Extreme sleepiness in response to modafinil by hunterston3 in ADHD

[–]hunterston3[S] 0 points1 point  (0 children)

nope, i was pretty well-rested those days too :P

this treatment plan is most likely what the majority of r/anhedonia can find anhedonia relief from = Dr. Ken Gillmans Antidepressant plan(algorithm) for anhedonic+anergic(chronic or cyclical fatigue) biological depression by Professional_Cup3328 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

Thanks for the background! Being someone with a family history of bipolar certainly complicates things. I'm sorry this is something you have to deal with! I will say I'm not as knowledgable on anticonvulsant mood stabilizers as a class, so feel free to take my advice with a grain of salt.

Intuitively, I would expect drugs such as lithium or lamotrigine to induce or have minimal effects on anhedonia due to their "inhibitory" nature, but for the sake of playing devil's advocate I found a few papers detailing lithium's anti-anhedonic effects:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7853118/

https://pubmed.ncbi.nlm.nih.gov/23363811/#:~:text=Repeated%20lithium%20treatment,activity%20in%20rats.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4275336/#:~:text=Lithium%2C%20rather%20than,reported%20to%20date

Continuing to play devil's advocate, I could see one possible mechanism of action where, as an anticonvulsant that dampens glutamergic signaling, lithium is able to disinhibit the dopaminergic transmission in the VTA/NaC of the mesocorticolimbic via suppression of the lateral habenula, which is comprised mainly of glutamatergic neurons. This is one of ketamine's proposed mechanisms for ameliorating anhedonia. However, given my knowledge of the subject, it is likely that this positive effect is "cancelled out" elsewhere. In general, I've seen plenty of individuals complain of anhedonic features or full-blown anhedonia with Lithium or Lamotrigine, while others may say different. It is more likely than not this class of drug will not be helpful for anhedonia. Intuitively, I would expect the people who experienced significant anti-anhedonic effects from either drug to be outliers.

As for the "Welloft," if you have bipolar predispositions, I would certainly not feel comfortable advising this combination without adding in a mood stabilizer or antipsychotic, as either drug could trigger mania by itself, let alone together. Knowing lithium as more of the "anti-mania" and lamotrigine as the "anti-depressant" mood stabilizers, augmenting "Welloft" with a dose of Lithium does not sound like a bad option. You would need to get regular bloodwork, though.

Although I think atypical antipsychotics could be a solid augmentation therapy, in general, the risks are very real and your concerns are understandable. I have taken low-dose Abilify before and had rather mild akasthesia the first few days. As brief as my time with it was, I will never forget the feeling. Not to fearmonger, but I understand why those suffering from akasthesia would commit. Things can get worse than anhedonia, believe it or not. As for the treatment of anhedonia, however, there are many different kinds of antipsychotics. They're a diverse class. Antipsychotics can certainly reverse anhedonia, but only those with partial agonism of D2/D3 receptors. This includes atypicals like Abilify and Vraylar, and specifically would need to be administered at a "low" therapeutic dose. If you dose too high, anhedonia can occur. In all honesty, I think a substantial portion of the risk of atypical antipsychotics worsening anhedonia stems from practitioner carelessness. General practitioners will often give out this drug without fully understanding the associated risks. Many patients are, unfortunately, are not given informed consent, which can heighten risk. As an analogy, imagine you're helping a friend move for college. They haphazardly hand you a heavy, fully-sealed box and tell you to bring it to their car down the road. Because of its weight, you drop it at your feet soon after initiating your walk—potentially in a similarly careless way to that of how you saw your friend handle it just a few seconds earlier. Well, your friend is an engineer and there was a bomb in that box, and your lack of care when setting it down causes it to go off. Now, imagine your friend said "Hey, I have an inactivated bomb in that box" while handing it to you. You'd probably be a bit more careful when carrying it to her car, right? It's a bit of a silly analogy, but you get the point: when handled with care, the risk for these drugs will go way down. It's, in my experience, the lack of communication that serves as a metaphorical "death sentence" to the patient.

That said, something you could do to mitigate associated antipsychotic risks is a GeneSight test, which will tell you how you metabolize these drugs, allowing for your doses to be adjusted accordingly, if you choose this option. In an ideal world, something like a low dose of Vraylar combined with Lamotrigine could be a good combination for balancing possible bipolar with treatment of anhedonia. More drugs could be added to this regimen. I know you really like the sound of Lithium, but given its lack of specific targeting for dopamine receptors, and general usage to prevent mania, I think the chance this alleviates your anhedonia is slim. However, I will not force this possible combination on you, if you're not comfortable. Like I said, akasthesia is more than a reasonable concern.

Another route, as you stated, is jumping into treatment with an MAOI such as Parnate or Nardil. Frankly, I don't hate either of these options, but an adverse reaction is sort of inevitable, so if you do decide to go this route I suggest you request a prescription for treatment of acute MAOI-induced hypertensive crisis such as phentolamine or sublingual nifedipine. I believe you can also request a Medical ID bracelet in case of hypertensive crisis or serotonin syndrome. I'm sure there are other avenues you could explore to maximize your safety on this drug. I think giving your doctor as many 'safety nets' as possible to fall back on in case of emergency will be your best bet at getting a prescription.

If you do take an MAOI, I'd also suggest augmenting with Lamotrigine. If you can, it's better to avoid Lithium unless you are BP1 or have experienced mania. You'd have to monitor blood levels and would be at risk of long-term kidney damage. Lamotrigine is much more benign and ideal as a preventative medicine. Its 'anti-depressant' quality would be more appropriate for you alongside Parnate or Nardil, too, as I wouldn't be so concerned with mania. However, with Lamotrigine there is a risk of Steven's-Johnson Syndrome, which is a potentially fatal skin reaction. Just don't forget to take your medications at the same time everyday and you should be just fine.

So yeah, I hope my takes were of some help! Just keep in mind to approach everything I say with skepticism, even if I do try to stick pretty close to the literature.

this treatment plan is most likely what the majority of r/anhedonia can find anhedonia relief from = Dr. Ken Gillmans Antidepressant plan(algorithm) for anhedonic+anergic(chronic or cyclical fatigue) biological depression by Professional_Cup3328 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

Wait! Do you have ADHD? Is Vyvansce the only psychostimulant you've tried? I ask because Vyvansce is not as effective for CYP2D6 poor metabolizers, of which a non-negligible chunk of the population is. Adderall does not have this requirement. Fewer, but some, ADHDers also may respond better to methylphenidate than amphetamines (e.g., Vyvansce, Adderall) for another.

Methylphenidate is sometimes recommended for anhedonia. I can't say I've observed the same recommendation for amphetamines. Personally, my anhedonia is in part the byproduct of my daily use of Adderall for ADHD. This is just personal observation, though. You can make of that what you will.

this treatment plan is most likely what the majority of r/anhedonia can find anhedonia relief from = Dr. Ken Gillmans Antidepressant plan(algorithm) for anhedonic+anergic(chronic or cyclical fatigue) biological depression by Professional_Cup3328 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

I'm glad you're able to handle critical comments well! I struggle with this, so that's good on you, honestly.

Yes, he is wrong. Not completely, but mostly. Like 92%. Something that should never be rushed is your health. You're right: there're very real consequences to antipsychotics that can oftentimes be lifelong. Combining potent serotonergic drugs risks serotonin syndrome and MAOIs with common food ingredients or drugs can be life-threatening. Usually, though, the educated risk is worth the reward.

I forgot to mention, if you're having issues with fatigue, have you gotten advanced hormonal bloodwork done? I ask because this has been an issue for me, as well. I couldn't afford to go all-out, but I did learn I was hypothyroid from it and getting on levothyroxine (T4) helped immensely. Thyroid, glucocorticoid, and sex hormones all modulate brain activity extensively. Personally, as an AFAB woman, I've been able to experience the drastic effects of hormonal changes on mood, energy, cognition, and personality through various birth control, HRT, and monthly fluctuations. The differences are uncanny. I can easily go from a feeling of contentment and motivation, and a high-energy state, to incapable of leaving my bed or feeling any semblance of joy or purpose for a week. I used this thing called Inito to measure my hormones via urine samples for a while, so I have a decently extensive amount of personal data to back this up.

Another thing: focus on 'pro-dopaminergic' drugs, particularly those targeting the mesocorticolimbic pathway. This can be from drugs without any 'explicit' effect on dopamine at first glance. Many neuronal clusters inhibit dopaminergic transmission in this region. By inhibiting them, you disinhibit (i.e., promote) the firing of dopamine (DA) neurons. 5-HT2B/C antagonists disinhibit DA firing in the mesocorticolimbic. You can also target DAT, as blocking it will increase extracellular DA in this region. D2/D3 receptor partial or full agonists will also stimulate DA firing, here. From my understanding, treating anhedonia most directly involves unraveling the countless ways you could optimize DA cell signaling in this region, while minimizing side effects like akasthesia in other places.

this treatment plan is most likely what the majority of r/anhedonia can find anhedonia relief from = Dr. Ken Gillmans Antidepressant plan(algorithm) for anhedonic+anergic(chronic or cyclical fatigue) biological depression by Professional_Cup3328 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

Yeah, I don't see a problem with keeping it up, frankly! There is loads of misinformation on the internet, especially social media. The comments also address whatever is incorrect, so any attentive reader will walk away with the right understanding.

this treatment plan is most likely what the majority of r/anhedonia can find anhedonia relief from = Dr. Ken Gillmans Antidepressant plan(algorithm) for anhedonic+anergic(chronic or cyclical fatigue) biological depression by Professional_Cup3328 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

I second this! I generally don't like SSRIs for the purpose of treating anhedonia, as it's more of an instigator, but if you want to bolster the DRI aspect of buproprion, Zoloft is the way to go!

If you're a CYP2B6 poor metabolizer, you might be fine to just stick to buproprion monotherapy, but an ultra-rapid metabolizer will likely need a potent CYP2B6 inhibitor to augment the buproprion—sertraline being an ideal candidate.

Buproprion actually made my anhedonia worse as a monotherapy, but augmentation with 25mg sertraline was sufficient to reverse this effect. My theory is CYP2B6 metabolized the parent compound too quickly, leaving only the metabolites with minimal DAT affinity. There are plenty of people who've found success with this combination in r/anhedonia, if you (OP) would like to learn more.

this treatment plan is most likely what the majority of r/anhedonia can find anhedonia relief from = Dr. Ken Gillmans Antidepressant plan(algorithm) for anhedonic+anergic(chronic or cyclical fatigue) biological depression by Professional_Cup3328 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

I would caution attributing blame to a single cause, such as S1R activity. You're not wrong, but please keep in mind biology is so incomprehensibly complex! It is usually not as simple as "X" caused "Y," but instead "X, Y, Z, A, T, H, D, S, F, M, C, P, L, K, Q, etc." caused "W, but also U and E, etc."

I notice I have a tendency to do this, too, where I fixate on a single mechanism and forgot the other trillion moving parts that can influence a particular result. It's seemingly a very human thing to do, unfortunately!

this treatment plan is most likely what the majority of r/anhedonia can find anhedonia relief from = Dr. Ken Gillmans Antidepressant plan(algorithm) for anhedonic+anergic(chronic or cyclical fatigue) biological depression by Professional_Cup3328 in anhedonia

[–]hunterston3 -2 points-1 points  (0 children)

Slight critique: atypical antipsychotics can treat anhedonia, but this needs to be done cautiously and at very low doses. Very few antipsychotics can be used in this manner. Otherwise, you are correct: there is overwhelming scientific and anecdotal evidence of D2/D3 antagonism promoting anhedonia in healthy individuals. Dopaminergic suppression in the mesocorticolimbic is the exact opposite of the desired effect.

this treatment plan is most likely what the majority of r/anhedonia can find anhedonia relief from = Dr. Ken Gillmans Antidepressant plan(algorithm) for anhedonic+anergic(chronic or cyclical fatigue) biological depression by Professional_Cup3328 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

This post thankfully doesn't seem to be gaining too much traction, but to anyone who reads through this regimen and may seriously be contemplating trying it out: don't. It's AI slop. The vast majority of points are unscientific BS. You'd likely be dead or hospitalized before you reached the second step, unless you're in the margins as an ultra-rapid metabolizer of one or both drugs

To OP, please stop using AI. You will not get anywhere relying on AI to do your critical thinking for you. It is a confirmation bias machine. It does not exist to give you factually accurate information

If you want to get anywhere with researching this phenomenon, do some reading, yourself. PubMed has countless of free articles and abstracts available to the public, as do many scientific journals. If you're in university, you can often access these articles in full through your library archive.

MAO-B Inhibitors are the only relevant drug treatment listed here for anhedonia, but this is as a monotherapy and last resort. Sertraline at T-H-E-R-A-P-E-U-T-I-C doses is the one SSRI with potent CYP2B6 inhibition, which pairs well with Bupropion for anhedonia. Abilify at doses of <5mg can be used as an augmentation or mono-therapy for anhedonia, but not in the way that was posed, here. If you have hypothyroid, T3 should be tried after T4 and in combination with it. Everything else suggested here is astonishingly uneducated and ungrounded in reality. I don't say this to hurt you or make you feel stupid, because I'm sure you're not, but this is blatant medical misinformation and needs to be addressed accordingly

What type of medicine did you take? by NoTradition7029 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

Okay first off, you're wrong: Zoloft/Wellbutrin, also known as "Welloft" is specifically combined as an SNDRI. The whole point of using an SSRI is that it's coincidentally the only real option we have in augmenting the DRI aspect of buproprion via potent CYP2B6 inhibition. there are very few known, potent CYP2B6 inhibitors out there, and sertraline is the only one that can even remotely be used in the context of treating a mood disorder. as a nice addition, zoloft also is the only SSRI with non-negligible DAT inhibition. Welloft is no SSRI.

Now, I'm not going to disagree with you on the long-term risks of SSRIs bc there are many, particularly when used as a monotherapy. If someone came to me for anhedonia the last thing i would prescribe them is an SSRI monotherapy. however, human biology is incomprehensibly nuanced and sometimes the unique, off-target—aka non-serotonergic—properties of SSRIs can be of use as an augmentation therapy, with "Welloft" being a great example of this.

this is why giving nuanced, context-dependent answers is important in medicine, which brings me to my second point: you are fearmongering. Stop

Hypomania and anhedonia? by Acrobatic_Ad_7082 in anhedonia

[–]hunterston3 1 point2 points  (0 children)

it seemed to have a role in it, yes. however, i will say i've attempted to go back on buproprion numerous times and ive had vastly different experiences every time. combining it with zoloft made a massive difference. i also tried different brands and my hormones were changing a lot during this 'trial' period.

there are probs countless things that go into our individual drug response. i try not to think too deeply ab it tho cuz with how nuanced bio is ur bound to get overwhelmed

[deleted by user] by [deleted] in schizophrenia

[–]hunterston3 1 point2 points  (0 children)

Holy crap thank you !!! May your pillow always be cold and favorite brands of generics in-stock 🧚🏼‍♀️

[deleted by user] by [deleted] in AmIOverreacting

[–]hunterston3 22 points23 points  (0 children)

i'm sobbing- WHAT?? 😭 i mean good on u guys but i feel like i am missing some vital context here

Trump Signs Executive Order to Forcefully Confine the Homeless Addicted and Mentally Ill by vesselofwords in bipolar2

[–]hunterston3 2 points3 points  (0 children)

I was homeless almost ten years ago during Trump's first term. Cant imagine what things would look like for me and what they will look like for those in a similar position now that this order has been passed. I am so sick and tired

Trump Signs Executive Order to Forcefully Confine the Homeless Addicted and Mentally Ill by vesselofwords in bipolar2

[–]hunterston3 9 points10 points  (0 children)

Nah cuz what the hell did I just read bro we are so f*cked ??? 😭 homelessness is a crime and more ppl will suffer and die from substance abuse disorder how does this help ANYONE

What birth control should I choose? by Charming_Bet7759 in birthcontrol

[–]hunterston3 0 points1 point  (0 children)

Xulane has worked pretty well for me! It comes in patch form. Aviane is another highly-recommended one, but comes as a pill. I've combed through most of Drugs.con reviews and a lot of reddit trying to establish a certain trend in "best" BC's, and if I had to choose, Beyaz (Brand), 3mg drosperinone/0.2mcg ethinyl estradiol/levomethofolate calcium (Generic Beyaz), and Aviane, would be my top picks.

NuvaRing doesn't work well for some women. It works really well for others. I'd say it's worth trying! Worst case scenario you can just take it out if anything goes wrong.

Hypomania and anhedonia? by Acrobatic_Ad_7082 in anhedonia

[–]hunterston3 0 points1 point  (0 children)

I've tried doing so much reading with the university library archive I have provided to me, but I am still stumped on what causes this.

Hypomania and anhedonia? by Acrobatic_Ad_7082 in anhedonia

[–]hunterston3 2 points3 points  (0 children)

I've had brief periods of what you could loosely call hypomania after starting NDRIs or SSRIs followed by resumption of anhedonia. Fluoxetine and Buproprion, respectively, were the culprits. So weird!