Why is it so hard to withdraw from some depression drugs?

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In a new study from the University of Illinois Chicago, researchers found why it is so difficult for people to withdraw from some antidepressant medications.

The current antidepressants can take approximately two months to take effect in patients who then continue taking these drugs for years.

Weaning patients from these drugs can result in unpleasant symptoms that can range from flu-like feelings and persistent pain or itch to Parkinson’s-like conditions that can last for weeks.

One in six Americans have, or will, suffer from depression; for veterans, the estimated rate is twice that.

Previous research has found that antidepressant drugs collect gradually in cholesterol-rich membrane structures called lipid rafts.

When a neurotransmitter (such as serotonin, which is involved with mood) binds to a receptor on the outside of a cell, a protein in the lipid raft –— called Gs alpha –— conveys the signal into the cell’s interior where it can elicit a variety of actions.

In the study, the team found that while withdrawal of some antidepressant drugs balances Gs alpha action in and out of the lipid rafts, other drugs suppress the return of Gs alpha to rafts.

This suppression, the researchers believe, is what causes persistent and undesired effects of some antidepressants.

Lipid rafts appear to be relevant for both the delayed therapeutic effects of antidepressants as well as the difficulty in weaning off from these drugs.

It takes a long time for these drugs to sort into rafts and a long time for the drugs to exit –— some more than others.

Curiously, rapid-acting antidepressants like ketamine have similar effects on Gs alpha and lipid rafts, but without the delay.

The team says the finding validates the notion that intracellular molecules that result from an active Gs alpha protein are a very good biomarker for the functioning of antidepressants.

They would like to move forward toward using technology to create a personalized treatment for depression.

By looking at how an individual patient’s cells metabolize Gs alpha proteins, researchers can better predict what antidepressant medication could work for them.

This can be accomplished in days and not weeks and months of trial and error to find the right medication.

If you care about depression, please read studies about people with depression need to protect their blood vessels carefully and findings of why ketamine could fight depression fast.

For more information about depression prevention and treatment, please see recent studies about people with depression more likely to have multiple chronic diseases and results showing that this thyroid problem may increase risk of depression and anxiety.

The study is published in Molecular Pharmacology. One author of the study is Mark Rasenick.

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