We previously used positron emission tomography (PET) measurement of
brain metabolism with 18fluorodeoxyglucose to show that patients
receiving selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan
depletion–induced return of depressive symptoms have an acute decrease
in metabolism in orbitofrontal cortex, dorsolateral prefrontal cortex, and
thalamus. Many patients with depression in remission while taking norepinephrine
reuptake inhibitors (NRIs) (but not SSRIs) experience a return of depressive
symptoms with depletion of norepinephrine and dopamine using α-methylparatyrosine
To assess brain metabolic correlates of AMPT administration in patients
with depression in remission while receiving NRIs.
Design, Setting, and Participants
Randomized, controlled, double-blind trial in which 18 patients recruited
in 1997-2000 from the general community who had depression in remission while
taking NRIs had PET imaging in a psychiatric research unit following AMPT
and placebo administration.
After initial medication with desipramine and follow-up until response,
patients underwent active AMPT (five 1-g doses administered orally over 28
hours) and placebo (diphenhydramine hydrochloride, five 50- mg doses administered
similarly) catecholamine depletion challenges in randomized order of assignment,
after which PET imaging was performed on day 3 of each condition. Both study
conditions were performed 1 week apart.
Main Outcome Measures
Regional brain metabolism rates in patients with and without AMPT-induced
return of depressive symptoms.
AMPT-induced return of depressive symptoms was experienced by 11 of
the 18 patients and led to decreased brain metabolism in a number of cortical
areas, with the greatest magnitude of effects in orbitofrontal (P = .002) and dorsolateral prefrontal (P =
.03) cortex and thalamus (P = .006). Increased resting
metabolism in prefrontal and limbic areas predicted vulnerability to return
of depressive symptoms.
Different neurochemical systems that mediate depression may have effects
on a common brain circuitry. Baseline metabolism in successfully treated depressed
patients may predict vulnerability to future episodes of depression.