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Serotonin and the Brain: Why Antidepressants Take Weeks to Work · Understanding the Brain

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  Speaker 1: Welcome back. Today we're going to take a deep dive
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  Speaker 1: into serotonin. Last time we talked about all four neurotransmitters,
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  Speaker 1: but this time we're going to go deeper into each one.
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  Speaker 1: First one off the get-go is melatonin, also called 5-hydroxytryptamine
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  Speaker 1: or 5-HT. It's a neurotransmitter synthesized from the amino acid tryptophan.
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  Speaker 1: Remember that one from the famous comparison with turkey? You
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  Speaker 1: can get a tryptophan. We'll talk more about that maybe
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  Speaker 1: another time. Tryptophan participates in what I call MASAP. So
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  Speaker 1: it's an acronym for mood, anxiety, sleep, appetite, and pain perception.
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  Speaker 1: Also has gastrointestinal functioning. Now the first one is mood regulation, anxiety, again, sleep, appetite,
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  Speaker 1: pain perception, and gastrointestinal functioning. So you can put it
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  Speaker 1: as MASAPG, M-A-S-A-P-G is the acronym. If you want, you
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  Speaker 1: can create another word with it. Although serotonin is frequently
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  Speaker 1: associated with happiness, its functions are considerably more complex. Depression
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  Speaker 1: is not simply caused by having too little And serotonin
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  Speaker 1: levels alone cannot establish a psychiatric diagnosis. So let's look
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  Speaker 1: at the serotonin receptors. That's going to be something that's important.
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  Speaker 1: Several serotonin receptor families influence psychiatric functioning. The 5-HT1A receptor
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  Speaker 1: participates in anxiety and mood regulation. Buspirone, for instance, commonly
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  Speaker 1: prescribed for generalized anxiety disorder, acts as a partial agonist
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  Speaker 1: at this receptor. The 5H2A receptor is associated with perception
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  Speaker 1: and cortical signaling. Many second-generation antipsychotics, including resveratone and olanzapine,
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  Speaker 1: antagonize this receptor alongside dopamine receptors. Including our 5HT3 receptor
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  Speaker 1: contributes to nausea and vomiting. So here you're looking at adenosatrone,
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  Speaker 1: an antiemetic, which blocks this receptor. So 5HT1A participates in
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  Speaker 1: anxiety and mood regulation. 5-H2A, associated with perception and cortical signaling.
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  Speaker 1: This is the P pain perception component. And 5-HT3 contributes
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  Speaker 1: to nausea, that's gastrointestinal functioning, and vomiting. These three receptor
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  Speaker 1: associations because they connect neurobiology with clinical prescribing. That's why
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  Speaker 1: it's important to remember So how do iodine depressants affect serotonin? Well, SSRIs,
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  Speaker 1: or selective serotonin reuptake inhibitors, block the serotonin transporter, reducing
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  Speaker 1: serotonin reuptake into presynaptic neurons. Examples, of course, include sertraline,
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  Speaker 1: which is Zoloft, fluoxetine, Prozac, cytotilopram, and paroxetine. So you've
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  Speaker 1: got Celexa, Lexapro, Paxil, additional ones. Although transporter inhibition occurs
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  Speaker 1: relatively quickly, meaningful antidepressant improvement often develops over several weeks.
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  Speaker 1: Adaptation and receptor signaling and neural circuits are believed to
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  Speaker 1: contribute to the delayed therapeutic response. Serotonin and norepinephrine reuptake inhibitors,
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  Speaker 1: including venloxifene and duloxetine, affect both serotonin and norepinephrine transporters.
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  Speaker 1: These medications are commonly used for depressive and anxiety disorders,
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  Speaker 1: while certain SNRIs also have indications for chronic pain conditions.
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  Speaker 1: So you've got serotonin and norepinephrine for the SNRI. How
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  Speaker 1: about serotonin syndrome? Consider another patient. A 45-year-old man taking
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  Speaker 1: cetraline develops agitation, sweating, diarrhea, tremor, and fever shortly after
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  Speaker 1: beginning tramadol for back pain. His temperature is 102.2, his
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  Speaker 1: heart rate is 122 beats per minute, and examination reveals
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  Speaker 1: hyperreflexia and inducible ankle clonus. What diagnosis should immediately concern you?
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  Speaker 1: If you said serotonin syndrome, you're right. This potentially life-threatening
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  Speaker 1: condition results from excessive serotonergic activity, often involving medication interactions.
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  Speaker 1: Its characteristic findings involve three domains, altered mental status, autonomic instability,
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  Speaker 1: and neuromuscular hyperactivity. Clonus and hyperreflexia are especially useful diagnostic clues.
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  Speaker 1: Management begins with immediately discontinuing serotonergic medications, urgent medical evaluation,
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  Speaker 1: supportive care, and benzodiazepines when indicated. So there you go.
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  Speaker 1: If you take fluoxetine and the patient develops agitation, diaphoresis, hyperthemia,
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  Speaker 1: and inducible clonus, then you've got serotonin syndrome. That's it
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  Speaker 1: for now, folks.