Pilot Study of Augmentation With Aripiprazole for Incomplete Response in Late-Life Depression

Sheffrin, Meera; Driscoll, Henry P.; Lenze, Eric J.; Mulsant, Benoit H.; Pollock, Bruce G.; Miller, Mark D.; Butters, Meryl A.; Dew, Mary Amanda; Reynolds, Charles F.

doi:10.4088/jcp.07m03805

Cited by 57 publications

(46 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, sideeffects do not explain the reduced efficacy of antidepressants. These findings are in line with clinical observations of reduced antidepressant effectiveness in older patients (Lenze et al, 2008;Sheffrin et al, 2009;Tedeschini et al, 2011) as well as increased side-effects of TCA (Mottram et al, 2006).…”

Section: Discussionsupporting

confidence: 89%

“…Unfortunately, the side-effects of antidepressants and other central nervous system drugs are increased in older patients (Turnheim, 2003;Trifirò and Spina, 2011), whereas their therapeutic effects have not been strongly supported. Although TCA and SSRIs are reported to be effective in clinical trials with older patients (Gareri et al, 2000;Salzman et al, 2002;Blazer, 2003), some authors have claimed that their effectiveness is reduced compared with YAs (Lenze et al, 2008;Sheffrin et al, 2009;Tedeschini et al, 2011). It is probable that such a decline begins at middle age (MA) as a modest reduction that becomes pronounced at senescence (Tedeschini et al, 2011), but studies testing this proposal have not been carried out.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Age-related changes in the antidepressant-like effect of desipramine and fluoxetine in the rat forced-swim test

Olivares-Nazario

Fernández‐Guasti

Martı́nez-Mota

2016

Behavioural Pharmacology

View full text Add to dashboard Cite

Some reports suggest that older patients are less responsive to antidepressants than young adults, but this idea has not been fully supported. Here, we investigated the role of aging in the behavioral effects of the antidepressants, desipramine (DMI) (5, 10, and 20 mg/kg) and fluoxetine (FLX) (5, 10, and 20 mg/kg) in young adults (3-5 months), middle-aged (MA, 12-15 months), and senescent (SE, 23-25 months) male rats in the forced-swim test. In addition, locomotor activity and motor coordination were assessed as side-effects. DMI and fluoxetine produced an antidepressant-like effect in YA and MA animals, although in the latter group, a shift to the right in the dose-response curve was found for DMI. Importantly, neither drug was effective in SE animals. Motor side-effects were produced mainly by DMI in MA and SE rats. Therefore, a decrease in the antidepressant-like effect is associated strongly with senescence as well as an increased vulnerability to motor side-effects, particularly of tricyclics. This study is significant because SE animals are scarcely studied in pharmacological screening tests, and our findings might be useful for improving antidepressant treatments for the increasing aged population.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Age-related changes in the antidepressant-like effect of desipramine and fluoxetine in the rat forced-swim test

Olivares-Nazario

Fernández‐Guasti

Martı́nez-Mota

2016

Behavioural Pharmacology

View full text Add to dashboard Cite

show abstract

“…On the other hand, for those patients who stayed on drug or placebo in both phases, there was a marginal increase in drug-placebo separation. A recent study that extended the aripiprazole antidepressant augmentation treatment for about 28 weeks showed no relapses in a small cohort of depressed patients [23]. It is also possible, given the evidence of differential responsiveness to antidepressant therapies of specific subtypes of MDD [24,25], that our findings may not be generalizable to all depressive subtypes, as the population enrolled in the study had an average MADRS score above 30, thereby consistent with more melancholic/endogenous forms of depression.…”

Section: Discussionmentioning

confidence: 99%

A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy among Depressed Outpatients with Inadequate Response to Prior Antidepressant Therapy (ADAPT-A Study)

Fava¹,

Mischoulon²,

Iosifescu³

et al. 2012

Psychother Psychosom

130

133

View full text Add to dashboard Cite

Background: We assessed the efficacy of low-dose aripiprazole added to antidepressant therapy (ADT) in major depressive disorder (MDD) patients with inadequate response to prior ADT. Methods: As per the sequential parallel comparison design, 225 MDD subjects were randomized to adjunctive treatment with aripiprazole 2 mg/day or placebo across two 30-day phases, with a 2:3:3 randomization ratio to drug/drug (aripiprazole 2 mg/day in phase 1; 5 mg/day in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1; aripiprazole 2 mg/day in phase 2). Eligible subjects were patients whose MDD was independently deemed ‘valid’ with SAFER criteria. Subjects had been receiving ADT for ≥8 weeks, and had inadequate response to ≥1 and <4 adequate ADTs in the current episode, as defined by the Antidepressant Treatment Response Questionnaire. Results: The pooled, weighted response difference between aripiprazole 2 mg/day and placebo in the two phases was 5.6% (p = 0.18; NS). The aripiprazole 2 mg/day-placebo difference on the Montgomery-Asberg Depression Rating Scale pooled across the two phases was –1.51 (p = 0.065; NS). Other secondary endpoint analyses showed nonsignificant pooled differences favoring aripiprazole over placebo. Of the 225 randomized subjects in phase 1, 2 dropped out in both arms, while in phase 2, of 138 phase 1 placebo nonresponders, 9 dropped out on aripiprazole and 5 on placebo. There were only minimal differences in adverse event rates between treatments, except for constipation, weight gain, and dry mouth, more common on aripiprazole. Conclusions: This study provides clear support for the tolerability of low-dose aripiprazole as an ADT-augmenting agent, with marginal efficacy.

show abstract

“…The studies were supported by the governments of the United States (14,15,19,24) and the Netherlands (20,21), university endowments (19,24), Forest Pharmaceuticals, Eli Lilly (19), Janssen Pharmaceutica (13), Wyeth (21), GlaxoSmithKline (15), and Bristol-Myers Squibb (24). Seven studies did not name a funding source (16-18, 22, 23, 25, 26).…”

Section: Description Of Included Studiesmentioning

confidence: 99%

A Systematic Review of Treatments for Refractory Depression in Older People

Cooper¹,

Katona²,

Lyketsos³

et al. 2013

FOC

View full text Add to dashboard Cite

Objective: The authors systematically reviewed the management of treatment-refractory depression in older people (defined as age 55 or older). Method: The authors conducted an electronic database search and reviewed the 14 articles that fit predetermined criteria. Refractory depression was defined as failure to respond to at least one course of treatment for depression during the current illness episode. The authors rated the validity of studies using a standard checklist and calculated the pooled proportion of response to any treatment reported by at least three studies. Results: All the studies that met inclusion criteria investigated pharmacological treatment. Most were open-label studies, and the authors found no double-blind randomized placebo-controlled trials. The overall response rate for all active treatments investigated was 52% (95% CI542-62; N5381). Only lithium augmentation was assessed in more than two trials, and the response rate was 42% (95% CI521-65; N557). Only two studies included comparison groups receiving no additional treatment, and none of the participants in these groups responded. In single randomized studies, extended-release venlafaxine was more efficacious than paroxetine, lithium augmentation more than phenelzine, and selegiline more than placebo.Conclusions: Half of the participants responded to pharmacological treatments, indicating the importance of managing treatment-refractory depression actively in older people. The only treatment for which there was replicated evidence was lithium augmentation. Double-blind randomized controlled trials for management of treatment-refractory depression in older people, encompassing pharmacological and nonpharmacological therapies and populations that reflect the levels of physical and cognitive impairment present in the general older population with depression, are needed.

show abstract

Pilot Study of Augmentation With Aripiprazole for Incomplete Response in Late-Life Depression

Cited by 57 publications

References 17 publications

Age-related changes in the antidepressant-like effect of desipramine and fluoxetine in the rat forced-swim test

Age-related changes in the antidepressant-like effect of desipramine and fluoxetine in the rat forced-swim test

A Double-Blind, Placebo-Controlled Study of Aripiprazole Adjunctive to Antidepressant Therapy among Depressed Outpatients with Inadequate Response to Prior Antidepressant Therapy (ADAPT-A Study)

A Systematic Review of Treatments for Refractory Depression in Older People

Contact Info

Product

Resources

About