Antidepressants linked to non-Hodgkin lymphoma

Long-term users of so-called tricyclic antidepressants are at increased risk of non-Hodgkin lymphoma (NHL), new research confirms.

"We previously reported an increased incidence of NHL among long-term users of tricyclic antidepressant medication in a population-based cohort of more than 30,000 users of antidepressant medications," Dr. Susanne Oksbjerg Dalton, of the Danish Cancer Society, Copenhagen, and colleagues point out.

Another population-based study did not confirm these findings, but "it did suggest a possible excess of NHL with tricyclic antidepressant medication among the long-term users," they also note.

In the July issue of Epidemiology, Dalton's group reports an update of their population-based cohort, increasing the sample size to the entire population of 354,551 adults in North Jutland County. Between 1989 and 2003, the researchers compared the incidence of NHL among antidepressant users and nonusers.

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Antidepressant Gatekeeper - Structural and functional studies point to tricyclics' mechanism of action

AN IMPORTANT CLASS of drugs-tricyclic antidepressants (TCAs)—binds in a surprising place. That finding, based on studies with a bacterial protein, could influence the design of new drugs for depression.

According to two new studies, TCAs seal off a molecular passageway in a bacterial counterpart of human neurotransmitter transporter proteins (Nature, DOI: 10.1038/nature06038 and Science, DOI: 10.1126/science.1147614). The work indicates a molecular mechanism of action for this compound class.

Since the 1950s, TCAs such as desipramine (Norpramin and Pertofrane) have been prescribed to treat symptoms of depression. They prevent reuptake of serotonin and norepinephrine by binding to corresponding membrane-spanning neurotransmitter transporter proteins

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Cheerful news for antidepressant research

Two research groups have independently reported new findings on the mechanism of action of an important class of antidepressant drugs. The work provides key insights into how tricyclic antidepressants interfere with neurophysiology at the molecular scale, and could eventually open the way to the development of more efficient therapies.

Tricyclic antidepressants (TCAs) are molecules that resemble a kite, with a central seven-membered ring trailing a short tail and flanked by two benzene rings. TCAs work by inhibiting neurons from taking up the monoamine neurotransmitters serotonin, norepinephrine and dopamine, which regulate mood. By blocking the re-uptake of these transmitters by their specific transporter proteins, the transmitter molecules remain in circulation for longer, prolonging their action.

However, the precise way in which the drugs work had remained unresolved. Now, Maarten Reith, Da-Neng Wang and colleagues1 at the New York University School of Medicine, US, and a team led by Eric Gouaux2 at the Oregon Health and Science University, US, have independently provided data on how TCA molecules bind to a bacterial analogue of a mammalian neurotransmitter transporter.

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