New Strategy For Developing Fast-acting Antidepressants
ScienceDaily (Dec. 10, 2007) -- Researchers may be able to develop an
antidepressant which takes effect almost immediately by directly
targeting novel molecules in the brain instead of taking a less direct
route, which can lead to longer times for medication to take effect,
according to a new study presented at the American College of
Neuropsychopharmacology annual meeting. The antidepressant is also
thought to be effective in people for whom previous treatments have
been ineffective. This human and rodent research is among the first to
examine the effects of rapid antidepressant strategies.
Lead researcher and ACNP member Husseini Manji, M.D., director of the
mood and anxiety disorders program at the National Institute of Mental
Health (NIMH), says one of the major limitations in existing
pharmacological treatments for major depression is the time between
starting to take the medication, and when it starts to alleviate the
depression, often a period of one month or longer. He adds that
strategies that work at much faster rates would have a tremendous
impact for Americans who suffer from depression -- nearly 21 million
annually, according to NIMH.
"Today's antidepressant medications eventually end up doing the same
thing, but they go about it the long way around, with a lot of
biochemical steps that take time. Now we've shown what the key targets
are and that we can get at them rapidly," says Dr. Manji. "This
research is leading to some very real possibilities for a whole new
generation of antidepressant medications."
The study looked at patients in a "difficult to treat" group, meaning
individuals who had not responded to other treatments including
psychotherapy, traditional antidepressants or electroconvulsive
therapy. This group did not attempt all treatment options, like
medication. Researchers treated the depressed patients intravenously
with ketamine, a general anesthetic usually used for minor surgical
procedures in which muscle relaxation is not required. The doses of
ketamine used in this study were considerably lower than when it is
used as an anesthetic.
Ketamine produced results much more quickly than traditional
antidepressants because it acted directly upon critical molecules in
important neuronal circuits instead of having to bypass multiple
locations en route to those circuits. Typically, currently available
antidepressant medications work via serotonin or norepinephrine,
neurotransmitters which act within the brain to help regulate emotion
and cognition.
The results showed that patients responded after only two hours, and
within 24 hours, 70% had responded. Patients were followed over time,
and 35% maintained their response for up to one week. Traditional
antidepressants usually take many weeks, or even months, to begin to
work. "This is intriguing data which suggests that targeting these
important molecules in critical circuits would be extremely helpful in
treating depression more quickly, before it worsens and becomes more
severe," Dr. Manji said.
The researchers also studied rodents to determine whether they could
get medication to highly responsive brain areas more quickly. By
looking at different biomarkers -- specific physical features used to
measure the progress of a disease or condition -- in mice and rats,
researchers came closer to identifying at what point in the
biochemical process medication might become effective, which would
ultimately lead to faster treatment.
Treating patients with rapid strategies is essential since some
patients who suffer from depression are tempted to stop their
medication if it doesn't work quickly enough.
Ongoing human studies using magnetoencephalography (MEG) are also
helping to identify the specific brain circuits through which these
rapid antidepressant effects occur. Identifying these precise circuits
may lead to the development of molecules with even more precise
effects, and therefore fewer side effects.
Adapted from materials provided by American College of
Neuropsychopharmacology.