Happy Days: Unraveling the Mystery of How Antidepressants Work

The mechanism behind antidepressant drugs is unveiled, which could lead to better treatments for depression and anxiety disorders.

New research shows how certain antidepressants work, paving the way to new, improved versions of the drugs used to treat depression, anxiety and attention deficit disorder.

Two separate studies—published this week in Science and Nature—provide a window into the way tricyclic antidepressants, such as clomipramine and desipramine, provide therapeutic relief by adhering to proteins on the part of a nerve cell's outer membrane that extends into the brain's synapses (spaces between the cells). These so-called transporter proteins, so-named because they carry molecules inside the nerve cell, gobble up neurotransmitters (chemical messengers such as norepinephrine, serotonin and dopamine) sent by neighboring cells. The drainage of these neurotransmitters from synapses—resulting, ironically, from the reimportation of the chemical just secreted by the sending neuron—has been linked to anxiety disorders; tricyclic antidepressants boost the activity of these neurotransmitters in synapses. But scientists have never been sure how this was accomplished.

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