Objective: Adults with major depressive disorder frequently do not achieve remission with an initial treatment. Addition of psychotherapy for patients who do not achieve remission with antidepressant medication alone can target residual symptoms and protect against recurrence, but the utility of adding antidepressant medication after nonremission with cognitive-behavioral therapy (CBT) has received little study. The authors aimed to evaluate the acute and long-term outcomes resulting from both sequences of combination treatments. Methods: Previously untreated adults with major depression who were randomly assigned to receive escitalopram, duloxetine, or CBT monotherapy and completed 12 weeks of treatment without achieving remission entered an additional 12 weeks of combination treatment. For patients who did not achieve remission with CBT, escitalopram was added (CBT plus medication group) to their treatment, and for those who did not achieve remission with an antidepressant, CBT was added (medication plus CBT group) to their treatment. Patients who responded to the combination treatment entered an 18-month follow-up phase to assess risk of recurrence. Results: A total of 112 patients who did not achieve remission with a monotherapy entered combination treatment (41 who responded to monotherapy but did not achieve remission and 71 who did not respond to monotherapy). Overall, remission rates after subsequent combination therapy were significantly higher among patients who responded to monotherapy but did not achieve remission (61%) than among patients who did not respond to monotherapy (41%). Among patients who responded to monotherapy but did not achieve remission, the remission rate in the CBT plus medication group (89%) was higher than in the medication plus CBT group (53%). However, among patients whose depression did not respond to monotherapy, rates of response and remission were similar between the treatment arms. Higher levels of anxiety, both prior to monotherapy and prior to beginning combination treatment, predicted poorer outcomes for both treatment groups. Conclusions: The order in which CBT and antidepressant medication were sequentially combined did not appear to affect outcomes. Addition of an antidepressant is an effective approach to treating residual symptoms for patients who do not achieve remission with CBT, as is adding CBT after antidepressant monotherapy. Patients who do not respond to one treatment modality warrant consideration for addition of the alternative modality.
Background Major depressive disorder (MDD) is a heterogeneous condition and individual patients are likely to be differentially responsive to specific treatments. In an exploratory factor analysis of three rating scales, the Genome-based Therapeutic Drugs for Depression (GENDEP) trial identified three factors that were differentially associated with outcome to nortriptyline and escitalopram. However, this factor analysis has neither been replicated or applied to a psychotherapy treatment. Methods We replicated the GENDEP analytic method in the Emory Predictors of Remission to Individual and Combined Treatments (PReDICT) study. The 17-item Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, and Beck Depression Inventory were administered to 306 MDD patients in the PReDICT study, which randomized previously untreated adults to 12 weeks of treatment with cognitive behavior therapy (CBT), escitalopram, or duloxetine. Utilizing Item Response Theory methodologies, factor scores were derived from the three scales and the efficacy of the three treatments was compared for the identified factor scores. Results Four factors were identified: “Despair,” “Mood and Interest,” “Sleep,” and “Appetite.” These factors closely aligned with the factors identified in GENDEP. Compared to CBT, escitalopram and duloxetine produced more rapid but ultimately similar improvement on the Despair and Mood and Interest factors; no significant differences between treatments emerged on the other factors. Limitations The scales contained differing numbers of items pertaining to specific depressive symptoms. Conclusion The heterogeneity of MDD can be parsed into a consistent factor structure, with the factors showing differential rapidity, but ultimately similar, improvement across treatments.
Summary
Meditation practices may impact physiological pathways that are modulated by stress and relevant to disease. While much attention has been paid to meditation practices that emphasize calming the mind, improving focused attention, or developing mindfulness, less is known about meditation practices that foster compassion. Accordingly, the current study examined the effect of compassion meditation on innate immune, neuroendocrine and behavioral responses to psychosocial stress and evaluated the degree to which engagement in meditation practice influenced stress-reactivity. Sixty-one healthy adults were randomized to 6 weeks of training in compassion meditation (n=33) or participation in a health discussion control group (n=28) followed by exposure to a standardized laboratory stressor (Trier Social Stress Test [TSST]). Physiologic and behavioral responses to the TSST were determined by repeated assessments of plasma concentrations of interleukin (IL)-6 and cortisol as well as total distress scores on the Profile of Mood States (POMS). No main effect of group assignment on TSST responses was found for IL-6, cortisol or POMS scores. However, within the meditation group, increased meditation practice was correlated with decreased TSST-induced IL-6 (rp =-0.46, p=0.008) and POMS distress scores (rp =-0.43, p=0.014). Moreover, individuals with meditation practice times above the median exhibited lower TSST-induced IL-6 and POMS distress scores compared to individuals below the median, who did not differ from controls. These data suggest that engagement in compassion meditation may reduce stress-induced immune and behavioral responses, although future studies are required to determine whether individuals who engage in compassion meditation techniques are more likely to exhibit reduced stress reactivity.
Early childhood and pregnancy are two sensitive periods of heightened immune plasticity, when exposure to adversity may disproportionately increase health risks. However, we need deeper phenotyping to disentangle the impact of adversity during sensitive periods from that across the total lifespan. This study examined whether retrospective reports of adversity during childhood or pregnancy were associated with inflammatory imbalance, in an ethnically diverse cohort of 53 low-income women seeking family-based trauma treatment following exposure to interpersonal violence. Structured interviews assessed early life adversity (trauma exposure ≤ age 5), pregnancy adversity, and total lifetime adversity. Blood serum was assayed for pro-inflammatory (TNF-a, IL-1ß, IL-6, and CRP) and anti-inflammatory (IL-1RA, IL-4, and IL-10) cytokines. CD14+ monocytes were isolated in a subsample (n = 42) and gene expression assayed by RNA sequencing (Illumina HiSeq 4000; TruSeq cDNA library). The primary outcome was a macrophage-associated M1/M2 gene expression phenotype. To evaluate sensitivity and specificity, we contrasted M1/M2 gene expression with a second, clinically-validated macrophage-associated immunosuppressive phenotype (endotoxin tolerance) and with pro-inflammatory and anti-inflammatory cytokine levels. Adjusting for demographics, socioeconomic status, and psychopathology, higher adversity in early life (ß = .337, p = 0.029) and pregnancy (ß = .332, p = 0.032) were each associated with higher M1/M2 gene expression, whereas higher lifetime adversity (ß = −.341, p = 0.031) was associated with lower immunosuppressive gene expression. Adversity during sensitive periods was uniquely associated with M1/M2 imbalance, among low-income women with interpersonal violence exposure. Given that M1/M2 imbalance is found in sepsis, severe COVID-19 and myriad chronic diseases, these findings implicate novel immune mechanisms underlying the impact of adversity on health.