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STAR*D study, 33% sucess with first AD

Posted by sam123 on September 12, 2007, at 9:55:54

In reply to Re: News - Antidepressants Vindicated? » linkadge, posted by Larry Hoover on September 12, 2007, at 9:38:45


> If you consider the more typical long-term treatment found in normal clinical practise, the limitation of most published studies to data obtained during the first six, eight, or twelve weeks of treatment actually biases the data towards capturing the treatment-emergent uptick in suicidality, which is an effect common to every class of antidepressants. In fact, it is just this effect that spurred the development of the SSRIs, as the prior generation of antidepressants, the TCAs, are far more toxic in overdose.
>


Thanks Lar.

The STAR*D study was a much longer study.

http://www.nimh.nih.gov/healthinformation/stard.cfm


My understanding is if people were not successful in phase 1 they moved to phase 2, ect. Med choices
were random within each phase.


5. What were the results?

A. In most clinical trials of treatment for depression, the measure of success (outcome) is called "response" to treatment, which means that the person's symptoms have decreased to at least half of what they were at the start of the trial. In STAR*D, the outcome measure was a "remission" of depressive symptoms—becoming symptom-free. This outcome was selected because people who reach this goal generally function better socially and at work, and have a better chance of staying well than do people who only achieve a response but not a remission.

In level 1, about one-third of the participants reached remission and about 10-15 percent more responded, but did not reach remission. Still, these are considered good results because study participants had high rates of chronic or recurrent depression and other psychiatric medical problems.

It took an average of six weeks of treatment for participants to improve enough to reach a response and nearly seven weeks of treatment for them to achieve a remission of depressive symptoms. In addition, participants visited their care providers an average of five to six times. Participants who achieved remission stayed on the treatment for an average of 12 weeks before going on to a 12-month follow-up period.

In the level 2 switch group, about 25 percent of participants became symptom-free. All three of the switch medications performed about the same and were equally safe and well-tolerated. In the add-on group, about one-third of participants became symptom-free. Those who added bupropion experienced less troublesome side effects and slightly more reduction of symptoms than those who added buspirone.

In levels 2 and 3 where participants were allowed to either add-on or switch medications, most participants found only one or the other treatment strategies acceptable. Because most participants did not agree to be randomly assigned to one or the other treatment strategy, the findings of the add-on and switch approaches cannot be compared. It is likely, however, that people being treated in the real world also tend to limit their treatment preferences to switching or adding on medications. In addition, the people in the switch and add-on groups were a little different. The group who chose and were assigned to a switch medication had more problematic side effects while taking the preceding medication (citalopram) than the group who chose and were assigned to an add-on medication.

Level 2 also included cognitive psychotherapy as a switch or add-on treatment. Results for the psychotherapy treatment are not yet available.

In the level 3 switch group, 12 to 20 percent of participants became symptom-free, and the two medications used fared about equally well, suggesting no clear advantage for either medication in terms of remission rates or side effects. In the add-on group, about 20 percent of participants became symptom-free, with little difference between the two treatments. However, the T3 treatment was associated with fewer troublesome side effects than lithium.

In level 4, seven to 10 percent of participants became symptom-free, with no statistically significant differences between the medications in terms of remission, response rates or side effect burden. However, those taking the venlafaxine-XR/mirtazapine combination experienced more of a reduction in depressive symptoms than those taking the tranylcypromine. Also, those who were treated with tranylcypromine were more likely to discontinue the treatment citing side effects as the reason. It is also possible that the dietary restrictions associated with taking an MAOI could have limited its acceptability as a treatment.

In conclusion, about half of participants in the STAR*D study became symptom-free after two treatment levels. Over the course of all four treatment levels, almost 70 percent of those who did not withdraw from the study became symptom-free. However, the rate at which participants withdrew from the trial was meaningful and rose with each level—21 percent withdrew after level 1, 30 percent withdrew after level 2 and 42 percent withdrew after level 3.


3. What were the treatments used in the study?

A. In level 1, participants were given the antidepressant citalopram (Celexa) for 12 to 14 weeks. Those who became symptom-free during this time could move on to a 12-month follow-up period during which the citalopram was continued, and patients were monitored. Those who experienced intolerable side effects or did not become symptom-free during this level could go on to level 2.

Citalopram is representative of the class of antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs). It was chosen as the first treatment because it generally is not associated with troublesome withdrawal symptoms when it is stopped, is easy to administer (once a day), and has been shown to be safe for older adults and medically fragile patients. It does not appear to interact unfavorably with other medications that some participants may have been taking for other medical problems.

Level 2 was designed to help determine an appropriate next treatment step if the first step did not work. Thus, in level 2, participants had the option of switching to a different medication or adding on to their existing citalopram.

Those who joined the "switch" group were randomly assigned to either sertraline (Zoloft), bupropion-SR (Wellbutrin), or venlafaxine-XR (Effexor). These medications were chosen for comparison because they represent three different types of medications. Sertraline is an SSRI, the same class as the citalopram used in level 1. Bupropion belongs to another class of antidepressant medications that work on different neurotransmitters than SSRIs. Venlafaxine is a "dual-action" medication that works on two neurotransmitters at the same time.

Those who joined the "add-on" group were prescribed either the non-SSRI antidepressant bupropion-SR (Wellbutrin), or buspirone (BuSpar), which is not an antidepressant but enhances the action of an antidepressant medication. Participants could also switch to, or add on, cognitive psychotherapy.

As in level 1, those who became symptom-free with their level 2 treatment could continue with that treatment and entered the follow-up period. Those who did not become symptom-free, or who experienced intolerable side effects, could continue on to level 3.

In level 3, which like level 2 was designed to compare medications that are thought to work differently in the brain and produce different results, participants again had the option of either switching to a different medication or adding on to their existing medication. Those who chose to switch their medication were randomly assigned to either mirtazapine (Remeron) — a different type of antidepressant — or to nortriptyline (Aventyl or Pamelor) — a tricyclic antidepressant—for up to 14 weeks. Both work differently in the brain than the SSRIs and other medications used in levels 1 and 2.

In the level 3 add-on group, participants were randomly prescribed either lithium — a mood stabilizer commonly used to treat bipolar disorder — or triiodothyronine (T3) — a medication commonly used to treat thyroid conditions — to add to the medication they were already taking. These medications were chosen because they have been shown to boost the effectiveness of antidepressant medications.

In level 4, participants who had not become symptom-free in any of the previous levels (and therefore considered to have highly treatment-resistant depression) were taken off all other medications and randomly switched to one of two treatments — the monoamine oxidase inhibitor (MAOI) tranylcypromine (Parnate) or the combination of venlafaxine extended release (Effexor XR) with mirtazapine (Remeron). These treatments were chosen for comparison because previous research had suggested that they may be particularly effective in people who had not received sufficient benefit from other medications.

http://www.nimh.nih.gov/healthinformation/stard-treatment-flowchart.pdf


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poster:sam123 thread:781684
URL: http://www.dr-bob.org/babble/20070911/msgs/782423.html