What long term changes do SSRI and SARI drugs cause?

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SUMMARY

The discussion focuses on the long-term effects of SSRIs (Selective Serotonin Reuptake Inhibitors) and SARIs (Serotonin Antagonist Reuptake Inhibitors) on neurotransmitter pathways, particularly regarding serotonin and adrenergic receptors. It is established that SSRIs inhibit serotonin reuptake, potentially leading to downregulation of 5-HT receptors due to increased synaptic serotonin levels. The conversation also highlights that long-term use of antidepressants may cause downregulation of adrenergic receptor subtypes, specifically α2 and β1, although the mechanism for SSRIs affecting these receptors remains unclear. SARIs like trazodone and mirtazapine exhibit complex interactions with various monoamine receptors, raising questions about their long-term receptor regulation and neurogenic effects.

PREREQUISITES
  • Understanding of neurotransmitter pathways, specifically serotonin and adrenergic systems.
  • Familiarity with pharmacological mechanisms of SSRIs and SARIs.
  • Knowledge of receptor downregulation and neurogenesis concepts.
  • Basic pharmacology terminology related to antidepressants.
NEXT STEPS
  • Research the mechanisms of action of SSRIs and their effects on 5-HT receptor regulation.
  • Explore the pharmacodynamics of SARIs, focusing on trazodone and mirtazapine.
  • Investigate the long-term neurobiological effects of antidepressants on hippocampal neurogenesis.
  • Study the implications of adrenergic receptor downregulation in the context of antidepressant therapy.
USEFUL FOR

This discussion is beneficial for pharmacologists, mental health professionals, and researchers interested in the long-term effects of antidepressants on neurotransmitter systems and receptor dynamics.

CrimpJiggler
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I read about long term use of these kinda antidepressants causing hippocampal neurogenesis and stuff like that but I'm focusing more on what long term use does to the various monoamine neurotransmitter pathways. I'll start with SSRIs because they are the simplest. Their main mechanism of action is inhibiting reuptake of serotonin. Would I be right in assuming that the surplus of serotonin in the synapse causes downregulation of 5-HT receptors? In my pharmacology book, they claimed that long term use of antidepressants cause downregulation of two of the subtypes (α2 and β1 I think it was) of adrenergic receptors but they didn't state what class of antidepressants do this. I can see why TCAs and other SNRIs would downregulate α and β receptors but I don't see why SSRIs would cause significant downregulation of adrenaline receptors. However, I know very little about what long term use of an SSRI does.

SARIs (serotonin antagonist reuptake inhibitors) are an even bigger mystery to me. Two that I'm familiar with are trazodone and mirtazapine. Trazodone binds strongly (and antagonises) various 5-HT receptors, as well as α1 receptors. It also has mild affinity for the serotonin transporter. Mirtazapine has a similar binding profile but its much less selective (i.e. it has significant anticholinergic and antihistamine properties). Since these drugs block various monoamine receptors, what kinda long term effects do they produce? I can't see how they would downregulate receptors (since the antagonism should counteract the reuptake inhibition) or produce long term trophic effects such as hippocampal neurogenesis.
 
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@BillTre may have an answer. Our neurobiology members are not very active lately.
 

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