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ORIGINAL CONTRIBUTION

Treatment of Dysthymia and Minor Depression in Primary Care A Randomized Controlled Trial in Older Adults John W. Williams, Jr, MD, MHS James Barrett, MD Tom Oxman, MD Ellen Frank, PhD Wayne Katon, MD Mark Sullivan, MD John Cornell, PhD Anjana Sengupta, PhD

A NTIDEPRESSANTS AND DEPRES- sion-specific psychothera- pies are clearly effective for major depression.1 Treat-

ments for major depression have been proved effective in both mental health specialty and primary care settings and in young and older adults.2-5 However, the effectiveness of treatments for less se- vere depressive disorders, particularly in older primary care patients with coex- isting medical illnesses, is less certain.4

Recent literature syntheses concluded that there is insufficient evidence to rec- ommend pharmacotherapy for minor de- pression. Evidence was also insufficient to recommend psychotherapy for ei- ther minor depression or dysthy- mia.4,6,7 This knowledge gap is particu- larly problematic because the prevalence of less severe depressive disorders ex- ceeds that of major depression, leaving primary care clinicians without evidence- based treatment recommendations for the majority of their depressed pa- tients.5,8,9

Author Affiliations and Financial Disclosure are listed at the end of this article. Corresponding Author and Reprints: John W.

Williams, Jr, MD, MHS, Ambulatory Care (11C-6), 7400 Merton Minter Blvd, San Antonio, TX 78284 (e-mail: [email protected]).

Context Insufficient evidence exists for recommendation of specific effective treat- ments for older primary care patients with minor depression or dysthymia.

Objective To compare the effectiveness of pharmacotherapy and psychotherapy in primary care settings among older persons with minor depression or dysthymia.

Design Randomized, placebo-controlled trial (November 1995–August 1998).

Setting Four geographically and clinically diverse primary care practices.

Participants A total of 415 primary care patients (mean age, 71 years) with minor depression (n = 204) or dysthymia (n = 211) and a Hamilton Depression Rating Scale (HDRS) score of at least 10 were randomized; 311 (74.9%) completed all study visits.

Interventions Patients were randomly assigned to receive paroxetine (n = 137) or placebo (n=140), starting at 10 mg/d and titrated to a maximum of 40 mg/d, or problem- solving treatment–primary care (PST-PC; n=138). For the paroxetine and placebo groups, the 6 visits over 11 weeks included general support and symptom and adverse effects monitoring; for the PST-PC group, visits were for psychotherapy.

Main Outcome Measures Depressive symptoms, by the 20-item Hopkins Symp- tom Checklist Depression Scale (HSCL-D-20) and the HDRS; and functional status, by the Medical Outcomes Study Short-Form 36 (SF-36) physical and mental components.

Results Paroxetine patients showed greater (difference in mean [SE] 11-week change in HSCL-D-20 scores, 0.21 [0.07]; P = .004) symptom resolution than placebo pa- tients. Patients treated with PST-PC did not show more improvement than placebo (difference in mean [SE] change in HSCL-D-20 scores, 0.11 [0.13] ; P = .13), but their symptoms improved more rapidly than those of placebo patients during the latter treat- ment weeks (P = .01). For dysthymia, paroxetine improved mental health functioning vs placebo among patients whose baseline functioning was high (difference in mean [SE] change in SF-36 mental component scores, 5.8 [2.02]; P = .01) or intermediate (difference in mean [SE] change in SF-36 mental component scores, 4.4 [1.74]; P = .03). Mental health functioning in dysthymia patients was not significantly improved by PST-PC compared with placebo (P$.12 for low-, intermediate-, and high-functioning groups). For minor depression, both paroxetine and PST-PC improved mental health function- ing in patients in the lowest tertile of baseline functioning (difference vs placebo in mean [SE] change in SF-36 mental component scores, 4.7 [2.03] for those taking par- oxetine; 4.7 [1.96] for the PST-PC treatment; P = .02 vs placebo).

Conclusions Paroxetine showed moderate benefit for depressive symptoms and men- tal health function in elderly patients with dysthymia and more severely impaired el- derly patients with minor depression. The benefits of PST-PC were smaller, had slower onset, and were more subject to site differences than those of paroxetine. JAMA. 2000;284:1519-1526 www.jama.com

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Dysthymia is a chronic depressive dis- order, characterized by functional im- pairment and at least 2 years of depres- sive symptoms.10 Minor depression is a less chronic illness than dysthymia, with fewer symptoms than major depres- sion, but it is associated with signifi- cant functional impairment and in- creased health care use.11-14 Psychological treatments are a particularly attractive option in the elderly since many pa- tients prefer such treatments, and they avoid drug interactions.15 In addition, brief psychotherapies that can be deliv- ered in primary care are needed be- cause many older adults are unlikely to accept or follow-through on referrals to specialty mental health settings. Never- theless, pharmacotherapy remains the most common treatment modality, in part because primary care clinicians are more comfortable treating with antide- pressants than engaging in psycho- therapy.16 Since antidepressant medica- tions are the number 1 or 2 pharmacy costs for many health plans, data that better define the patient groups in which they are useful would have important policy implications.

To address the lack of evidence on how to treat these disorders, we con- ducted an 11-week, multicenter, ran- domized controlled trial. We com- pared the effectiveness of placebo plus clinical management with paroxetine, a member of the most widely pre- scribed antidepressant drug class, and Problem-Solving Treatment–Primary Care (PST-PC), a behaviorally based psychotherapy designed specifically for primary care.17-19 The study focuses on older primary care patients with dysthymia or minor depression and u s e s b r o a d i n c l u s i o n c r i t e r i a t o improve its applicability in primary care settings.

METHODS Our methods have been described in de- tail elsewhere19and summarized briefly herein. The institutional review boards for each participating site approved the study. Patients gave written informed consent.

Patients and Setting Patients aged 60 years or older were re- cruited through referral and screening at community, Veterans Affairs, and aca- demic-affiliated primary care clinics. The 4 participating centers were chosen for geographic diversity and diversity of clinical populations. Eligible patients met Diagnostic and Statistical Manual of Men- tal Disorders, Revised Third Edition (DSM- III-R) criteria10 for dysthymia or crite- ria for minor depression and scored 10 or higher on the 17-item Hamilton De- pression Rating Scale (HDRS).20,21 Cri- teria for minor depression were adapted from the DSM-IV research criteria. We required symptoms for at least 4 weeks rather than 2 weeks, and 3 or 4 symp- toms, rather than 2 to 4 symptoms. A past history of major depression was not an exclusion criterion. Depression diagnoses were made by a research psychiatrist or psychologist using the Primary Care Evaluation of Mental Dis- orders (PRIME-MD), a diagnostic in- strument designed for use in primary care.21 Patients were excluded for: ma- jor depression, psychosis, schizophre- nia or schizo-affective disorder, bipo- lar affective disorder, alcohol or other substance abuse within the past 6 months, antisocial personality disor- der, borderline personality disorder, se- rious suicidal risk, moderate or severe cognitive impairment (Folstein Mini- Mental State Examination score #2322), and medical illness with a prognosis of less than 6 months to live. In addition, patients in current treatment were ex- cluded, with an exception for patients willing to discontinue treatment who were taking 50 mg or less of amitripty- line or its equivalent.

Design Patients were randomly assigned to pla- cebo, paroxetine, or PST-PC. Random- ization was blocked and stratified by site and diagnosis using a computer- generated random allocation table. The coordinating center created consecu- tively numbered envelopes containing concealed assignment codes that were as- signed sequentially to eligible patients by a research associate. To preserve blind-

ing, treatment assignments were held by the study statistician.

Treatment All patients were scheduled for 6 treat- ment sessions over 11 weeks. Treat- ment sessions took place in the general medical setting. For patients assigned to receive medication, visits occurred at weeks 1, 2, 4, 6, 8, and 11. For patients assigned to receive PST-PC, the final treatment visit was at 10 weeks instead of 11 weeks to permit any effect of the last treatment session to be demon- strated at the final 11-week assessment. Medication therapists included general internists and psychiatrists; visits con- sisted of medication dose titration, symp- tom assessment, a review of adverse ef- fects, and general support. Visits were designed to last approximately 15 min- utes. Specific psychological treatments were prohibited. Identically appearing tablets containing paroxetine or pla- cebo were given in a double-blind man- ner. Paroxetine was initiated at 10 mg/d and, if well tolerated, was increased at week 2 to the target dose of 20 mg/d. At week 4 or 6, the dose could be in- creased to 30 mg/d and at week 6 or 8 to 40 mg/d for patients who showed par- tial or no improvement. Placebo was ti- trated in an identical manner. At each visit, patients self-reported medication adherence.

The PST-PC therapists included 7 psy- chologists with doctorates of philoso- phy and 3 social workers and 2 coun- selors with a master’s degree. All therapists received a treatment manual and training consisting of a short theo- retical course, role playing in a clinical setting, and watching a training video- tape. Subsequently, therapists treated at least 4 “practice” patients. Prior to see- ing a study patient, therapists had to be certified as competent in the technique (Mark Hegel, PhD, unpublished data, 1999). The PST-PC technique is based on cognitive-behavioral principles and includes 3 main steps: (1) the patient’s symptoms are linked with their prob- lems in living; (2) the problems are de- fined and clarified; and (3) an attempt is made to solve the problems in a struc-

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tured way.18 Sessions lasted approxi- mately 1 hour for the first visit, and 30 minutes for each subsequent visit. Antidepressant medication use was pro- hibited.

Assessments Sociodemographic and clinical infor- mation was collected at baseline. Co- existing medical illness was evaluated by physician chart review using the Duke Severity of Illness Index.23 This index ranges from 0 to 100 with higher scores indicating greater morbidity. In addition, chronic medical conditions were categorized by organ systems us- ing International Classification of Dis- eases, Ninth Revision (ICD-9) classifi- cation (eg, respiratory, endocrine, cardiovascular, etc).10,24

Outcome measurements included self- report and interviewer-rated instru- ments. Raters who were blinded to the patient’s treatment assignment and not involved in patient assignments or treat- ment scored the latter instruments. The primary outcome measure was a 20-item self-report scale consisting of the 13 items from the Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and 7 additional depression-related items added to increase responsiveness.25,26 Items were averaged, yielding a continuous score ranging from 0 to 4 with higher scores indicating more severe symptoms. The HSCL-D-20 was administered at base- line and at each follow-up visit. In addi- tion, the 17-item HDRS (a measure of severity) and the Medical Outcomes Study Short-Form 36 (SF-36) (a mea- sure of functional status) were rated at baseline and at 6 and 11 weeks.20,27-29

Data Analysis For continuous demographic and clini- cal data, parametric and nonparamet- ric analysis of variance was used to ana- lyze baseline differences across site, diagnostic group, and treatment assign- ment. Stratified contingency table analy- ses were used to analyze baseline dif- ferences in categorical patient variables.

Treatment efficacy was based on an assessment of 4 outcome measures: HSCL-D-20 depression scale, the HDRS,

and the SF-36 mental and physical com- ponent scores. Analyses were per- formed using an intent-to-treat prin- ciple that included all randomized patients and using an adequate treat- ment exposure subgroup, defined as completing at least 4 treatment ses- sions. The adequate exposure analysis was performed to give clinicians a bet- ter estimate of treatment effects for patients who receive an adequate course of treatment. Both HSCL-D-20 and SF-36 measures were treated as continuous response measures. For the HDRS, patients were classified as remitters (score ,7) or nonremitters at week 11.30

The HSCL-D-20 was analyzed using a nonlinear piecewise random coeffi- cient model with 2 random intercepts and a random slope fit to the individual patient data.31,32 Random intercepts were defined at baseline and week 2. The sec- ond random intercept at week 2 en- abled us to model a nonlinear response to treatment. Treatment effects were evaluated by comparing the slopes of the fitted function from weeks 2 through 11. Restricted maximum likelihood estima- tion was used to fit the random coeffi- cients model to the data.33 Subgroup analyses were performed for each diag- nostic group. A generalized linear model with binomial response and logit link function was used to analyze the HDRS remission data. Six-week assessments were used for patients who discontin- ued treatment and were unavailable at the 11-week follow-up; complete data were available for 323 subjects (95.6%). Mixed-model analysis of covariance was used to analyze the SF-36 mental and physical component scores. Baseline SF-36 mental and physical component scores served as covariates in each re- spective analysis. Because baseline men- tal component scores interacted signifi- cantly with treatment assignment and diagnosis, these results are presented by tertiles of baseline functioning.

RESULTS Patient Enrollment and Characteristics

Of the 629 patients who were as- sessed, 415 (66.0%) were eligible and

randomized. Among the 214 patients assessed but not randomized, 17 (7.9%) were eligible but refused participation and 197 (92.1%) were ineligible (FIGURE 1). The most common rea- sons for ineligibility were no depres- sion diagnosis (n = 59), major depres- sion (n = 58), and depression with an HDRS score of less than 10 (n = 43). No patients were excluded because of se- vere coexisting medical illness with lim- ited life expectancy.

Patients were randomized to receive paroxetine (n = 137), PST-PC (n = 138), or placebo (n = 140). Sociodemo- graphic and clinical characteristics were similar for the 3 treatment groups (TABLE 1). The average age of partici- pants was 71 years (range, 60-93 years), 172 (41.5%) were women, and 90 (21.8%) were from minority ethnic groups. Patients averaged 3.4 chronic medical conditions and scored a mean (SD) of 24.4 (12.8) on the Duke Sever- ity of Illness Scale. The most common systems affected by illness were cardio- vascular in 294 patients (70.8%), endo- crine in 239 (57.6%), musculoskeletal in 194 (46.8%), and gastrointestinal in 123 (29.6%). Comorbid anxiety disor- ders were present in 121 participants (29.2%). Of the 415 subjects, 211 (51%) met criteria for dysthymia with the re- maining 204 (49%) meeting criteria for minor depression. At baseline, depres- sion severity was mild to moderate as shown by a median HDRS score of 13 (interquartile range, 12-15) and an HSCL-D-20 score of 1.4 (interquartile range, 0.9-1.9). Mental health function- ing (median, 38.9; interquartile range, 32.4-45.1) and physical functioning (median, 37.4; interquartile range, 29.3- 47.5) were markedly impaired. At base- line, patients with dysthymia and mi- nor depression had similar levels of impairment on all scales.

Treatment Received and Follow-up Of 415 patients randomized, 338 (81.4%) attended at least 4 treatment sessions, the minimum number con- sidered to be an adequate test of treat- ment efficacy (Figure 1). A total of 311 (74.9%) completed all scheduled treat-

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ment sessions. Patients discontinued treatment for the following reasons: ad- verse effects (n = 20, 4.8%) and medi- cal illness (n = 8, 1.9%); 33 patients (7.7%) dropped out after randomiza- tion and did not attend any treatment sessions. Drop-out rates and reasons for discontinuation did not differ signifi- cantly between treatment groups.

Adherence to paroxetine and pla- cebo was high. Patients reported tak- ing 96% of scheduled doses. By the sec- ond treatment visit, 194 (77.0%) of 252 patients initiating treatment achieved the target dose of 20 mg/d, and by study end 228 (90.5%) had achieved the tar- get dose. Seventy-three patients (55.3%) randomized to receive placebo were in- creased to tablets equivalent to 30 mg/d or more vs 43 (35.8%) who were tak- ing paroxetine (P,.01). Treatment at- tendance was high among those as- signed to the PST-PC therapy. Of those beginning treatment, 108 (83.1%) of 130 patients completed all 6 treat- ment sessions.

Outcomes: Intent to Treat The primary outcome measure, speci- fied a priori, was the change in depres- sive symptoms on the HSCL-D-20 score. All groups showed improve- ment over the 11-week treatment pe- riod, with mean (SE) HSCL-D-20 scores decreasing by an average of 0.61 (0.05) points for patients taking paroxetine, 0.52 (0.05) for those receiving PST- PC, and 0.40 (0.05) for those taking pla- cebo and receiving clinical manage- ment. In the intent-to-treat analysis, paroxetine was more effective than pla- cebo (difference in mean (SE) change at 11 weeks, 0.21 [0.07]; P=.004). Those in the PST-PC therapy did not differ sig- nificantly from placebo (difference in mean [SE] change in scores, 0.11 [0.13]; P = .13) or from paroxetine (dif- ference in mean [SE] change in score, 0.09 [0.07]; P = .17). The rate of symp- tom resolution was similar and rapid during the first 2 weeks of treatment, slowing and diverging during weeks 2 through 11 (FIGURE 2). Compared with

placebo, paroxetine showed a greater rate of symptom resolution during weeks 2 through 11. Although the over- all mean improvement in symptoms for PST-PC did not differ from placebo, those in the PST-PC therapy showed more rapid symptom resolution dur- ing weeks 2 through 11 (P = .01). De- pression diagnosis did not interact with treatment (P = .36), indicating a simi- lar effect for dysthymia and minor de- pression (FIGURE 3 and FIGURE 4). The interaction term for clinical site and treatment was not significant, indicat- ing similar effects across sites (P = .25).

Treatment effects on mental health functioning were complex, varying by diagnosis and baseline functioning (TABLE 2). For patients with dysthy- mia, mental health functioning im- proved by a mean (SE) of 5.8 (2.02) points more among those taking par- oxetine than those taking placebo (P = .01) in patients at the highest ter- tile of baseline functioning, and by a mean (SE) score of 4.4 (1.74) points (P = .03) in those with intermediate baseline functioning. A 5-point differ- ence on this scale is considered clini- cally significant.34 For dysthymia pa- tients treated with PST-PC, mental health function did not improve sig- nificantly more than those receiving pla- cebo. Both paroxetine and PST-PC ben- efited mental health functioning in patients with minor depression in the lowest tertile of baseline functioning by a mean (SE) score of 4.7 (1.96) points for those treated with PST-PC and 4.7 (2.03) for those taking paroxetine com- pared with those taking placebo (P = .02). Compared with placebo, treat- ment with paroxetine or PST-PC did not affect physical functioning (P = .65).

Outcomes: Adequate Treatment To give clinicians a better estimate of treatment effects for patients who re- ceive an adequate course of treatment, we report results based on individuals completing at least 4 treatment ses- sions. The pattern and magnitude of im- provement in self-reported symptoms on the HSCL-D-20 were similar to the intent-to-treat analysis. Patients treated

Figure 1. Participant Flow and Treatment Visits Completed

197 Not Eligible 59 No Depression Diagnosis 58 Major Depression 43 Hamilton Depression Rating Score <10 37 Other

629 Patients Assessed

415 Randomized

432 Eligible

137 Assigned to Receive Paroxetine 138 Assigned to Receive Problem- Solving Treatment–Primary Care

140 Assigned to Receive Placebo

17 Did Not Receive Any Treatment 8 Did Not Receive Any Treatment 8 Did Not Receive Any Treatment

106 Completed 4 Visits

94 Completed Trial (6 Visits)

113 Completed 4 Visits

108 Completed Trial (6 Visits)

119 Completed 4 Visits

109 Completed Trial (6 Visits)

14 Withdrew∗ 12 Adverse Effects 4 Medical Illness

17 Withdrew 0 Adverse Effects 2 Medical Illness 4 Treatment Inconvenient 3 Change in Psychiatric Condition 2 Noncompliance 1 Preferred Alternate Treatment 5 Other

13 Withdrew 8 Adverse Effects 2 Medical Illness 1 Treatment Inconvenient 2 Noncompliance

17 Refused Participation

Asterisk indicates that 2 patients gave medical illness and adverse effects equal weight as reasons for withdrawal.

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with paroxetine showed greater im- provement than those taking placebo. Those treated with PST-PC did not dif- fer overall from placebo plus clinical management or paroxetine but showed more rapid symptom resolution than those taking placebo during weeks 2 through 11.

Next, we compared the proportion of patients achieving remission using an HDRS of less than 7. Treatment effects varied significantly across the 4 sites and by diagnostic group, differences that were only slightly attenuated after ad- justment for sex, severity of medical ill- ness, and education. A test for the more complex interaction of site, treat- ment, and diagnosis was not signifi- cant (P = .42). For descriptive pur- poses, we report these results separately for each diagnosis and site (TABLE 3). Several points deserve comment. First, patients randomized to receive pla- cebo had relatively high remission rates, 25 (40.3%) of 62 with dysthymia and 28 (49.1%) of 57 with minor depres- sion. Second, 113 (51.6%) of 219 sub- jects did not remit with either depres- sion-specific treatment. Third, PST-PC showed the greatest variability in re- mission rates across sites, ranging from 33.3% to 80% for dysthymia and 26.7% to 100% for patients with minor de- pression. Compared with placebo plus clinical management, PST-PC was highly effective at one site (Lebanon, Pa) for both dysthymia (P,.001) and minor depression (P = .03), but less ef- fective at other sites on an absolute ba- sis and relative to placebo treatment.

COMMENT Evidence-based guidelines are avail- able to direct primary care physicians in treating major depression. When implemented well, these guidelines im- prove patient outcomes.26,35,36 For mi- nor depression and dysthymia, evi- dence-based guidelines are unavailable because the evidence base is insuffi- cient to develop recommendations. Fur- thermore, since existing trials typi- cally have been conducted in relatively healthy, younger adults, treatment out- comes may differ substantially for older,

Figure 2. Mean Hopkins Symptom Checklist Depression Scale (HSCL-D-20) Scores by Treatment Assignment

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0 1 2 3 4 5 6 7 8 9 10 11

0.5

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Treatment Week

Paroxetine (n=137)

Placebo (n=140)

Problem-Solving Treatment– Primary Care (n=138)

Estimated from random regression model.

Figure 3. Mean Hopkins Symptom Checklist Depression Scale (HSCL-D-20) Scores of Patients With Dysthymia

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Paroxetine (n = 69)

Placebo (n = 70)

Problem-Solving Treatment– Primary Care (n = 72)

Estimated from random regression model.

Table 1. Sociodemographic and Clinical Characteristics*

Characteristics Paroxetine (n = 137)

Problem-Solving Therapy–Primary Care

(n = 138) Placebo (n = 140) P Value

Age, mean (SD), y 71 (6.8) 71 (7.0) 71 (7.2) .66

Female, No. (%) 53 (39) 56 (41) 63 (45) .55

Ethnic background, No. (%)† Non-Hispanic white 113 (82.5) 104 (75.4) 106 (75.7)

Latino 15 (11.0) 17 (12.3) 17 (12.1) .55

Black 8 (6.0) 16 (11.6) 14 (10.0)

Other 1 (1.0) 1 (1.0) 1 (1.0)

Married, No. (%) (52) (52) (54) .95

Employed, No. (%) Full-time (7) (6) (9)

.84 Part-time (7) (8) (7)

Median income, range, US $ 15 000-20 000 15 000-20 000 15 000-20 000 .76

Median education, y 12 12 13 .89

Clinical characteristics Depression diagnosis, No. (%)

Minor depression (50) (48) (50) .93

Dysthymia (50) (52) (50)

Hopkins Symptom Checklist-20 score,

mean (SD)

1.4 (0.64) 1.4 (0.72) 1.4 (0.67) .50

Hamilton Depression Scale score, mean (SD)

13.8 (3.04) 13.3 (2.56) 13.2 (2.44) .19

Anxiety disorder, No. (%) Panic disorder 5 (3.7) 1 (0.7) 6 (4.3) .21

Generalized anxiety disorder

18 (13.1) 24 (17.4) 24 (17.1) .57

Anxiety not otherwise specified

12 (8.8) 14 (10.1) 17 (12.1) .65

Duke severity of illness, mean (SD)

26.2 (13.13) 22.7 (12.57) 24.3 (12.48) .08

Chronic medical conditions, mean (SD)

3.3 (1.44) 3.4 (1.39) 3.4 (1.38) .59

*Percentages may not add to 100 due to rounding. †Ethnic background is missing for 2 patients.

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more physically ill primary care pa- tients. This primary care based study, with broad inclusion criteria to in- crease generalizability, sought to ad- dress this gap.

We found that treatment with parox- etine improved depressive symptoms to a greater degree and more rapidly than placebo plus clinical management. The positive effects of paroxetine on depres- sive symptoms were moderate and simi- lar for dysthymia and minor depres-

sion. The similar effect may reflect our requirement that patients have 3 to 4 DSM-IV symptoms for at least 4 weeks and a Hamilton Depression score of at least 10 to meet minor depression cri- teria. In addition, diagnostic distinc- tions between minor depression and dys- thymia may be less certain in primary care than those portrayed in the DSM-IV diagnostic manual. Although the differ- ence in symptom improvement was rela- tively small, the more rapid symptom resolution was associated with a clini- cally and statistically significant im- provement in mental health function- ing for the majority of patients with dysthymia and for the most function- ally impaired patients with minor de- pression. Considering effects on depres- sive symptoms and function, the positive effects of paroxetine were somewhat more consistent and stronger for dys- thymia than minor depression. Over- all, patients treated with PST-PC did not have significantly greater improve- ment but did show more rapid late- course resolution of symptoms than did patients treated with placebo plus clini- cal management. The PST-PC treat- ment approach led to functional im- provement for fewer patients than

paroxetine and showed significant vari- ability across sites when comparing re- mission rates.

These results are particularly impor- tant because they are derived from an ethnically and socioeconomically di- verse sample of older patients with mul- tiple chronic coexisting medical ill- nesses, a group for which there is little treatment data. How do these findings fit with the extant literature? Two re- cent literature syntheses examined the efficacy of pharmacotherapy for dysthy- mia.4,7,37 Overall, 26 trials compared an antidepressant with placebo. In aggre- gate, these trials found that antidepres- sant treatment is efficacious, increasing response rates significantly from 37% with placebo to 59% with active treat- ment. These response rates are greater than what was seen in our study. How- ever, only 2 studies focused on dysthy- mia in older adults and only 2 included primary care settings. Compared with the current study, prior studies had signifi- cantly higher depressive symptoms at baseline and frequently excluded pa- tients with chronic medical illness.38-40

These differences are important be- cause other studies have shown less de- finitive treatment effects in patients with milder symptoms and in patients with chronic medical illness. In the largest study of younger adults with similar baseline depression severity (HDRS < 13), sertraline-treated patients showed improvements on the 13-item Hopkins Symptom Checklist Depression Subs- cale that were comparable with the im- provements patients taking paroxetine in our study experienced.41

Controlled trials of psychological treat- ments for dysthymia are sparse. This is

Figure 4. Mean Hopkins Symptom Checklist Depression Scale (HSCL-D-20) Scores of Patients With Minor Depression

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Paroxetine (n = 68)

Placebo (n = 70)

Problem-Solving Treatment– Primary Care (n = 66)

Estimated from random regression model.

Table 2. Effects on Mental Health Functioning: Mean Differences in Medical Outcomes Study Short-Form 36 (SF-36) Mental Component Scores at 11 Weeks

Baseline Mental Health Function†

Dysthymia Minor Depression

Paroxetine vs Placebo

PST-PC vs Placebo

Paroxetine vs Placebo

PST-PC vs Placebo

High 5.8 (2.02)‡ 3.6 (1.76) 0.2 (1.96) 1.4 (1.84)

Intermediate 4.4 (1.74)§ 2.2 (1.59) 2.3 (1.65) 2.9 (1.60)

Low 2.7 (2.17) 0.4 (2.04) 4.7 (2.03)‡ 4.7 (1.96)‡

*PST-PC indicates Problem-Solving Treatment–Primary Care. Data are mean (SE). †The baseline SF-36 mental component high score is 45 or more; intermediate, 33 to 44; and low, 32 or less. ‡P,.05. §P,.005.

Table 3. Remission Rates for Patients Attending 4 or More Treatment Sessions by Diagnosis and Site*

Site

Dysthymia (n = 182), No. (%) Minor Depression (n = 156), No. (%)

Paroxetine PST-PC Placebo Paroxetine PST-PC Placebo

Lebanon, Pa 8/12 (66.7)† 8/10 (80.0)† 3/10 (30.0) 5/10 (50.0) 8/8 (100)† 7/12 (58.3)

Pittsburgh, Pa 7/13 (53.8) 5/13 (38.5) 5/11 (45.5) 7/10 (70.0) 5/14 (35.7) 11/17 (64.7)

San Antonio, Tex 8/21 (38.1) 7/21 (33.3) 10/27 (37.0) 8/14 (57.1) 5/13 (38.5) 5/14 (35.7)

Seattle, Wash 3/11 (27.3) 12/19 (63.2) 7/14 (50.0) 6/15 (40.0) 4/15 (26.7) 5/14 (35.7)

All sites 26/57 (45.6) 32/63 (50.8) 25/62 (40.3) 26/49 (53.1) 22/50 (44.0) 28/57 (49.1)

*Remission was defined as a Hamilton Depression Rating Scale score of less than 7. PST-PC indicates Problem-Solving Treatment–Primary Care. †P,.05 compared with placebo.

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unfortunate since many patients, par- ticularly in certain ethnic groups, pre- fer psychological treatments for depres- sion.15 Psychological treatments are particularly appealing in older individu- als because they avoid adverse drug- drug and drug-disease interactions. De- spite its inherent appeal, a review of the International Cochrane Collaboration’s trials registry showed no controlled tri- als with appropriate controls.42 A small, 16-week trial43 comparing cognitive be- havioral treatment with fluoxetine showed no difference between treat- ments. Our study is the first test, that we know of, to evaluate the effects of PST-PC on patients with dysthymia. The PST-PC approach has been proved efficacious for major depression and has several poten- tial advantages in primary care.17 These advantages include relatively few, brief sessions, compared with the typical 12 to 16 used for cognitive or interper- sonal psychotherapy. In addition, PST-PC has been efficacious when used by nonphysicians, including nurses, which could increase its applicability in primary care.18,44,45 How did it work for older adults with milder forms of de- pression? When results are combined across all sites, PST-PC was not consis- tently better than placebo plus clinical management. However, the response to PST-PC was highly variable with par- ticularly strong effects at 1 of the 4 sites. Although a variety of factors may ex- plain site variability, the most plausible is varying experience and skill among the therapists. At the site with the best re- sponse, the primary therapist was a be- havioral therapist with a doctorate in phi- losophy who had a such an affinity for this therapy that he has become a trainer of other therapists.

The evidence base for treating mi- nor depression is more limited than for dysthymia. Only 2 studies have com- pared antidepressants with placebo: one study showed no effect for amitripty- line38; the other study showed small but significant effects for minaprine in geriatric patients with “prolonged de- pressive reaction.”46Two studies com- paring multifaceted interventions (in- cluding pharmacotherapy) to usual

primary care for depression showed im- portant positive effects for the sub- group with major depression but not for minor depression.26,47 Both the mul- timodal intervention and usual-care treatments produced very high, 65% to 70% response rates, for patients with minor depression. In addition, 2 tri- als44,48 evaluated psychosocial interven- tions. Miranda and Munoz48 evaluated 8 sessions of cognitive behavioral therapy in an ethnically diverse, ur- ban, primary care population. At 4 months’ postintervention in the sub- group with minor depression, cogni- tive behavior therapy showed a de- layed positive effect that persisted to the 12-month follow-up visit.48 An under- powered trial in family practice showed positive but statistically insignificant ef- fects of a telephone-based problem solv- ing treatment.44 In our study, PST-PC showed inconsistent effects for minor depression with a 100% remission rate at 1 site but poor efficacy at the other 3 sites. The more rapid symptom im- provement during weeks 2 through 11 was encouraging, and it will be inter- esting to see if patients with minor de- pression show a delayed treatment ef- fect similar to that observed by Miranda and Munoz.

Our study has potential treatment im- plications for primary care clinicians. Al- though depression-specific psychothera- pies are proved effective for major depression, we cannot yet recommend PST-PC for older persons with minor de- pression or dysthymia because of our weak, inconsistent positive effects on outcomes and the lack of other convinc- ing studies. Consistent with trials in younger and more symptomatic pa- tients, pharmacotherapy with a seroto- nin reuptake inhibitor was effective for older patients with dysthymia, improv- ing both depressive symptoms and func- tion. We recommend pharmaco- therapy as first-line treatment but caution that the benefits may be more modest in older persons with relatively low symptom severity.

Because treatment effects were less consistent for minor depression, our data suggest that clinicians should con-

sider antidepressant treatment only for those with more severe functional im- pairment and a 4- to 6-week trial of watchful waiting for all others. This is not a recommendation to do nothing. We underscore the fact that placebo- treated participants received face-to- face attention of a physician who was focusing on their depressive symp- toms 6 times over an 11-week period, as well as the attention of their clinical evaluator and of other clinic person- nel. Clinicians should support, edu- cate, and reevaluate all patients, prob- ably in several face-to-face contacts before concluding either that the de- pression is resolved or there is a need for further intervention. For individu- als who worsen or have persistent symptoms and increasing functional impairment, a trial of antidepressant treatment should be considered. Fi- nally, these findings reinforce the im- portance of a careful diagnostic assess- ment that evaluates the severity of depressive symptoms and the degree of functional impairment when making treatment decisions for older primary care patients.

Author Affiliations: The South Texas Veterans Af- fairs Health Care System, Audie Murphy Division and Divisions of General Internal Medicine (Drs Williams and Cornell) and Geriatrics (Dr Cornell), University of Texas Health Science Center at San Antonio; Depart- ments of Community and Family Medicine (Drs Bar- rett, Oxman, and Sengupta) and Psychiatry (Dr Ox- man), Dartmouth Medical School, Hanover, NH; Department of Psychiatry, Western Psychiatric Insti- tute and Clinic, University of Pittsburgh, Pittsburgh, Pa (Dr Frank); and Department of Psychiatry and Be- havioral Sciences, University of Washington, Seattle (Drs Katon and Sullivan). Financial Disclosure: Dr Frank is a traveling scholar and serves on the speaker’s bureau for SmithKline Beecham. Funding/Support: Supported by grants from the John A. Hartford Foundation of New York and the John D. and Catherine T. MacArthur Foundation. SmithKline Beecham supplied medication and placebo. Dr Wil- liams is supported by a Veterans Affairs Health Ser- vices Research Career Development Award. Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Acknowledgment: We thank the participating prac- tices, study clinicians, and research associates who played vital roles in the successful completion of the project. We thank Elizabeth O. Cain who assisted with manuscript preparation.

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