Ssri’s for depression

SSRI medication is the most commonly prescribed psychotropic medication utilized today. A frequent question is whether there is a difference between the SSRI’s such as Zoloft, Prozac, Paxil, Lexapro, Celexa and Luvox. They all share the common mechanism of being a serotonin reuptake inhibitor which means they block the proteins responsible for the reuptake of serotonin in the neuronal circuits which leads to increased levels of serotonin in the synaptic clefts.

This is simplistic however and unrelated to how the medications actually help alleviate depression. While several mechanisms of action are known for SSRI’s, the truth is none of them decisively explain why they help with depression. They all work to effect dozens neuronal networks and signaling pathways that are far more complex than their name suggests. One such pathways is Brain Derived Neuro-trophic factor (BDNF) which is a critical neuronal protein responsible for organization of neuronal pathways and is responsible for synaptic plasticity. This is an example of one protein that effects numerous downstream proteins which in turn regulate a variety of receptors and circuits. Little detail has been elucidated however which leave the vast majority of people to still associated their effect with serotonin re-uptake.

While all of the SSRI’s effect many of the same protein pathways, each of them effect unique circuits as well. This explains while some people respond to one SSRI but not another. In practice however, I have found very few people who respond to one SSRI if they have not responded to another one given a fair trial, proper dosing and of course the proper diagnosis. This is evidence that science is still lacking in terms of the elucidation of their true mechanism of action, despite being the most utilized psychotropic medication available.

When it comes to side-effects, there are patients who can tolerate one SSRI over another however and this is one of the few times I will switch to another SSRI. If one fails to respond to one SSRI however I will not waste the time switching to another SSRI but instead switch to a new class of medication. Evidence has supported both techniques however clinical experience has proven to show me that switching is the more effective strategy in terms of relieving depression or anxiety most rapidly.

The most common mistake I see in the treatment of depression is the incessant use of multiple SSRI’s despite continued failure to respond. At the most 2 SSRI’s should be tried and after that evidence supports always switching. There is never a clinical scenario where trying a 3rd SSRI would be warranted.

Michael Yasinski MD