Many patients treated for major depressive disorder (MDD) continue to experience depressive symptoms after weeks of antidepressant treatment. Since failure to achieve remission is associated with a higher risk of recurrence and worse outcomes, complete remission of depressive symptoms within 6 to 12 weeks of starting treatment is a widely accepted goal.
Several strategies to improve response to antidepressant treatment are evidence-based, including dose optimization, switching antidepressants within or between classes, and augmentation with an antidepressant from a different class or with other medications. While most guidelines support reviewing diagnosis, assessing treatment adherence, and optimizing antidepressant dosage as first steps in managing partial response or nonresponse to treatment, there is little agreement regarding the superiority of medication switching compared to medication escalation strategies . There is consensus that escalation is the preferred strategy when there is an initial partial response, while switching within or between antidepressant classes is preferred for lack of response.
The 2010 American Psychiatric Association Practice Guideline for the Treatment of Patients with Major Depressive Disorder recommended 3 treatment escalation strategies “with moderate clinical confidence” : atypical antipsychotics, lithium, and thyroid hormone. In the following years, evidence grew supporting the use of these and other medications for augmentation treatment.
In the present study, data from a representative survey of the general population were used to examine the prevalence of non-remission and augmentation medication use in adults receiving treatment for depression.
| Results |
The majority of respondents were female, ≥50 years old, non-Hispanic white, with household income ≥200% of the federal poverty level (NFP), college education, private insurance, and at least one medical condition. Selective serotonin reuptake inhibitors (SSRIs) were the most common class of antidepressants used for depression. More than two-thirds had been using the same medication for more than 2 years.
Of the 869 respondents who used antidepressants for at least 3 months, 43.5% were in remission; 56.5% experienced residual symptoms. The most common residual symptoms were “feeling tired or having low energy” and “problems falling asleep or staying asleep or sleeping too much.” 41.5% (n = 227) of non-referred respondents reported feeling tired or low energy. energy and 36.7% reported sleep problems almost every day in the last 2 weeks.
Compared with non-remitted respondents, those in remission reported much less difficulty at work, taking care of household things, and getting along with people. While 22.7% of respondents who were not in remission reported that depression had made it very or extremely difficult to perform these tasks; Less than 0.01% of those whose depression had remitted reported this level of difficulty.
In adjusted analyses, adults ≥ 65 years of age had higher odds of remission than those 18 to 29 years of age (51.3% vs. 41.6%), as did respondents with household income ≥ 200% of NFP vs. those with family income <100% (50.2% vs 20.7%).
Among physical health comorbidities, only heart disease was significantly associated with lower adjusted odds of remission compared with no heart disease (26.1% vs. 45.1%). A greater number of health care visits in the past year was also associated with lower odds of remission compared to 0–3 visits (38.1% vs. 59.4% for 4–9 visits; 29.4% vs. 59.4% for ≥ 10 visits), as well as any contact with mental health services in the past year compared to no contact (31.5% vs. 50.6%).
Of the different types of insurance, private insurance was significantly associated with higher odds of remission vs. not having this coverage (51.7% vs. 32.2%) and Medicare with lower odds of remission (40.8% vs. 44.9%). Duration of antidepressant treatment was not significantly associated with remission.
In sensitivity analyses, 28.3% of the 869 respondents scored ≥ 10 on the Patient Health Questionnaire (PHQ-9) and 71.8% scored < 10. Results of multivariable analyzes for correlates of a PHQ-9 score < 10 were similar to those in the main analyses. Adults ≥65 years of age had higher odds of remission, as did those with a college education and those with private insurance. In contrast, respondents with heart disease were less likely to score in this range compared to those without heart disease, as were respondents with more health care visits and contacts with mental health professionals compared to those without such contacts.
28.1% of the 540 respondents whose depression had not subsided were using increased medication. The most common augmentation treatments were antidepressants of a different class (71.7%), followed by atypical antipsychotics (25.7%).
In the adjusted analysis, adults aged 40 to 49 years had significantly higher odds of using augmentation than those aged 18 to 29 years (32.5% vs. 16.5%), as did respondents with secondary education or educational development overall compared to those with less education (36.9% vs. 18.2%) and respondents who had contact with a mental health professional compared to those who did not (36.0% vs. 21.7%) . In contrast, adults from another racial/ethnic group were less likely to use augmentation treatment compared to non-Hispanic white respondents (21.8% vs. 29.8%).
In sensitivity analyses, 32.6% of respondents who scored ≥ 10 on the PHQ-9 reported using augmentation treatment. Adults ages 30 to 39 were more likely to use augmentation treatment, as were those with income ≥200 NFP, secondary education/SDR, heart disease, and contacts with mental health professionals. In contrast, respondents from other racial/ethnic groups were less likely to use augmentation treatment compared to non-Hispanic white respondents.
| Discussion |
This study presents a broad overview of the prevalence and correlates of depression non-remission and antidepressant escalation treatment use in US adults. There were two main findings. First, most respondents in treatment for depression for 3 months or longer experienced residual depressive symptoms for a longer period of time and were not in remission based on a PHQ-9 cutoff score ≥ 5. They also experienced difficulties in daily life. associated with these symptoms. These findings are consistent with the results of previous clinical studies.
Persistent depressive symptoms put patients at higher risk of relapse and are associated with other adverse outcomes. A lower prevalence of remission in low-income adults with heart disease highlights the importance of socioeconomic and health factors in depression remission. In contrast, lower referral rates among respondents with more health care contacts and with no mental health contacts likely represent greater use of services and a greater likelihood of receiving care from mental health professionals in people with depression. more severe and persistent.
In previous studies, poor physical health and lower socioeconomic status have been consistent predictors of poor response to treatment and course of depression, highlighting the role of social and health adversities in this picture. The association between heart disease and depression without remission underscores the need for coordinated mental and physical health care. Collaborative care interventions have been shown to improve care and outcomes in patients with depression and provide opportunities to address physical and mental health needs.
A second finding was that augmentation treatment was received by only a small fraction of antidepressant-treated adults with unremitted depression. The low use of proven augmentation strategies, such as lithium, is consistent with previous research. Escalation strategies, along with optimizing antidepressant dosage or changing medications, may help increase the likelihood of remission. Most respondents on antidepressants in the present study had not achieved remission, even though most remained on the same medication for more than 2 years. This suggests missed opportunities to optimize medication regimens and improve the chances of remission.
Few studies have examined the prevalence of depression augmentation treatment in the general population. Other forms of enhancing treatment were not evaluated, and furthermore, the remission status of the patients could not be analyzed in any of the studies.
Failure to recognize residual symptoms of depression may contribute to low uptake of antidepressant augmentation. Monitoring treatment response with validated measures and adjusting treatment accordingly—generally known as “measurement-based care”—can potentially improve recognition of residual symptoms and their management.
When interpreting these results, several limitations should be considered.
1. First, symptom ratings at the start of antidepressant treatment were not captured.
2. Second, other strategies such as changing antidepressant doses or changing medications, as well as possible previous escalation attempts, could not be evaluated because information on the history of previous medication use was not collected. Information on psychotherapy was also not collected. However, a considerable proportion of the sample, especially those with unremitted depression, had contact with mental health professionals.
3. Third, the most common residual depression symptoms were fatigue and sleep problems, which are difficult to distinguish from similar complaints in physical conditions.
4. Fourth, many patients who start taking antidepressants remit and discontinue the medication shortly thereafter. These patients would be underrepresented in a cross-sectional sample of patients currently receiving antidepressant treatment, while long-term medication users would be overrepresented.
5. Fifth, a causal relationship between physical health conditions and non-remission of depression could not be established in this cross-sectional study. The relationship between physical health conditions and depression is believed to be bidirectional. Finally, depression diagnoses were based on self-reported symptoms for which respondents were receiving antidepressants rather than research diagnoses.
In the context of these limitations, this study provides an overview of the prevalence of non-remission and medication escalation treatment in people receiving antidepressant treatment. The high prevalence of residual symptoms in individuals who had remained on the same antidepressant medications for long periods is concerning and calls for greater attention to evidence-based strategies to improve the pharmacological management of depression in adults.
