Clinical Application of Prazosin & Clonidine - Role of Alpha (α) Adrenergic Receptors (α1 and α2)

Dr Sanil Rege starts this video by discussing the Alpha 1 and Alpha 2 adrenergic receptors and their mechanism of action. He then discusses the mechanism of action of Prazosin and Clonidine in the context of the Alpha 1 and Alpha 2 receptors. Prazosin is an Alpha 1 adrenergic receptor antagonist and Clonidine is an Alpha 2 adrenergic receptor agonist. Finally, he shares his practical clinical experience with regards to both agents covering indications, optimum doses and side effects.
00:00 - Intro
00:37 - Role of Alpha 1 receptor and Prazosin
02:55 - Role of Alpha 2 receptor | Clonidine and Guanfacine
06:41 - Clinical application of Clonidine and Prazosin in Psychiatry
Discussion points:
Prazosin
• Unique therapeutic effects on nightmares and sleep disturbance associated with PTSD
• Orthostatic hypotension as a main side effect
• Minimum abuse potential
Clonidine
• Sleep deprivation is known to affect the clearance of metabolic waste products in the wakefulness pathways governed by locus coeruleus (NA neuron projections)
• Thus, manipulation of noradrenergic tone may enhance glymphatic clearance providing a neuroprotective effect for the brain.
• Clonidine is an α2 agonist (high affinity for all 3 α2 -receptor subtypes, α2A, α2B and α2C) which is known to increase NREM sleep. While low doses (e. g., 25 μg) have little effect on REM sleep, 150 mcg clonidine reduces REM sleep by about 50 %.
• Indications include primary insomnia in the paediatric population, insomnia in the context of ADHD, ASD, PTSD and Borderline personality disorder. [Nguyen et al., 2013], [Broese et al., 2012]
• Guanfacine is also an α2 agonist (specific α2A). Higher doses of about 2 mg can reduce REM sleep by 26 % which is less marked than clonidine.
Read more
Diagnosis and Management of ADHD - psychscenehub.com/psychinsigh...
Insomnia Neurobiology - psychscenehub.com/psychinsigh...

[@karielaine]

As a scientist who likes to REALLY understand medications I'm prescribed... this video is fantastic! I always remind my doctors or pharmacists that I WANT them to actually tell me everything they know about how stuff works. Some of them really get a kick out of being allowed to geek out in a way that most patients DON'T want. I don't want to take up their time too much though, so this video answered all of the detailed questions I had about how Clonidine works and was easy to follow. Thanks again!

[@PsychiatrySimplified]

Thank you for your feedback.

[@hannahnicholas6375]

I Just discovered your channel. As someone who is on a number of medications that have been explained in your videos, I really appreciate that you explain how they work in a way that I can understand.

[@PsychiatrySimplified]

Thanks for the feedback

[@saxotonie]

please keep these videos coming!

[@Mfox-]

great video, thanks mate. just put on clonidine for thrombocytosis of all things... chronic pain improved, now i know why

[@PsychiatrySimplified]

Good to know!

[@sarahzitzmann8860]

Thank you

[@jacklinemmochi6433]

Great video Gained a lot of information

[@robertmccarrick8410]

Very good...the science...your teaching skills...your heart...please carry on the great work... Thank you

[@PsychiatrySimplified]

Thank you for the feedback. Appreciate it 🙏🏻

[@Umargaming000]

Excellent sir

[@PsychiatrySimplified]

Thank you for your feedback 🙏🏼

[@yogi9631]

Great video 👍👍

[@PsychiatrySimplified]

Thank you for your feedback.

[@sywakit]

thanks

[@roshanalilakho]

Very informative lectures .thanks Dr.great work

[@PsychiatrySimplified]

Thank you 🙏🏻

[@traviskemp0326]

I like how you explain it like I'm a dummy. I'm not. Just an observation. I never really looked at all the factors you have to take into account for the tx of adhd. For myself Adderall 20 mg b.i.d. helps me tremendously. I live in south Georgia and can't find a doctor because they think I'm just trying to get the drug when I'm really seeking relief. Until you know you don't know...

[@CopperKettle]

Thank you, it's quite interesting. Nice pronunciation.

[@jossyantony1708]

This is brilliant Sanil. It would be good to add propranolol as well to the mix. Thank you!

[@PsychiatrySimplified]

Thanks for the feedback. Will keep that one in mind. 🙏

[@Gabby-hw7my]

This video is great. I have a very tough situation that my doctors are having trouble doing anything about and I’d really appreciate your information. Of course, I will not take anything you say as medical advice. I suffered an ischemic repurfusion injury and resulting peripheral neuropathy after getting frostbite in one of my limbs. I’m in severe pain constantly and unable to walk for normal intervals. I have reduced blood flow to the limb and nerve pain. I am on both prazosin and Clonodine for sleep and nighttime anxiety. I am now worried that by being on this heavy combo and reducing my blood pressure so much, I am further reducing blood flow- impeding healing, and even causing ischemic repurfusion by going back and forth between hypotension and regular BP. I’ve been suffering from this for 2 years unable to walk normally and I am so desperate to heal so I’m very worried at this possibility. Is this a possibility? And if I were to go off of one, which one have the least risk of reducing blood flow? I don’t want to choose the one that has the biggest anxiety or pain relieving properties, I am on drugs for that already, but I want to choose the one that has the least risk of reduced blood flow. Thank you so much if you can answer.

[@OnlyAbuseMeLiver]

Would it make sense that 150mcg clonidine before bed gave me insomnia, yet in the past ive taken lower doses and experienced acute relaxation - mentally and physically that never occured with the 150mcg dose.

[@PsychiatrySimplified]

Yes there is a dose dependent effect - principle of hormesis. Pre synaptic - reduction of arousal , post synaptic - activating.

[@patted17j]

undoubtedly prazosin which I've been on medication recently for chronic nightmares / hyperactivity has promising results and immediate relief as well. Infact no ssri or snri which I used almost for 2 years has that strong effect as prazosin. I've no idea about clonidine as such because, I'm unaware of that drug.

[@PsychiatrySimplified]

Thanks for sharing. Clonidine has very similar effects.

[@user-zk6xg8gs2f]

Thanks!

[@PsychiatrySimplified]

Thank you for your support

[@horatiogrant8018]

How might one reverse down regulation of alpha 2c caused by clonidine use? quite sure this occurred in just one month use lowest dose at bedtime. less noradrenaline? but how does one achieve that to get 2c to open more receptors?

[@PsychiatrySimplified]

Usually there is a quick rebound post clonidine cessation. Clonidine usually reduces hyperarousal but also has some post synaptic activity on alpha 2A , C. Guanfacine on the other hand is more post synaptic.

[@Plink451]

How serious are the risks of discontinuation/withdrawal/rebound effects with Clonidine? There's really not much information on that online, at least not at the same as other medications. Most tapering schedules that do exist are for BP patients, not for ADHD or any of the other uses that it is currently prescribed for. For example, if a patient was using it as needed or short term (2-3 weeks) what kind of taper if any would be suggested? What is considered long term use with Clonidine? A week? A month? 6 months?

[@PsychiatrySimplified]

In general the rule is gradual tapering and avoid sudden stop ( rebound increase in BP). Long term could be longer than a year. It does not follow a hyperbolic curve like antidepressants do so gradual reduction over a few weeks under medical supervision is usually the way for doses 150mg and below. For higher doses this reduction may stretch out. Essentially patient BP is monitored and the speed of reduction depends on this as aim is to avoid rebound High BP. This may vary if it is used for BP Rx. The tapering over a few weeks is usually for psychiatric conditions. If however it is being discontinued for low BP - then usually it is stopped immediately as it is a SE. Ps- this is in general only and not specific medical advice

[@ilikepingpong]

Thanks for this information! I have a question about dosage, specifically for Guanfacine. And yes, I did watch your other content where you go over Guanfacine. But in this video, you refer to the inverted U shape for optimal levels of catecholamine activity. Does the administration and dosage of alpha 2 agonists (mostly Guanfacine) associate directly with this U shape, in the same way that we would expect stimulants to do? I have not been able to find very much information on what "too little" or "too much" looks like when it comes to Guanfacine dosage, whereas the advice for stimulants seems to pretty pretty straightforward (too little = no effect, too much = hyperarousal). Perhaps this is less understood for Guanfacine. Also, the benefits CAN be immediate for Guanfacine, but usually take several days to weeks to appear, which makes this question more complicated. Personal context, if interested : After a few months of trying ADHD stimulants for the first time (minimal benefit), I recently started adding Guanfacine to my Vyvanse (30mg). A titration period of 2 weeks at 1mg, then 2mg. After 2 weeks at 2mg, I reflected back and had the impression of just the slightest bit of general benefit to impulsivity & time management, but it's often very difficult to say. However, talking with the pharmacist, we decided to try moving forward with 3mg. I immediately felt the sedative effects, which lasted just over a week. After the sedative effects stabilized however, I did not notice any general benefits to ADHD, still after almost 4 weeks (even taking a week off Vyvanse). And I would say that I even feel some hyperarousal, mentally & emotionally (physically, no). I personally believe that I may be dealing with some high glutamate levels, which might explain why the stimulants I have tried (adderall & Vyvanse) were only slightly helpful, but are a double-edged sword. So I was hoping the theoretic benefits of Guanfacine on inhibiting glutamate transmission would provide a more balanced focus, but I don't understand dosage (and neither does my doctor, to be honest!). So this is where my concerns are coming from. But perhaps I should shift my thinking from optimizing catecholamines and look more at the GABA balance. But I would love any insight you have on the Guanfacine! Thanks for the great content.

[@PsychiatrySimplified]

Hi, Yes, the Alpha2 receptor operates on the same basis. guanfacine plus Vyvanse can activate the alpha 2 and D1 - which can shift the individual towards the right side. too much. Before increasing the dose of a stimulant or adding an alpha 2 postsynaptic agonist- it becomes important to rule out hyperarousal e.g sleep difficulties, impulsivity, racing thoughts etc; if this is resent the benefits of PFC augmentation may be short-lived.

[@ilikepingpong]

@@PsychiatrySimplified Hi, thanks for the response & good information. As I mentioned, it seems very likely that there is Hyperarousal. (impulsivity, racing thoughts, etc) If this is the case, how can this be ruled out? Also, how can treating both Hyperarousal & ADHD be addressed at the same time? The combination of guanfacine + stimulant might complicate the issue as you're saying, but does guanfacine on its own address both of these conditions, theoretically? Or, would you know of other possible considerations? And how can the hyperarousal itself be addressed? (I will speak with my doctor first, but it is helpful to get some orientation to know where to start) Thanks for the information!

[@PsychiatrySimplified]

Here is a video explaining things in more detail kzbin.info/www/bejne/i6C2aoqObZh3f9Usi=FaElgxE_9hkghlrB

[@jamescullen-657]

Hi rege, Would beta blockers be useful in hyperaousal? Are alpha blocker more effective then beta blocker for hyperarousal treatment. If they are why so?

[@PsychiatrySimplified]

Beta blockers tend to have a greater peripheral actions rather than central. Centrally propranolol mainly crosses the BBB - but it reduces production thin o melatonin so can lead to nightmares ⬆️hyperarousal indirectly in some. Alpha 2 receptors are pre synaptic and hence act as feedback and reduce NA centrally and peripherally. Alpha 1 similarly does this. So overall for central hyperarousal alpha blockers would be preferred / beta blockers for peripheral e.g HR ⬆️ . This is a simple answer .

[@jamescullen-657]

Thanks

[@mp4115]

Thank you for this informative video! Appreciate it a lot! But I have one question: Is it possible to differentiate between an elevated norepinephrine level and a lowered level? They would both lead to an underactive PFC, thereby causing typical ADHD symptoms in each case .

[@PsychiatrySimplified]

Noradrenaline release is part of a stress response. NA acts in conjunction with other neurotransmitters hence clinical symptoms provide a better guide for management. For example a patient with ‘ADHD’ symptoms can have multiple other associated symptoms that helps build the formulation. Noradrenergic activation in the mesolimbic system can coexist with a reduced alpha 2 stimulation ( noradrenergic receptor for cognitive flexibility) in the PFC as alpha-1 ( noradrenergic receptor but excess stimulation leads to cognitive rigidity) overrides the alpha 2 a receptor. Hope that makes sense. Neurotransmitters operate as a group modulation, activation with the aim of reaching homeostasis. Clinical features act as clues telling us what the management plan should be to assist the individual to achieve this homeostasis. The video release on Sunday covers this in more detail.

[@jsv07018]

Can you please elaborate on 15 hours wash out of prazosin please? Kind of confused

[@PsychiatrySimplified]

95 percent of the medication is out of body by 15 days approx. It has a short half life - 3-5 hrs - so multiply by 5 - get apoox 15-25 hrs. Hence dose many need to adjusted by the treating doctor. Given once / twice / 4 times depending on clinical symptoms.

[@laurenpeyrouton8351]

When using Clonodine for akathisia, ptsd, how long to you typically wait to see if it is effective for a patient? Should it be immediately apparent?

[@PsychiatrySimplified]

Generally a week or two there should be a reasonable (30-50% ) reduction in intensity then the dose adjustment can be made for the rest. It can be quicker than that as well.

[@Idmoment]

What do think of nudexa. In geriatric agitation?

[@PsychiatrySimplified]

"The combination of dextromethorphan and quinidine sulfate is approved for pseudobulbar affect, and may be effective in managing agitation in dementia. A review of literature found only one randomized controlled trial that evaluated the use of dextromethorphan-quinidine for the management of agitation in dementia when compared to placebo" .

[@achimfx]

In patients with ADHD, hyperarousal and sleep disorders, do you think it could be useful to combine Guanfacine during the day with clonidine at night (under monitoring blood pressure)? Do you have any further insights on clonidine and SubstanceP? One finds little information on this unfortunately. Substance P also seems to be associated with fibromylagia and tinnitus. And fibromylagia also occurs together with ADHD. Do you have any insights from your practice that tolerance can occur with cloning and guanafcaine over time? Thanks a lot!

[@PsychiatrySimplified]

In adhd and hyperarousal / sleep. There are both NA and DA affected. The main receptors that we aim to target are alpha 2a and D1 as they lead to therapeutic effects in frontal cortex. Alpha-2A in spinal cord postsynaptic facilitates descending pain inhibition. Alpha-2 a presynaptic agonist reduces hyperarousal and promotes sleep. Dopamine receptors improve cognition and also are effective at pain relieving. NA increase in brain facilitates pain inhibition. Clonidine is mainly a presynaptic agonist so helpful in reducing hyperarousal and promoting sleep. Pain reducing properties through reduction of amygdala hyperarousal and gaba pathways. It’s mild post synaptic activity also promotes sleep. Guanfacine is predominantly post synaptic alpha 2 - so main effects on cogntion. To some extent on pain ( but not used for this reason). As you can see in this regime to target adhd , sleep ( besides hyperarousal - dopamine is needed for REM sleep) and pain dopamine is missing along with increase in NA. So while Guanfacine and clonidine can be combined theoretically the rationale is not clear and therefore not commonly done. For adhd stimulants are first line to which either of these can be added as augmentation. If there are contraindications then other agents that increase DA and NA can be considered. Ps not medical advice

[@achimfx]

In a patient dominated with ptsd, hyperarousal, and sleep disturbances, clonidine would be the first choice in treating adhd in practice, correct?

[@PsychiatrySimplified]

@@achimfx depends on if they have nightmares and sleep difficulties. If present it can be indicated and evidence based.

[@jocs8824]

@@PsychiatrySimplified does tolerance occur in Guanfacine or Clonidine or Prazosin for that matter? If different for each, can you explain why? Should tolerance occur to these drugs, does the reset of the HPA axis from using alpha 2 drugs allow patient to come off drug without noticing the increased stress response of the upregulation of noradrenaline receptors ( should they occur in time from alpha drugs ) as cortisol now comes in to stop the CRF going on too long? Is the sign to cease the drug when missed doses show little withdrawal symptoms or during new onset of some type of chronic stress the patient has less chronic adrenaline type feeling without needing a dose increase? Is the morning blood cortisol result is in top third of normal range in patients usually on bottom of range an indicator to cease the alpha drug too as hpa axis has been reset by then? And how do SSRIs worsen PTSD as these are activating drugs - how do they activate - is it by serotonin on 2a/2c ? these increase CRF right?

[@PsychiatrySimplified]

@@jocs8824 Tolerance based on neuroscientific definition linked to addiction does not occur. Medications may stop providing benefits. This is usually because other mechanisms are at play. Tolerance is caused by adaptations leading to reduced sensitivity of neurotransmission systems targeted by particular drugs to maintain a homeostatic balance. Withdrawal symptoms are associated with these neuroadaptations. With clonidine etc increased doses will have an effect but side effects are more likely. Clinical symptoms are best gauge to reduction or cessation. Sudden cessation of medications alpha-blockers can result in rebound Sx, rebound REM sleep (heightened NA tone) etc. Early relapse signs are a better gauge than biomarkers. both short and long-term Sx have to be evaluated.

[@jocs8824]

If cortisol turns off the noradrenaline and that reduces the loop of constant CRF/NE then why wouldn't a course of hydrocortisone help reverse PTSD? tapered off carefully of course! In PTSD the alpha 2 drugs would drop cortisol further until the hps axis is reset so how does a patient cope with the lowered cortisol in the interim if there is inflammation? I realise hydrocortisone is not good for the gut long term but can PTSD be reversed within several months on hydrocortisone? There are studies showing quick intervention with hydrocortisone prevents first development of PTSD when one faces a single traumatic event such as car accident or natural disaster? What would the effect of hydrocortisone be as it is linked to causing depression if taken chronically or is this effect desired in PTSD as noradrenic tone is opposite in these conditions....?

[@PsychiatrySimplified]

Good question again - Because cortisol is only one part of the equation. While it may, in the short term, help to a certain extent with amygdala NA reduction, it does not provide a sustained effect; hence the studies show benefits in the prevention and consolidation of memories. When PTSD has developed, the PFC is involved to a greater extent. Here cognition and reward pathways involving DA have also been affected as the illness has progressed. Plus, steroid administration will lead to adaptation, side effects notwithstanding. While the NA effect is increased in limbic pathways / endogenous levels of NA are low in synaptic cleft as the production cannot keep pace with release leading to an overall deficit. As long as this deficit is present, excess NA is released presynaptically (as the pre-synaptic feedback is affected). Hope this helps. this is why clonidine is used to activate pre-synaptic alpha 2 receptors. Hope this makes sense. The pathophysiology is discussed in more detail here. psychscenehub.com/psychinsights/post-traumatic-stress-disorder/

[@hanskraut2018]

Thanks adhd trying desperately to find the perfect med mix why is there no automated programm i ask myself

[@perceptioniseverything648]

I’m going to start using them for nightmares and PTSD. Which one would have a greater effect on the optic nerves as my neuro-ophthalmologist mention calcium channel blockers

[@PsychiatrySimplified]

They are not calcium channel blockers. What is the issue with optic nerves?

[@perceptioniseverything648]

@@PsychiatrySimplified optic nerve atrophy after intracranial hypertension. I’m looking for one medication with the least side effects that would help with reducing the intensity of lucid and vivid dreams and as well as helping heal the optic nerves creating axons or calcium channel blockers for vessel dilation etc. Some thing that could help with my mood at the same time.

[@PsychiatrySimplified]

@@perceptioniseverything648 clonidine is evidence based in Rx of intracranial hypertension and also helps in sleep reducing Lucid dreaming / vivid dreams effectively. Of course if the doctor thinks it's indicated then it's appropriate. Wish you well.

[@perceptioniseverything648]

@@PsychiatrySimplified thank you very much for your contact. I truly appreciate it I’ll talk about it with my doctor

[@RajSingh-jz5ll]

Sir alpha 2 receptor present on trabecular meshwork also?? In some article say that activation of alpha 2 receptor cause decreased in aqueous secretion present on ciliary process and increased outflow which is present on trabecular meshwork. ?????????

[@PsychiatrySimplified]

While ophthalmology is not out specialty there is evidence that clonidine reduces aqueous secretion. For the treatment of glaucoma, alpha-2 adrenergic receptor (a2-AR) agonists are thought to lower intraocular pressure primarily by decreasing aqueous humor production. “

[@RajSingh-jz5ll]

@@PsychiatrySimplified so alpha2 receptor not present on trabecular meshwork??

[@PsychiatrySimplified]

@@RajSingh-jz5ll Cultured human trabecular meshwork cells express functional alpha 2A adrenergic receptors.

[@RajSingh-jz5ll]

@@PsychiatrySimplified sir sorry I do not get it properly I mean it’s present or not ?? Yes or no

[@PsychiatrySimplified]

@@RajSingh-jz5ll present Alpha-adrenoceptors are widely dis­ tributed in the eye, especially in the smooth muscle cells of the iris, the blood vessels of the conjunctiva as well as those of the ciliary pro­cesses and the aqueous outflow tract. www.aoa.org/assets/documents/EBO/CRG%20-%20GLAUCOMA%204/934-003ARTHUR2011.pdf

[@jocs8824]

How would I treat suspected high noradrenaline with prazosin if alpha 1 agonist reduces crf as my cortisol is already low (from fast deactivation into cortisone we suspect as thorough testing of the hpa axis was done)? Wouldn't insufficient cortisol lead to worse depression though as inflammation goes up then and this reduces serotonin? I have depression and anxiety. Am hypertensive.

[@PsychiatrySimplified]

In depression it is the HPA axis dysfunction that is a key issue. If amygdala is activated due to stress or anxiety then the constant hpa activation dysregulates it. Unless low cortisol is part of say Addison’s disease in which case it should be treated by an endocrinologist. Prazosin or clonidine are indicated to reduce the hyperarousal so that this HPA axis can reset. The ‘low cortisol’ in trauma related aspects or depression is due to desensitisation of the receptors so they don’t respond to acth - which is the axis dysregulation. Treatment can assist . Ps - Not advice. We have covered the neurobiology of stress where we go into more detail about this.

[@jocs8824]

@@PsychiatrySimplified is the non response to crf an epigenetic change perhaps? in which case Hdac inhibition with sodium valproate can reverse? is that drug used in ptsd?

[@PsychiatrySimplified]

@@jocs8824 females have a more sensitive amygdala due to CRF1 differences. Yes epigenetic changes can also occur via trauma, stress that affect the HPA axis which in depression leads to a hyper cortisol state. Trauma is usually associated with low cortisol state with elevated CRF. Agents that reduce amygdala activation may reduce the ‘stress’ response. That could include mood stabilisers. Amygdala has NA, DA excitatory neurons and GABA as inhibitory to reduce the stress response

[@jocs8824]

@@PsychiatrySimplified I will show this response to my new psychiatrist as the old one just wanted me on Lyrica. It isn't suitable if I also have depression though so I am not taking it. The depression is as bad as the anxiety. Not minor.

[@PsychiatrySimplified]

@@jocs8824 I would recommend not showing a youtube response to your doctor as 1. it carries little weight. 2 worse can be misconstrued as medical advice by the doctor, which it is not. This can make it seem irresponsible by this channel. here is a reference article - for discussion with your doctor www.intechopen.com/chapters/54675

[@psychiatrist123]

Does any of these give restful refreshing sleep ?

[@PsychiatrySimplified]

Clonidine is one of the few agents to improve NREM sleep and reduce restless REM sleep addressing the disturbed sleep architecture associated with many types of insomnia. So yes it can be very effective when prescribed appropriately. Prazosin can but is shorter acting so depends on the severity

[@psychiatrist123]

@@PsychiatrySimplified thank you.

[@Brazilian_Lioness]

Hi Dr.Sanil I tried prescribed Guanfacine for ADHD (I am primarily hyperactive but also inattentive) 1mg at night and never have been on stimulant meds But I notice on different attempts that after 4 consecutive days of taking nightly, I start to feel side effects like feeling sad and no pleasure or reward feeling and apathetic and just different at the 4th day mark. I don't have any mood disorder btw. Do you have any advice on why I may react that way after 4 days on Guanfacine ? I am an adult female Your video definitely helped me understand the mechanisms alot better thank you !🇧🇷🙌🥺

[@PsychiatrySimplified]

Which specific sx has it been helpful for? Iattention / hyperactivity / impulse control? The symptoms you are.describing are.linked to a D1 Receptor which are unlikely to be stimulated by guanfacine. So it may indicate that it treats the alpha2 sX but not d1 Receptor ( which requires stimulants ) for reward based learning, activity, pleasure, mood. Ps not medical advice

[@Brazilian_Lioness]

@@PsychiatrySimplified Hi Dr.Sanil That's so cool you wrote me back 🙌😄 thank you ! And Guanfacine for me, worked for my hyperactivity like you mentioned in your video especially at night. Is it possible that addressing the hyperactivity through Guanfacine, it indirectly depletes my dopamine release since it's already low in those with ADHD? In other words, could adding a stimulant prevent the 4th day symptoms I experience or do you suspect it would continue to happen?

[@Brazilian_Lioness]

@@PsychiatrySimplified and guanfacine also helped my impulse control to interrupt, impatience, be on the go etc.

[@PsychiatrySimplified]

@@Brazilian_Lioness it's not that guanfacine is depleting it ; it is highlighting the residual symptoms that need treating. More like an onion with multiple layers ; I often say once one layer is peeled underlying aspects ( residual aspects) may be seen - so that's what I meant by the D1 receptors not being addressed which are addressed by a stimulant ( ps not advice ) .

[@Brazilian_Lioness]

@@PsychiatrySimplified wow that makes sense thank you. Hmm when I don't take guanfacine I am hyper active (fidgeting, on the go, always doing something, or finding stimulation by things I'm interested in, or doodling in class etc.) But I am happy mostly just channeling the impatience, restlessness, impulses into a way I can stand the boredom during obligations school work or in conversation etc. I mean I still struggle with keeping some focus etc. But not so much the lack of pleasure or rewards feeling or apathy or unhappiness like guanfacine unlayers I only ask because if the guanfacine takes away my hyperactivity I'm left with an exposure of truly low dopamine that affects my mood/reward-pleasure etc. So ultimately is my hyperactivity the way my body/I try to create my own dopamine ?

[@GeoffreyPilkington]

I’ve been on 1 mg of Guanfacine for one month for ADHD and it causes me sexual dysfunction and gives me no benefits for ADHD. Others have reported this side effect too. Why would Guanfacine cause this side effect? Do A2 receptors connect to sex area of brain?

[@PsychiatrySimplified]

Rare side effect but yes can happen . There is evidence for a direct adrenergic regulation of penile veins, the predominant effect occurs through the alpha1- adrenoceptors but there remains the potential involvement of alpha2-adrenoceptors. Stimulation of the alpha2 -adrenoceptors in the cavernosal smooth muscle is known to be involved in erectile dysfunction. The predominant effect occurs through the alpha1-adrenoceptors but there remains the potential involvement of alpha2-adrenoceptors. Guanfacine is a alpha 2 agonist .

[@GeoffreyPilkington]

@@PsychiatrySimplified thanks for the info. Some have suggested a switch to clonidine. But one doctor friend said if Guanfacine didn’t help adhd for you and gave you sexual dysfunction, clonidine likely wouldn’t be any better for adhd for you and likely would give you even worse sex side effect. (Plus they said it’s often much more sedating)

[@PsychiatrySimplified]

@@GeoffreyPilkington it depends on what symptoms one is trying to treat as part of adhd. Clondine is more pre synaptic so more calming but unlikely to have sexual side effects for this reason but cognitive benefits directly are less ( more due to better sleep) . Have stimulants not been considered ?

[@GeoffreyPilkington]

@@PsychiatrySimplified yes, I have lots to say re: stimulants. I went on Adderall ir in 2015 for adhd. My response was robust. It gave me 3 great years and 2 pretty good years. Started at 10 mg / day in 2015 and over 5 years gradually built it towards 60 mg / day. (30 in morning, 30 in afternoon) however in the last 2 years the effect had faded somewhat. (One error was I was taking 1000 mg of vitamin C and drinking fruit juice all day the last 2 years which I found out just recently can have a big effect.) However just know I have / had a terrific initial response to the amphetamines which lasted me a period of years with just a little dry mouth at times being the only side effect. They helped me focus, they gave me more empathy, I was way more motivated, I listened way better, people seemed way less boring. The drug changed my life for the better. Anyway, my psychiatrist tried adderall xr and Concerta in 2021 when the adderall ir was fading (neither of which I responded to)… he didn’t want to prescribe me a higher dose than 60 mg per day of adderall ir. Dunno why. Fyi My bp is good. It IS a bit elevated at times. But not high. I’ve had that since 2005. My dads was always a little elevated. Most of the time it’s normal though. he also tried me on Zoloft, Luvox, and Trintellix from October 2021 to March 2022(2 months each) for some “mild depression”. All Zoloft and Luvox did was give me sexual dysfunction and fatigue. 2 months each. They didn’t help me at all. Trintellix had no side effects and also did nothing for me. I was later told in a 2nd opinion that I don’t have depression. (I Never thought I did so the antidepressants were a complete misfire and waste of time) Recently he moved me to Vyvanse 60 mg / day and it’s less Effective than the adderall jr. (However I’ve read it’s 1/3 the amount of dex however it’s metabolized more efficiently so it’s roughly half of what adderall ir is.) The only time I noticed Vyvanse working (I’ve been on it a month) was when I took TWO 60 mg of Vyvanse in one day. One in the morning and one in afternoon. This may be a clue that with the amphetamines it may be a dosage issue with me. He did up the dose of Vyvanse last week to 70 mg / day but it’s not doing anything. (Unless I take 2 in one day then I’m sure it’d be great) Coincidentally I start with a new psychiatrist tomorrow. It was time for a change and a fresh start. Any thoughts or advice? I’m a bit of a puzzle. It’s clear the amphetamines are the class of drug my system likes and Responds to however for whatever reason my previous doctor just couldn’t get the dosage right. I’m very frustrated obviously. Any advice appreciated. Thanks!

[@PsychiatrySimplified]

@@GeoffreyPilkington have a discussion with the doctor. Depends on age and specific symptoms. Ofcourse main aim is to get the cognitive aspects and then motivation in initial stages - d1 receptor stimulation which happens with high levels of dopamine but then the shift is towards the action areas - goal directed and habit areas of striatum where D1 receptors are situated - this happens through action , routine , specific goals and then d1 receptors get stimulated through unexpected rewards as we start putting plans in place for goals. Often if the medication is judged only on the ‘feeling aspect’ this wanes because of dopamine sensitisation in the reward pathway of liking ; this becomes the salience towards experiencing the pulsatile dopamine release. This may not be the case and it may be a dose issue but this a common issue that individuals come with - the group that has moved to action generally tend to have less of a ‘waning’ or need minor dose adjustments. Hence important to evaluate the key aims and symptoms. Wish you well

[@thevibe9437]

Please help me

[@thevibe9437]

I need to talk to you but i cant afford a therapy :(

[@elizabethread6878]

Are you a certain type of psychiatrist ? It seems no one else knows what they are doing .

[@PsychiatrySimplified]

That is a difficult question to answer. All of these aspects are part of treating patients in psychiatry.

[@elizabethread6878]

@@PsychiatrySimplified thank you. I’ve had had a terrible time finding someone who doesn’t just push an ssri and i have massive nervous system dysregulation and am bedridden

[@PsychiatrySimplified]

@@elizabethread6878 sorry to hear. Really hope you find the appropriate treatment.

[@jocs8824]

@@elizabethread6878 have you found what helps you yet? You sound similar to me.

[@elizabethread6878]

@@jocs8824 no. Only benzos but i even crash first from those.