniques.

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