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Guest Editorial
From Counting to Understanding: The Evolving Epidemiologic Approach to Dementia
Ian McDowell, PhD
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In Review
More Than the Epidemiology of Alzheimer’s Disease: Contributions of the Canadian Study of Health and Aging
Joan Lindsay, Elizabeth Sykes, Ian McDowell, René Verreault, Danielle Laurin
(PDF)

Alzheimer’s Disease, Genes, and Environment: The Value of International Studies
Hugh C Hendrie, Kathleen S Hall, Adesola Ogunniyi, Sujuan Gao
(PDF)

Original Research
Hidden Cardiac Lesions and Psychotropic Drugs as a Possible Cause of Sudden Death in Psychiatric Patients: A Report of 14 Cases and Review of the Literature
Dominique Frassati, Alain Tabib, Bernard Lachaux, Natalie Giloux, Jean Daléry, François Vittori, Dorothée Charvet, Cécile Barel, Bernard Bui-Xuan, Rachel Mégard, Louis Pierre Jenoudet, Jacques Descotes, Thierry Vial, Quadiri Timour
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The 5-Factor Model of Personality and Antidepressant Medication Compliance
Nicole L Cohen, Erin C Ross, R Michael Bagby, Peter Farvolden, Sidney H Kennedy
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Social, Demographic, and Clinical Factors Related to Disruptive Behaviour in Hospital
Andrea K Boggild, Marnin J Heisel, Paul S Links
(PDF)

The Course of Depressive Illness in General Practice
Frédéric Limosin, PhD, Jean-Yves Loze, Myriam Zylberman-Bouhassira, Mark E Schmidt, Eléna Perrin, Frédéric Rouillon
(PDF)

Review Paper
Prevalence and Incidence Studies of Mood Disorders: A Systematic Review of the Literature
Paul Waraich, Elliot M Goldner, Julian M Somers, Lorena Hsu
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Brief Communication
Bupropion Sustained Release Treatment Reduces Fatigue in Cancer Patients
Jodi L Cullum, Agnieszka E Wojciechowski, Guy Pelletier, J Steven A Simpson
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Patient Factors Associated With Missed Appointments in Persons With Schizophrenia
Shalom Coodin, Douglas Staley, Barb Cortens, Rob Desrochers, Sandy McLandress
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Book Reviews
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The Treatment of Anxiety Disorders: Clinical Guides and Patient Manuals. 2nd ed Reviewed by
Richard Swinson, MD

Cognitive-Behavioral Group Therapy for Social Phobia: Basic Mechanisms and Clinical Strategies
Reviewed by
Michael Van Ameringen, MD, FRCPC

Letters to the Editor
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Aripirazole–Olanzapine Combination for Treatment of Schizophrenia

Improvement of Torticollis With Quetiapine in a Schizophrenia Patient

Internalizing Antecedents of Conduct Disorder

Travel Time and the Use of Psychiatric Outpatient Clinic Services in Coastal Northern Norway

Respiratory Panic Disorder Treatment With Clonidine

Original Research

The Course of Depressive Illness in General Practice

Frédéric Limosin, MD, PhD¹, Jean-Yves Loze, MD², Myriam Zylberman-Bouhassira, MD³, Mark E Schmidt, MD³, Eléna Perrin, MD3³, Frédéric Rouillon, MD⁴

More patients with mental disorders are cared for in the primary care sector than in the mental health sector (1). Depression is the most common mental disorder general practitioners (GPs) encounter, with very high prevalence rates currently reported among populations of patients consulting in the primary care sector (10% to 25%) (2–4). However, attending physicians often fail to diagnose and treat patients suffering from depression (5), especially in the absence of psychological complaints or when patients present with predominantly somatic symptoms, such as general fatigue, weight loss, or pain (6). In their study of 558 primary care physicians, Wittchen and colleagues found that physicians failed to diagnose 35.7% of major depressive episodes (MDEs) (7). Moreover, women are more likely than men to be diagnosed with depression by their primary care physician (8). Depression is also a major health care problem owing to the burden of its morbidity and mortality, causing a high level of disability and health care use (9). The World Health Organization Global Burden of Disease Survey estimates that by the year 2020, major depression will be second only to ischemic heart disease in the degree of disability experienced by sufferers (3). Consequently, education and training of GPs would seem to be essential aims (10). Most individuals with depression can be managed in primary care, but GPs must recognize that patients with depression do not improve very quickly, often do not respond, and frequently relapse; more vigorous treatment is often needed. The study by Wittchen and Pittrow, conducted in a representative sample of 412 primary care settings, revealed a major depression point prevalence of 10.9% and showed that 51% of cases had a chronic or recurrent course (11).

Most studies have been conducted on psychiatric inpatients or outpatients, with an overrepresentation of relatively recurrent depressive illness and disabling concomitant diseases. Thus, one challenge in studying the course of major depressive illness in primary care is to avoid this bias. This study describes depressive illness (in general practice) in terms of patient characteristics and treatment modalities to delineate the course of illness with the aim of observing the rate of recovery and identifying factors predictive of relapse.

Methods

Study Design
This was a longitudinal study performed in France by 560 GPs and 140 coordinating local psychiatrists who trained the GPs both in the diagnostic assessments and in using the rating scales. The 560 GPs were randomly selected from the register of all French GPs in practice at the time of the study. The GPs involved in the study were trained to assess patients with the French version of the Structured Clinical Interview for DSM-III-R (SCID) (12), the Clinical Global Impression (CGI), and the Montgomery–Asberg Depression Rating Scale (MADRS) (13,14). The 140 coordinating local psychiatrists trained the GPs using video recordings of patients suffering from MDE. Each GP was commissioned to enrol the first patient to respond to DSM-III-R criteria for MDE (15) and to follow this patient for a maximum of 6 months. The practitioner freely chose the treatment, the duration, and the frequency of consultation. The only obligation was to assess the therapeutic outcome in terms of efficacy and safety at the end of the 6-month treatment period or, if the patient was treated for a shorter period, at the end of treatment.

Clinical Sample
Patients eligible for the study were outpatients in general practice who fulfilled the DSM-III-R criteria for an MDD and who also scored 20 or more on the MADRS. Subjects considered for participation were men and women over 18 years of age.

Clinical Measures
Patients fulfilling the DSM-III-R criteria for MDD were evaluated at baseline by the French version of the SCID, by the CGI, and by the MADRS. The baseline assessment also included an evaluation of the severity of psychosocial stress factors according to DSM-III-R Axis IV.

According to the CGI scale, response to treatment was defined as “a severity of illness score of 2 or less at the final assessment for those patients with a score of 3 or more at baseline.”(16)

Relapse was defined as a symptomatic exacerbation (MADRS score > 20) among patients who had responded to treatment but had not yet been well for a sufficient amount of time (under 6 months).

Statistical Methods
We used simple, descriptive statistics: counts and frequencies for categorical data; mean and standard deviation for continuous variables. Potentially predictive variables for recovery were entered and tested in a backward stepwise logistic regression. All statistics were performed using SAS computer software (17).

Results

Of the 492 patients involved, 16 could not be traced after initial assessment. Of the 476 remaining patients, 424 had intermediate and final evaluations, 46 had intermediate but no final evaluations, and 6 had final but not intermediate evaluations. Most of the 492 patients were women (n = 353, 71.7%), and patients ranged in age from 18 to 87 years (overall mean 44.9 years, SD 13.9; men’s mean age 46.3 years, SD 14.3 years; women’s mean age 44.3 years, SD 13.7 years). Table 1 shows other demographic data.

History
A total of 107 (21.7%) patients had a psychiatric illness in their family, and 179 (36.4%) had a personal psychiatric history. For 189 (38.4%) patients, the current episode was not the first. Among these, the mean number of previous episodes was 2.1, SD 1.7 (range 1 to 12); the time between the first and the current episode was 5.9 years, SD 5.8 years (range 0.5 to 30 years); and the mean duration of previous episodes was 5.5 months, SD 5.5 months (range 1 to 36 months).

Description of Current Depressive Episode
A total of 430 (87.4%) patients had a primary depression, 18 (3.7%) showed a depression secondary to organic disorders, and 41 (8.3%) had depression associated with another psychiatric disorder; for 3 patients the depression was not specified. Of the 41 patients with another psychiatric disorder, 12 had substance-related disorders, 12 had phobia, 9 had panic disorder, 1 had an obsessive–compulsive disorder, 4 had eating disorders, and 5 had other disorders. By DSM-III-R criteria, 341 (69.3%) patients had a diagnosis of single MDE and 124 (25.2%) of recurrent depressive disorder. The mean duration of the current episode was 2.8 months, SD 7 months (range 0.5 to 8 years). Regarding the severity of the current episode, the mean MADRS score was 31.3, SD 6.2 (range 20 to 51).

Previous Treatment
A total of 194 (39.4%) patients had a psychotropic treatment during the previous 6 months. Of these patients, 158 had been prescribed anxiolytics, 38 were prescribed hypnotics, and 2 were prescribed antidepressants (1 being prescribed fluox- etine and 1, fluvoxamine).

Treatment of the Current Episode
A total of 483 (98.2%) patients received antidepressants, and of these, 475 (98.3%) had a single antidepressant. Of the 483 patients, 338 (70.0%) received a selective serotonin reuptake inhibitor, 62 (12.8%) received a tricyclic antidepressant, and 91 (18.8%) received others (that is, an monoamine oxidase inhibitor, viloxazine, mianserin, or tianeptine). A total of 398 (80.9%) patients received other psychotropic drugs: 358 (72.8%) received anxiolytics, 105 (21.3%) received hypnotics, and 52 (10.6%) received others. The most-prescribed anxiolytics were bromazepam (118 patients), alprazolam (66 patients), and nitrazepam (52 patients). For 217 (44.1%) patients, some measure other than drug treatment was taken: 177 (75.6%) patients took leave from work for a mean 2.9 weeks, SD 3.2 weeks (range 1 to 26); 37 (15.8%) received family help; 7 (1.4%) followed psychotherapy; and 13 (2.6%) had other types of therapy (for example, acupuncture).

Follow-up
The average duration of follow-up was 187.2 days, SD 49.8 days (range 7 to 347 days). Most patients were consulted at least once monthly. Among the 476 followed-up patients, all received an antidepressant treatment, and 383 (80.5%) had no modification of this treatment during the 6-month period. The total duration of treatment was under 3 months for 194 patients (40.8%): under 30 days for 51 patients (10.7%), between 30 and 60 days for 101 (21.2%) patients, and between 60 and 90 days for 42 (8.8%) patients. Duration of treatment was between 3 and 6 months for 67 (14.1%) patients and 6 months or over for 215 (45.2%) patients.

Recovery and Relapse
At their last assessment and according to the CGI, 308 (64.7%) of the 476 followed-up patients had recovered without relapse, 117 (24.6%) developed a chronic condition, and 51 (10.7%) relapsed after a recovery. Backward stepwise logistic regression to test predictors of relapse showed that, among explicative variables entered in the model (Table 2), only 1 remained finally in the model. Indeed, history of recurrent MDD was associated with a higher risk of relapse (P = 0.04; OR = 1.6; 95%CI, 1.08 to 3.43).

Discussion

Of the 492 patients diagnosed with MDE according to DSM-III-R, 483 (98.2%) had been given an antidepressant therapy. The psychotropic concomitant prescription rate was high: 398 patients (80.9%) received other psychotropic drugs, mostly in the form of anxiolytics (69.5%). The mean duration of treatment was short—under 3 months for 194 (40.8%) patients—reflecting a tendency to early termination of treatment by the patients themselves. Of the 476 followed-up patients, 308 (64.7%) were cured without relapse, 117 (24.6%) developed a chronic disorder, and 51 (10.7%) had an early relapse after initial improvement. The high rate of recovery without relapse observed in our study is not consistent with results reported from several other naturalistic studies (18–21), which found a probability of recovery at about 50% within a single year. These discrepancies between studies can, to some extent, be attributed to methodological and population differences, especially the length of the follow-up periods and the type of populations studied (that is, inpatients or outpatients). For example, our results agree with those of Sargeant and colleagues, who observed 23.6% of not recovered or relapsed patients in a 1-year follow-up of 423 patients with depression recruited from the general population (22). Lin and colleagues studied the course of depression in primary care and found that 37.1% of the patients reported relapse within the 1-year relapse-risk period (23). Our relapse rate among primary care patients treated for depression approached that of specialty samples, with more than one-third reporting relapse in a single year.

Many authors have studied prognosis factors and reported different risk factors. For example, Faravelli and colleagues found that patients who suffered a relapse showed higher levels of residual symptoms, which would be consistent with an incomplete recovery from the index episode, inferior social adaptation, and a more pathological personality profile (19). Lewinsohn and colleagues concluded that the risk of relapse was related to the number of previous episodes, to the severity of depression at the time of interview, and to being female, but not to age at onset (24). Coryell and colleagues showed that youth and a history of nonaffective illness, such as alcoholism, drug dependence, or anxiety disorder, increased the risk of relapse into MDD (25). In the study by Keitner and colleagues that examined inpatients, the main factors predicting recovery were length of hospital stay, older age at onset of depression, better family functioning, fewer than 2 previous hospitalizations, and absence of any concurrent illness (20). Recovery was not associated with severity of illness at hospitalization or number of previous depressive episodes. Lin and colleagues found that, in primary care, the 2 major risk factors associated with relapse were 1) persistence of subthreshold depressive symptoms 7 months after the initiation of anti- depressant therapy and 2) history of 2 or more episodes of major depression or chronic mood symptoms for 2 years (23). Patients with both risk factors were approximately 3 times more likely to relapse than patients with none. In conclusion, among all the often-contradictory factors used to report an increased relapse rate, the most frequent were a history of recurrence, young age, and a diagnosis of secondary depression (26,27). In our study, only previous depressive episode predicted a higher risk of relapse or chronicity. None of the other demographic, clinical, or therapeutic factors were able to predict the course of the illness, including stressful life events. Indeed, in the literature, other psychosocial factors seem to interact more with the time elapsed until recovery than with the rate of relapse (28,29). Nevertheless, family conflict and lack of family and confidant support may be important risk factors that could predict poorer long-term outcome of depression in addition to traumatic experiences, temperament (neuroticism) and genetic factors (30), and comorbidity (20,25). Finally, our study shows that two-thirds of primary care patients with depression did not recover after a mean follow-up of 187.2 days, SD 49.8 days (range 7 to 347 days). Our 6-month observation period may have been too short. Ormel and colleagues, in 1-year and 3.5-year primary care studies, established that depression has a better outcome after a longer follow-up (31). However, according to the results of the National Comorbidity Survey (32), the rate of patients with recurrent course seems to be the same for minor depression (72.1%) and major depression (72.3%). Despite high rates of relapse and recurrence, few primary care patients with recurrent or chronic depression receive continuation and maintenance-phase treatment (33). Several studies showed that a relapse-prevention program targeting primary care patients with a high risk of relapse or recurrence who had largely recovered after antidepressant treatment significantly improved their antidepressant adherence and depressive symptom outcomes (33–36).

Funding and Support

This study was supported by a grant from Lilly France

References

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Author(s)

Manuscript received April 2003, revised, and accepted November 2003.

1. Hospital Practitioner, Department of Psychiatry, Albert Chenevier Hospital, Créteil, France

2. Assistant Professor and Biostatistician, Department of Psychiatry, Albert Chenevier Hospital, Créteil, France.

3. AResearch Fellow, Lilly France, Suresnes, France.

4. Professor, Department of Psychiatry, Albert Chenevier Hospital, Créteil, France

Address for correspondence: F Limosin, Department of Psychiatry, Albert Chenevier Hospital, 40 rue de Mesly, F-94000 Créteil, France.

e-mail: frederic.limosin@wanadoo.fr

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