Posted by AndrewB on April 30, 2000, at 19:33:32
Can fast trials be effective and, probably more to the point, can fast trials work for everybody or just a subpopulation. There are a couple studies which examine the predictive value of an early improvement in mood with an SSRI. Nothing earth shattering here. The studies just show some people respond faster than others to SSRIs. (Some people on this board respond incredibly fast!) In general an improvement or a lack of improvement within the first 2 or 4 weeks often indicates whether or not the SSRI will work for someone in the long run. But these studies also indicate the need for longer trials (6 weeks?) with SSRIs because of the large number of people who will show an initial improvement which fades away (placebo?) and the large number of people who will respond to an SSRI only after 6 or 8 weeks. Here are some excerpts from the abstracts:
*******Eighty-two subjects (57.3%) who started the trial responded by week 8. Of those subjects who showed no improvement at weeks 2, 4, and 6, the proportions of responders at week 8 were 36.4%, 18.9%, and 6.5%, respectively...... The proportion of patients with no response to antidepressant treatment by 4 or 6 weeks who responded by week 8 was substantially less than that for subjects who had at least a partial response. Nonresponse as early as week 2 predicted 8-week outcome.
From study entitled: Early nonresponse to fluoxetine as a predictor of poor 8-week outcome******Early responders at weeks 1, 2, and 3 were statistically significantly more likely to experience marked improvement or remission than those lacking early response. However, at week 3, this criterion correctly classified only about three-fourths of patients with regard to marked improvement and only about two-thirds with regard to remission. Moreover, about one-third of patients predicted to experience marked improvement and about three-fifths of those predicted to remit did not.
From a study entitled: Predicting response to fluoxetine in geriatric patients with major depressionThe next study is very interesting. It indicates that SSRI and buspirone trials may be shortened by the augmentation with propanol.
*****It has been reported that the 5-HT1A autoreceptor antagonist pindolol can accelerate the antidepressant response to the selective serotonin (5-HT) reuptake inhibitor (SSRI) paroxetine, presumably by preventing the initial decrease in firing activity of 5-HT neurons produced by the SSRI. The administration of the selective 5-HT1A agonist buspirone (20 mg/day for 1 week and 30 mg/day thereafter) with pindolol (2.5 mg TID) was used to activate selectively postsynaptic 5-HT1A receptors. This combination produced a greater than 50% reduction of depressive symptoms in the first week in 8 of 10 patients and the response was sustained for the remainder of the trial. The combination of the SSRI fluvoxamine (50 mg/day for 1 week and 100 mg/day thereafter) with pindolol produced a marked antidepressant effect but did not act as rapidly as the buspirone plus pindolol combination with none, four, and eight patients achieving a 50% amelioration after 7, 14, and 21 days of treatment, respectively
From a study entitled: Selective activation of postsynaptic 5-HT1A receptors induces rapid antidepressant response.Though SSRI trials may for many need to last 6 weeks or longer, many studies indicate that 2 week trials will suffice for MAOIs and tricyclics. Studies show a strong relationship between an improvement after 2 weeks and a long term response. Here are 2 study excerpts:
******The early onset of improvement (with moclemide, imipramine or amitriptyline) or was highly predictive of later outcome: on average, 70% of patients showing improvement within the first 14 days became responders. Differences between active treatments and placebo emerged within the first five days and reached a point of maximum distinction around day 14.
From, ‘Delayed onset of action of antidepressant drugs? Survey of results of Zurich meta-analyses’****** Onset of improvement occurred in the great majority of patients (79.1%) within the first 12 days of study, independently of the severity of depression at baseline. Early improvement was highly predictive of later outcome....
From, ‘The speech analysis approach to determining onset of improvement under antidepressants’If two week trials should be possible with MAOIs and tricyclics, even faster trials are possible with direct acting D2 and D3 meds. such as amisulpride, sulpiride, pramipexole, ropinirole and amineptine. Their fast antidepressant action is probably due to their direct action on the D2/D3 receptors within the nucleus accumbens. The neurotransmission of this area of the brain is improved by use of various antidepressants (SSRIs, MAOIs, etc.), but the direct acting D2/D3 drugs are able to act on this area more rapidly.
poster:AndrewB
thread:31785
URL: http://www.dr-bob.org/babble/20000429/msgs/31785.html