Disclaimer: I am NOT a medical professional. I am not a scientist. I do work for our local health authority in data/research for Mental Health and Substance Use so I read quite a few academic papers. I’m also doing a second bachelor's in Neuropsychology. I’m going to try to use layman’s terms to explain how venlafaxine works in the brain receptors (at least how I make sense of it!) This is an extremely oversimplified version. Please correct me if I'm wrong! I've been on Venlafaxine XR for almost 4-5 years now and I really do care about the brain altering drugs I'm willingly putting into my body daily.
Basic Clarifications:
- Effexor = Venlafaxine. Effexor is simply the brand name for the pills that Pfizer makes, Venlafaxine is the generic name. Same as Advil and Ibuprofen.
- Venlafaxine is used to treat depression, generalized anxiety, panic disorder, and social phobia. It is also used off-label for BPD, diabetic neuropathy, migraine prevention, and chronic pain.
- Starting dosage is 37.5mg with the “typical maximum” being 225mg and the exceptional max to 375mg
Venlafaxine is a SEROTONIN-NOREPINEPHINE REUPTAKE INHIBITOR (SNRI). What does this mean?
- There are a couple big classes of antidepressants:
- Selective Serotonin Reuptake Inhibitor (SSRIs) which would be Prozac, Lexapro etc
- Serotonin-Norepinphine Reuptake Inhibitor (SNRI) <— THIS IS US!
- Tricyclic Antidepressants — these are not prescribed as often because they have fairly high rates of side effects while being similarly effective to SNRIs)
- Monoamine Oxidase Inhibitors (MAOIs) which are mostly used for atypical depression or panic/phobia disorders
- Your brain has a couple key neurotransmitters that act together to essential cause depression/anxiety/etc. The “big 6” are the major actors that affect your brain and body.
- Glutamate which is present in like 90% of your brain synapses and acts as an “excitatory” messenger, sending signals between your brain
- GABA aka the opposite of Glutamate, it is inhibitory and reduces activity in the nervous system and blocks signals
- Dopamine!! This is the brain’s reward system!! It drives behaviour towards pleasurable rewarding goals.
- Adrenaline — which is the fight or flight response
- Oxytocin which helps form bonds/attachments through loyalty/trust/touch
- Serotonin is the key hormone in stabilizing mood/feeling happiness
(yes I know I haven’t mentioned Norepinephine yet)
- What the fuck does reuptake mean????????
- When the signal reaches the end of a neutron it releases small sacs (vesicles) that contain the neurotransmitters.
- Then the neurotransmitters form connections called “synapses” where it kind of hops from one cell to another by going to a receptor.
- Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal or glial cell after it has performed its function of transmitting a neural impulse
- BASICALLY after a neurotransmitter was used instead of throwing it away reuptake inhibitor means it doesn’t allow it to go back and it forces it to stick around
- This means that there are extra neurotransmitters in your brain now that would have otherwise been reabsorbed
- In the case of venlafaxine it blocks the receptors for serotonin and norepinephine so there is more of it in your brain (and in rlly high dosages dopamine because of the lack of norepinephrine reuptake in your frontal cortex). It also indirectly affect the opioid receptors which lower pain threshold.
- So why does having more serotonin and norepinephrine help depressive symptoms? Also ma’am you still haven’t told us about norepinephrine????
- Serotonin is often dumbed down to just “what makes you happy” but really it has many purposes within your body. It mediates your brains perception of outside stimuli. Humans have 14 different variants of serotonin for different effects including mood, anxiety, sleep, temperature, sex, and even your digestive system! Serotonin (within the brain) is produced mostly in the raphe nuclei which impacts your pain sensation and emotional regulation
- How does this affect your brain? It calms you down!
- Norepinephrine is similar to adrenaline and glutamate in that it mobilizes your body for action and essentially increase alertness/focus/energy. Norepinephrine is produced in the nuclei in the locus coeruleus (area responsive to stress/action) in the pons (larger general area that relays sensory info and movement).
- How does this affect your body? It increases cardiac activity along with activation signals for major organs.
- How does this affect your brain? It increases alertness, arousal, and action. More specifically this allows your brain react differently because it changes the activity in the prefrontal cortex and it enhances attention and memory formation.
- Thinking back to common depressive symptoms:
- Serotonin can affect the appetite, sleep, anxiety, and stabilize the mood
- Norepinephrine can reduce some fatigue and help with concentration
- Serotonin is often dumbed down to just “what makes you happy” but really it has many purposes within your body. It mediates your brains perception of outside stimuli. Humans have 14 different variants of serotonin for different effects including mood, anxiety, sleep, temperature, sex, and even your digestive system! Serotonin (within the brain) is produced mostly in the raphe nuclei which impacts your pain sensation and emotional regulation
Other fun comments:
- Why do antidepressants decrease libido? Most current antidepressants have an element of increasing serotonin (SSRIs, SNRIs). Because serotonin calms your brain and body down, it also calms down what would activate your sex drive.
- Venlafaxine is KNOWN for being difficult to stop — withdrawal symptoms make sense since your brain is used to getting this help, the lack of will obviously cause an imbalance. With Effexor, it has a relatively short half life so the effects are felt all at once rather than gradually.
- Compared to SSRIs, SNRIs are slightly more successful due to its dual mechanism. (Study: doi:10.1016/j.biopsych.2007.03.027)
- In the US, it is the 40th most commonly prescribed drug!
(Side Comment)
Regarding academic research - because of ~ethics~ in prisoning people and putting them under different medical conditions and then cutting open their brains is not allowed so academic research is often skewed to what is possible to do which means (1) a lot of neuroscience research even on medications is done on animals (2) there are specific vulnerable groups that often don’t get specific research as its deemed dangerous — ex: there’s a big issue currently pregnant women being given contradictory advice regarding the hazards of continuing psychiatric medication (3) really long term statistically significant results are incredibly difficult to come by.
Further Reading!!! (I just picked a couple I liked)
- Singh D, Saadabadi A. Venlafaxine. [Updated 2021 Aug 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535363/
- Gelenberg AJ, Lydiard RB, Rudolph RL, Aguiar L, Haskins JT, Salinas E. Efficacy of Venlafaxine Extended-Release Capsules in Nondepressed Outpatients With Generalized Anxiety Disorder: A 6-Month Randomized Controlled Trial. JAMA. 2000;283(23):3082–3088. doi:10.1001/jama.283.23.3082
- Li X, Zhu L, Su Y, Fang S (2017) Short-term efficacy and tolerability of venlafaxine extended release in adults with generalized anxiety disorder without depression: A meta-analysis. PLOS ONE 12(10): e0185865. https://doi.org/10.1371/journal.pone.0185865
- Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, et al. (February 2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis". Lancet. 373 (9665): 746–58. doi):10.1016/S0140-6736(09)60046-5
- Goeringer KE, McIntyre IM, Drummer OH (2001). "Postmortem tissue concentrations of venlafaxine". Forensic Science International. 121 (1–2): 70–5. doi):10.1016/S0379-0738(01)00455-8
- Nakhai-Pour HR, Broy P, Bérard A (2010). "Use of antidepressants during pregnancy and the risk of spontaneous abortion". Canadian Medical Association Journal. 182 (10): 1031–1037. doi):10.1503/cmaj.091208
- Masand, P.S., Gupta, S. Long-Term Side Effects of Newer-Generation Antidepressants: SSRIS, Venlafaxine, Nefazodone, Bupropion, and Mirtazapine. Ann Clin Psychiatry 14, 175–182 (2002). https://doi.org/10.1023/A:1021141404535
FUN BONUS: https://www.tiktok.com/@your.psych.pharmacist/video/7006461091064630534?lang=en&is_copy_url=0&is_from_webapp=v1&sender_device=pc&sender_web_id=7021039507433014790 is an awesome tiktok from a psychiatric pharmacist!!
ok it's 2:30am in pnw i'm logging out <33
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