Low Doses of Controlled-Release Paroxetine in the Treatment of Late-Life Depression
Department of Psychiatry, David Geffen School of Medicine at UCLA, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. The Journal of Clinical Psychiatry
(Impact Factor: 5.5).
12/2008; 70(1):46-57. DOI: 10.4088/JCP.06m02996
To evaluate the efficacy and tolerability of low daily doses of controlled-release (CR) paroxetine in patients with late-life depression.
This was a 10-week, multicenter, placebo-controlled, double-blind, fixed-dose trial randomly assigning patients >or= 60 years old to daily doses of paroxetine CR 12.5 mg (N = 168), paroxetine CR 25 mg (N = 177), or placebo (N = 180). Patients had major depressive disorder (DSM-IV criteria) and 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of >or= 18. The primary efficacy variable was the change from baseline to study endpoint in total HAM-D scores. The study was conducted from June 2003 to October 2004.
The drug/placebo difference in HAM-D change from baseline at study endpoint was -1.8 (95% CI = -3.41 to -0.19, p = .029) for paroxetine CR 12.5 mg, and -3.3 (95% CI = -4.84 to -1.68, p < .001) for paroxetine CR 25 mg. A significantly larger percentage of patients achieved remission (HAM-D total score <or= 7 at endpoint) with paroxetine CR 25 mg (41%), but not with 12.5 mg (31%), as compared with placebo (28%) (p = .008). Both doses of paroxetine CR also achieved statistical significance compared to placebo for the Clinical Global Impressions-Severity of Illness scale (p < .01) and the patient-rated measures of depression severity (p < .05) and quality of life (p <or= .001). Both active treatments were generally well tolerated, with adverse event withdrawal rates of 6%, 8%, and 7% for paroxetine CR 12.5 mg, paroxetine CR 25 mg, and placebo, respectively.
These data demonstrate that paroxetine CR 12.5 mg and 25 mg daily are efficacious and well tolerated in the treatment of major depressive disorder in patients >or= 60 years of age, although effect sizes are relatively smaller with the 12.5 mg/day dose.
Available from: Peter Krummenacher
- "Differences between Hedges's g were calculated using a one-way ANOVA, whereas the effect sizes were weighted by the sample size divided by s 2 (i.e., n/var; Lipsey and Wilson, 2001). Four studies included two treatment groups and one placebo group (Katona et al., 2012; Rapaport et al., 2003, 2009; Schatzberg and Roose, 2006). To deal with the resulting dependency in these cases, we included both comparisons using the same mean for each placebo sub-group but used half the sample size for n when weighting (n/var) the means of the placebo group in each comparison. "
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ABSTRACT: Baseline severity is a crucial moderator of trial outcomes in adult depression, with the advantage of antidepressants over placebo increasing as severity increases. However, this relationship has not been examined in late-life depression.
PubMed, Embase, Web of Science, PsycINFO, and Cochrane were searched for studies published through September 2014. Randomized, acute phase, and double-blind studies comparing an antidepressant group with a placebo group in depressed elderly patients were included.
Nineteen studies met all inclusion criteria. Within-group effect sizes revealed significant improvement in antidepressant groups (g=1.35, p<.000), as well as in placebo groups (g=.96, p<.000). Change in depressive symptoms assessed by Hamilton Depression Rating Scale (HDRS) was moderated by baseline severity in antidepressant groups (Z=2.67, p=.008) and placebo groups (Z=4.46, p<.000). However, this would be expected as a result of regression toward the mean, and mean differences between groups did not increase (r=.19, p=.469) as a function of baseline severity.
Limited to published data and information was only analyzed at the level of treatment groups.
Baseline severity was not associated with an antidepressant-placebo difference and placebo responses are large in the treatment of depressed elderly people. We propose a stepwise approach, i.e., to initially offer elderly depressed patients psychosocial interventions and only consider antidepressants if patients do not respond.
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Available from: Kaloyan Kamenov
- "In addition, there were some main categories, which did not meet the same ranking of significance when the different sources of information were compared. Pain [39–41] and sleep [42, 43], for example, were among the most important categories according to the literature, but in the focus group and individual interviews they were not emphasized notably by patients. "
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ABSTRACT: Despite all the knowledge on depression, it is still unclear whether current literature covers all the psychosocial difficulties (PSDs) important for depressed patients. The aim of the present study was to identify the gaps in the recent literature concerning PSDs and their related variables. Psychosocial difficulties were defined according to the World Health Organization International Classification of Functioning, Disability and Health (ICF). A comparative approach between a systematic literature review, a focus group, and individual interviews with depressed patients was used. Literature reported the main psychosocial difficulties almost fully, but not in the same degree of importance as patients' reports. Furthermore, the covered areas were very general and related to symptomatology. Regarding the related variables, literature focused on clinical variables and treatments above all but did not report that many psychosocial difficulties influence other PSDs. This study identified many existing research gaps in recent literature mainly in the area of related variables of PSDs. Future steps in this direction are needed. Moreover, we suggest that clinicians select interventions covering not only symptoms, but also PSDs and their modifiable related variables. Furthermore, identification of interventions for particular psychosocial difficulties and personalisation of therapies according to individuals' PSDs are necessary.
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ABSTRACT: Late-life depression is an important public health issue, given the growing proportion of the elderly relative to the general population in the developed world. The purpose of this study was to examine the efficacy of antidepressants for the treatment of major depressive disorder (MDD) in elderly patients.
PubMed/MEDLINE was searched for randomized, double-blind, placebo-controlled trials of antidepressants for treatment of both adult (nonelderly) MDD (patients aged < 65 years) and late-life MDD (patients aged ≥ 55 years). The search was limited to articles published between January 1, 1980, and March 3, 2010 (inclusive). The year 1980 was used as a cutoff in our search to decrease diagnostic variability, since the DSM-III was introduced in 1980. Our search cross-referenced the term placebo with each of the following antidepressants: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. We also reviewed the reference lists of all studies identified through the PubMed/MEDLINE search.
Articles were selected that reported on randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD and that met numerous a priori criteria pertaining to MDD diagnosis criteria, study duration, study design, drug formulation, original data, age thresholds, primary and secondary outcome measures, and exclusions of other disorders. Final inclusion of articles was determined by consensus between the authors. Seventy-four articles were found eligible for inclusion in our analysis (15 late-life MDD trials and 59 adult MDD trials).
Antidepressants were found to be efficacious for late-life MDD (age 55 and older; P < .0001), although there was evidence for heterogeneity across studies (Q22 = 67.302, P < .001). However, antidepressants were not found to be efficacious in the subset of studies using age thresholds of 65 years or older (older late-life MDD) (P = .265). Finally, when we controlled for study design characteristics, antidepressant but not placebo response rates were lower among late-life MDD patients than among adult MDD patients.
The present meta-analysis suggests that antidepressants are efficacious in late-life MDD, but significant study heterogeneity suggests that other factors may contribute to these findings. A secondary analysis raises the possibility that efficacy of these agents may be reduced in trials involving patients aged 65 years or older. Why antidepressants may be less efficacious in elderly versus younger subjects remains unclear.
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