Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor (SSRIs) are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders.
They are also typically effective and used in treating some cases of insomnia.
SSRIs are believed to increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor.
They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having only weak affinity for the noradrenaline and dopamine transporter.
SSRIs are the most widely prescribed antidepressants in many countries.
The efficacy of SSRIs is being disputed. A 2010 meta-analysis indicated that:
"The magnitude of benefit of antidepressant medication compared with placebo ... may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial."
For the occasional "on-demand" treatment, a few hours before coitus, clomipramine gave better results than paroxetine in one study, while in another study both sertraline and clomipramine were indistinguishable from the pause–squeeze technique and inferior to paroxetine. The most recent research, conducted in 2007, suggests that on-demand treatment with sildenafil (Viagra) offers a dramatic improvement in ejaculation delay and sexual satisfaction as compared with daily paroxetine, with on-demand sertraline, paroxetine or clomipramine,
- dextromethorphan (cough suppressant) - increased risk of serotonin syndrome/toxidrome
- tramadol (synergistic serotoninergic effect said to increase risk of seizure or serotonin syndrome/toxidrome)
- pethidine/meperidine - increased risk of serotonin syndrome/toxidrome
SSRIs also directly interfere with ligands of 5-HT receptors, like the psychedelics and entactogens. SSRIs strongly attenuate the effects of tryptamine psychedelics like psilocybin and LSD, and almost completely eliminate the serotonergic effects of phenethylamine psychedelics like mescaline and MDMA. The exact mechanism that causes this interaction is still unclear.
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