Prozac: Self-Destructive But Still Helpful

“Thus Prozac, which initially improves serotonin transport, eventually fails because it facilitates the destruction of that which is being transported. In this view, Prozac is like a trucker who is careless with his perishable cargo, allowing much of it to spoil en route.” Sanford Rose

Dolors& Sense

By Sanford Rose

 

KISSIMMEE Florida—(Weekly Hubris)—11/05/2012—Anti-depressant drugs like Prozac have a mixed track record. They’re supposed to help people with severe depression but are not very much more effective than sugar pills for people with moderate depression.

Those who take these drugs usually fall victim to what is known as Prozac Poop-Out—the need constantly to increase dosages in order to obtain the same effect. Ultimately this reaction curtails usage or forces a shift to another drug class that targets a different neurotransmitter.

Prozac allegedly works by trapping serotonin, one of the calming neurotransmitters, in the space between neurons, called the synaptic cleft, instead of allowing it to be taken up and returned to those parts of the nerve cell that originally secreted it. The more serotonin that resides in the synaptic cleft, the greater is its intercellular flow throughout the nervous system, and the more tranquil we feel. Or at least that’s one theory.

It is often noted, however, that while it takes only a short time for serotonin to build up in the cleft, it usually takes quite a bit longer for depressive symptoms to abate, even a tad.

This suggests that the build-up in the cleft may be irrelevant to the drug’s therapeutic action.

Or worse, argue harsher critics.

The body has a finite amount of neurotransmitters like serotonin or dopamine, the chemical that fuels passion. Anti-depressant drugs can’t increase this amount; they can only redistribute it.

But redistribution has its perils. When serotonin is confined to the cell sections where it is manufactured, it is safe from metabolism. But when it lounges in the synaptic cleft, it is prey to certain enzymes that quickly chew it up.

Thus Prozac, which initially improves serotonin transport, eventually fails because it facilitates the destruction of that which is being transported. In this view, Prozac is like a trucker who is careless with his perishable cargo, allowing much of it to spoil en route.

Is there a way to prevent spoilage?

Certainly, argue some. Prozac is self-destructive because serotonin doesn’t cross the blood-brain barrier. So it can’t replicate itself in the brain, replacing the molecules subject to that enzymatic carnage in the synaptic cleft.

The amino-acid precursors of serotonin don’t share this disability. Amino acids like L-tryptophan, which is essential to the manufacture of serotonin, readily cross the barrier.

It would seem to follow that if these substances can be added to one’s diet in the right quantities, they can assist the body in rebuilding the serotonin molecules that are perishing through enzymatic action.

And indeed some researchers have found that patients on Prozac and a carefully formulated cocktail of amino-acid serotonin (and dopamine) precursors don’t suffer from any poop-out at all. Their depression remains under reasonable control without the need to elevate drug dosages.

It has recently been suggested that the mechanism by which Prozac alleviates depression may in fact have nothing to do with serotonin itself, whether it takes up residence in the cleft or elsewhere. The drug may be needed because, while stimulating the serotonin system, it also spurs the body to produce another substance, which turns out to be the real depression fighter.

That substance is BDNF, brain-derived neurotrophic factor.

BDNF energizes neuronal growth and repair in the hippocampus, the part of the brain that controls new memories and that tends to atrophy in depression victims.

So Prozac could have great value—not for its advertised benefits but for collateral ones that are as yet imperfectly understood.

Note: If interested in reading further re BDNF, of possible interest are: http://scientopia.org/blogs/scicurious/2010/12/13/bdnf-and-depression/; http://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor; and http://www.livestrong.com/article/214646-brain-derived-neurotrophic-factor-exercise/, among many other listings.