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Experimental Medication Kicks Depression in Hours
Current antidepressants usually take four to eight weeks to exert their effects.
In a preliminary new study, a single intravenous dose of ketamine, a medication
usually used in higher doses as an anesthetic, brought symptom relief to people
with treatment-resistant depression in as little as two hours.
 Ketamine
blocks a brain protein called the N-methyl-D-aspartic acid (NMDA) receptor.
NMDA receptors are critical for receiving the signals of glutamate, a brain chemical
that several emerging lines of evidence suggest plays a role in mood disorders.
Agents that block the NMDA receptor reduce depression-like behaviors in animals,
and a preliminary study in humans showed that ketamine had a rapid antidepressant
effect .
Researchers at NIH's National Institute of Mental Health set out to further
explore ketamine's potential to treat human depression. They randomly assigned
18 treatment-resistant, depressed patients to receive either a single intravenous
dose of ketamine or a placebo (an inactive compound). One week later, the participants
were given the opposite treatment, unless the beneficial effects of the first
treatment were still evident. This "crossover" study design strengthens the validity
of the results.
In the August issue of the Archives of General Psychiatry, the researchers
report that depression improved within one day in 71% of the patients who received
ketamine, with 29% of these becoming nearly symptom-free. Over a third of the
patients who received ketamine still showed benefits a week later. In contrast,
those receiving a placebo infusion showed no improvement. None of the patients
had serious side effects.
Scientists think the reason that current antidepressant medications take weeks
to work is that they act on targets close to the beginning of a series of biochemical
reactions regulating mood. The medications' effects have to trickle down through
the rest of the system, which takes time. Ketamine's target, the NMDA receptor,
may be closer to the end of this series of reactions.
"This may be a key to developing medications that eliminate the weeks or months
patients have to wait for antidepressant treatments to kick in," lead researcher
Dr. Carlos A. Zarate Jr. said.
Ketamine, while important for research, is unlikely to become a widely-used
clinical treatment for depression because of its potential side effects, including
hallucinations and euphoria, at higher doses. Nevertheless, scientists say this
research could point the way toward development of a new class of faster- and
-longer-acting medications. The research team is now zeroing in on other areas
of the glutamate system. Learning which components of the system are affected
by compounds such as ketamine may help scientists understand how and why depression
occurs and point the way to more precise targets for new diagnostic tests and
medications.
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