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Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Depression can adversely affect employment status.
To examine whether there is a relative advantage of cognitive therapy or
antidepressant medication in improving employment status following
treatment, using data from a previously reported trial.
Random assignment to cognitive therapy (n = 48) or the
selective serotonin reuptake inhibitor paroxetine (n =
93) for 4 months; treatment responders were followed for up to 24 months.
Differential effects of treatment on employment status were examined.
At the end of 28 months, cognitive therapy led to higher rates of
full-time employment (88.9%) than did antidepressant medication among
treatment responders (70.8%), χ21 = 5.78, P = 0.02, odds ratio (OR) = 5.66,
95% CI 1.16–27.69. In the shorter-term, the main effect of treatment on
employment status was not significant following acute treatment
(χ21 = 1.74, P = 0.19, OR = 1.77, 95% CI
0.75–4.17); however, we observed a site×treatment interaction
(χ21 = 6.87, P = 0.009) whereby cognitive
therapy led to a higher rate of full-time employment at one site but not
at the other.
Cognitive therapy may produce greater improvements in employment
v. medication, particularly over the longer term.
There is conflicting evidence about comorbid personality pathology in depression treatments.
To test the effects of antidepressant drugs and cognitive therapy in people with depression distinguished by the presence or absence of personality disorder.
Random assignment of 180 out-patients with depression to 16 weeks of antidepressant medication or cognitive therapy. Random assignment of medication responders to continued medication or placebo, and comparison with cognitive therapy responders over a 12-month period.
Personality disorder status led to differential response at 16 weeks; 66% v. 44% (antidepressants v. cognitive therapy respectively) for people with personality disorder, and 49% v. 70% (antidepressants v. cognitive therapy respectively) for people without personality disorder. For people with personality disorder, sustained response rates over the 12-month follow-up were nearly identical (38%) in the prior cognitive therapy and continuation-medication treatment arms. People with personality disorder withdrawn from medication evidenced the lowest sustained response rate (6%). Despite the poor response of people with personality disorder to cognitive therapy, nearly all those who did respond sustained their response.
Comorbid personality disorder was associated with differential initial response rates and sustained response rates for two well-validated treatments for depression.
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