Vitamodo School · Bundle 5: Pharmacotherapy Without Myths · Brochure 2 of 10 · Version 1.0
Andris Saulitis, MD
For those who: want the honest pharmacology — what is known at the receptor level, what is partly understood at the clinical-effect level, and how to think about taking medication whose mechanism is partially mapped.
Not for those who: want a confident chemical-imbalance story or a wholesale dismissal of the science. The careful position is more accurate and more useful than either.
What this is — the clinical reality
The question what does this medication actually do in my brain is one that patients have substantial reason to want answered carefully. The standard answer they get is some version of it corrects the chemical imbalance — a story that, as Bundle 4 of this series has covered, has been substantially retracted by careful clinical neuroscience and that the discipline has been slow to update in patient-facing communication. The polemical answer they often encounter — the science is a fraud, we know nothing about what these medications do — is also wrong; we know substantial amounts about what these medications do, just less than the discipline's confident communication suggested and more than the polemical critique allows.
This brochure is for the reader who wants the honest neuroscience — the careful account of what is known, what is not known, and how to think about taking a medication whose mechanism is, in important respects, partially understood. It is not a textbook on psychopharmacology; it does not give specific drug recommendations; it does not replace the clinical conversation with a prescriber. It does try to give you a working framework for understanding what is happening in your brain when you take one of these medications, and for asking the careful clinical questions that the framework supports.
A note before we go further. The science of psychiatric medication has several layers. At the receptor level — what the molecule does to specific neurotransmitter receptors in the brain — the knowledge is substantial and increasingly detailed. At the circuit level — how the receptor effects produce changes in larger brain networks — the knowledge is real but partial. At the level of clinical outcome — how those network changes translate into changes in mood, thought, behaviour, and subjective experience — the knowledge is genuinely incomplete in ways the discipline does not always acknowledge. The gap between we know the receptor effect and we know the clinical effect is one of the most important features of present psychiatric pharmacology, and the careful reading holds the gap visible.
Three frames carry the pharmacology.
The first frame is the receptor-level knowledge that is established. What we genuinely know about what these molecules do at the cellular level.
Antidepressants of the SSRI class (fluoxetine, sertraline, citalopram, paroxetine, escitalopram, fluvoxamine) block the serotonin transporter, which is the protein that normally pulls serotonin back into the neuron after it has been released into the synaptic gap. The blockade results, in the short term, in increased serotonin available in the synapse. This is well established and can be measured directly. SNRIs (venlafaxine, duloxetine) do the same thing for serotonin and norepinephrine. Tricyclic antidepressants, the older class, do the same thing across several neurotransmitter systems and additionally affect histamine, muscarinic, and adrenergic receptors, which accounts for their broader side-effect profile. The newer antidepressants — bupropion (dopamine and norepinephrine), mirtazapine (multiple receptor effects), vortioxetine (multimodal serotonin) — have specific receptor profiles that have been carefully mapped.