SSRIs are also dopaminergic

  • Posted by Matt Dorsey on October 17, 2022 at 12:09 am

    The most commonly prescribed medications for depression are Selective Serotonin Reuptake Inhibitors. This name gives the impression that they only work on serotonin, but in fact many of them also work on the dopamine system.

    Since the right hemisphere tends toward sadness and depression, it would stand to reason that boosting dopamine would be an effective way to increase left hemisphere activity, which may result in greater ‘balance’ (using this word loosely).

    There are of course various antidepressants that are considered SDRIs (Selective Dopamine Reuptake Inhibitors), but it’s interesting that the lines between SSRIs and SDRIs are a bit blurrier than one might imagine.

    However, even if SSRIs’ dopaminergic activities are not mediated by effects on dopamine reuptake, but rather other mechanisms, what really matters is the end result. In other words, whether or not they meet the technical definition of SDRIs is inconsequential if they are proven to enhance dopaminergic activity.

    Here are several papers / articles that discuss SSRIs’ dopaminergic effects with comments:

    1. Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial

    “The present findings support that dopamine neurotransmission is crucially involved in the therapeutic mechanisms of SSRIs” (medication used: escitalopram)

    2. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex

    “Amongst the SSRIs examined, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex, suggesting that fluoxetine is an atypical SSRI.”

    It’s particularly noteworthy that the authors even went so far as to refer to Prozac (fluoxetine) as an ‘atypical antidepressant’, which is not remotely in keeping with the consensus on this extremely common drug, which is that it’s a prototypical SSRI with only serotonergic effects. Note also that this study only looked at the PFC.

    3. SSRI antidepressants involve dopamine as well as serotonin signaling

    “…revealed that SSRIs can have more complex effects on neurotransmitter traffic in the brain than just altering serotonin levels. They found that higher serotonin concentrations caused by SSRIs can “trick” transporters of another key neurotransmitter, dopamine, into retrieving serotonin into dopamine vesicles. Dopamine transporters have a low affinity for serotonin, but the higher serotonin levels result in its uptake by the dopamine transporters, found the scientists.”

    4. Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats

    “…sertraline administration increased extracellular dopamine concentrations in the nucleus accumbens and striatum.”

    Zoloft (sertraline) is known to have high affinity for dopamine transporters, even though it’s still pigeonholed as an SSRI.


    Matt Dorsey replied 1 year, 9 months ago 1 Member · 0 Replies
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