Vyvanse is currently in phase three trials as an adjunct to major depression treatment, if that isn't evidence enough I don't know what is.
And they had more advanced scientific techniques back then for studies than is popularly thought.
Can you source that its loses its AD effect? Remember, we're talking about treatment for depression, not a high.
What makes it so different from bupropion?
Being in a phase 3 trial = proof of long term antidepressant efficacy? After learning a bit about the industry and the research process, I'm generally skeptical (until I see more evidence) of efficacy claims of drugs that get approved, let alone ones that are still in trials. Many approved antidepressants are known sometimes to lose efficacy in the long term.
Vyvanse certainly has a short antidepressant effects, and also I suspect has a clinical role as an adjunctive to an AD, and I'm sure in certain treatment resistant cases it could be the thing that makes the difference. But there is a reason that stimulants went from the first line treatment for depression to rarely if ever used for that indication. Leslie Iversen's excellent 2006 book
Speed, Ecstasy, Ritalin: The science of amphetamines includes a discussion of the history of their use in depression and cites some of the turning point studies. A 2009
review of 24 randomized controlled trials of psychostimulants for depression found that "There is some evidence that in the short-term, PS reduce symptoms of depression. Whilst this reduction is statistically significant, the clinical significance is less clear." A 2007 review
article argued that stimulants have a role, albeit limited to certain situations, in the treatment of depression, although the evidence it cites is also short term.
Looking through some of the older studies, there are a lot of reasons to question the long term utility of amph as an antidepressant. For example, in Ann Intern Med. 1 April 1971;74(4):605-610, "Amphetamine was found to be less effective than placebo in the treatment of depressed outpatients by British general practitioners... In still another British study, amphetamine also proved less effective than phenelzine, and no better than placebo, in the treatment of depresion. In a Veterans Administration study, dextroamphetamine was no more effective than placebo in treating hospitalized depressed patients." (p. 606).
Joseph Schildkraut, the guy that came up with and popularized the catecholamine hypothesis of affective disorders, similarly took a negative view:
"The psychomotor stimulants (for example, amphetamine, methamphetamine and methylphenidate) cause mood elevation, increased alertness and enhanced performance in normal subjects.42.43 These drugs may alleviate some of the symptoms of depression in certain depressed patients, but such beneficial effects are often transient and may be accompanied by a number of unwanted side effects. A review of the clinical pharmacology of these compounds may he found elsewhere.2.42 It is fairly generally agreed that the psychomotor stimulants have relatively little to offer in the treatment of the major depressive disorders. 1·2.5·7 These drugs, however, may prove to be of some value experimentally, in separating the various types of depressive disorders. For example, in one study, after the acute administration of methamphetamine, patients with the diagnosis of "neurotic depression"* were found to have a euphoric response, whereas patients with "psychotic depressions"* experienced dysphoria.44 Recent preliminary findings suggest also that the response to d-amphetamine may be useful in predicting the clinical response to imipramine in depressed patients." (pp. 198-199)
(Schildkraut, J. J. (1969). Neuropsychopharmacology and the affective disorders. (First of three parts). The New England Journal Of Medicine, 281(4), 197-201.)
Anyway -- this, and my personal experience, has lead me to believe that the antidepressant effect of amphetamines is not lasting. I think part of the problem is that it can have a tendency to destabilize mood. I'm not talking about at recreational doses-- just normal doses, I feel better than normal when it is kicked in, and mildly irritable when it wears off. Perhaps I'm wrong -- I certainly wouldn't tell anyone who experienced lasting anti-depressant efficacy from amphetamine that their experience is wrong. I just think it would be uncommon.
As for bupropion, I don't understand your question. Are you asking why it works? Are you suggesting that if it works, then amphetamine has to work because they are similar? Anyone who has taken bupropion and amphetamine I think knows that the subjective experience is not really similar. Bupropion's antidepressant effect, unlike that produced by amphetamine, takes a week or more to show up generally, and the mechanisms are poorly understood (as is the case with all antidepressants) but I think there is good evidence that the final common pathway is neurogenesis in the hippocampus, as every effective antidepressant regardless of pharmocological mechanism induces this effect via downstream changes. There are some people who don't totally accept the hypothesis and there is some evidence that is difficult to explain, but I'll leave it to the neuroscientists. Bupropion induces this neurogenesis, amphetamine doesn't (though unlike bupropion, amphetamine does induce neurogenesis in the ventral tegmental area and the substantia nigra pars compacta). If you are asking why they work differently, that's a complicated question but in short they don't have the same mechanism of action.
