Sunday, December 19, 2010

Antidepressants May Affect Stuttering

Antidepressants such as Prozac, Zoloft, Celexa, and a host of others are known to affect levels of the neurotransmitter serotonin in the brain alleviating depression.. But the question is: How might they affect stuttering?

Antidepressants are selective serotonin reuptake inhibitors (SSRIs), which means that they:

     - reduce reuptake of serotonin into presynaptic neurons
     - increasing serotonin concentrations in the synapses between the pre- and post-
       synaptic neurons
     - encouraging uptake into the post-synaptic neurons.

(see the August 25, 2010 post entitled "Stuttering and Neurons" for a graphical depiction of the workings of neurons)

In this way, SSRIs allow serotonin to perform its task as a chemical messenger enabling neurons to trigger nerve impulses in neighboring neurons, which presumably reduces symptoms of depression.

However, recent research has raised the possibility that SSRIs may have a more complex effect on neurotransmission. Reduction of depression may result also from SSRI's activation of the dopaminergic system in addition to the serotonergic system.

SSRIs prevent reuptake of serotonin by inhibiting the action of serotonin transporters (SERTs). These are molecular cargo carriers that recycle serotonin back neuronal storage sacs called vesicles located on presynaptic neurons.

But in addition to SERTs, there also are dopamine transporters (DATs) that are involved in a similar fashion with dopamine reuptake. Increased DAT activity has been associated with clinical depression since they act to reduce the levels of synaptic dopamine. Normally DATs exhibit a low affinity for serotonin, but higher serotonin levels lead to the uptake of serotonin by DATS. In this way, the DATs are effectively highjacked by higher serotonin concentrations and cannot function as "dopamine absorbers" leading to

       - less reuptake of dopamine by the presynaptic neurons
       - greater concentrations of dopamine in the synapses
       - enhanced dopamine uptake into postsynaptic neurons

This enhancement of the dopaminergic system reduces the symptoms of depression. The relatively inefficient and slow process of the hijacking of DATs by serotonin may explain why it takes weeks before anti-depressive effects are observed during SSRI treatment.

But while enhanced dopaminergic activity may be beneficial for relieving depression, it might not be appropriate for improving fluency if the dopaminergic hypothesis of stuttering is correct. Among stutterers using antidepressants there have been reports of greater disfluency. although, to my knowledge, no large scale studies regarding the effects of antidepressants on fluency have been conducted.


Anonymous said...

I have come across quite an old publication that speaks of Celexa and Xanax to improve fluency in a patient. This was from 1993.

Surely there are newer and possibly "better" options available today (Seroquel, Saphris, etc).

But those without excellent insurance may find the price tag too steep on these new drugs ($500+ per month).

Celexa is available in a generic for a fraction of the cost..

Great post as usual.

stutter-mind-body said...

There is a lot of chatter on blogs re co-treatment with Xanax and celexa. I am aware of the 1993 Brady study using these drugs, but remember his sample size was only four individuals. Why was not a larger scale followup study conducted? Surely the pharmaceutical companies making these drugs should be interested in demonstrating the possible efficacy of this drug protocol from the purely economic view. And were there any long term followups of these individuals (years)?

Anonymous said...

It boggles the mind that we don't have a drug or drug combination formulated to relieve the pain and suffering of stuttering. Pagoclone reduced my anxiety and my stuttering by about 30 percent. That was enought to take off the edge and improve the quality of my life. Most doctors are resistance to treating stutterers with drugs since the drug companies show no interest in it.