Research Therapies — 18 December 2014

SCIENTISTS say they have worked out why popular depression drugs make people feel worse before they get better, sometimes increasing the risk of suicide.

The findings, revealed this morning in the journal Trends in Cognitive Sciences, could pave the way for new drugs to help sufferers through peaks in their depression.

“Selective serotonin reuptake inhibitors”, which increase levels of a brain chemical linked to motivation, are among the world’s most prescribed drugs for depression, anxiety and eating disorders. But while they can boost serotonin levels in under an hour, they take about two weeks to relieve symptoms.

During this period the drug can aggravate depression, making suicidal thoughts “a major problem during SSRI treatment”, the paper says.

Human and animal studies have also found that SSRIs entrench habits and encourage impulsive behaviour — things the drugs are supposed to suppress. Now German and Dutch researchers have found an explanation for these “puzzling” results.

They say that while SSRIs boost serotonin, they suppress levels of another chemical — glutamate — which is associated with pleasure and learning, and is the target of different types of antidepressants.

The theory builds on 20 year-old findings that brain cells which produce serotonin also release glutamate. A 2011 study found that the two chemicals acted on “different timescales”, while Chinese research on mice this year found that the two chemicals interfered with each other if serotonin production was artificially boosted.

The latest study has found that while serotonin production is immediately amplified by SSRIs, glutamate is “acutely suppressed”. “(This) is only normalised after several days of drug treatment,” said lead author Adrian Fischer of Otto-von-Guericke University in Magdeburg, Germany.

“These differential time courses may help to explain the paradox of SSRI effects.”

The findings suggest that the anaesthetic ketamine and the antibiotic cycloserine — both of which boost glutamate production, and are being trialled as treatments for bipolar disorder — could “decrease the initial side effects of SSRI treatment, especially in subjects at higher risk for self-harm”.

“Patients at higher risk from suicide (could) benefit more from a treatment targeted at both serotonergic and glutamatergic components”, the paper says.

This article first appeared on ‘The Australian’ on 18 December 2014.

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