Up to a third of elderly patients with major depressive disorder are treatment resistant, yet little objective evidence is available to guide the clinician in managing these patients. We report here our experience with elderly subjects with prospectively defined treatment-resistant depression in 2 separate research studies: one entailing an augmentation strategy, the other a change to venlafaxine extended release (XR).
Fifty-three elderly subjects with major depressive disorder according to DSM-IV criteria who failed treatment with paroxetine plus interpersonal psychotherapy received 1 to 3 trials of augmentation with bupropion sustained release, nortriptyline, or lithium. Successively fewer subjects entered each sequential trial of augmentation. Twelve subjects subsequently received venlafaxine XR monotherapy. Response to treatment was defined as a 17-item Hamilton Rating Scale for Depression score of < 10 for 3 weeks.
Sixty percent of subjects (N = 32) responded to some form of augmentation, with 45% (24/53), 31% (5/16), and 43% (3/7) responding to the first, second, and third augmentation trials, respectively. The mean time to response after starting the first augmentation trial was 6.0 (SD = 5.8) weeks. Forty-two percent (N = 5) of the venlafaxine XR-treated subjects responded with the mean time to response of 6.4 (SE = 0.9) weeks. Adverse effects leading to treatment discontinuation and falls were more common in the augmentation subjects than in the venlafaxine XR subjects.
We observed similar rates and speed of response with an augmentation strategy and a strategy of switching to venlafaxine XR in elderly subjects with prospectively defined treatment-resistant major depressive disorder. Venlafaxine XR was generally better tolerated than the augmentation strategies. Further investigation of venlafaxine XR as a preferred strategy for treatment-resistant geriatric depression is warranted.
"A majority of physicians agree that medications for depression are effective. However, studies indicate that one third of older adults are treatment-resistant and that response time to remission can start at 2 weeks but may take up to 12 weeks to occur (Alexopoulos, 2008; Whyte et al., 2004). Our mediation model suggests that tailored daily recreation therapy for 2 weeks changes behaviors in a much shorter time period. "
[Show abstract][Hide abstract] ABSTRACT: This article examines the moderating effect of depression on interdisciplinary treatment approaches for behaviors in dementia. A secondary analysis of data collected on tailored treatment of 105 long-term care residents with dementia found a significant relationship between treatment and passivity (p < 0.001), treatment and agitation (p = 0.001), and the mediating effect of change in passivity on change in agitation (p < 0.001). The moderating effect of depression was found as a significant factor. For participants with depression and agitation, a significant change in passive behavior was related to significant change in agitated behavior. Thus, by focusing treatment on passivity, both types of neuropsychiatric behaviors improved. The implications of thoroughly assessing not only a behavior problem such as agitation but also other neuropsychiatric symptoms that complicate the delivery of the intervention are discussed.
Research in Gerontological Nursing 07/2010; 3(3):221-32. DOI:10.3928/19404921-20100601-02 · 0.64 Impact Factor
"Geriatric depression is a syndrome often characterized by a slow response to treatment, a failure to fully remit, and a high propensity for relapse (Dew et al., 2007, Little et al., 1998, Whyte et al., 2004). A number of neurobiological abnormalities, particularly in frontolimbic networks, often are present in the illness; however, the specific contributions of these abnormalities to the clinical presentation and the course of the illness remain unclear. "
"The mean HAM-D score at randomization was 20.1 (3.3), and the mean MMSE score was 27.9 (2.5). As described elsewhere (Whyte et al., 2004), all patients had received acute pharmacotherapy with paroxetine (median final dose: 30 mg/day); 69 had also received augmentation with nortriptyline, bupropion, or lithium. Participants randomly assigned to maintenance pharmacotherapy received the medications at doses associated with sustained response. "
[Show abstract][Hide abstract] ABSTRACT: Many older patients who recover from an episode of major depression continue to suffer from depressed mood, anxiety, and sleep problems. Our study assesses the impact of these residual symptoms on the risk of recurrence during maintenance treatment of late-life depression.
We analyzed data from a randomized clinical trial of maintenance treatment in patients with unipolar depression aged > or =70, 116 of whom remitted and remained stable during open pharmacotherapy and interpersonal psychotherapy (IPT) and were randomized to clinical management/pharmacotherapy; clinical management/placebo; monthly maintenance IPT/ pharmacotherapy; or monthly maintenance IPT/placebo. We assessed the impact of overall residual symptoms (based on the Hamilton Depression Rating Scale (HAM-D) total score) and of specific residual symptom clusters - mood symptoms (depressed mood, guilt, suicidality, energy/interests), sleep disturbance (early, middle, late insomnia), and anxiety (agitation, psychic and somatic anxiety, hypochondriasis) measured at randomization. Sleep disturbance was also assessed with the Pittsburgh Sleep Quality Index (PSQI). We used Cox proportional hazards regression models controlling for assignment to antidepressant medication versus placebo to identify predictors of recurrence.
Residual anxiety and residual sleep disturbance (as measured by the PSQI but not the HAM-D) independently predicted early recurrence.
Use of HAM-D clusters to define residual symptoms; analysis limited to completers of acute and continuation treatment.
In patients with late-life depression who have remitted with pharmacotherapy and psychotherapy, the deleterious effect of residual symptoms is due to persisting anxiety and, possibly, residual sleep disturbance.
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