0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Articles   |    
Moderators of Outcome in Late-Life Depression: A Patient-Level Meta-Analysis
J. Craig Nelson, M.D.; Kevin L. Delucchi, Ph.D.; Lon S. Schneider, M.D.
Am J Psychiatry 2013;170:651-659. doi:10.1176/appi.ajp.2012.12070927
View Author and Article Information

Dr. Nelson has served as a consultant, adviser, or speaker for, received research support or travel support from, or participated in CME for AstraZeneca, Avanir, Bristol-Myers Squibb, Cenestra Health, Corcept, Eli Lilly, Eli Lilly Global, Forest, Health Resources and Services Administration, Labopharm, Lundbeck, Medtronic, Merck, Merck Asia, Mylan/Dey Pharma, NIMH, Orexigen, Otsuka, Otsuka Asia, Pfizer, Sunovion, and Theracos; he has provided expert testimony for Finnegan, Henderson et al. on behalf of Eli Lilly, and he owns stock in Atossa. Dr. Schneider has received consulting fees from AC Immune, Allon, AstraZeneca, Baxter, Biogen-Idec, Chiesi, Elan, Eli Lilly, En Vivo, GlaxoSmithKline, Ibsen, Johnson & Johnson, Lundbeck, Merck, Pfizer, Roche, Takeda, Toyama, and Zinfandel; he and University of Southern California have received research grants from Baxter, Eli Lilly, Genentech, Novartis, and Pfizer. Dr. Delucchi reports no financial relationships with commercial interests.

From the Department of Psychiatry, University of California San Francisco; and the Departments of Psychiatry and Behavioral Sciences and of Neurology, Keck School of Medicine, and the Leonard Davis School of Gerontology, University of Southern California, Los Angeles.

Address correspondence to Dr. Nelson (craign@lppi.ucsf.edu).

Copyright © 2013 by the American Psychiatric Association

Received July 16, 2012; Revised November 08, 2012; Revised December 12, 2012; Accepted December 19, 2012.

Abstract

Objective  The authors sought to identify factors that moderate outcome in late-life major depression and that identify patients for whom antidepressants have clinically meaningful effects.

Method  A previous systematic review identified 10 placebo-controlled trials of second-generation antidepressants in outpatients with major depressive disorder who were age 60 or older. For the present study, the authors obtained from the sponsors of the 10 trials individual patient data, including age, sex, duration of illness (current age minus age at onset), course (single episode or recurrent depression), baseline depression severity, treatment assignment, and outcomes. Logistic regression models were estimated and tested to examine the association of potential moderator variables with treatment response and the treatment group-response interaction.

Results  All moderator variables were collected and documented for seven of the 10 trials (N=2,283). Univariate and multivariate analyses were restricted to these seven trials. Illness duration was the only variable significantly associated with drug-placebo differences in the multivariate model. In patients with an illness duration >10 years, baseline depression severity was also significantly associated with drug-placebo differences. In those with an illness duration >10 years and a Hamilton Depression Rating Scale score ≥21, the drug-placebo difference in response rates was relatively robust (number needed to treat=4). In the remaining patients, the drug-placebo difference in response rates was small (46.3% compared with 41.5%).

Conclusions  Older patients with a long illness duration and moderate to severe depression appear to benefit from antidepressants as compared with placebo. Antidepressants do not appear to be effective for older patients with short illness duration.

Abstract Teaser
Figures in this Article

Depression is a common disorder in older adults that reduces quality of life, increases disability, and increases risk of suicide (14). Depression is frequently associated with medical disorders that are common in older adults, and it can aggravate the course of medical illness and increase mortality (59).

Antidepressants have been the mainstay of treatment for late-life depression. In a 2008 meta-analysis of placebo-controlled trials of second-generation antidepressants in adults age 60 and older with major depression, we found that antidepressants were more effective than placebo, but the advantage was modest (10). Pooled response rates were 44.4% and 34.7% for drug and placebo, respectively, resulting in a number needed to treat of 11. The findings raise the question of whether factors can be determined that identify patients who will have a robust drug response as well as those who will not.

Studies of predictors of outcome in late-life depression are limited. Some studies found no predictors (1113). A few predictors have been suggested in individual studies. Advanced age, for example, was predictive of poorer outcome in four studies (1417). One prospective placebo-controlled study of patients age 75 and older with major depression found no significant advantage for citalopram in that age group (18). A greater medical burden has been associated with poor outcome in open-label studies (1921), although placebo-controlled studies have not found a decrement in the acute-phase drug effect (22, 23). One study found greater medical burden to be associated with higher recurrence rates during maintenance treatment (24). These findings emphasize the important distinction between predictors of global outcome and moderators of drug effects specifically (drug-placebo differences). Greater baseline depression severity has been found to predict poorer global response (25), but a substantial literature in mixed-age placebo-controlled trials indicates that greater severity is often associated with larger drug-placebo differences in change scores (2628). Recurrent depression has been reported to be associated with less global improvement (29, 30), but in mixed-aged studies, recurrent depression has been reported to have larger drug-placebo differences in response rates (31, 32). Flint and Rifat (33) found that age at onset was not predictive of outcome in elderly patients. Roose et al. (18) found evidence suggestive of an effect of age at onset on drug-placebo differences, but the number of early-onset patients was small and the effect not significant. In mixed-aged samples, female sex was associated with better global outcome in open-label studies (34), but male sex was associated with greater drug-placebo differences (35). Open-label studies of late-life depression have found that anxious depression predicts poorer global outcome (36, 37), but a trial-level meta-analysis found that anxious depression was not associated with lower drug-placebo differences in older depressed patients (38).

Impaired cognition has also received attention. A recent meta-analysis of seven placebo-controlled trials (39) and a recent large placebo-controlled trial of sertraline and mirtazapine (40) found no significant antidepressant effects in older depressed patients with dementia. Open-label studies (4143) and one secondary analysis of a placebo-controlled trial (44) found lower antidepressant response rates in patients with major depression who had executive dysfunction.

In this study, we examined possible moderators of antidepressant response in elderly depressed patients participating in randomized placebo-controlled clinical trials. Our objective was to identify variables that moderate clinically meaningful differences in response between antidepressant and placebo. We specifically examined two hypotheses, namely, that advanced age is associated with lower drug-placebo differences and that early age at onset or long duration of illness, recurrent depression, and greater baseline depression severity are each associated with greater drug-placebo differences.

In a previous systematic review (10), we identified 10 placebo-controlled trials, published or presented by December 2006, of second-generation antidepressants (non-tricyclic antidepressants) marketed in the United States. We required that the trials included patients age 60 or older who had major depressive disorder and were living in the community and that the trials were not restricted to one medical disorder (e.g., poststroke depression). For that study, we searched MEDLINE and the Cochrane clinical trials database, examined references cited, and searched presentations at national meetings to identify the 10 trials. Before conducting the present analysis, we repeated the literature search through December 2010. Four trials that were initially presented as posters had since been published, but we found no new trials meeting our criteria.

Based on this literature review, we selected factors that have been associated with either antidepressant response or antidepressant-placebo differences and that are commonly documented in clinical trials. The factors were age, age at illness onset, sex, course of illness (single episode or recurrent depression), baseline depression severity, and cognitive impairment. We elected to examine the duration of illness computed as current age minus age at onset, rather than as a threshold age at onset, because it was more informative in older patients. These factors were examined to determine whether they moderated differences between drug and placebo response. Medical burden was not included because it was not documented in a uniform or quantified manner in the studies we examined.

In our previous meta-analysis of antidepressant efficacy (10), we examined published trial-level outcome data. In the present study, we used individual patient data for the variables of interest, as well as treatment assignment and outcomes on the Hamilton Depression Rating Scale (HAM-D) (45) and the Montgomery-Åsberg Depression Rating Scale (MADRS) (46).

+

Statistical Analysis

Response to treatment was defined as a change ≥50% from baseline in HAM-D or MADRS score. Baseline depression severity was defined using the 17-item HAM-D score. Scores from one trial using the 24-item HAM-D were converted to 17-item HAM-D scores using a proportional estimate based on maximal possible scores in nonpsychotic patients. To convert MADRS scores to 17-item HAM-D scores in one trial, we used a factor derived from a late-life major depression study that used both scales (47). Analyses were performed on data from the intent-to-treat samples.

We first performed univariate analyses to determine the association of each variable with response and with the treatment group-response interaction while controlling for study. The interaction term in the model tests whether the difference in response between the placebo and active drug groups differs as a function of the covariate. For example, is the difference in response between placebo and active drug groups the same for males and females? To facilitate comparisons among the variables, we limited analyses to the trials that collected data for all the variables. Age, illness severity, and illness duration were converted to categorical variables, which normalized their distribution and facilitated inspection of response rates by category. Measures of age and depression severity according to the HAM-D were divided into quartiles (age categories were 60–65, 66–69, 70–75, and 76–98 years; HAM-D score categories were <19, 19–20, 21–23, and >23). Because about one-third of the patients had a short duration of illness (<2 years), this measure was divided into tertiles (<2, 2–10, >10 years). Linearity of the relationship of response with drug or placebo was assessed with Jonckheere-Terpstra tests (48). Effect sizes of the difference in response rates for variable categories were calculated as follows: (2×arcsin [square root of drug response rate]) – (2×arcsin [square root of placebo response rate]) (49). Variables were also entered in a regression model using maximum likelihood estimation using the PROC LOGISTIC procedure in SAS, version 9.3 (SAS Institute, Cary, N.C.) to estimate their association with response and with the treatment group-response interaction. In two trials with an active comparator, we collapsed the two active arms in those studies into a single active treatment group. In one trial comparing two formulations of the same medication and one trial comparing two dosages of a medication, we combined the drug groups within the trial.

Potential covariates (sample size, number of sites, number of treatment arms, year of publication, trial duration, drug tested, and dropout rates) were examined, as was an unordered categorical variable indicating the study in which the participant was enrolled. Several covariates, such as the sample size, were collinear with the study variable. Other covariates were examined for their association with outcome, but none was significantly associated with the treatment group-response interaction. As a consequence study alone was entered as a covariate in the regressions.

Individual patient data for the variables of interest were obtained from the sponsors of all 10 trials identified in the search (18, 47, 5057). Information on age, sex, and baseline depression severity was collected and documented in all trials (Table 1). Course of illness was documented in eight trials, and age at onset in seven. Data for all of the moderator variables were available in seven of the trials (N=2,283), and the data from these trials were used in our analyses. The characteristics of the seven trials are summarized in Table 2. Trial duration varied from 8 to 12 weeks. Selective serotonin reuptake inhibitors were examined in five trials, and duloxetine and bupropion were examined in one trial each. The seven trials included a total of 2,488 patients (1,607 women and 881 men), of whom 1,494 received active drug and 994 received placebo. All trials were sponsored by the manufacturer of the antidepressant and had Jadad scores of 4 or 5, indicating that the trials were of good to excellent methodological quality (58).

 
Anchor for Jump
TABLE 1.Patient Characteristics in Randomized Placebo-Controlled Trials of Second-Generation Antidepressants in Late-Life Depression
Table Footer Note

a Studies that had values for all the variables of interest were included in the present analyses; studies that did not collect data for one of the variables of interest were excluded.

Table Footer Note

b Duration of illness was computed as current age minus age at onset.

Table Footer Note

c Depression severity was measured with the 17-item Hamilton Depression Rating Scale.

Table Footer Note

d Course of illness was either single episode or recurrent.

 
Anchor for Jump
TABLE 2.Randomized Placebo-Controlled Trials of Second-Generation Antidepressants in Patients 60 Years and Older With Major Depressive Disordera
Table Footer Note

a MMSE=Mini-Mental State Examination; HAMD17, HAMD21, and HAMD24=17-, 21, and 24-item Hamilton Depression Rating Scale; MADRS=Montgomery-Åsberg Depression Rating Scale; CR=controlled release; XL=extended release.

Table Footer Note

b Studies that had values for all the variables of interest were included in the present analyses; studies that did not collect data for one of the variables of interest were excluded.

Table Footer Note

c DSM-III-R and DSM-IV required a 2-week duration of symptoms. Some studies required 4 weeks, as indicated.

Table Footer Note

d Modified intent-to-treat sample with at least one posttreatment rating, last observation carried forward.

We requested information regarding cognitive status on the Mini-Mental State Examination (MMSE) (59), which was used in all studies; however, several trials documented only whether or not the MMSE threshold was met rather than the score. Four trials included patients with MMSE scores below 24, but in none of those trials were there more than 10 patients in that category. Hence, we did not assess the influence of MMSE score on outcome.

+

Response to Treatment

Response rates to active drug and placebo were examined using individual patient data while controlling for study. Overall, active drug treatment was more effective than placebo (response rates were 48.7% and 40.0%, respectively; χ2=17.30, df=1, p<0.0001).

+

Moderators of Response

Response rates by category for the five variables are summarized in Figure 1. Univariate analyses of the association of the variables with the treatment group-response interaction indicated that duration of illness (Wald χ2=7.74, df=2, p=0.02) and baseline depression severity (Wald χ2=7.96, df=3, p=0.047) were significantly associated with drug-placebo differences. Significant linearity was demonstrated for the relationship of duration of illness and response rates in the placebo group (z=−3.81, p=0.0001) but not with response rate in the drug group. Baseline depression severity was associated with response rate in the drug group (z=3.40, p=0.0007) but not in the placebo group. Course of illness (single episode or recurrent depression), sex, and age were not significantly related to the treatment group-response interaction.

 
Anchor for JumpAnchor for Jump
FIGURE 1.Response Rates for Drug and Placebo, by Age, Depression Severity, Illness Duration, Sex, and Course of Illnessa

a Categories are defined by quartiles for age and severity, by tertiles for illness duration, and in terms of single episode or recurrent depression for course. Severity was measured with the 17-item Hamilton Depression Rating Scale (HAM-D). Illness duration was computed as current age minus age at onset. Error bars indicate 95% confidence intervals.

In the multivariate logistic regression, only duration of illness was associated with the interaction of treatment group and response, that is, associated with the drug-placebo difference (Table 3). We also performed a multivariate regression using the endpoint HAM-D score (last observation carried forward) as a continuous dependent variable and entering the baseline score as a covariate. Duration of illness remained significantly associated with the treatment group-response interaction (F=4.03, df=2, 2255, p=0.02). Age, sex, and course were not significantly associated. The strength of the association of depression severity with the treatment group-response interaction was essentially the same as that using response as the outcome (F=2.62, df=3, 2255, p=0.049).

 
Anchor for Jump
TABLE 3.Analysis of Association of Age, Illness Duration, Course, Sex, and Depression Severity With Response and With Interaction of Treatment Group and Response, Controlling for Study
Table Footer Note

a The treatment group-response interaction reflects the drug-placebo difference.

Table Footer Note

b Age and depression severity were assessed by quartiles.

Table Footer Note

c Duration of illness (computed as current age minus age at onset) was assessed by tertiles.

+

Duration of Illness and Drug-Placebo Differences

Drug-placebo differences were greatest in the tertile with illness duration >10 years. Among patients with an illness duration >10 years, a logistic regression entering age, sex, illness course, and baseline depression severity and controlling for study demonstrated that severity was also associated with the treatment group-response interaction (the drug-placebo difference) (Wald χ2=8.54, df=3, p=0.04). The interaction of duration of illness and depression severity with the effect size of the drug-placebo difference is illustrated in Figure 2. In the 385 patients with a long duration of illness (>10 years) and moderate to severe depression (HAM-D score ≥21), response rates were 58.0% and 31.4% in the drug and placebo groups, respectively (the effect size for the drug-placebo difference was 0.54), but in the remaining patients, the effect size was small (effect size=0.09).

 
Anchor for JumpAnchor for Jump
FIGURE 2.Effect Size of Drug-Placebo Differences, by Depression Severity, in Patients With Long Duration of Depressive Illness (>10 Years)a

a Depression severity is defined in quartiles. Illness duration was computed as current age minus age at onset.

Our findings suggest that the duration of depressive illness moderates antidepressant response in patients over age 60. Patients with an illness duration >10 years showed greater drug-placebo differences, while those with a short illness duration showed no drug effect. In patients with a duration of illness >10 years, baseline depression severity contributed to drug-placebo differences. Illness duration and severity identify a subgroup of patients with clinically meaningful drug-placebo differences, resulting in a number-needed-to-treat of 4. Yet, only 385 of the 2,235 late-life depression patients in these seven clinical trials had a long duration of illness and at least moderate depression severity. It is unclear whether the proportion of patients with long-duration depression in these clinical trials is similar to that among patients in the community. Age, sex, and course of illness (single episode or recurrent depression) did not moderate response in this sample.

Our findings are similar to those of previous studies examining relationships of illness course and severity to treatment response in nongeriatric samples. Two antidepressant trials of depression patients with cardiac disease (the Sertraline Antidepressant Heart Attack Trial [SADHART] [31] and the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy [CREATE] Trial [32]) found antidepressants more effective than placebo, but post hoc analyses showed that single-episode patients had a high rate of response to placebo with no incremental advantage for active drug. Although these were both mixed-aged samples and used single-episode versus recurrent course to examine differences in response to drug and placebo, both samples were relatively older (mean ages, 57 years and 58 years), and single episodes are likely to be associated with a shorter duration of illness than recurrent episodes. In both of those studies, drug treatment did show an advantage in patients with recurrent depression. With respect to depression severity, two meta-analyses of mixed-age samples found that the effect size of mean score drug-placebo differences increased with severity (27, 28). The SADHART study also noted that active drug was not more effective than placebo in patients with a HAM-D score <20.

In the present study, antidepressants offered no advantage over placebo in patients with a short duration of illness (<2 years), that is, late-onset depression. The response rate to placebo in this group was 47.7%, significantly higher than in those with a long duration of illness (32.8%). This pattern of placebo response appears similar to that observed in the CREATE and SADHART trials in single-episode and recurrent-episode patients with depression. The late-life depression trials were not designed to examine what factors mediate placebo response, but these data suggest either that patients with late-onset depression are more likely to remit spontaneously or that they are responsive to the nonspecific supportive elements associated with frequent visits in clinical trials.

The greater benefits of antidepressants in patients with a long duration of illness may be consistent with models of depression emphasizing kindling with repeated episodes of depression (60). Perhaps the neuroprotective effects of antidepressants are more important in such patients (61).

Our findings do not indicate what explains the lack of drug effects (drug-placebo differences) in late-onset depression. Historically, late-onset depression has been associated with degenerative brain disease, which may reduce antidepressant effectiveness. Studies reviewed previously (3944) found that depressed patients with executive dysfunction or Alzheimer’s dementia are less responsive to antidepressants. However, in the placebo-controlled trials of antidepressants in depressed patients with Alzheimer’s disease, only two of the nine trials studied limited patient selection to moderately severe depression (mean HAM-D score >20 or equivalent MADRS score) (62, 63), and in the two largest trials (40, 64), about three-quarters of the patients had late-onset depression (P. Rosenberg and S. Banerjee, personal communication, 2011). The effectiveness of antidepressants in Alzheimer’s patients who are similar to the drug-responsive subgroup identified in this report (those with a long illness duration and at least moderate depression severity) has not been explored.

While patients with late-life depression and a short duration of illness did not show a clinically meaningful drug effect during acute-phase treatment, our findings do not indicate that antidepressant treatment is of no value in this group. About half of these patients failed to respond to either drug or placebo, and further treatment may be useful. The open-label acute phase of a maintenance treatment study is informative in this respect (24, 65). Patients who did not remit after 8 weeks of treatment with paroxetine could receive up to three open-label augmentation trials with bupropion, nortriptyline, or lithium. Sixty percent of those who received augmentation were in their first episode of depression, and with successive treatments, 50% of them achieved remission, suggesting a possible value of adjunctive medication in patients with late-life depression for whom initial treatment fails. In addition, maintenance treatment studies suggest the potential value of antidepressants in first-episode patients. Paroxetine with or without augmentation has been reported to reduce recurrence relative to placebo in many older patients in their first episode of depression (24). In another maintenance study (66), citalopram was found to be more effective than placebo in preventing recurrence during the 48-week randomized phase. In that trial, 85% of the patients had no prior episodes of major depression, which suggests that maintenance treatment may be of value for at least some first-episode patients. Alternatively, Wilson et al. (67) did not find a significant advantage for sertraline relative to placebo in a 2-year maintenance trial in which 72% of participants were in their first episode. These studies indicate a potential role for medication in maintenance treatment of patients with first-episode late-life depression.

This analysis is somewhat unusual. Most individual-patient-level meta-analyses of depression treatment have been limited to trials conducted by one sponsor using their data. An exception is the Fournier et al. analysis of the effects of illness severity on antidepressant outcome (28). In that analysis, the authors were able to obtain individual patient-level data from six of 23 trials in the domain selected. In the present analysis, individual patient data were obtained for all 10 of the published randomized controlled trials of second-generation antidepressants in outpatients over age 60 with major depression. To our knowledge, these trials represent the entire domain of randomized controlled trials that meet the defined criteria.

This study has some limitations. First, the analysis was limited to the data commonly collected in the 10 trials described. There may be other variables not commonly documented, such as cognitive deficits, that also moderate treatment response. These trials excluded patients with severe or unstable medical illness; however, stable medical illness was common. For example, in the Schneider et al. trial of sertraline (52), 93% of the patients had medical illness, and the average number of medical disorders was 4.3. Such patients are representative of many older depressed outpatients. While the findings may not generalize to the frail elderly, it seems unlikely that this patient group would be more responsive to drug treatment.

Difficulties in determining the exact age at onset of major depression is another limitation, as none of the trials provided a detailed description of how this was ascertained. Categorizing illness duration as short (<2 years), moderate (2–10 years), or long (>10 years) may mitigate the imprecision of estimates of age at onset and provide sufficient accuracy. We also note that in these randomized trials, any biases and imprecision in these data are randomly distributed between treatments. These illness duration categories did identify subgroups with different drug-placebo characteristics. While requiring confirmation, the potential importance of illness duration in moderating drug-placebo differences in these trials underscores the need for reliable methods of assessing illness duration and suggests that this measure be routinely determined.

Another potential limitation of the data is the large effect of the study covariate on response. Such a variable reflects other aspects of the studies that are unaccounted for. We attempted to control for this in our regression model, which allowed us to examine the independent relationship of our variables of interest with response. In addition, while the variability of the study covariate could reflect design problems or measurement error, it could also indicate heterogeneity among the patients that could enhance generalizability.

Finally, we acknowledge that our examination of moderators is a post hoc exploratory analysis and may overemphasize patient and depression characteristics that are unique to this sample. The predictive value of the moderators and the model generated will require replication. As noted above, however, our findings are similar to those of previous meta-analyses and large trials with mixed-aged samples (27, 28, 31, 32).

In summary, data from the seven placebo-controlled acute-phase trials conducted in late-life depression suggest that antidepressants are not effective in older patients with late-onset depression of short duration. Clinicians should reconsider the prevailing practice of simply prescribing an antidepressant in these patients. Antidepressants were effective, however, in patients with a longer duration of illness that was at least moderately severe. These moderators appear to be useful for tailoring treatment to the patient.

Blazer  D;  Hughes  DC;  George  LK:  The epidemiology of depression in an elderly community population.  Gerontologist 1987; 27:281–287
[CrossRef] | [PubMed]
 
Bondareff  W;  Alpert  M;  Friedhoff  AJ;  Richter  EM;  Clary  CM;  Batzar  E:  Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life.  Am J Psychiatry 2000; 157:729–736
[CrossRef] | [PubMed]
 
Bruce  ML;  Seeman  TE;  Merrill  SS;  Blazer  DG:  The impact of depressive symptomatology on physical disability: MacArthur Studies of Successful Aging.  Am J Public Health 1994; 84:1796–1799
[CrossRef] | [PubMed]
 
Conwell  Y:  Suicide, in  Late Life Depression . Edited by Roose  SP;  Sackeim  HA.  Oxford, UK,  Oxford University Press, 2004, pp 95–114
 
Pratt  LA;  Ford  DE;  Crum  RM;  Armenian  HK;  Gallo  JJ;  Eaton  WW:  Depression, psychotropic medication, and risk of myocardial infarction: prospective data from the Baltimore ECA follow-up.  Circulation 1996; 94:3123–3129
[CrossRef] | [PubMed]
 
Simonsick  EM;  Wallace  RB;  Blazer  DG;  Berkman  LF:  Depressive symptomatology and hypertension-associated morbidity and mortality in older adults.  Psychosom Med 1995; 57:427–435
[PubMed]
 
Bruce  ML;  Leaf  PJ;  Rozal  GP;  Florio  L;  Hoff  RA:  Psychiatric status and 9-year mortality data in the New Haven Epidemiologic Catchment Area Study.  Am J Psychiatry 1994; 151:716–721
[PubMed]
 
Pulska  T;  Pahkala  K;  Laippalla  P;  Kivelä  SL:  Major depression as a predictor of premature deaths in elderly people in Finland: a community study.  Acta Psychiatr Scand 1998; 97:408–411
[CrossRef] | [PubMed]
 
Whooley  MA;  Browner  WS; Study of Osteoporotic Fractures Research Group:  Association between depressive symptoms and mortality in older women.  Arch Intern Med 1998; 158:2129–2135
[CrossRef] | [PubMed]
 
Nelson  JC;  Delucchi  K;  Schneider  LS:  Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence.  Am J Geriatr Psychiatry 2008; 16:558–567
[CrossRef] | [PubMed]
 
Small  GW;  Hamilton  SH;  Bystritsky  A;  Meyers  BS;  Nemeroff  CB; Fluoxetine Collaborative Study Group:  Clinical response predictors in a double-blind, placebo-controlled trial of fluoxetine for geriatric major depression.  Int Psychogeriatr 1995; 7(suppl):41–53
[CrossRef] | [PubMed]
 
Georgotas  A;  McCue  RE;  Cooper  T;  Chang  I;  Mir  P;  Welkowitz  J:  Clinical predictors of response to antidepressants in elderly patients.  Biol Psychiatry 1987; 22:733–740
[CrossRef] | [PubMed]
 
Nelson  JC;  Holden  K;  Roose  SP;  Salzman  C;  Hollander  SB;  Betzel  JV:  Are there predictors of outcome in depressed elderly nursing home residents during treatment with mirtazapine orally disintegrating tablets? Int J Geriatr Psychiatry 2007; 22:999–1003
[CrossRef] | [PubMed]
 
Nelson  JC;  Mazure  CM;  Jatlow  PI:  Desipramine treatment of major depression in patients over 75 years of age.  J Clin Psychopharmacol 1995; 15:99–105
[CrossRef] | [PubMed]
 
Salzman  C:  Practical considerations for the treatment of depression in elderly and very elderly long-term care patients.  J Clin Psychiatry 1999; 60(suppl 20):30–33
[PubMed]
 
Katon  W;  Russo  J;  Frank  E;  Barrett  J;  Williams  JW  Jr;  Oxman  T;  Sullivan  M;  Cornell  J:  Predictors of nonresponse to treatment in primary care patients with dysthymia.  Gen Hosp Psychiatry 2002; 24:20–27
[CrossRef] | [PubMed]
 
Mitchell  AJ;  Subramaniam  H:  Prognosis of depression in old age compared to middle age: a systematic review of comparative studies.  Am J Psychiatry 2005; 162:1588–1601
[CrossRef] | [PubMed]
 
Roose  SP;  Sackeim  HA;  Krishnan  KRR;  Pollock  BG;  Alexopoulos  G;  Lavretsky  H;  Katz  IR;  Hakkarainen  H; Old-Old Depression Study Group:  Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial.  Am J Psychiatry 2004; 161:2050–2059
[CrossRef] | [PubMed]
 
Iosifescu  DV;  Nierenberg  AA;  Alpert  JE;  Smith  M;  Bitran  S;  Dording  C;  Fava  M:  The impact of medical comorbidity on acute treatment in major depressive disorder.  Am J Psychiatry 2003; 160:2122–2127
[CrossRef] | [PubMed]
 
Keitner  GI;  Ryan  CE;  Miller  IW;  Kohn  R;  Epstein  NB:  12-month outcome of patients with major depression and comorbid psychiatric or medical illness (compound depression).  Am J Psychiatry 1991; 148:345–350
[PubMed]
 
Löwe  B;  Schenkel  I;  Bair  MJ;  Göbel  C:  Efficacy, predictors of therapy response, and safety of sertraline in routine clinical practice: prospective, open-label, non-interventional postmarketing surveillance study in 1878 patients.  J Affect Disord 2005; 87:271–279
[CrossRef] | [PubMed]
 
Evans  M;  Hammond  M;  Wilson  K;  Lye  M;  Copeland  J:  Treatment of depression in the elderly: effect of physical illness on response.  Int J Geriatr Psychiatry 1997; 12:1189–1194
[CrossRef] | [PubMed]
 
Sheikh  J;  Cassidy  EL;  Doraiswamy  PM;  Salomon  RM;  Hornig  M;  Holland  PJ;  Mandel  FS;  Clary  CM;  Burt  T:  Efficacy, safety, and tolerability of sertraline in patients with life-life depression and comorbid medical illness.  J Am Geriatr Soc 2004; 52:86–92
[CrossRef] | [PubMed]
 
Reynolds  CF  3rd;  Dew  MA;  Pollock  BG;  Mulsant  BH;  Frank  E;  Miller  MD;  Houck  PR;  Mazumdar  S;  Butters  MA;  Stack  JA;  Schlernitzauer  MA;  Whyte  EM;  Gildengers  A;  Karp  J;  Lenze  E;  Szanto  K;  Bensasi  S;  Kupfer  DJ:  Maintenance treatment of major depression in old age.  N Engl J Med 2006; 354:1130–1138
[CrossRef] | [PubMed]
 
Gildengers  AG;  Houck  PR;  Mulsant  BH;  Dew  MA;  Aizenstein  HJ;  Jones  BL;  Greenhouse  J;  Pollock  BG;  Reynolds  CF  3rd:  Trajectories of treatment response in late-life depression: psychosocial and clinical correlates.  J Clin Psychopharmacol 2005; 25(suppl 1):S8–S13
[CrossRef] | [PubMed]
 
Khan  A;  Brodhead  AE;  Kolts  RL;  Brown  WA:  Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials.  J Psychiatr Res 2005; 39:145–150
[CrossRef] | [PubMed]
 
Kirsch  I;  Deacon  BJ;  Huedo-Medina  TB;  Scoboria  A;  Moore  TJ;  Johnson  BT:  Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.  PLoS Med 2008; 5:e45
[CrossRef] | [PubMed]
 
Fournier  JC;  DeRubeis  RJ;  Hollon  SD;  Dimidjian  S;  Amsterdam  JD;  Shelton  RC;  Fawcett  J:  Antidepressant drug effects and depression severity: a patient-level meta-analysis.  JAMA 2010; 303:47–53
[CrossRef] | [PubMed]
 
Bosworth  HB;  Hays  JC;  George  LK;  Steffens  DC:  Psychosocial and clinical predictors of unipolar depression outcome in older adults.  Int J Geriatr Psychiatry 2002; 17:238–246
[CrossRef] | [PubMed]
 
Driscoll  HC;  Basinski  J;  Mulsant  BH;  Butters  MA;  Dew  MA;  Houck  PR;  Mazumdar  S;  Miller  MD;  Pollock  BG;  Stack  JA;  Schlernitzauer  MA;  Reynolds  CF  3rd:  Late-onset major depression: clinical and treatment-response variability.  Int J Geriatr Psychiatry 2005; 20:661–667
[CrossRef] | [PubMed]
 
Glassman  AH;  Bigger  JT;  Gaffney  M;  Shapiro  PA;  Swenson  JR:  Onset of major depression associated with acute coronary syndromes: relationship of onset, major depressive disorder history, and episode severity to sertraline benefit.  Arch Gen Psychiatry 2006; 63:283–288
[CrossRef] | [PubMed]
 
Lespérance  F;  Frasure-Smith  N;  Koszycki  D;  Laliberté  MA;  van Zyl  LT;  Baker  B;  Swenson  JR;  Ghatavi  K;  Abramson  BL;  Dorian  P;  Guertin  MC; CREATE Investigators:  Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial.  JAMA 2007; 297:367–379
[CrossRef] | [PubMed]
 
Flint  AJ;  Rifat  SL:  Effect of demographic and clinical variables on time to antidepressant response in geriatric depression.  Depress Anxiety 1997; 5:103–107
[CrossRef] | [PubMed]
 
Trivedi  MH;  Rush  AJ;  Wisniewski  SR;  Nierenberg  AA;  Warden  D;  Ritz  L;  Norquist  G;  Howland  RH;  Lebowitz  B;  McGrath  PJ;  Shores-Wilson  K;  Biggs  MM;  Balasubramani  GK;  Fava  M; STAR*D Study Team:  Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice.  Am J Psychiatry 2006; 163:28–40
[CrossRef] | [PubMed]
 
Khan  A;  Kolts  RL;  Thase  ME;  Krishnan  KR;  Brown  W:  Research design features and patient characteristics associated with the outcome of antidepressant clinical trials.  Am J Psychiatry 2004; 161:2045–2049
[CrossRef] | [PubMed]
 
Saghafi  R;  Brown  C;  Butters  MA;  Cyranowski  J;  Dew  MA;  Frank  E;  Gildengers  A;  Karp  JF;  Lenze  EJ;  Lotrich  F;  Martire  L;  Mazumdar  S;  Miller  MD;  Mulsant  BH;  Weber  E;  Whyte  E;  Morse  J;  Stack  J;  Houck  PR;  Bensasi  S;  Reynolds  CF  3rd:  Predicting 6-week treatment response to escitalopram pharmacotherapy in late-life major depressive disorder.  Int J Geriatr Psychiatry 2007; 22:1141–1146
[CrossRef] | [PubMed]
 
Alexopoulos  GS;  Katz  IR;  Bruce  ML;  Heo  M;  Ten Have  T;  Raue  P;  Bogner  HR;  Schulberg  HC;  Mulsant  BH;  Reynolds  CF  3rd;; PROSPECT Group:  Remission in depressed geriatric primary care patients: a report from the PROSPECT study.  Am J Psychiatry 2005; 162:718–724
[CrossRef] | [PubMed]
 
Nelson  JC;  Delucchi  K;  Schneider  LS:  Anxiety does not predict response to antidepressant treatment in late life depression: results of a meta-analysis.  Int J Geriatr Psychiatry 2009; 24:539–544
[CrossRef] | [PubMed]
 
Nelson  JC;  Devanand  DP:  A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia.  J Am Geriatr Soc 2011; 59:577–585
[CrossRef] | [PubMed]
 
Banerjee  S;  Hellier  J;  Dewey  M;  Romeo  R;  Ballard  C;  Baldwin  R;  Bentham  P;  Fox  C;  Holmes  C;  Katona  C;  Knapp  M;  Lawton  C;  Lindesay  J;  Livingston  G;  McCrae  N;  Moniz-Cook  E;  Murray  J;  Nurock  S;  Orrell  M;  O’Brien  J;  Poppe  M;  Thomas  A;  Walwyn  R;  Wilson  K;  Burns  A:  Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial.  Lancet 2011; 378:403–411
[CrossRef] | [PubMed]
 
Kalayam  B;  Alexopoulos  GS:  Prefrontal dysfunction and treatment response in geriatric depression.  Arch Gen Psychiatry 1999; 56:713–718
[CrossRef] | [PubMed]
 
Baldwin  R;  Jeffries  S;  Jackson  A;  Sutcliffe  C;  Thacker  N;  Scott  M;  Burns  A:  Treatment response in late-onset depression: relationship to neuropsychological, neuroradiological, and vascular risk factors.  Psychol Med 2004; 34:125–136
[CrossRef] | [PubMed]
 
Alexopoulos  GS;  Kiosses  DN;  Heo  M;  Murphy  CF;  Shanmugham  B;  Gunning-Dixon  F:  Executive dysfunction and the course of geriatric depression.  Biol Psychiatry 2005; 58:204–210
[CrossRef] | [PubMed]
 
Sneed  JR;  Culang  ME;  Keilp  JG;  Rutherford  BR;  Devanand  DP;  Roose  SP:  Antidepressant medication and executive dysfunction: a deleterious interaction in late-life depression.  Am J Geriatr Psychiatry 2010; 18:128–135
[CrossRef] | [PubMed]
 
Hamilton  M:  A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960; 23:56–62
[CrossRef] | [PubMed]
 
Montgomery  SA;  Åsberg  M:  A new depression scale designed to be sensitive to change.  Br J Psychiatry 1979; 134:382–389
[CrossRef] | [PubMed]
 
Bose  A;  Li  D;  Gandhi  C:  Escitalopram in the acute treatment of depressed patients aged 60 years or older.  Am J Geriatr Psychiatry 2008; 16:14–20
[CrossRef] | [PubMed]
 
Hollander  M;  Wolfe  DA:  Nonparametric Statistical Methods , 2nd ed.  New York,  John Wiley & Sons, 1999
 
Cohen  J:  Statistical Power Analysis for the Behavioral Sciences .  Hillsdale, NJ,  Lawrence Erlbaum, 1988
 
Tollefson  GD;  Bosomworth  JC;  Heiligenstein  JH;  Potvin  JH;  Holman  S; the Fluoxetine Collaborative Study Group:  A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression.  Int Psychogeriatr 1995; 7:89–104
[CrossRef] | [PubMed]
 
Kasper  S;  de Swart  H;  Friis Andersen  H:  Escitalopram in the treatment of depressed elderly patients.  Am J Geriatr Psychiatry 2005; 13:884–891
[PubMed]
 
Schneider  LS;  Nelson  JC;  Clary  CM;  Newhouse  P;  Krishnan  KR;  Shiovitz  T;  Weihs  K; Sertraline Elderly Depression Study Group:  An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression.  Am J Psychiatry 2003; 160:1277–1285
[CrossRef] | [PubMed]
 
Rapaport  MH;  Schneider  LS;  Dunner  DL;  Davies  JT;  Pitts  CD:  Efficacy of controlled-release paroxetine in the treatment of late-life depression.  J Clin Psychiatry 2003; 64:1065–1074
[CrossRef] | [PubMed]
 
Schatzberg  A;  Roose  S:  A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression.  Am J Geriatr Psychiatry 2006; 14:361–370
[CrossRef] | [PubMed]
 
Raskin  J;  Wiltse  CG;  Siegal  A;  Sheikh  J;  Xu  J;  Dinkel  JJ;  Rotz  BT;  Mohs  RC:  Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial.  Am J Psychiatry 2007; 164:900–909
[CrossRef] | [PubMed]
 
Rapaport  MH;  Lydiard  RB;  Pitts  CD;  Schaefer  D;  Bartolic  EI;  Iyengar  M;  Carfagno  M;  Lipschitz  A:  Low doses of controlled-release paroxetine in the treatment of late-life depression: a randomized, placebo-controlled trial.  J Clin Psychiatry 2009; 70:46–57
[CrossRef] | [PubMed]
 
Hewett  K;  Chrzanowski  W;  Jokinen  R;  Felgentreff  R;  Shrivastava  RK;  Gee  MD;  Wightman  DS;  O’Leary  MC;  Millen  LS;  Leon  MC;  Briggs  MA;  Krishen  A;  Modell  JG:  Double-blind, placebo-controlled evaluation of extended-release bupropion in elderly patients with major depressive disorder.  J Psychopharmacol 2010; 24:521–529
[CrossRef] | [PubMed]
 
Jadad  AR;  Moore  RA;  Carroll  D;  Jenkinson  C;  Reynolds  DJ;  Gavaghan  DJ;  McQuay  HJ:  Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17:1–12
[CrossRef] | [PubMed]
 
Folstein  MF;  Folstein  SE;  McHugh  PR:  “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician.  J Psychiatr Res 1975; 12:189–198
[CrossRef] | [PubMed]
 
Post  RM:  Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.  Am J Psychiatry 1992; 149:999–1010
[PubMed]
 
Duman  RS;  Monteggia  LM:  A neurotrophic model for stress-related mood disorders.  Biol Psychiatry 2006; 59:1116–1127
[CrossRef] | [PubMed]
 
Lyketsos  CG;  DelCampo  L;  Steinberg  M;  Miles  Q;  Steele  CD;  Munro  C;  Baker  AS;  Sheppard  JM;  Frangakis  C;  Brandt  J;  Rabins  PV:  Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS.  Arch Gen Psychiatry 2003; 60:737–746
[CrossRef] | [PubMed]
 
de Vasconcelos Cunha  UG;  Lopes Rocha  F;  Avila de Melo  R;  Alves Valle  E;  de Souza Neto  JJ;  Mendes Brega  R;  Magalhães Scoralick  F;  Araújo Silva  S;  Martins de Oliveira  F;  da Costa Júnior  AL;  Faria Alves  VX;  Sakurai  E:  A placebo-controlled double-blind randomized study of venlafaxine in the treatment of depression in dementia.  Dement Geriatr Cogn Disord 2007; 24:36–41
[CrossRef] | [PubMed]
 
Rosenberg  PB;  Drye  LT;  Martin  BK;  Frangakis  C;  Mintzer  JE;  Weintraub  D;  Porsteinsson  AP;  Schneider  LS;  Rabins  PV;  Munro  CA;  Meinert  CL;  Lyketsos  CG; DIADS-2 Research Group:  Sertraline for the treatment of depression in Alzheimer disease.  Am J Geriatr Psychiatry 2010; 18:136–145
[CrossRef] | [PubMed]
 
Dew  MA;  Whyte  EM;  Lenze  EJ;  Houck  PR;  Mulsant  BH;  Pollock  BG;  Stack  JA;  Bensasi  S;  Reynolds  CF  3rd:  Recovery from major depression in older adults receiving augmentation of antidepressant pharmacotherapy.  Am J Psychiatry 2007; 164:892–899
[CrossRef] | [PubMed]
 
Klysner  R;  Bent-Hansen  J;  Hansen  HL;  Lunde  M;  Pleidrup  E;  Poulsen  DL;  Andersen  M;  Petersen  HE:  Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy.  Br J Psychiatry 2002;181:29–35
[CrossRef] | [PubMed]
 
Wilson  KC;  Mottram  PG;  Ashworth  L;  Abou-Saleh  MT:  Older community residents with depression: long-term treatment with sertraline: randomised, double-blind, placebo-controlled study.  Br J Psychiatry 2003; 182:492–497
[CrossRef] | [PubMed]
 
References Container

FIGURE 1. Response Rates for Drug and Placebo, by Age, Depression Severity, Illness Duration, Sex, and Course of Illnessa

a Categories are defined by quartiles for age and severity, by tertiles for illness duration, and in terms of single episode or recurrent depression for course. Severity was measured with the 17-item Hamilton Depression Rating Scale (HAM-D). Illness duration was computed as current age minus age at onset. Error bars indicate 95% confidence intervals.

FIGURE 2. Effect Size of Drug-Placebo Differences, by Depression Severity, in Patients With Long Duration of Depressive Illness (>10 Years)a

a Depression severity is defined in quartiles. Illness duration was computed as current age minus age at onset.

Anchor for Jump
TABLE 1.Patient Characteristics in Randomized Placebo-Controlled Trials of Second-Generation Antidepressants in Late-Life Depression
Table Footer Note

a Studies that had values for all the variables of interest were included in the present analyses; studies that did not collect data for one of the variables of interest were excluded.

Table Footer Note

b Duration of illness was computed as current age minus age at onset.

Table Footer Note

c Depression severity was measured with the 17-item Hamilton Depression Rating Scale.

Table Footer Note

d Course of illness was either single episode or recurrent.

Anchor for Jump
TABLE 2.Randomized Placebo-Controlled Trials of Second-Generation Antidepressants in Patients 60 Years and Older With Major Depressive Disordera
Table Footer Note

a MMSE=Mini-Mental State Examination; HAMD17, HAMD21, and HAMD24=17-, 21, and 24-item Hamilton Depression Rating Scale; MADRS=Montgomery-Åsberg Depression Rating Scale; CR=controlled release; XL=extended release.

Table Footer Note

b Studies that had values for all the variables of interest were included in the present analyses; studies that did not collect data for one of the variables of interest were excluded.

Table Footer Note

c DSM-III-R and DSM-IV required a 2-week duration of symptoms. Some studies required 4 weeks, as indicated.

Table Footer Note

d Modified intent-to-treat sample with at least one posttreatment rating, last observation carried forward.

Anchor for Jump
TABLE 3.Analysis of Association of Age, Illness Duration, Course, Sex, and Depression Severity With Response and With Interaction of Treatment Group and Response, Controlling for Study
Table Footer Note

a The treatment group-response interaction reflects the drug-placebo difference.

Table Footer Note

b Age and depression severity were assessed by quartiles.

Table Footer Note

c Duration of illness (computed as current age minus age at onset) was assessed by tertiles.

+

References

Blazer  D;  Hughes  DC;  George  LK:  The epidemiology of depression in an elderly community population.  Gerontologist 1987; 27:281–287
[CrossRef] | [PubMed]
 
Bondareff  W;  Alpert  M;  Friedhoff  AJ;  Richter  EM;  Clary  CM;  Batzar  E:  Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life.  Am J Psychiatry 2000; 157:729–736
[CrossRef] | [PubMed]
 
Bruce  ML;  Seeman  TE;  Merrill  SS;  Blazer  DG:  The impact of depressive symptomatology on physical disability: MacArthur Studies of Successful Aging.  Am J Public Health 1994; 84:1796–1799
[CrossRef] | [PubMed]
 
Conwell  Y:  Suicide, in  Late Life Depression . Edited by Roose  SP;  Sackeim  HA.  Oxford, UK,  Oxford University Press, 2004, pp 95–114
 
Pratt  LA;  Ford  DE;  Crum  RM;  Armenian  HK;  Gallo  JJ;  Eaton  WW:  Depression, psychotropic medication, and risk of myocardial infarction: prospective data from the Baltimore ECA follow-up.  Circulation 1996; 94:3123–3129
[CrossRef] | [PubMed]
 
Simonsick  EM;  Wallace  RB;  Blazer  DG;  Berkman  LF:  Depressive symptomatology and hypertension-associated morbidity and mortality in older adults.  Psychosom Med 1995; 57:427–435
[PubMed]
 
Bruce  ML;  Leaf  PJ;  Rozal  GP;  Florio  L;  Hoff  RA:  Psychiatric status and 9-year mortality data in the New Haven Epidemiologic Catchment Area Study.  Am J Psychiatry 1994; 151:716–721
[PubMed]
 
Pulska  T;  Pahkala  K;  Laippalla  P;  Kivelä  SL:  Major depression as a predictor of premature deaths in elderly people in Finland: a community study.  Acta Psychiatr Scand 1998; 97:408–411
[CrossRef] | [PubMed]
 
Whooley  MA;  Browner  WS; Study of Osteoporotic Fractures Research Group:  Association between depressive symptoms and mortality in older women.  Arch Intern Med 1998; 158:2129–2135
[CrossRef] | [PubMed]
 
Nelson  JC;  Delucchi  K;  Schneider  LS:  Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence.  Am J Geriatr Psychiatry 2008; 16:558–567
[CrossRef] | [PubMed]
 
Small  GW;  Hamilton  SH;  Bystritsky  A;  Meyers  BS;  Nemeroff  CB; Fluoxetine Collaborative Study Group:  Clinical response predictors in a double-blind, placebo-controlled trial of fluoxetine for geriatric major depression.  Int Psychogeriatr 1995; 7(suppl):41–53
[CrossRef] | [PubMed]
 
Georgotas  A;  McCue  RE;  Cooper  T;  Chang  I;  Mir  P;  Welkowitz  J:  Clinical predictors of response to antidepressants in elderly patients.  Biol Psychiatry 1987; 22:733–740
[CrossRef] | [PubMed]
 
Nelson  JC;  Holden  K;  Roose  SP;  Salzman  C;  Hollander  SB;  Betzel  JV:  Are there predictors of outcome in depressed elderly nursing home residents during treatment with mirtazapine orally disintegrating tablets? Int J Geriatr Psychiatry 2007; 22:999–1003
[CrossRef] | [PubMed]
 
Nelson  JC;  Mazure  CM;  Jatlow  PI:  Desipramine treatment of major depression in patients over 75 years of age.  J Clin Psychopharmacol 1995; 15:99–105
[CrossRef] | [PubMed]
 
Salzman  C:  Practical considerations for the treatment of depression in elderly and very elderly long-term care patients.  J Clin Psychiatry 1999; 60(suppl 20):30–33
[PubMed]
 
Katon  W;  Russo  J;  Frank  E;  Barrett  J;  Williams  JW  Jr;  Oxman  T;  Sullivan  M;  Cornell  J:  Predictors of nonresponse to treatment in primary care patients with dysthymia.  Gen Hosp Psychiatry 2002; 24:20–27
[CrossRef] | [PubMed]
 
Mitchell  AJ;  Subramaniam  H:  Prognosis of depression in old age compared to middle age: a systematic review of comparative studies.  Am J Psychiatry 2005; 162:1588–1601
[CrossRef] | [PubMed]
 
Roose  SP;  Sackeim  HA;  Krishnan  KRR;  Pollock  BG;  Alexopoulos  G;  Lavretsky  H;  Katz  IR;  Hakkarainen  H; Old-Old Depression Study Group:  Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial.  Am J Psychiatry 2004; 161:2050–2059
[CrossRef] | [PubMed]
 
Iosifescu  DV;  Nierenberg  AA;  Alpert  JE;  Smith  M;  Bitran  S;  Dording  C;  Fava  M:  The impact of medical comorbidity on acute treatment in major depressive disorder.  Am J Psychiatry 2003; 160:2122–2127
[CrossRef] | [PubMed]
 
Keitner  GI;  Ryan  CE;  Miller  IW;  Kohn  R;  Epstein  NB:  12-month outcome of patients with major depression and comorbid psychiatric or medical illness (compound depression).  Am J Psychiatry 1991; 148:345–350
[PubMed]
 
Löwe  B;  Schenkel  I;  Bair  MJ;  Göbel  C:  Efficacy, predictors of therapy response, and safety of sertraline in routine clinical practice: prospective, open-label, non-interventional postmarketing surveillance study in 1878 patients.  J Affect Disord 2005; 87:271–279
[CrossRef] | [PubMed]
 
Evans  M;  Hammond  M;  Wilson  K;  Lye  M;  Copeland  J:  Treatment of depression in the elderly: effect of physical illness on response.  Int J Geriatr Psychiatry 1997; 12:1189–1194
[CrossRef] | [PubMed]
 
Sheikh  J;  Cassidy  EL;  Doraiswamy  PM;  Salomon  RM;  Hornig  M;  Holland  PJ;  Mandel  FS;  Clary  CM;  Burt  T:  Efficacy, safety, and tolerability of sertraline in patients with life-life depression and comorbid medical illness.  J Am Geriatr Soc 2004; 52:86–92
[CrossRef] | [PubMed]
 
Reynolds  CF  3rd;  Dew  MA;  Pollock  BG;  Mulsant  BH;  Frank  E;  Miller  MD;  Houck  PR;  Mazumdar  S;  Butters  MA;  Stack  JA;  Schlernitzauer  MA;  Whyte  EM;  Gildengers  A;  Karp  J;  Lenze  E;  Szanto  K;  Bensasi  S;  Kupfer  DJ:  Maintenance treatment of major depression in old age.  N Engl J Med 2006; 354:1130–1138
[CrossRef] | [PubMed]
 
Gildengers  AG;  Houck  PR;  Mulsant  BH;  Dew  MA;  Aizenstein  HJ;  Jones  BL;  Greenhouse  J;  Pollock  BG;  Reynolds  CF  3rd:  Trajectories of treatment response in late-life depression: psychosocial and clinical correlates.  J Clin Psychopharmacol 2005; 25(suppl 1):S8–S13
[CrossRef] | [PubMed]
 
Khan  A;  Brodhead  AE;  Kolts  RL;  Brown  WA:  Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials.  J Psychiatr Res 2005; 39:145–150
[CrossRef] | [PubMed]
 
Kirsch  I;  Deacon  BJ;  Huedo-Medina  TB;  Scoboria  A;  Moore  TJ;  Johnson  BT:  Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.  PLoS Med 2008; 5:e45
[CrossRef] | [PubMed]
 
Fournier  JC;  DeRubeis  RJ;  Hollon  SD;  Dimidjian  S;  Amsterdam  JD;  Shelton  RC;  Fawcett  J:  Antidepressant drug effects and depression severity: a patient-level meta-analysis.  JAMA 2010; 303:47–53
[CrossRef] | [PubMed]
 
Bosworth  HB;  Hays  JC;  George  LK;  Steffens  DC:  Psychosocial and clinical predictors of unipolar depression outcome in older adults.  Int J Geriatr Psychiatry 2002; 17:238–246
[CrossRef] | [PubMed]
 
Driscoll  HC;  Basinski  J;  Mulsant  BH;  Butters  MA;  Dew  MA;  Houck  PR;  Mazumdar  S;  Miller  MD;  Pollock  BG;  Stack  JA;  Schlernitzauer  MA;  Reynolds  CF  3rd:  Late-onset major depression: clinical and treatment-response variability.  Int J Geriatr Psychiatry 2005; 20:661–667
[CrossRef] | [PubMed]
 
Glassman  AH;  Bigger  JT;  Gaffney  M;  Shapiro  PA;  Swenson  JR:  Onset of major depression associated with acute coronary syndromes: relationship of onset, major depressive disorder history, and episode severity to sertraline benefit.  Arch Gen Psychiatry 2006; 63:283–288
[CrossRef] | [PubMed]
 
Lespérance  F;  Frasure-Smith  N;  Koszycki  D;  Laliberté  MA;  van Zyl  LT;  Baker  B;  Swenson  JR;  Ghatavi  K;  Abramson  BL;  Dorian  P;  Guertin  MC; CREATE Investigators:  Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial.  JAMA 2007; 297:367–379
[CrossRef] | [PubMed]
 
Flint  AJ;  Rifat  SL:  Effect of demographic and clinical variables on time to antidepressant response in geriatric depression.  Depress Anxiety 1997; 5:103–107
[CrossRef] | [PubMed]
 
Trivedi  MH;  Rush  AJ;  Wisniewski  SR;  Nierenberg  AA;  Warden  D;  Ritz  L;  Norquist  G;  Howland  RH;  Lebowitz  B;  McGrath  PJ;  Shores-Wilson  K;  Biggs  MM;  Balasubramani  GK;  Fava  M; STAR*D Study Team:  Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice.  Am J Psychiatry 2006; 163:28–40
[CrossRef] | [PubMed]
 
Khan  A;  Kolts  RL;  Thase  ME;  Krishnan  KR;  Brown  W:  Research design features and patient characteristics associated with the outcome of antidepressant clinical trials.  Am J Psychiatry 2004; 161:2045–2049
[CrossRef] | [PubMed]
 
Saghafi  R;  Brown  C;  Butters  MA;  Cyranowski  J;  Dew  MA;  Frank  E;  Gildengers  A;  Karp  JF;  Lenze  EJ;  Lotrich  F;  Martire  L;  Mazumdar  S;  Miller  MD;  Mulsant  BH;  Weber  E;  Whyte  E;  Morse  J;  Stack  J;  Houck  PR;  Bensasi  S;  Reynolds  CF  3rd:  Predicting 6-week treatment response to escitalopram pharmacotherapy in late-life major depressive disorder.  Int J Geriatr Psychiatry 2007; 22:1141–1146
[CrossRef] | [PubMed]
 
Alexopoulos  GS;  Katz  IR;  Bruce  ML;  Heo  M;  Ten Have  T;  Raue  P;  Bogner  HR;  Schulberg  HC;  Mulsant  BH;  Reynolds  CF  3rd;; PROSPECT Group:  Remission in depressed geriatric primary care patients: a report from the PROSPECT study.  Am J Psychiatry 2005; 162:718–724
[CrossRef] | [PubMed]
 
Nelson  JC;  Delucchi  K;  Schneider  LS:  Anxiety does not predict response to antidepressant treatment in late life depression: results of a meta-analysis.  Int J Geriatr Psychiatry 2009; 24:539–544
[CrossRef] | [PubMed]
 
Nelson  JC;  Devanand  DP:  A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia.  J Am Geriatr Soc 2011; 59:577–585
[CrossRef] | [PubMed]
 
Banerjee  S;  Hellier  J;  Dewey  M;  Romeo  R;  Ballard  C;  Baldwin  R;  Bentham  P;  Fox  C;  Holmes  C;  Katona  C;  Knapp  M;  Lawton  C;  Lindesay  J;  Livingston  G;  McCrae  N;  Moniz-Cook  E;  Murray  J;  Nurock  S;  Orrell  M;  O’Brien  J;  Poppe  M;  Thomas  A;  Walwyn  R;  Wilson  K;  Burns  A:  Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial.  Lancet 2011; 378:403–411
[CrossRef] | [PubMed]
 
Kalayam  B;  Alexopoulos  GS:  Prefrontal dysfunction and treatment response in geriatric depression.  Arch Gen Psychiatry 1999; 56:713–718
[CrossRef] | [PubMed]
 
Baldwin  R;  Jeffries  S;  Jackson  A;  Sutcliffe  C;  Thacker  N;  Scott  M;  Burns  A:  Treatment response in late-onset depression: relationship to neuropsychological, neuroradiological, and vascular risk factors.  Psychol Med 2004; 34:125–136
[CrossRef] | [PubMed]
 
Alexopoulos  GS;  Kiosses  DN;  Heo  M;  Murphy  CF;  Shanmugham  B;  Gunning-Dixon  F:  Executive dysfunction and the course of geriatric depression.  Biol Psychiatry 2005; 58:204–210
[CrossRef] | [PubMed]
 
Sneed  JR;  Culang  ME;  Keilp  JG;  Rutherford  BR;  Devanand  DP;  Roose  SP:  Antidepressant medication and executive dysfunction: a deleterious interaction in late-life depression.  Am J Geriatr Psychiatry 2010; 18:128–135
[CrossRef] | [PubMed]
 
Hamilton  M:  A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960; 23:56–62
[CrossRef] | [PubMed]
 
Montgomery  SA;  Åsberg  M:  A new depression scale designed to be sensitive to change.  Br J Psychiatry 1979; 134:382–389
[CrossRef] | [PubMed]
 
Bose  A;  Li  D;  Gandhi  C:  Escitalopram in the acute treatment of depressed patients aged 60 years or older.  Am J Geriatr Psychiatry 2008; 16:14–20
[CrossRef] | [PubMed]
 
Hollander  M;  Wolfe  DA:  Nonparametric Statistical Methods , 2nd ed.  New York,  John Wiley & Sons, 1999
 
Cohen  J:  Statistical Power Analysis for the Behavioral Sciences .  Hillsdale, NJ,  Lawrence Erlbaum, 1988
 
Tollefson  GD;  Bosomworth  JC;  Heiligenstein  JH;  Potvin  JH;  Holman  S; the Fluoxetine Collaborative Study Group:  A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression.  Int Psychogeriatr 1995; 7:89–104
[CrossRef] | [PubMed]
 
Kasper  S;  de Swart  H;  Friis Andersen  H:  Escitalopram in the treatment of depressed elderly patients.  Am J Geriatr Psychiatry 2005; 13:884–891
[PubMed]
 
Schneider  LS;  Nelson  JC;  Clary  CM;  Newhouse  P;  Krishnan  KR;  Shiovitz  T;  Weihs  K; Sertraline Elderly Depression Study Group:  An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression.  Am J Psychiatry 2003; 160:1277–1285
[CrossRef] | [PubMed]
 
Rapaport  MH;  Schneider  LS;  Dunner  DL;  Davies  JT;  Pitts  CD:  Efficacy of controlled-release paroxetine in the treatment of late-life depression.  J Clin Psychiatry 2003; 64:1065–1074
[CrossRef] | [PubMed]
 
Schatzberg  A;  Roose  S:  A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression.  Am J Geriatr Psychiatry 2006; 14:361–370
[CrossRef] | [PubMed]
 
Raskin  J;  Wiltse  CG;  Siegal  A;  Sheikh  J;  Xu  J;  Dinkel  JJ;  Rotz  BT;  Mohs  RC:  Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial.  Am J Psychiatry 2007; 164:900–909
[CrossRef] | [PubMed]
 
Rapaport  MH;  Lydiard  RB;  Pitts  CD;  Schaefer  D;  Bartolic  EI;  Iyengar  M;  Carfagno  M;  Lipschitz  A:  Low doses of controlled-release paroxetine in the treatment of late-life depression: a randomized, placebo-controlled trial.  J Clin Psychiatry 2009; 70:46–57
[CrossRef] | [PubMed]
 
Hewett  K;  Chrzanowski  W;  Jokinen  R;  Felgentreff  R;  Shrivastava  RK;  Gee  MD;  Wightman  DS;  O’Leary  MC;  Millen  LS;  Leon  MC;  Briggs  MA;  Krishen  A;  Modell  JG:  Double-blind, placebo-controlled evaluation of extended-release bupropion in elderly patients with major depressive disorder.  J Psychopharmacol 2010; 24:521–529
[CrossRef] | [PubMed]
 
Jadad  AR;  Moore  RA;  Carroll  D;  Jenkinson  C;  Reynolds  DJ;  Gavaghan  DJ;  McQuay  HJ:  Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17:1–12
[CrossRef] | [PubMed]
 
Folstein  MF;  Folstein  SE;  McHugh  PR:  “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician.  J Psychiatr Res 1975; 12:189–198
[CrossRef] | [PubMed]
 
Post  RM:  Transduction of psychosocial stress into the neurobiology of recurrent affective disorder.  Am J Psychiatry 1992; 149:999–1010
[PubMed]
 
Duman  RS;  Monteggia  LM:  A neurotrophic model for stress-related mood disorders.  Biol Psychiatry 2006; 59:1116–1127
[CrossRef] | [PubMed]
 
Lyketsos  CG;  DelCampo  L;  Steinberg  M;  Miles  Q;  Steele  CD;  Munro  C;  Baker  AS;  Sheppard  JM;  Frangakis  C;  Brandt  J;  Rabins  PV:  Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS.  Arch Gen Psychiatry 2003; 60:737–746
[CrossRef] | [PubMed]
 
de Vasconcelos Cunha  UG;  Lopes Rocha  F;  Avila de Melo  R;  Alves Valle  E;  de Souza Neto  JJ;  Mendes Brega  R;  Magalhães Scoralick  F;  Araújo Silva  S;  Martins de Oliveira  F;  da Costa Júnior  AL;  Faria Alves  VX;  Sakurai  E:  A placebo-controlled double-blind randomized study of venlafaxine in the treatment of depression in dementia.  Dement Geriatr Cogn Disord 2007; 24:36–41
[CrossRef] | [PubMed]
 
Rosenberg  PB;  Drye  LT;  Martin  BK;  Frangakis  C;  Mintzer  JE;  Weintraub  D;  Porsteinsson  AP;  Schneider  LS;  Rabins  PV;  Munro  CA;  Meinert  CL;  Lyketsos  CG; DIADS-2 Research Group:  Sertraline for the treatment of depression in Alzheimer disease.  Am J Geriatr Psychiatry 2010; 18:136–145
[CrossRef] | [PubMed]
 
Dew  MA;  Whyte  EM;  Lenze  EJ;  Houck  PR;  Mulsant  BH;  Pollock  BG;  Stack  JA;  Bensasi  S;  Reynolds  CF  3rd:  Recovery from major depression in older adults receiving augmentation of antidepressant pharmacotherapy.  Am J Psychiatry 2007; 164:892–899
[CrossRef] | [PubMed]
 
Klysner  R;  Bent-Hansen  J;  Hansen  HL;  Lunde  M;  Pleidrup  E;  Poulsen  DL;  Andersen  M;  Petersen  HE:  Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy.  Br J Psychiatry 2002;181:29–35
[CrossRef] | [PubMed]
 
Wilson  KC;  Mottram  PG;  Ashworth  L;  Abou-Saleh  MT:  Older community residents with depression: long-term treatment with sertraline: randomised, double-blind, placebo-controlled study.  Br J Psychiatry 2003; 182:492–497
[CrossRef] | [PubMed]
 
References Container
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Articles
Books
DSM-5™ Clinical Cases > Chapter 17.  >
APA Practice Guidelines > Chapter 0.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 44.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 9.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 53.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles