Antidepressant Prescribing in Primary Care to Older Adults Without Major Depression

Depression among older adults has been the subject of a significant amount of research and education over the past 20 years. Initially, the work highlighted that depression often went unrecognized in typical care settings and that when it was diagnosed, it was often undertreated (1). Subsequently, significant efforts were made to improve detection and treatment of depression in primary care (2,3), given that few older adults have access to specialty mental health care. Although a variety of models to improve the detection and treatment of depression have been studied, collaborative care has been particularly effective (4). However, implementation of these models has lagged far behind their evidence base, largely because of a lack of sustainable reimbursement models (5). Yet, even as the most effective models of depression care go unimplemented, use of antidepressants continues to increase (6), with pervasive use among older adults seen in outpatient care (7).

Recent analyses of nationally representative surveys have suggested that there is extensive use of antidepressants without a diagnosis of major depressive disorder (MDD) or significant depressive symptoms (8,9). In addition, analyses of national claims data from the U.S. Department of Veterans Affairs system (10) and a private insurance claims database (11) have also suggested that a significant proportion of antidepressant use occurs without a psychiatric diagnosis. However, these survey and administrative data do not contain information about a patient’s clinical status at the time of the prescription. What appears to be antidepressant use without a psychiatric indication could be due to the survey format (for example, limited space to list diagnoses) or clinician oversight (for example, not adding MDD as a billing diagnosis after having recognized it as present). However, in another study, when patients were contacted by telephone shortly after a new antidepressant was prescribed, the majority described depressive symptoms that were not severe enough to suggest the presence of MDD (12). Finally, a recent analysis of participants in the Baltimore Epidemiologic Catchment Area Study, which followed participants for four survey waves (1981–2005), found that 69% of antidepressant users in the final wave did not currently meet criteria for MDD and had never met the criteria on the basis of their survey assessments over the preceding two decades. Even a recent analysis arguing that antidepressant use without MDD is not a significant problem found that 26% of persons ages 65 or older who had been newly prescribed an antidepressant had symptoms below the threshold that suggests MDD (13).

A relatively conservative interpretation of these analyses, when taken together, suggests that at least one-quarter of antidepressant use occurs in the absence of significant depressive symptoms. Although antidepressants are effective in treating MDD, patients with less severe symptoms are unlikely to benefit from antidepressant treatment, yet they are still subject to the medication’s side effects and adverse events (14–16), along with the unnecessary cost and risks of polypharmacy. However, a key limitation of each study was the lack of information about the prescribers’ rationale. It may be that providers were responding to some other psychological or emotional distress that is not being captured by a standard inventory of depressive symptoms. In addition, some amount of antidepressant use may have been off label for reasons such as insomnia or neuropathic pain, a practice that is not uncommon (17) and is arguably appropriate.

In this analysis, we used data from the Treatment Initiation and Participation (TIP) Program study, a randomized controlled trial of an intervention to improve antidepressant adherence and depression outcomes among older adults. TIP was sponsored by the National Institutes of Health (NIH). This study recruited older adults from primary care practices in New York and Michigan who had been newly prescribed an antidepressant and who had been prescribed the medication, according to chart review, for the purpose of treating depression. However, according to the baseline study assessment, a significant proportion of patients did not have MDD. We hypothesized that receipt of antidepressants, regardless of whether patients had a diagnosis of MDD, would be associated with a similar burden of both general medical illness and psychosocial distress, suggesting that providers are prescribing an antidepressant in response to patient distress that may not precisely fit the constellation of symptoms required for a diagnosis of MDD. In addition, on the basis of prior work demonstrating an association between demographic characteristics and antidepressant use among patients without a diagnosis of MDD (8,11,18), we hypothesized that prescribing antidepressants to patients without MDD would be associated with female gender, older age, and white race.

Methods

Sample

The study population comprised participants in the TIP study, an NIH-sponsored randomized controlled trial. The study was completed at three primary care practice sites, one in New York City and two in southeastern Michigan. Adults ages 55 or older who received a new antidepressant prescription for depression (defined as having not been on an antidepressant during the previous six months) were eligible. Participants were identified by physician referral as well as by chart review, with chart review completed for all patients to confirm that the antidepressant was prescribed for depression rather than for another reason, such as neuropathy or insomnia. Patients prescribed an antidepressant for both depression and a comorbid condition were eligible. Older adults meeting any of the following criteria were excluded: presence or history of psychotic or bipolar disorder, suicidal intent or plan in the immediate future, Mini–Mental State Examination score <24, and alcohol or substance dependence. [A CONSORT diagram of study enrollment is available as an online supplement to this article.]

Participants were randomly assigned to the TIP intervention or treatment as usual, with research assessments conducted at study entry and multiple time periods up to 24 weeks. This analysis used only baseline data collected at study entry and included data from all participants, regardless of whether they were assigned to the intervention or to treatment as usual. The study was approved by the institutional review boards of Weill Cornell Medical College and the University of Michigan Medical School.

Baseline evaluations of study participants were conducted by research assistants from March 6, 2011, to January 9, 2015, within ten days of participants’ receiving a prescription for an antidepressant from their primary care provider. The Structured Clinical Interview for DSM-IV (SCID) was conducted by research staff to establish the presence of a depressive disorder and to screen for the exclusion criteria. The SCID data were reviewed by a clinical psychologist to establish the final diagnosis of MDD, minor depressive disorder, or no depressive disorder. Minor depression is defined by DSM-IV as two to four symptoms of depression, at least one of which is depressed mood or anhedonia, for a duration of two or more weeks. So that the burden of depressive symptoms could be assessed, each participant completed the Patient Health Questionnaire–9 (PHQ-9) depression scale (19) and the 24-item Hamilton Depression Rating Scale (HDRS) (20).

Participant Characteristics

This analysis used demographic and clinical covariates from the baseline assessment that have been shown to influence clinicians’ assessment of MDD (for example, race, gender, and comorbidity [21,22]). The primary TIP intervention study, given its goal of improving antidepressant treatment initiation and participation, included a variety of other measures to assess psychosocial features that may influence perceived need for or engagement in treatment. From among these additional measures, we selected measures that a clinician might perceive as markers of distress.

Demographic variables included age, gender, race, living alone or with others, and education. Clinical variables included the Chronic Disease Score, a measure of medical comorbidity derived from prescription medications (23); the 12-item Short-Form Health Survey (SF-12) physical component summary (PCS) score, a measure of the participant’s perception of overall physical well-being (24); the Cornell Services Index, which captures service utilization, specifically acute care (emergency department and inpatient admission), outpatient medical care, and other support services (such as home health aides and home meal delivery) over the prior 90 days (25); self-reported history of prior antidepressant use; and time spent by the provider in discussion about the newly prescribed antidepressant, as reported by the participant.

Psychosocial variables included distress arising from interpersonal problems, as measured by the Inventory of Interpersonal Problems (26); beliefs and fears about somatic sensations, as measured by subscales of the Anxiety Sensitivity Index–Revised, given that these beliefs could influence antidepressant adherence (27); perceived need, which was assessed by the response to the question, “In the past month have you had severe enough personal, emotional, behavior, or mental problems that you needed help with?” (28); perceived support and understanding from family and friends, as measured by the Duke Social Support Index (29); hopelessness, as measured by the Beck Hopelessness Scale (30); perceived ability to cope with problems in life, as measured by the General Self-Efficacy Scale (31); and perception of overall emotional well-being, as measured by the SF-12 mental component summary (MCS) score (24).

Statistical Methods

A total of 231 participants completed the baseline assessment. For this analysis, patients diagnosed as having MDD (N=100) were compared with those without MDD (N=131, including 63 patients with minor depression and 68 patients with symptoms below the threshold for minor depression). The patients without MDD were grouped together, given that the evidence of efficacy for antidepressants in minor depression is limited (32,33). Groups were initially compared on the characteristics described above by using t tests for continuous variables and chi-square tests for categorical variables. We used multivariable logistic regression to test the association of patient characteristics with the outcome of antidepressant use without a diagnosis of MDD. This model adjusted for all demographic characteristics, site, and the clinical and psychosocial characteristics that were significant at p<.10 in the bivariate analysis. As a sensitivity analysis of our decision to group together all patients without MDD, we performed a multinomial regression comparing the association of the patient characteristics with antidepressant use among those with no depression, minor depression, and MDD. For final results, a p value of <.05 was used as the level of statistical significance.

Results

Baseline participant characteristics are shown in Table 1. [A table showing participant characteristics by site is available as an online supplement to this article.] A total of 131 (57%) participants did not have MDD, whereas 100 (43%) had MDD. Those without MDD had significantly lower mean scores on the PHQ-9 and HDRS compared with their counterparts with MDD. Participants without a diagnosis of MDD were older and disproportionately white; there was no association with gender.

Although participants did not vary by burden of chronic disease, the group without MDD reported slightly higher mean PCS scores, indicating better perceived physical well-being. They also reported having fewer outpatient medical visits as well as receiving fewer support services. Participants without MDD had better scores on every psychosocial measure except the perceived need item.

Before the regression model was performed, a correlation matrix was performed using the psychosocial variables, given their strong association with the presence of MDD. As the single psychosocial variable most closely correlated with the others, the SF-12 MCS was chosen for the regression. In the final model, being white (adjusted odds ratio [AOR]=3.11, p=.03) and reporting higher mean MCS scores (AOR=1.16, p<.001), indicating better emotional well-being, were the only characteristics significantly associated with being prescribed an antidepressant without having an MDD diagnosis (Table 2). In the sensitivity model, the patients with minor depression more closely resembled patients with no depressive symptoms than those with MDD, confirming our a priori grouping decision.

Discussion

In this study of older adults newly prescribed an antidepressant to treat depression, the majority of patients did not meet criteria for MDD; 29% did not even meet criteria for minor depression. Those prescribed an antidepressant in the absence of MDD were older and were more likely to be white. However, rather than reporting equivalent levels of distress, patients without MDD generally reported better health and well-being on all measures compared with patients with MDD. Other than race, the only significant factor in the final regression was emotional well-being—patients prescribed antidepressants without having a diagnosis of MDD reported better well-being, contrary to our hypothesis.

The proportion of patients who were prescribed an antidepressant without having a depression diagnosis reported in this study was less than the proportion (72.7%) described by Mojtabai and Olfson (8) in their analysis of the National Ambulatory Medical Care Survey (NAMCS) yet was higher than the proportion (26%) reported by Simon and others (13), which is likely a function of the respective data sources. NAMCS respondents may report up to three diagnoses for each visit; some visits for MDD may not get captured because three other, more high-priority diagnoses were reported. In contrast, Simon and colleagues used data from health systems participating in the Mental Health Research Network and limited their analysis to patients who received a baseline PHQ-9. It might be expected that the sensitivity and specificity of depression treatment in such settings might be better than average (a Mental Health Research Network where PHQ-9s are routinely administered). Our results are consistent with an analysis by Wiechers and others (11) of a commercial claims database, which found that 52% of antidepressant use occurred in the absence of a psychiatric diagnosis.

We hypothesized that the group without MDD would have a burden of general medical illness and levels of psychosocial distress similar to those of the group with MDD. Such findings would be consistent with literature suggesting that older adults experience depression differently than younger counterparts—reporting feelings of hopelessness and social isolation rather than sadness (34–36)—in which case, providers in this study were perhaps responding appropriately by prescribing antidepressants. However, that appears not to have been the case: on the basis of the SF-12 MCS, which was included in the final model as the representative psychosocial variable, the group without MDD reported significantly better well-being compared with the group with MDD.

Age was associated with the presence of MDD among users of antidepressants in the initial analysis, but the association was not significant in the final model. Although age can make identification of depression more challenging among older adults compared with younger adults, this age differential may not apply within an older population. There was no association between the diagnosis of MDD among users of antidepressants and gender, contrary to our hypothesis. The association of white race with antidepressant treatment among patients without MDD may be an unanticipated but logical consequence of utilization patterns among white older adults, who are both more likely to receive care for depression (37) and more likely to find antidepressants acceptable compared with other racial and ethnic groups (38).

What exactly is driving the use of antidepressants for patients without MDD? It is possible that providers (correctly) did not believe that MDD was present but chose to prescribe the antidepressant for subsyndromal symptoms. There is substantial evidence that such symptoms have a significant impact on function, mortality, and health care costs for older adults (39–41). There is no evidence, however, that antidepressants are beneficial for these symptoms (32,33,42). Perhaps this pattern is a case of treating the “worried well,” such that antidepressant use is prompted more by concern about depression than by the actual presence of the disorder. The threshold for prescribing antidepressants may also be getting lower, as changing public attitudes toward antidepressant use and mental illness, as well as direct-to-consumer advertising, may lead older patients to be more open to trying an antidepressant (43,44). Last, the use of antidepressants for patients without MDD may simply be a case of incorrect diagnosis, given the difficulty of accurately diagnosing depression in primary care settings (45). Although the mean PHQ-9 scores (8.9 out a possible 27) of those without MDD were not insignificant, comorbid medical conditions may contribute to symptoms such as low energy, poor sleep, and poor appetite, while the cardinal features of anhedonia or depressed mood are absent, generating an elevated PHQ-9 score even if MDD is not present.

Our analysis had several limitations. First, the generalizability of the findings may be limited because the study was conducted in just three primary care practices. However, as noted above, the proportion of antidepressant users without MDD is consistent with other analyses of national data and the clinical sites serve a diverse population of patients. Second, there was no information about the providers’ thought process at the time of prescription, although the chart review established that the antidepressant was meant to treat depression. Third, the baseline assessment may have been completed as many as ten days after the prescription, and thus the patient may have changed clinically since being seen by the provider. However, given the time span over which antidepressants work, it is unlikely that there would have been a significant reduction in the burden of depressive symptoms within, at most, ten days.

This analysis of older adults who were prescribed antidepressants for depression confirms what other data sources have suggested: a significant amount of antidepressant use meant to treat depression is being prescribed for patients without depression or with milder forms of the disorder that do not warrant pharmacotherapy. The extent of inappropriate use is especially concerning given the emphasis on screening for depression in primary care, which is reimbursed by Medicare and is required as a quality measure for Medicare accountable care organizations (46). Although screening may be critical to detect undiagnosed MDD, the potential for increased overdiagnosis and overtreatment must be acknowledged. In a meta-analysis of identification of depression in primary care, Mitchell and others (45) examined the prevalence of depression in primary care and the sensitivity and specificity of providers’ ability to diagnose MDD. They found that misidentification of depression outnumbered missed cases. When older patients are prescribed antidepressants even though they lack the condition for which an antidepressant might provide benefits, they are still subject to the potential side effects, adverse events, and risks of polypharmacy (14–16) associated with use, along with the unnecessary cost.

Conclusions

Depression has a significant adverse impact on older adults and magnifies the morbidity associated with other chronic medical illness. Although improving the recognition and treatment of depression in primary care has been an important focus of research and policy, it is important to recognize the potential for overtreatment. Providers and the public increasingly recognize depression as a medical problem meriting treatment; however, they should be aware that antidepressants are not beneficial for depressive symptoms that do not meet the criteria for MDD, but their potential side effects and costs remain regardless of whether MDD is present. Primary care continues to be both the de facto and the preferred mental health treatment setting for older adults (7,47), and collaborative care continues to be the standard for addressing depression in primary care (48). It is critical to consider how such a model might support the efforts of primary care providers to reduce both undertreatment and overtreatment of depression.