Is it generally harder to taper off of Gabapentin or an SSRI antidepressant, and why?
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SPeaking in the case of SSRIs – this is complicated to going for a layperson explanation, not a 5 year old.
SSRIs need to be tapered off for the same reason that they generally take a few weeks to start showing a clinical effect. This is because SSRIs change the amount endogenous (internal/ self made) serotonin which is released. But this only happens after a time of a few weeks.
The explanation for this mechanism can starts with the name. Selective Serotonin *Reuptake* Inhibitors. These drugs percent Ser from being reuptaken into the neurons which released them. This is the common way of terminating the action of the neurotransmitter after release, along with metabolism. The result of this is that Ser remains active in the synapse for longer. This expectedly causes more activity in serotonergic pathways, because more Ser is available to bind and activate post-synaptic neurons.
Over time, however, a different mechanism comes into play, which changes the brain’s own response to serotonin release. Normally some of the released serotonin tells the neuron that released it to stop releasing more serotonin by binding to an autoinhibitory (self stopping) receptor. This is called negative feedback. However, the presence of long term elevated Ser in the synapse (as explained previous paragraph) actually decreases the amount of these autoinhibitory receptors in a process called receptor downregulation. The net result is that less negative feedback can occur, and thus more Ser is released upon every activation of that neuron (this is what we want to achieve in order to treat depression). At this stage, the “brain chemistry” has been changed by the drug.
Stopping the SSRI cold turkey forces a very sharp adaptation back to the pre-drug baseline, as the continued presence SSRI is important to maintain the *new brain chemistry* explained above. The expected amounts of Ser at play would dramatically change. Tapering is thus used to allow a smoother transition back to pre-treatment brain chemistry.
SOme version of such a process is applicable to any drug which induces a change in neuronal function over a period of weeks. Such drugs would require a tapering off period.
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