What You Can Do

By David Bjerklie

We've come a long way from Freud's couch. The big breakthrough arrived in the late 1980s with the advent of safer and more widely effective drugs, like Prozac. According to Dr. Bruce Cohen of Harvard's McLean Hospital, we're on the cusp of a new era in treatment as the search for a single magic pill for depression gives way to a broad spectrum of therapies.

DRUGS

TODAY'S TREATMENTS Most antidepressants work by tweaking levels of various neurotransmitters, the chemicals that carry signals from one neuron to another. Prozac, Paxil, Zoloft and the other SSRIs slow the absorption of serotonin. Effective antidepressants that act on both serotonin and norepinephrine include Effexor and Remeron. Drugs like Wellbutrin work in a similar way but probably on the neurotransmitters norepinephrine and dopamine. The tricyclic antidepressants (such as Elavil and Tofranil) also blocked the absorption of neurotransmitters, especially norepinephrine, but the drugs had significant side effects. Another class of first-generation drugs, the monoamine oxidase inhibitors (MAOIs) such as Nardil and Marplan, can be effective but can also produce dangerous side effects. A transdermal patch just approved by the Food and Drug Administration will give new life to MAOIs by reducing the side effects they sometimes caused when taken orally.

ON THE HORIZON Researchers are exploring two related molecules, gaba and glutamate, that are responsible for 90% of chemical signaling in the brain. Because they control so much of the brain's activity, the trick is to fine-tune their levels in ways that relieve depression but don't affect other brain functions. Other targets of drug development: the sex hormone testosterone (a transdermal patch proved effective in a recent clinical trial for men); the stress hormone cortisol, which researchers are trying to regulate with the abortion drug RU 486 and compounds called CRF antagonists; the dynorphins (the evil twins of feel-good endorphins); and a chemical called substance P, involved in pain pathways closely related to depression.

ELECTRICAL AND MAGNETIC

TODAY'S TREATMENTS Electroshock therapy, despite its unsavory reputation, is actually quite effective, especially for patients who don't respond to drugs and seniors for whom drug interactions pose problems. The treatment today uses a small current to trigger a mild seizure--a rhythmic firing of neurons--that can push a depressed brain out of its rut.

ON THE HORIZON Researchers are exploring a similar technique that sends an electrical current through the vagus nerve--a major conduit wiring the heart and intestines--which then delivers it to the brain. Another approach, called regional transcranial magnetic stimulation, uses an electric coil shaped like a figure eight to create a magnetic field inside the pre-frontal cortex, which plays a key role in mood regulation.

TALKING CURES

TODAY'S TREATMENTS Most research today is focused on the physiology of depression, yet clinicians find that approaches combining medical and psychological treatments are still the most effective. Freud's techniques have been adapted and streamlined, but analysts still try to get patients to probe the unconscious roots of their problems.

Newer techniques like cognitive therapy, by contrast, teach patients to recognize destructive patterns in their lives and develop practical steps for changing bad mental habits.

ON THE HORIZON Meditation, mindfulness training and biofeedback have long been championed as proven stress relievers. Now proponents believe these techniques may also provide relief to people with depression by lowering levels of cortisol.

ALTERNATIVE THERAPIES

TODAY'S TREATMENTS More patients today help themselves to over-the-counter aids, from St.-John's-wort to ginkgo biloba and soybean extracts. But herbs, like prescription drugs, can have side effects, and researchers are investigating their efficacy. The popular supplement DHEA, for example, has been linked to an increased risk of cancer.

ON THE HORIZON Omega-3 fatty acids (in fish oils) are good for the heart and also may be good for the brain by promoting the health of nerve-cell membranes. Studies are under way. --By David Bjerklie