A generation ago, geriatric depression was regarded as either a natural reaction to the privations and multiple losses that accompany old age, or an irreversible consequence of cerebral degeneration heralding a dementia. Even if physicians overcame their expectation of the inevitability of depression in old age, an unhealthy nihilism concerning the effects of antidepressant treatment in this group held sway (Ford & Sbordone, 1980). Because Freud had taught that patients over the age of 45 years were resistant to change in psychoanalysis, even talking therapies were closed to this group. There is an inescapable irony in that Freud was himself in his 40s when he took this position—now regarded as not only ageist but essentially untrue (Jarvik & Small, 1989).

The antidepressant literature for depression in late life tends to be interpreted as saying that certain antidepressant medications—e.g., nortriptyline, doxepin, fluoxetine—have fewer and milder side effects than others, whereas overall efficacy is equivalent (Plotkin et al., 1987; Rush, 1993; Salzman et al., 1995; Schneider, 1994). Further examination of this literature, however, suggests that both efficacy and side effect rates for any particular medication vary among trials, and often depend on the medications being compared, the use of placebe, the dose, and the design of the trial.

In this report we review selected clinical trials, and summarize and discuss a previously published meta-analysis. Treatment recommendations from the 1991 NIH Consensus Development Conference on the Diagnosis and Treatment of Depression in Late Life and from the Agency for Health Care Policy Research are discussed. Directions for fume research are suggested.

Both antidepressant medications and brief structured psychotherapies have efficacy in the acute treatment of elderly depressed outpatients with major unipolar, nondelusional depression. Effective treatment for depression involves consideration of the type and severity of illness, adequate prescribing, patient education, and regular patient monitoring for compliance, symptom change, side effects, and intercurrent medical disorders, which may complicate antidepressant therapy.

Major depression in the elderly is often a relapsing, chronic illness with high risk for chronic invalidism, poor treatment compliance, and suicide. In most cases, maintenance treatment to prevent recurrence and to enhance the quality of life is thought to be indicated. We review recent data from our onging studies that support both the efficacy and the safety of pharmacotherapeutic and psychotherapeutic maintenance treatments. However, the challenges of conducting maintenance therapy research (particularly with a placebo control) with the elderly are many, involving such areas as recruitment, retention, compliance, choice of outcome measures, and informed consent. We discuss each of these challenges and our responses to them. Finally, we suggest that maintenance therapy trials should be extended in several directions: (a) long-term treatment of bipolar and delusional subtypes in the elderly, as well as depression associated with progressive neurodegenerative disorders such as Alzheimer's dementia; (b) assessment of the benefits and risks of long-term therapy with other than tricyclic and monoamine oxidase inhibitor antidepressant agents, such as selective serotonin reuptake inhibitors; and (c) development of models of long-term course, including the interaction of treatments with medical and psychosocial variables that can have a profound impact on illness onset and offset. These issues are illustrated with a discussion of a new protocol designed to test the acute and maintenance efficacy of antidepressant therapy for depressed patients with Alzheimer's disease.

Background: We attempted to determine baseline characteristics predicting response in a 6-week, double-blind, geriatric depression trial, which showed a significantly higher remission rate for fluoxetine (20 mg daily) than for placebo (31.6% vs. 18.6%, p < .001). Methods: Outpatients (N = 671) were 60 years or older (mean ± SD = 67.7 ± 5.7), met Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev., American Psychiatric Association, 1987) criteria for unipolar major depression, had baseline scores on the 17-item Hamilton Depression Rating Scale (HAMD17) of 16 or more, and were randomized after a 1-week placebo lead-in. Potential baseline predictors of percentage change in last-visit-carried-forward HAMD21 total scores were entered into a stepwise regression model. The sample was randomly divided into two groups (development and validation data sets) so that potential predictors could be confirmed in a second analysis. Results: Of the 266 variables considered for their prognostic ability, 13 were found to be significant predictors using the development data set, including (a) presence of somatic complaints, absence of agitation, and presence of previous accidental injury for fluoxetine response: and (b) reported feelings of emptiness, absence of somatic complaints, and absence of early insomnia for placebo response. The second analysis using the validation data set failed to confirm statistical significance of predictors identified in the development data set. Conclusions: Although potentially useful baseline characteristics were initially identified as response predictors, conservative statistical methods failed to confirm any significant predictors of differential responses between fluoxetine and placebo in this double-blind, placebo-controlled trial.

This article reviews the evidence that antidepressants have improved the prognosis of geriatric depression. It examines studies carried out in the acute, continuation, and maintenance stages of treatment. Naturalistic studies carried out after the introduction of electroconvulsive therapy indicate that about one quarter of patients with major depression in later life remain symptom-free, approximately one third experience at least one relapse but with further recovery, and the remainder have residual symptoms. In about 10% of all cases, depressive symptoms remain severe and intractable. These proportions appear to have altered little since tricyclic antidepressants became available, although recent research into drug prophylaxis suggests that better outcomes may be possible. The article reviews some of the methodological problems that research workers must address. The role of newer antidepressants in prognosis is also discussed.

The 5-year prognosis of 42 elderly patients with major depression (mean age 73.2 ± 6.3 years for men and 73.0 ± 7.3 years for women) is described. Furthermore, the clinical outcome of elderly patients with major depression is compared to that of 199 elderly patients with dysthymic disorder (mean age 69.6 ± 7.2 years for men and 71.3 ± 7.7 years for women) described in a previous article.

Twelve percent of patients with major depression recovered, 26% still had depression after 5 years, 12% had possible dementia, 45% had died, and 5% could not be contacted. The outcome did not significantly differ between the sexes or the two age groups (65–74 and 75+). A poor clinical outcome of patients with major depression was related to a greater number of diagnosed diseases, strong feelings of restlessness, and higher sexual interest at the beginning of the follow-up. A poor prognosis was also found for the patients whose functional abilities and hobby activities declined during the follow-up. A poor prognosis tended to be related to absence of hypertension, frequent trembling of hands, low activity in listening to music, and high activity in watching TV at the onset, and to absence of malignant disease and occurrence of a high number of negative and positive life events during the follow-up period.

Thirty-six percent of dysthymic patients recovered, 26% still had depression after 5 years, 9% had possible dementia, 25% had died and 4% could not be contacted. The outcome of dysthymic patients did not significantly differ between the sexes or the two age groups (65–74 and 75+). The clinical outcome of dysthymic patients tended to be more favorable than that of patients with major depression. The factors related to a poor outcome differed between patients with major depression and dysthymic patients.

Apparent treatment-resistant depression (TRD) is frequently encountered by and poses particular challenges for the old-age psychiatrist. The prevalence of true nonresponse to treatment is not known with accuracy but reports put it at 18% to 40% for the elderly. This article reviews the concept of TRD in the elderly, discussing the factors involved in apparent resistance and the treatment of this group. We suggest that absolute TRD may be a rarer entity than the estimated 18% to 40% if depressed patients are treated carefully and vigorously.

The aim of this article is to suggest that hostile behavior in elderly patients is often caused by a reversible mood disorder rather than by a personality disorder or dementia, even if these two last diagnoses are already well established. Sedatives, often prescibed for hostile behavior, can induce confusion, falls, and bedridden states, and can actually increase the rate of mortality. The mood disorder can be a hostile agitated depression or a mixed affective state. The hypothesis of a mood disorder calls for an antidepressant trial, possibly combined with a mood stabilizer.

Treatment studies of delusional major depression demonstrate a poor response to standard antidepressant medications. Longitudinal studies demonstrate high relapse rates, even in patients receiving postdischarge antidepressants. The poor medical and psychiatric outcomes for late-life delusional depression and the increased risk for adverse medication reactions in this population underscore the importance of developing effective postrecovery treatments.

Studies of mixed-age adults demonstrate the effectiveness of acute treatment with either electroconvulsive therapy or combination pharmacotherapy with high doses of neuroleptics and antidepressants. In considering these results in relation to the treatment of late-life delusional depression, attention must be given to the particular vulnerabilities to medication side effects of elderly patients.

The potential effectiveness of continuation treatment with combined antidepressant-neuroleptic therapy is discussed. Clinical and methodologic issues related to studying the effectiveness of combination treatment in elderly patients are emphasized.

In a randomized 6-week trial comparing fluoxetine with placebo, the Medical Outcomes Study 36-Item Short-Form Health Status Survey (SF-36) scales were used to measure the effects of treatment on functional health and well-being among elderly (age ≥ 60 years) outpatients with major depression. In the fluoxetine and placebo groups, 261 and 271 patients, respectively, completed the SF-36 before treatment and at Weeks 3 and 6. Compared with national norms for individuals over age 60, study patients before treatment exhibited baseline decrements on the following SF-36 scales: mental health, role limitations due to emotional problems, social functioning, vitality, role limitations due to physical problems, and bodily pain. Analyses of SF-36 changed scores from baseline to Week 6 revealed that the fluoxetine group improved more than the placebo group across all scales. Differences in changes of scores between groups were significant (p < .05), favoring the fluoxetine group for the scales of mental health, role limitations due to emotional problems, physical functioning, and bodily pain. Improvements observed in the fluoxetine group were both clinically and socially significant.

Late-life depression is an immense public health problem for which research on treatment interventions is very much needed. Between 1950 and 1990, average longevity worldwide increased from 46.6 years to 64.7 years (United Nations, 1993). With this surge in the elderly population has come an increased prevalence of late-life depression and its sometimes severe consequences. Older people with depressive symptoms have a threefold increase in mortality (Ashby et al., 1991). As many as 15% to 25% of nursing home residents in the United States have major depression (NIH Consensus Development Panel, 1992), and between 50% and 80% of elderly people who commit suicide have major depression (Clark, 1991; Conwell et al., 1991; Finkel & Rosman, 1995).