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What SSRIs Actually Do to the Brain · Understanding the Brain

• 0:01
  Speaker 1: We decided the podcast is going pretty fast, so we
• 0:03
  Speaker 1: decided to do an extra episode this week. So let's
• 0:07
  Speaker 1: start off with a case scenario. You have a 28-year-old
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  Speaker 1: woman presenting with persistent sadness, insomnia, fatigue, and difficulty concentrating.
• 0:15
  Speaker 1: She meets diagnostic criteria for a major depressive disorder and
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  Speaker 1: has no history of mania or hypomania. You decide to
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  Speaker 1: prescribe a selective serotonin reuptake inhibitor, SSRI. Which medication should
• 0:27
  Speaker 1: you choose? These are important questions. So let's look at
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  Speaker 1: the six major SSRIs, fluoxetine, also known as Prozac, sertraline, Zoloft, paroxetine, Paxil,
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  Speaker 1: and there's different types of Paxils, citalopram, which is Celexa, citalopram, Lexapro,
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  Speaker 1: and fluvoxamine, which is Luvox. Those are the common U.S.
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  Speaker 1: brand names. SSRIs inhibit the serotonin transport known as SIRT,
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  Speaker 1: preventing serotonin reuptake into presynaptic neurons. This increases serotonin availability
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  Speaker 1: in the synaptic cleft. Although this action begins relatively quickly,
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  Speaker 1: meaningful antidepressant improvement typically requires several weeks. And patients should
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  Speaker 1: understand that side effects may appear before the therapeutic effects.
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  Speaker 1: It's really important for people to know that. Especially gastrointestinal issues,
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  Speaker 1: that's something they're going to feel really quickly. Especially remember, serotonin,
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  Speaker 1: 90% of it is in your gut. So fluoxetine or
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  Speaker 1: Prozac has a long half-life, reducing the likelihood of discontinuation symptoms. However,
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  Speaker 1: it has clinically important drug interactions because it inhibits CYP2D6,
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  Speaker 1: and we'll expand on these later when we talk about
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  Speaker 1: each of the medications. Sertraline or Zoloft is widely prescribed
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  Speaker 1: for depression, panic disorder, OCD, PTSD, and social anxiety disorder.
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  Speaker 1: Zoloft has gastrointestinal effects. particularly diarrhea, may occur again. It
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  Speaker 1: usually tends to go away after three to five days.
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  Speaker 1: Paroxetine or Paxil has relatively prominent anticholinergic effects. So you'll
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  Speaker 1: see sexual dysfunction and discontinuation symptoms is generally avoided in
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  Speaker 1: older adults when suitable alternatives exist. Celexa requires attention to
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  Speaker 1: dose-dependent QT interval prolongation in the heart. The FDA recommends
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  Speaker 1: a maximum of 20 milligrams daily for adults older than
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  Speaker 1: 60 and and certain other high-risk groups. As a Tylopram,
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  Speaker 1: Lexapro is approved for major depressive disorder and generalized anxiety
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  Speaker 1: disorder and is frequently selected for its tolerability. Fluoxamine, or Luvox,
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  Speaker 1: is particularly associated with obsessive-compulsive disorder and has several important
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  Speaker 1: CYP-mediated drug interactions. Important adverse effects in the class, SSRI
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  Speaker 1: adverse effects include nausea, headache, insomnia, sexual dysfunction, and early
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  Speaker 1: treatment-related agitation. SSRI carry an FDA box warning about increased
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  Speaker 1: suicidal thoughts and behaviors in children, adolescents, and young adults.
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  Speaker 1: One of the things you have to be careful with
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  Speaker 1: is if the energy increases but the depression doesn't go away,
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  Speaker 1: that's a warning sign. Additional concerns include hyponatremia, particularly in
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  Speaker 1: older adults, and increased bleeding risk when combined with NSAIDs
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  Speaker 1: or anticoagulants. Always screen for bipolar disorder before initiating antidepressant
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  Speaker 1: monotherapy because antidepressants can precipitate mania or hypomania. Serotonin syndrome
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  Speaker 1: is also another problem to work and watch out for.
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  Speaker 1: Results from excessive serotonergic activity often following medication interactions, for example,
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  Speaker 1: combining an SSRI with linazolid, tramadol, or MNMAO inhibitor may
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  Speaker 1: increase risk. Symptoms include agitation, sweating, hyperthermia, tremor, hyperreflexia, and clonus.
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  Speaker 1: Suspected serotonin syndrome requires immediate discontinuation of serotonergic agents under
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  Speaker 1: urgent medical management. The discontinuation syndrome, abrupt discontinuation can produce dizziness, nausea, insomnia, anxiety,
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  Speaker 1: and electric shock sensations. Paroxetine or Paxil is particularly associated
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  Speaker 1: with discontinuation symptoms, particularly because of its relatively short half-life. Remember,
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  Speaker 1: Prozac has a long half-life, so it has much lower risk.
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  Speaker 1: There's a minimum five-week washout required when switching from fluoxetine
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  Speaker 1: to an MAOI because of its long half-life, which is
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  Speaker 1: a little different. Some of the other ones are about
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  Speaker 1: two to three weeks. So if you have a 67-year-old
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  Speaker 1: patient with depression and a history of prolonged QT interval
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  Speaker 1: requires antidepressant treatment, which medication warrants particular caution? A, Zoloft, B, Celexa,
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  Speaker 1: or C, Prozac? If you said B for Celexa, citalopram,
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  Speaker 1: you are right. If you also were curious about what
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  Speaker 1: is the QT interval, The QT interval is a measurement
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  Speaker 1: on the ECG electrocardiogram that reflects the total time required
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  Speaker 1: for the heart's ventricles to electrically activate and then recover.
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  Speaker 1: So it roughly corresponds to the duration of ventricular contraction
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  Speaker 1: and relaxation. So it's measured from the very beginning of
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  Speaker 1: the Q wave on the ECG to the end of
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  Speaker 1: the T wave. In addition to that, we mentioned a
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  Speaker 1: word named clonus. It's an abnormal neurological reflex characterized by
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  Speaker 1: a series of involuntary rhythmic movements alternating muscle contractions and
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  Speaker 1: relaxations triggered by a sudden sustained stretch of a muscle tendon.
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  Speaker 1: So in a healthy nervous system, the brain and descending
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  Speaker 1: motor tracts send continuous inhibitory signals to spinal reflex arcs,
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  Speaker 1: keeping deep tendon reflexes regulated. However, when there's an upper
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  Speaker 1: motor neuron lesion disrupts these descending inhibitory pathways, the spinal
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  Speaker 1: stretch reflex arc becomes hyper excitable, called hyperreflexia. The sudden
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  Speaker 1: passive stretch excites muscle spindles and triggers a reflex contraction.
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  Speaker 1: As the muscle contracts and relaxes, the continuous stretch re-triggers
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  Speaker 1: that reflex loop, creating this rapid oscillatory beats. That's it
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  Speaker 1: for now.