Changes
in brain function indicate susceptibility to
antidepressant side effects
Administration
of antidepressants is frequently accompanied by
the undesirable adverse events which are
associated with decreased quality of life and
frequent discontinuation of pharmacotherapy.
Side effects can be induced by pharmacodynamic
(receptor interactions, genetic polymorphisms of
metabolising enzymes, for example) and/or
non-pharmacodynamic factors such as expectations
of side effects (the so-called "nocebo" effect).
Several studies have compared changes in brain
function with clinical response to
antidepressant medication vs placebo in
depression. A recent study, explored the
relationship between side effects and changes in
brain activity.
Thirty-two healthy subjects with no history of
depression received 1 week of placebo before
randomization to 4 weeks of double-blind
treatment with the antidepressant venlafaxine (n
= 17) or placebo (n = 15). Quantitative
electroencephalographic (QEEG) cordance recorded
brain function was assessed at each visit and
side effects were determined using
interviews.
A greater number of side effects were reported
in venlafaxine subjects than in placebo subjects
at all post-randomization time-points: 48 h, 1
week, 2 weeks, 3 weeks and 4 weeks. Cordance
changes from baseline were correlated with side
effect burden in the venlafaxine group but not
in the placebo group. Side effect burden in the
subjects treated with venlafaxine was not only
associated with decreases in prefrontal cordance
at 2 weeks, and 4 weeks post randomization but
also at the end of placebo lead-in before any
exposure to the drug.
Changes in prefrontal brain function during
placebo lead-in which were associated with later
antidepressant side effects could indicate a
susceptibility to developing medication side
effects. These results clearly merit
replication. In addition future studies
should test this hypothesis in depressed
subjects, which could contribute considerably to
the management of side effects of antidepressant
drugs. Hunter
AM, Leuchter AF, Morgan ML, Cook IA, Abrams M,
Siegman B, DeBrota DJ, Potter WZ.
Neurophysiologic correlates of side effects in
normal subjects randomized to venlafaxine or
placebo. Neuropsychopharmacology 2005,
30:792-799.