Exploring SNRIs' Unique SERT and NAT Ratios - Why They Are Not All the Same!

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Exploring SNRIs' Unique SERT and NAT Ratios - Why They Are Not All the Same!

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Psychiatry Simplified - Dr Sanil Rege

Күн бұрын

Пікірлер: 49

@Hilbregirl 6 ай бұрын

I found this really helpful to gain a better sense of why certain drugs work so well for me. I have ADHD and occasional episodes of severe true melancholic depression. When l was last very depressed my psychiatrist prescribed duloxetine, Atomoxetine, and 2x5mg Ritalin. My depression has resolved completely and my adhd symptoms in all areas of life continue to improve beyond the benefit l had when l was only taking a stimulant. Thanks again for your work here on KZfaq.

@PsychiatrySimplified 6 ай бұрын

That’s great to hear !

@user-du8hf4pg8q 5 ай бұрын

Thank you so much!

@PsychiatrySimplified 5 ай бұрын

Pleasure

@jocs8824 5 ай бұрын

Would love a deep dive video on pain management, noradrenaline and endorphins - the way they boost each other's effect by receptor upregulation. Low Dose Naltrexone and how it might be working for pain.

@PsychiatrySimplified 5 ай бұрын

I will keep that in mind. It’s a great suggestion! Thanks

@jocs8824 5 ай бұрын

Thanks!

@PsychiatrySimplified 5 ай бұрын

Thank you. I appreciate the gesture 🙏🏻

@drkhan5401 6 ай бұрын

Dear Dr Rege thank you for this wonderful video. Kindly make more such videos in the future as well on other different psychotropics.

@PsychiatrySimplified 6 ай бұрын

Thanks for tne feedback. We've got a few on there. Antipsychotics, antidepressants etc. But sure have always got more in mind.

@jacklinemmochi6433 6 ай бұрын

Good stuff . I see why one of my patients had dramatic withdrawals from engine when were reducing the dose- opioid properties 🎶

@joshuafuryon7874 6 ай бұрын

I love your break down of these mechanisms , i was diagnosed with ADHD at 44 at this time i was also being treated for anxiety /depression with Mainserine . ive been taking ritalin and mainserine for 2 years now on and off trying to find out best cyclic rate and dosage in waves as constant daily doesn't work, mainserine is very sedative but regulates my sleep and removes the need to constantly urinate, alll in all its been a difficult couple of years trying to come to terms with my past and accepting the personality changes or not if i discontinue the meds, i was diagnoses in france and find it very dificult to get any advice or info on whats meds i could be taking instead.as most Doctors here in France dont think ADHD is a real thing. or stop taking like Ritalin which makes me isolate and zone out or vegetate sometimes. any advice would be most welcome :)

@PsychiatrySimplified 6 ай бұрын

1. What are main symptoms to be targeted ( specific descriptions) 2. What are doses and formulation? 3. What comorbidities besides depression and anxiety - sleep dysfunction. oSA , iron deficiency etc ? 4. Is it anxiety or hyperarousal - hyperarousal occurs with nightmares , or vivid dreams. Not waking up refreshed. Racing thoughts , not all at same time - but any of these can be present.

@nancycm 6 ай бұрын

Thank you!

@PsychiatrySimplified 6 ай бұрын

You're welcome!

@eirini98 6 ай бұрын

Dr. Senil. Your videos have helped me a lot, and I hope the KZfaq algorithm catches you and your channel and gives you the credit you deserve. I have a question regarding ADHD medication, specifically LDX. In the clinical studies, it's said that lisdexamfetamine has a duration of effectiveness of up to 14 hours in adults. This might be true for the first week or two, but hearing this causes all sorts of problems for so many, who complain that its therapeutic effects wear off after, say, 4-5 hours. Dr. Russell Barkley made a video arguing that although you might not "feel" it working, it most likely is. This is important as people tend to equate "feelings" with efficacy, and I agree that the medication could still be working (e.g. you're able to do stuff you couldn't do before taking the medication) even when you don't "feel" anything. As great as they are, I don't remember any of your videos talking about this specifically. But it's a MASSIVE deal among the ADHD population, and I think you're more than able to explain complex matters to the layman. Could you make a video on the issue, maybe teaching us about tolerance, boosters, nutrition, how to know the medication is working, etc? You're the guy that knows. I'm just concerned that many people are getting unnecessary boosters (like 30mg extra of LDX from their doctors), and going way beyond what it "recommended" e.g. 70mg daily, setting themselves up for potential cardiovascular problems in the future. Thanks. Sorry for the long message

@Nazula236 6 ай бұрын

Interesting. If people have an initial duration of 14 hours for a week or two and then it decreases to 5 to me that would point more towards a tolerance of those subjective effects of "feelings." To my understanding generally tolerance to the clinically therapeutic effects of amphetamines or lisdexamfetamine in this case is very uncommon barring large weight changes (growth spurts as a child/teen), etc. It would be more along the line of the euphoria and other effects that will diminish over time using the same dosage, similar to how drug users have to continue to increase the dose of their drug in order to feel similar effects. There is limited research in general surrounding this topic. There is certainly a psychological component to it as well, where if a patient doesn't believe that their medication is working, then it may not work quite as effectively than in someone who believes that it does. All this to say that patient education and expectations are very important for any psychiatric medication, including agents for ADHD. If someone consistently has a therapeutic effect of 4-5 hours since initiation then that would point more towards an individuals variance in metabolism for a shorter duration.

@eirini98 6 ай бұрын

@@Nazula236 I may have exaggerated the "week or two" aspect. But I was referring to the fact that many people complain that LDX loses its efficacy - sometimes sooner, sometimes later, but eventually. I would like to see what the doctor thinks about this. Is it true tolerance? Have the patients misunderstood the intended functions of the medication (i.e to treat symptoms of their ADHD, and not to give them "happy feelings")? Are boosters a good idea? It's just a suggestion that I believe would help many people.

@Nazula236 6 ай бұрын

@@eirini98 I'd imagine that he would be open to discussing this whenever he next uploads a video on stimulants. As a student I admire his talent at discussing and presenting topics to laypeople and hope to become as competent when conversing with my future patients. I do believe you are on to something in terms of the misunderstanding of the intended function of the medication, which highlights why proper pt education is important. In terms of boosters, it is definitely evidence based to prescribe a booster dose of stimulant to extend therapeutic coverage if the long-acting agent isn't sufficient. However, it is typically done with an immediate release formulation rather than another 30mg of LDX like your previous comment referenced. This is in order to prevent adverse effects like insomnia if a long-acting med is taken too late in the day. For a "true tolerance" it is unlikely but not impossible -- there is further research needed.

@PsychiatrySimplified 6 ай бұрын

Great point re the duration of action of LDX. The conversion from LDX to Dex occurs in 1.5 hrs and the duration of action is anywhere between 1.5-13 hrs - it isn’t 13 hrs as often thought. I have included this in the teaching lectures and the 13.5 hr masterclasses for clinicians. Clinically it is evident that LDX action does not last for the duration needed in all patients. In some a dip can occur even 3-4 hrs later. Yes boosters are added - but it’s probably not the best way. There are some methods of extending the duration but they are hit and miss. One way is BD administration - similar issues occur with concerta and BD administration is a documented strategy . Ps not advice . For clinicians the masterclass I was talking about - www.academy.psychscene.com/courses/clinical-excellence-in-adult-adhd-a-comprehensive-curriculum/ @nazula236 @bigsan98

@PsychiatrySimplified 6 ай бұрын

@bigsan98 @nazula236 There is the other issue of losing ‘effectiveness’ . This is difficult to put on a post - best illustrated through case studies. The initial stage of a stimulant prescription results in increase of the extracellular DA ( there is NA and 5HT with Dex / LDX - but let’s leave those) which targets the D1 receptor in PFC ( main DA receptor and requires significantly higher DA levels I.e phasic DA to be stimulated compared to D2 which is easily stimulated - mainly in striatum) . D1 is needed for early reward learning - but repeated phasic DA mimics substance use - sensitisation and is not adaptive. I covered this in a short , snippet from the courses. D1 is subsequently stimulated by unexpected rewards which needs action and engagement with the environment - goals etc. D2 receptor tonic activation is the basis of stability with occasional D1 phasic through unexpected rewards for learning I.e goal directed plans etc. note reward is not pleasure but rather reward learning. Secondly ADHD and it’s comorbidities are not addressed which is one of the most common reasons for loss of effectiveness of agents. 60-80% comorbidity. Finally ADHD is about addressing the following domains 1. Cognition 2. Activity 3. Emotion and reward sensitivity 4. Behavioural activation 5. Behavioural inhibition 6. Fight and flight responses. Working only on stimulants misses the nuances required in these domains. Further more gender differences are to be considered .

@bishalgupta7083 6 ай бұрын

Thanks for nice video

@PsychiatrySimplified 6 ай бұрын

🙏🏼 pleasure

@DanielSRosehill 6 ай бұрын

Great video Ty

@PsychiatrySimplified 6 ай бұрын

Glad you found it useful

@richwoodcutterbro8581 Ай бұрын

How is duloxetine considered as an SNRI when literature states no tyramine pressor response, unlike with venlafaxine and chlomipramine?

@PsychiatrySimplified Ай бұрын

Inhibits TYP response at higher doses. Venlafaxine as well > 225 mg. Clomipramine a true SNRI 2:1 ratio of SERT : NAT compared to venlafaxine 30:1 and Duloxetine 10:1

@V8-friendly 6 ай бұрын

Thanks for this upload. In many publications that I read, it says, “the working mechanism is BELIEVED to be…” meaning nobody seems to know for sure how that SSRI/SNRI stuff really works on the brain. Also how bizarre, that it takes 4-6 weeks before it starts working, I think. For example, if I take a Benzo, it works on the brain’s Gaba receptor, and within an hour, you feel calm. So on anxiolytics I get it. On antidepressants I don’t get it.

@PsychiatrySimplified 6 ай бұрын

That is acts on SERT and NAT inhibition is not belief - as that can be shown through imaging and other studies. The belief but is when they say treatment of depression because how SERT inhibition and NAT inhibition ‘treats’ depression and anxiety is not exactly known. However in clinical practice effects are seen in the first two weeks and recent articles on switching or augmentation also talk about 2 weeks for a response. Effects if dose is increased can be in a week. Benzodiazepines act as GABA agonists - straight at the receptor and action. SSRIs , SNRIs do not directly act at receptor level - they have to act on the transporter and then the levels in synaptic cleft have to build up for effects to occur. There are other reasons as well. So a two step process in a way and hence the lag.

@V8-friendly 6 ай бұрын

⁠@@PsychiatrySimplified Thank you very much, for this in-depth explanation, much appreciated. I was given any antidepressants out there (about 15 different ones) including tricyclics, none of them worked. Most caused very uncomfortable side effects, some didn’t cause anything at all. Zoloft was the worst, felt like rat poison, got so sick. Atypical antipsychotics also did not work for me. Diagnosed as “treatment resistant” with F43.12 in the very end. I will subscribe to your channel in order to learn more. Thanks for your time replying to me, and have a great weekend. Oddly enough, Benzos also seem to have an uplifting mood effect for some reason, but are very addictive unfortunately, and tolerance builds up quickly. Only thing that somewhat works for me is Mirtazipine.

@PsychiatrySimplified 6 ай бұрын

Thanks for subscribing. What symptoms are you looking to change? Or address?

@V8-friendly 6 ай бұрын

@@PsychiatrySimplified Right now Mirtazipine to some degree does the trick. I think, depression can also come from anxiety and the other way around - comorbidity? But also here over 20 medications were tried, none of them worked the slightest bit, except for long acting B. Lower gastrointestinal chronic pain 16 hrs a day from waking up to falling asleep kills your quality of life. Colonoscopy and Endoscopy negative. CT, MRI, blood tests, etc. all negative. They say, it’s in my mind: brain-gut connection. Nobody can or will help me, so I basically have given up.

@PsychiatrySimplified 6 ай бұрын

@@V8-friendly have a listen to the melancholic depression video. When pain or any other stimulus becomes all consuming ; anxiety changes to hyperarousal or agitation. This is different from anxiety. So if there is agitation, insomnia, all consuming thoughts ( ruminations) including bodily symptoms this can be a manufestsrion of melancholic depression. Pls see the video