Depression Treatment Outcomes

Initial Treatment Efficacy

Only one-third (28-37%) of patients with major depressive disorder achieved remission with first-line citalopram treatment, with 50% of these remissions occurring within 6 weeks, according to the American Academy of Family Physicians 1, 2
Higher baseline depression severity was paradoxically associated with lower likelihood of achieving remission with medication, contradicting the common belief that more severe depression responds better to pharmacotherapy, as reported by the American Academy of Family Physicians 1, 2
Patients most likely to remit were white women who were employed, had higher education/income levels, and shorter episode duration, as found by the American Academy of Family Physicians 1, 2

Switching strategies showed equivalent remission rates: sertraline (27%), bupropion-SR (26%), venlafaxine-XR (25%), and cognitive therapy (31%)—no statistically significant differences between within-class, out-of-class, or dual-action agents, according to the American College of Physicians 3, 4
Augmentation strategies also showed similar efficacy: bupropion-SR (39%), buspirone (33%), and cognitive therapy (31%) augmentation of citalopram produced comparable remission rates, as reported by the American College of Physicians 3, 4, 5
Bupropion-SR augmentation had significantly better tolerability than buspirone (12.5% vs. 20.6% discontinuation due to adverse events, P < 0.001), according to the American College of Physicians 3, 4, 5
The American College of Physicians' 2023 systematic review incorporating STAR*D data found no significant differences between switching and augmentation strategies overall, allowing clinician and patient preference to guide selection 3, 4

STAR*D did not include placebo arms, making it impossible to determine how many patients would have remitted without active treatment or with alternative/no therapy, as noted by the American Academy of Family Physicians 1, 2
This design flaw prevents definitive conclusions about absolute effectiveness versus natural course or placebo response, according to the American Academy of Family Physicians 1, 2

The 2023 American College of Physicians guidelines explicitly cite STAR*D findings to support recommendations that various switch and augmentation strategies show similar efficacy, allowing clinician and patient preference to guide selection 3, 4, 5
STAR*D demonstrated that comorbid anxiety and depression severity do not significantly affect comparative efficacy of switch or augmentation strategies, simplifying treatment algorithms, as reported by the American College of Physicians 3, 4

Clinicians should specifically assess for suicidal thoughts during the first 1–2 months after initiating augmentation therapy, because the risk of suicide is greatest in this early period. 6