A Vaccine for Depression?
Since 2005, the suicide rate among U.S. war veterans has nearly doubled; in the first half of 2012, more service members died by suicide than in combat.
.. The chief downside of these drugs, called monoamine oxidase inhibitors (MAOIs), is that they require a strict diet: no aged cheeses, wine, beer, or cured meats. Combined with these foods, the drugs can cause deadly spikes in blood pressure, a hassle that often inclines patients to ditch them. (The novelist David Foster Wallace took an MAOI for decades; in part to escape the food restrictions, he got off the drug months before his suicide.) On the other hand, tricyclic antidepressants, like imipramine, work by blocking the re-absorption of serotonin and norepinephrine.
.. All of these changes increase the number of glutamate ships left in the synapse, flooding the cell with aberrant signals. Indeed, depressed people’s brains, or at least animal models of depression, show all three of these problems, leading to long-lasting excesses of glutamate in key portions of the brain.
This superabundance of glutamate makes a neuron fire sooner than it should and triggers a cascade of signals inside the cell, damaging its structure.
.. This harmful process, called excitotoxicity, is thought to be involved in bipolar disorder, depression, epilepsy, and neurodegenerative diseases like Alzheimer’s, Huntington’s, and Parkinson’s.
.. The human brain’s flexibility allows regeneration, but also renders it vulnerable to being altered by stress. Subjected to the trauma of war, a bad breakup, or a bout of homelessness, a person with a genetic predisposition may find his mind stuck in a loop of chronic fear or depression.
.. Ketamine also works for bipolar people in depressive phases, without triggering mania, as classic antidepressants sometimes do. The majority of depressed people studied have responded to ketamine. For patients who are often suicidal, this fast response can be lifesaving. Some 50 doctors in the U.S. now offer ketamine infusions for depression.
.. Today ketamine is offered by psychiatrists and anesthesiologists, at prices ranging from $300 to $1,000 per dose, for people who are morbidly depressed or have chronic pain. Insurance doesn’t usually cover the cost of an infusion, because even though it is FDA approved as an anesthetic, it has not been approved as an antidepressant. Each new use of a drug requires multiphase clinical trials for FDA approval, usually funded by pharmaceutical companies, which have little incentive to invest in a drug they can’t monetize. Ketamine got its original patent in 1966, and that expired long ago. So even if drug companies steered ketamine through the expensive approval process as an antidepressant, doctors could still prescribe the cheap, generic versions already available for anesthesia instead of pricier, patented versions intended for depression. This is an old story. Lithium carbonate, which also acts on glutamate receptors, is still one of the most reliable drugs for treating bipolar disorder. But lithium, which is an element, can’t be patented. So, despite their effectiveness, these generic pills do not attract many corporate dollars.