Objective: Few evidence-based guidelines exist to guide clinicians in choosing pharmacotherapy for older depressed patients with treatment resistant depression, i. e., not responding to antidepressant trials of adequate dose and duration. We report on our experiences with treatment resistant depression in two consecutive geropsychiatric studies.
Design: Current antidepressant therapy was augmented with a second antidepressant in one study and switched to a different antidepressant in the other. We compared the rates and speed of treatment responses as well as the side effects associated with both treatment strategies.
Materials and Methods: 53 depressed subjects aged 70 or greater failed initial treatment with paroxetine monotherapy as part of a large, late life depression study. They then received 1, 2, or 3 trials of augmentation therapy with lithium carbonate, nortriptyline, or bupropion-SR. 12 subjects at various treatment stages from this group were switched to an open study of venlafaxine-XR (VFX-XR) monotherapy. Subjects were assessed at baseline and in study visits with the Hamilton Rating Scale for Depression (HAM-D). Falls and reasons for medication discontinuation were reviewed.
Results: Both subjects who received 1 to 2 trials of augmentation and those who switched to VFX-XR experienced a 38-42% response rate. Few subjects responded to a third trial of augmentation (17%). The median time to response was 5.7 and 6.4 weeks for augmentation and VFX-XR therapies respectively. Adverse effects led 51% of subjects to discontinue an augmentation therapy and 8% of subjects to discontinue VFX-XR. The rate of falls in subjects receiving augmentation therapy was 42% compared to 24% in subjects receiving VFX-XR.
Conclusion: Our post-hoc analysis indicates similar, modest rates and speed of response for the augmention and switching strategies. The higher rates of falls and discontinuation related to adverse effects with augmentation therapy relative to VFX-XR is an important concern for treating clinicians. Given this evidence of its better tolerability in older depressed subjects, a controlled evaluation of VFX-XR as a first line agent for treatment resistant, late life depression appears to be warranted.
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