Antidepressant Treatment Strategy for Major Depressive Disorder with High Anxiety: A Multicenter Study
Major depressive disorder (MDD) is a widespread and disabling mental illness. What makes it even more challenging is that up to 90% of MDD patients also experience anxiety symptoms. High anxiety levels can lead to worse clinical outcomes as they may predict poor response to MDD pharmacotherapy. This raises the question: How can we optimize antidepressant treatment for these patients?
A recent study by Xue-Mei Liao, Yun-Ai Su, Ying Wang, Xin Yu, and Tian-Mei Si from Peking University and the 984th Hospital of the Chinese People’s Liberation Army aimed to address this. The study was a post-hoc analysis of a multicenter, randomized, parallel-controlled, open-label study.
Study Design and Participants
The researchers recruited 245 patients aged 18 – 65 years diagnosed with MDD based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. These patients had a current major depressive episode (Hamilton Depression Rating Scale 17-item (HAMD – 17) total score ≥17) and high anxiety symptoms (Hamilton Anxiety Rating Scale (HAMA) total score ≥14 at baseline).
All eligible patients received at least 6 weeks of follow – up and antidepressant treatment. This included selective serotonin reuptake inhibitors (SSRIs) alone or combined with a flexible dose of tandospirone. Sedative – hypnotic drugs were permitted for short – term use if needed for sleep disorders.
Outcome Measures
Efficacy was measured at week 2, week 4, and week 6 using HAMD – 17 total scores, HAMA total scores, Clinical Global Impressions Severity Subscale (CGI – S) score, and short form – 12 (SF – 12) physical component score (PCS) and mental component score (MCS) for quality of life assessment. Remission was defined as an HAMD – 17 total score ≤7 points.
Results
At the end of week 2, 240 patients remained. They were divided into two groups: early – improvement group (≥20% decrease in HAMD – 17 total score, n = 134) and early – unimproved group (<20% decrease in HAMD – 17 total score, n = 106). By the end of the 6 – week follow – up, 230 patients completed the study (128 in the early – improvement group and 102 in the early – unimproved group).
Group Comparisons
- Baseline Demographics: Except for the number of patients taking sedative – hypnotic drugs (more in the early – improvement group, 12.7% vs. 1.9%, P = 0.002), baseline demographic data were similar between the two groups.
- Baseline Scores: The early – improvement group had significantly higher HAMD – 17 (24.76 vs. 23.11, P = 0.007) and CGI – S (4.89 vs. 4.54, P = 0.002) scores at baseline, and significantly lower SF – 12 (PCS) (38.77 vs. 41.65, P = 0.022) and SF – 12 (MCS) (26.01 vs. 28.05, P = 0.035) scores.
- Outcome Scores: From week 2 to 6, the early – improvement group showed statistical superiority in HAMD – 17 total score, HAMA total score, CGI – S total score, SF – 12 (PCS) score in week 6, and SF – 12 (MCS) score. At the endpoint visit, the early – improvement group had lower HAMD – 17 (6.48 vs. 12.17, P < 0.001), HAMA (7.19 vs. 11.8, P < 0.001), and CGI – S (1.91 vs. 2.65, P < 0.001) scores. They also had greater improvements in SF – 12 (PCS) (48.26 vs. 45.36, P = 0.014) and SF – 12 (MCS) (44.21 vs. 36.36, P < 0.001) scores. Additionally, the remission rate in week 6 was significantly higher in the early – improvement group (62.8% vs. 29.4%, P < 0.001).
Influencing Factors of Early Improvement
Using logistic regression, the researchers found that combination with sedative – hypnotic drugs was a significant predictor of early improvement in week 2 (odds ratio: 7.556, 95% confidence interval: 1.607–35.530, P = 0.010). Benzodiazepines, which are commonly used as sedative – hypnotics in MDD patients to relieve anxiety and insomnia, may contribute to this early response as they act faster on anxiety symptoms than antidepressants alone.
Implications
This study replicates previous findings that early improvement (within the first 2 weeks of antidepressant treatment) is a strong predictor of outcome in MDD patients. Specifically, it shows that this also holds true for MDD patients with high anxiety. The short – term combination with sedative – hypnotic drugs in the first few weeks may enhance the early – onset improvement of antidepressant therapy.
For healthcare providers, this suggests that closely monitoring patients in the early weeks of treatment and considering short – term combination therapies (like with sedative – hypnotics) for MDD patients with high anxiety could lead to better clinical outcomes. For patients, it offers hope that early signs of improvement can be a positive indicator of long – term recovery.
This study was published in the Chinese Medical Journal in 2020. The DOI for this article is 10.1097/CM9.0000000000000673.
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