Posted by Jost on October 4, 2006, at 21:55:16
In reply to Re: Can't Take it AnyMore ! Bad news - Good news » Jost, posted by SLS on September 25, 2006, at 0:06:48
Here are a few excerpts from the report in APJ on the third level of the Star*d study.. Citation: "A Comparison of Lithium and T^sub 3^ Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report,"
Andrew A Nierenberg, Maurizio Fava, Madhukar H Trivedi, Stephen R Wisniewski, et al. The American Journal of Psychiatry. Washington: Sep 2006. Vol. 163, Iss. 9; p. 1519 (12 pages)"While ainticiepressant (sic)medications are effective for major depressive disorder, only 25%-45% of patients experience remission after one acute trial of an antidepressant (1-3). For patients whose depression does not remit after an adequate trial, clinicians generally switch to a different antidepressant, add a second antidepressant to the initial one, or augment the antidepressant with another agent. The most widely studied medications used for augmentation of antidepressant treatment are lithium and triiodothyronine (T^sub 3^), but most of the evidence supporting their use in augmentation was collected in studies with patients who did not respond initially to tricyclic antidepressants (4). We know of no studies that have compared the effectiveness of these two augmentation treatments as third-step options for depressed patients who did not receive sufficient benefit from treatment trials with selective serotonin reuptake inhibitors (SSHIs) or other second-generation antidepressants.
Augmentation With Lithium or T^sub 3^
The rationale for using lithium as an augmenting agent in antidepressant treatment for patients with major depression was based on preclinical data showing that lithium increases the presynaptic formation, storage, and release of serotonin (5). It was postulated that the increase in serotonergic function induced by lithium would have a synergistic effect on the mechanism of action of antidepressants. Most tudies of lithium augmentation used small samples of patients who had not responded to tricyclic antidepressants, and most found that augmenting a tricyclic with lithium was effective. A meta-analysis of nine placebo-controlled studies (total N=234) supported the conclusion that lithium augmentation was effective, with a number needed to treat of 3.8 (6). Patients who responded and who continued taking lithium in addition to their antidepressant stayed well longer than those who were randomly switched to placebo augmentation (7). However, there is no good evidence that lithium is effective in augmentation of scrotonin reuptake inhibitors (8). The hypothalamic-pituitary-thyroid axis and its reciprocal relationship with depression have long been a subject of inquiry (9, 10). Although pretreatment thyroid function may or may not mediate response to antidepressunts (11, 12), thyroid hormone augmentation is useful even in the absence of thyroid abnormalities (13). Putative mechanisms of action include desensitization of 5-HT^sup 1A^ inhibitory receptors, direct effects on nuclear receptors affecting gene expression (14), and increased brain metabolism (15). A meta-analysis of eight studies (total N=292) supported the efficacy of T^sub 3^ augmentation, with a number needed to treat of 4.3 (16). In contrast to lithium augmentation, to our knowledge no studies have examined the durability of response to T^sub 3^ augmentation with a placebo substitution design. A meta-analysis (17) showed that T^sub 3^ augmentation may speed up response to antidepressants, especially in women, but neither an acceleration effect nor a gender effect was replicated in a small controlled study with paroxetine (18).
Effectiveness and Comparison Studies
Few studies have assessed the effectiveness (that is, in representative patients treated in typical practice settings) of using other agents to augment antidepressants, particularly to augment the more modern antidepressants. Even fewer studies have prospectively generated a cohort of patients who obtained insufficient benefit from adequately delivered initial treatments and then underwent randomized assignment to receive augmentation with lithium or other agents (8, 19, 20). Similarly, few studies have examined the efficacy or effectiveness of T^sub 3^ augmentation for patients with major depression who did not have an adequate response to one of the second-generation antidepressants (15). Joffeet al. (21), in the only study we know of that directly compared lithium and T^sub 3^ augmentation of tricyclic antidepressants as a second-step treatment, found the two agents to be equally effective and more effective than placebo.
...The study participants had not obtained adequate benefit from prospective treatment with two or more trials of antidepressiint monotherapy or an initial trial of monotherapy with citalopram followed by a second trial in which citalopram was augmented with buspirone or sustained-release bupropion. In addition, a small number of patients who entered this trial (N=9) initially received citalopram, then received cognitive therapy either alone or combined with citalopram, and then underwent randomized assignment to either sustained-release bupropion or extendedrelease venlafaxine alone before moving on to the augmentation treatment we report here....
Method
This trial was conducted as part of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, which was designed to assess the effectiveness of medications or cognitive therapy for outpatients who had not had a satisfactory response to an initial treatment or to one or more subsequent prospective treatments (3, 22-24). The rationale, design, and methods of STAR*D have been detailed elsewhere (25, 26)....
....Among the strengths of this study are that it was conducted in representative real-world practices with patients who presented for care-they were not recruited through advertising. Participants had undergone two prospectively administered medication trials that had failed to bring them to remission. This effectiveness design enhances the ecological validity and the generalizability of the study's results. Medication treatment was open-label, and clinicians used evidence-based guidelines to optimize dose and duration of treatment. The primary outcome measures were collected by assessors who were blind to participants' treatments.This study also had several limitations. First, it did not have the statistical power to reliably detect small differences in remission rates between the augmentation therapies. second, we did not systematically assess laboratory indices, including pretreatment assessment of thyroid function and serial monitoring of lithium levels. Third, we used open-label administration of the augmentation therapies. Fourth, the study design did not include a placebo control group-a particularly noteworthy limitation, given the low remission rates: it is not possible to confirm that either augmentation therapy was more effective than supportive clinical management along with ongoing anti-depressant therapy. Finally, participants in the lithium augmentation group took relatively low doses because of intolerable side effects, and as a result they had minimal blood lithium levels. This limitation leaves open the question of whether keeping the doses of lithium small limits its effectiveness for augmentation (6, 7). Yet, as noted earlier, patients in this study took the highest tolerable doses, reflecting the reality of prescribing lithium to patients with major depressive disorder who present for care in everyday practice."
[end of quotation]
Note: I may not have indicated properly where I omitted text. This quoted text cites some of the more important conclusions, but may not read through ie there may be gaps not noted. However, there is mostly omission of details of the prior parts of Star*d and some detail about the treatments. (I don't think this would lead to misinterpretation of the study.)
It's also notable that although the study was similar to "RL" conditions,--with all the pros and cons of that-- and that if the patients could only tolerate small doses of lithium, those who tolerate higher doses may get stronger effects.
It seemed that the statistical data are refineable to the level of distinguishing lesser variations of response, so that short of remission, it's hard to tell if Tsub3 is better than lithium as doses clinically usable by most patients.
I haven't come across the MAOI arm of Star*D.
Jost
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URL: http://www.dr-bob.org/babble/20061003/msgs/691937.html