In patients with more severe illness the results
were not so favorable. Neither study in moderateto-severe
depression differentiated SJW from
placebo, tempering the generally positive findings
observed in the studies of mild-to-moderate
depression. It had been anticipated that the two
large, rigorously conducted U.S. studies in more
severely ill patients would help resolve the lingering
questions regarding the efficacy of SJW, but the
negative findings probably raised more questions
than answers. Following release of these findings,
much speculation ensued regarding what factors
might have contributed to the poor results (e.g.,
low assay sensitivity, study design issues, treatment
resistant populations, or sponsor bias).54 !e
general lack of any clear trends for SJW efficacy in
both studies suggests that it simply is not effective
in more severely depressed patients. !e lone
long-term SJW relapse-prevention study also did
not produce a statistically significant difference
between SJW and placebo on the primary endpoint.
!erefore, while SJW appears to be a suitable
alternative to conventional antidepressants for
short term use in mild-to-moderate depression,
there are currently no data from placebo-controlled
studies demonstrating acute efficacy in more
severe depression or convincing data to demonstrate
the long-term maintenance of its antidepressant
effects.
!e SAM-e efficacy findings, while very intriguing,
are more difficult to interpret. On the one
hand, the majority of studies reported positive
results, including in subjects with more severe
symptoms, and produced impressive effect sizes.
On the other hand, all studies exhibited methodological
flaws – some extensive. !e lack of rigor
was evidenced by poorly-defined diagnostic
approaches, inadequate sample sizes, and questionable
approaches to identifying primary datasets.
Many studies included data from “completer”
datasets only. !us, patients dropping out for any
reason (e.g., lack of efficacy, poor tolerability) were
excluded from the efficacy analyses. Studies
exhibiting such deficiencies often produce exaggerated
or inflated treatment effects, which can be
further magnified by the very small sample sizes to
begin with. !erefore, these data must be interpreted
with caution. In addition, there are no
long-term studies that adequately assess the
maintained treatment effect for SAM-e in any
depressed population. Although a U.S. Department
of Health and Human Services report concluded
that “SAMe is more effective than placebo for relief
of symptoms of depression…and was equivalent to
standard therapy for depression,”64 until further
data are generated from more rigorously controlled
and analyzed studies, it would seem premature to
conclude it is a suitable alternative to conventional
antidepressant therapy. !is is particularly true for
more severe illness. !e authors of that commissioned
report acknowledged the need for caution in
interpreting their findings, noting that possible
publication bias was identified that might “temper
the strength of the conclusions we report.”64
In patients with more severe illness the resultswere not so favorable. Neither study in moderateto-severedepression differentiated SJW fromplacebo, tempering the generally positive findingsobserved in the studies of mild-to-moderatedepression. It had been anticipated that the twolarge, rigorously conducted U.S. studies in moreseverely ill patients would help resolve the lingeringquestions regarding the efficacy of SJW, but thenegative findings probably raised more questionsthan answers. Following release of these findings,much speculation ensued regarding what factorsmight have contributed to the poor results (e.g.,low assay sensitivity, study design issues, treatmentresistant populations, or sponsor bias).54 !egeneral lack of any clear trends for SJW efficacy inboth studies suggests that it simply is not effectivein more severely depressed patients. !e lonelong-term SJW relapse-prevention study also didnot produce a statistically significant differencebetween SJW and placebo on the primary endpoint.!erefore, while SJW appears to be a suitablealternative to conventional antidepressants forshort term use in mild-to-moderate depression,there are currently no data from placebo-controlledstudies demonstrating acute efficacy in moresevere depression or convincing data to demonstratethe long-term maintenance of its antidepressanteffects.!e SAM-e efficacy findings, while very intriguing,are more difficult to interpret. On the onehand, the majority of studies reported positiveresults, including in subjects with more severesymptoms, and produced impressive effect sizes.On the other hand, all studies exhibited methodologicalflaws – some extensive. !e lack of rigorwas evidenced by poorly-defined diagnosticapproaches, inadequate sample sizes, and questionableapproaches to identifying primary datasets.Many studies included data from “completer”datasets only. !us, patients dropping out for anyreason (e.g., lack of efficacy, poor tolerability) wereexcluded from the efficacy analyses. Studiesexhibiting such deficiencies often produce exaggeratedor inflated treatment effects, which can befurther magnified by the very small sample sizes tobegin with. !erefore, these data must be interpretedwith caution. In addition, there are nolong-term studies that adequately assess themaintained treatment effect for SAM-e in anydepressed population. Although a U.S. Departmentof Health and Human Services report concludedthat “SAMe is more effective than placebo for reliefof symptoms of depression…and was equivalent tostandard therapy for depression,”64 until furtherdata are generated from more rigorously controlledand analyzed studies, it would seem premature toconclude it is a suitable alternative to conventionalantidepressant therapy. !is is particularly true formore severe illness. !e authors of that commissionedreport acknowledged the need for caution ininterpreting their findings, noting that possiblepublication bias was identified that might “temperthe strength of the conclusions we report.”64
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