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Major Depression and Its Response to Sertraline in Primary Care vs. Psychiatric Office Practice Patients

Results of an Open-Label Trial in Argentina

Received November 25, 1997; revised March 4, 1998; accepted March 13, 1998. From the Neuropsychiatry and Memory Group of The Johns Hopkins University and Hospital and from the Neuropsychiatry Group (Siren) of the Centro de Enseanza Medica e Investigaciones Clinicas (CEMIC), Buenos Aires, Argentina. Address correspondence and reprint requests to Dr. Lyketsos, Osler 320, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287.

ABSTRACT

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Great strides have been achieved in recent years in the detection and treatment of major depressive disorder (MDD) in primary care settings. Little is known about the types or patients with MDD seen in primary care as compared with those seen in psychiatric office practice. Few studies have compared clinical outcomes after treatment with antidepressants in these two settings. In Argentina, the authors conducted an open-label treatment study of MDD patients in primary care (n=469) and psychiatric office practice (n=299). The patients were compared on baseline sociodemographic and clinical variables. These same patients were treated with sertraline 50–100 mg per day for 8 weeks. At baseline, the patients in psychiatric office practice were younger, more likely to abuse alcohol, less likely to have comorbid medical disorders, and more likely to have failed a prior treatment for depression during the current episode. The two groups did not differ significantly on depression severity or in depressive symptom profile on the Hamilton Depression Rating Scale (Ham-D). After 8 weeks of treatment, mean Ham-D scores were reduced comparably in both groups, from about 25 to about 10. Rates of adverse events were 14%–29%, depending on the follow-up interval. Adherence with treatment was high in both groups (over 95%). The patients in primary care and psychiatry office practice are similar in several ways. Significant reductions in depressive symptoms are possible in both settings, in large numbers of patients, by using doses of sertraline in the 50–100 mg range.

Key Words: Depression • Sertraline • Primary Care

INTRODUCTION

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Major depressive disorder (MDD) affects 6%–10% of patients in primary care settings and is associated with substantial personal, social, and economic costs. Failure to detect MDD, diagnostic variations in defining depression, and suboptimal use of antidepressant therapies have all been reported in the primary care literature.^1–4 Such reports have resulted in significant efforts to improve the diagnosis and treatment of depression in primary care.

Recent research has shown that it is possible to use structured interventions to improve detection of MDD in primary care.^2,3,5,6 In addition, structured interventions have been found superior to "usual care" in reducing depression and improving functioning in primary care,^7–10 although this is not a universal finding.⁵ One study has documented the ability to produce substantial depression reduction in very large patient populations (N=1,098) in primary care.¹¹ Both pharmacologic and psychosocial interventions appear to be effective.^7–14

Despite these advances, several questions remain. Major depression is a common disorder in the population, and most persons who suffer from the effects of depression do not receive treatment.¹⁵ Most patients with MDD are first seen in the primary care setting. As many as 10% to 15% of MDD patients are seen initially in psychiatric office practices. An unknown number of others are immediately referred to psychiatrists from the primary care setting upon presenting with depressive symptoms. The most common site of treatment for MDD is the primary care setting.¹⁵ However, many patients with MDD are treated in psychiatric office practice as well.

It is important to develop a better understanding of the patients with MDD who are seen in primary care as compared with those seen in psychiatric office practice. It is not known whether treatment outcomes in primary care are comparable to those achieved in psychiatric office practice. Finally, most studies of the efficacy and effectiveness of treatment for major depression have involved patients recruited from academic medical centers. There is appropriate concern as to whether such findings are generalizable to the broader patient populations seen in primary care or psychiatric office practice as well.

This study, conducted in 1996, sought to answer some of these questions. One aim was to compare the clinical profile of patients with major depression seen in primary care office practice with that of those seen in psychiatric office practice. A second aim was to investigate whether comparable treatment outcomes regarding depression remission can be achieved in both settings, using a structured, open-label pharmacologic intervention.

METHODS

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Design
This was a comparative, open-label study of patients with major depression in primary care or psychiatric office practice in Buenos Aires, Argentina.

Participants
There were 469 participants from primary care and 299 participants from psychiatric office practice, for a total of 768 patients. This was a consecutive series of patients who met the following inclusion and exclusion criteria.

Inclusion Criteria.

1. Males and females older than 18 years.
2. Females with childbearing potential with a negative pregnancy test who practiced successful contraception for at least 3 months before entering the study.
3. Patients met DSM-IV¹⁶ criteria for MDD.
4. A score of at least 10 points on the 17-item Hamilton Depression Rating Scale (Ham-D¹⁷).

Exclusion Criteria.

1. Women who were pregnant, lactating, or of childbearing potential; not using reliable contraception; or who intended to become pregnant within 3 months of study entry.
2. Diagnosis of seizure disorder, organic brain disease, malignancy, schizophrenia, psychotic disorder, anorexia nervosa, or bulimia nervosa.
3. Severe allergies or multiple adverse drug reactions by history.
4. Hypertensive patients being treated with reserpine or alpha methyldopa.
5. Other clinically significant current active medical disorder that would interfere with study participation.
6. Known hypersensitivity to sertraline or lactose.
7. History of alcoholism, drug abuse, personality disorder, poor motivation, or other emotional problems likely to invalidate informed consent.
8. Very high current suicidal risk, in the opinion of the treating physician.

Recruitment
The patients were recruited by their primary care physician or psychiatrist within the context of his/her office practice. There were 113 primary care office practitioners and 44 psychiatrist office practitioners involved in the study. Each of the primary care practitioners contributed between 3 and 15 patients to the study. Each of the psychiatrists contributed between 3 and 20 patients. All patients gave informed consent before their participation in the study.

Procedure
All participating physicians received a half-day training by a board-certified psychiatrist in the diagnosis of MDD and in the scoring of the Ham-D. They were also provided with a checklist of depressive symptoms to assist in the diagnosis of MDD. This training also included a review of clinical research, the study's procedures, and how to record study data in special patient booklets. The study was monitored by support staff who visited the practices to provide medication supplies, answer design questions, and collect the data.

The patients were enrolled into the study at the time that the diagnosis of MDD (by DSM-IV criteria) was made by their psychiatrist or primary care physician. At that time, demographic and clinical information was also collected, and the patients were rated on the Ham-D. Subsequently, the patients were started on open-label therapy with sertraline beginning at 50 mg per day for 4 weeks. After 4 weeks (at follow-up Day 29), the treating physicians had the choice of increasing the dose of sertraline to 100 mg.

The patients were seen for follow-up at Days 8, 15, 29, and 56 after initiation of treatment. At each follow-up visit, they were rated on the Ham-D. Side effects and adverse events were recorded at each follow-up, and the physicians also conducted pill counts to document compliance.

Outcome Measures
The primary outcome measure was the Ham-D.¹⁷ Secondary outcome measures included rates and severity of adverse events, reasons for discontinuation, compliance (>80% of doses taken), and the number of patients who required antidepressant dose escalation at the Day 29 visit.

Analyses
The baseline sociodemographic and clinical profile, as well as primary and secondary outcome data, were compared between those patients seen in primary care and psychiatric office practice. For patients who discontinued medications, the last observation carried-forward method was used to estimate Ham-D scores at follow-up. Continuous variables such as age, educational level, and scores on the Ham-D scale were compared by using Student's t-test. Discrete variables, such as gender and rates of adverse events, were compared in contingency tables by using the chi-square test.

RESULTS

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Table 1 compares the 469 patients seen in primary care office practice with the 299 seen in psychiatric office practice on sociodemographic and clinical variables. The results of statistical comparisons between the two groups are also shown. The patients in primary care were older by an average of 8 years, more likely to have active medical illnesses, less likely to be abusing alcohol, and less likely to have received prior treatment for depression during the present episode. The two groups were comparable on other variables in Table 1.

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TABLE 1.

The Ham-D mean scores, as well as means for individual Ham-D items, are in Table 2. The groups were similar in mean baseline Ham-D scores and had comparable mean scores for all the Ham-D items, except for two: those seen in primary care were more likely to have early insomnia and less likely to have decreased libido.

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TABLE 2.

Treatment outcomes between the two groups are compared in Figure 1 and in Table 3. Figure 1 shows mean scores on the Ham-D at baseline and at each follow-up visit. Both groups exhibited a steady decline in mean Ham-D scores. At each follow-up visit, the mean decrease in Ham-D was statistically significant when compared with baseline (P<0.01 in all cases by repeated measures t-test). By Day 56, mean Ham-D scores for the two groups had dropped to the 9–10 range from a baseline mean of around 25.

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FIGURE 1. Changes in mean Hamilton Depression Rating Scale over the study visits, by patient group Note: No data were collected on Days 22, 36, 43, and 50.

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TABLE 3.

Comparison of mean scores at each follow-up visit using t-tests indicated no significant difference between the two groups at Days 8, 15, and 29 (in all cases P>0.10). However, the difference between the two groups at Day 56 was statistically significant, with the primary care office practice patients having lower mean scores (t=5.8, df=1, P=0.016).

With regard to adverse events at each follow-up visit (Table 3), 71%–87% of the patients in both groups were reporting no adverse events. The most common adverse events were nausea, stomach upset, insomnia, tremor, restlessness, and headaches. Mild adverse events were reported by 8%–17% at follow-up visits. Smaller numbers reported more severe adverse events. The rates of adverse events were comparable between the primary care and psychiatric office practice groups (Table 3).

By the end of the study, 422 (89.9%) patients in primary care and 268 (89.6%) in psychiatric office practice continued to take sertraline. This difference in rates of discontinuation was not statistically significant (²=4.4, df=6, P=0.62). The most common reason for sertraline discontinuation in both groups was an adverse event (4% across both groups). The second most common reason was patient withdrawal of consent (2.6%). Other reasons for discontinuation included protocol violations in five patients and "unspecified" in the rest.

At each follow-up visit, about 97% of the patients were found to be adherent with their medication regimen (over 80% of doses taken). A series of chi-square tests comparing the patients in primary care with those in psychiatric office practice indicated no significant differences in rates of adherence between the two groups (in all comparisons P>0.17).

Regarding dose escalation, the patients in primary care were less likely to require an escalation of their medication dose to 100 mg per day. Specifically, 143 (33%) patients in primary care, compared with 143 (43%) in psychiatric practice, had this dosage adjustment (²=9.19, df=1, P=0.002). To confirm that dose escalation was clinically appropriate, comparisons were made by conducting a t-test of Ham-D scores at Day 29 between the patients whose dose was escalated and those whose dose was not. The patients whose dose was escalated had a mean Ham-D score at Day 29 of 17.3, compared with 12.1 for those who did not have the dose escalated (t=19.6, df=1, P<0.0001). Given that those in primary care and psychiatric office practice had comparable Ham-D mean scores at Day 29, it would seem that the psychiatrists were more likely to increase the dose for patients with comparable levels of depression.

DISCUSSION

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We present results from a large, open-label, clinical trial of antidepressant treatment for major depression in primary care patients compared with psychiatric office practice patients. The patients with major depression in primary care were older, more likely to have comorbid medical illnesses, less likely to have comorbid alcohol abuse, and less likely to have received recent treatment for depression. However, from the point of view of depression severity and symptom profile, the two groups of office practice patients were comparable, except for small differences in individual depressive symptoms, which may have been due to chance.

Treatment outcomes in primary care and psychiatric office practice were also comparable from the point of view of depression reduction after 8 weeks of treatment. Even though the depression reduction in primary care was statistically different at Day 56, the difference in mean Ham-D scores was minimal in magnitude—a mean Ham-D of about 9 vs. a mean of about 10. It is noteworthy that the majority of the patients had significant depression reduction on 50 mg of sertraline and did not require dose escalation.

Rates of adverse events were relatively small and comparable between the two groups of patients. Treatment adherence was excellent in both groups. The patients in psychiatric practices had more treatment-resistant depression, as they were more likely to have failed a prior antidepressant treatment for the current episode and were more likely to require sertraline dose escalation. Substantial mean reductions in depressive symptomatology were achieved in both groups.

This study confirms that, in both primary care and psychiatric office practice, it is possible, through a structured antidepressant protocol, to produce substantial reductions in depressive symptomatology over an 8-week period, with very few risks. This study also indicates that patients in psychiatric office practice are more likely to have their medication dose increased after 1 month of treatment, even though on average they are no more depressed at that time than their primary care counterparts.

This work is comparable to similar open-label or controlled medication trials in primary care that found reductions in depressive symptomatology comparable to what we found here.^11–13 We are aware of no other studies comparing psychiatric office practice to primary care with regard to clinical characteristics or treatment outcomes of patients with MDD.

Several methodological limitations of this study must be considered. The participating patients were recruited from the private offices of primary care and psychiatric practitioners in Argentina. Thus, these results may not be generalizable to patients in other practices or in other nations. Given that at least one other study has shown comparable results in Europe,¹¹ it is likely that the results are generalizable to patients worldwide. Another methodological limitation is that the patients in the study were not evaluated in a structured diagnostic examination. This would have been expensive in this size study. To guard against diagnostic inaccuracies, the physicians making diagnoses were trained in diagnostic assessment for the study and in rating the Ham-D, and a minimal rating of 10 on the Ham-D was required for study inclusion.

Another methodologic limitation is that this was an uncontrolled study using a specific treatment modality for depression. The patients were not provided with psychotherapy, there were no comparison medications, and there was no placebo or combined medication–psychotherapy intervention. A final methodologic limitation was that the outcomes were limited to depressive symptomatology, adverse events, and compliance measures. It is uncertain whether this reduction in depressive symptomatology led to improvements in functioning for the depressed patients who got better.

However, it appears that the pharmacologic treatment of MDD in primary care and psychiatric office practice produces substantial reductions in depressive symptomatology in large numbers of patients over 8 weeks by using a straightforward intervention protocol.

FOOTNOTES

 
This study was supported by grants from CEMIC and from the Pfizer Corporation.

REFERENCES

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Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Lyketsos, C. G. Articles by Paz, J. Search for Related Content PubMed Citation Articles by Lyketsos, C. G. Articles by Paz, J. Primary Care Depression

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