The article describes its first subject as having been diagnosed with simply "depression", but describes their medication regime as including lithium and lamotrigine which in combination is strongly suggestive of treatment for bipolar depression in particular. Given that the described behavior sounds very much like a manic episode, the article should have explained this connection before attempting to focus the blame on pramipexole.

Most antidepressants, even SSRIs, are medically recognized as potentially triggering mania in bipolar patients. While compulsive gambling and hypersexuality are associated with dopamine agonists, I think it may be misleading for the article to focus so heavily on a possible manic episode without discussing bipolar disorder at all and while implying that this was a unique effect of dopamine agonists.

I agree about it sounding like a manic episode a lot.

If I were to put up an opposing opinion -- some caveats here: cluster B disorders and autism both can include lithium (and symptoms not too dissimilar from mania), lamotrigine too on the BPD front. Mood stabilizers are prescribed in combination for a variety of conditions, I feel like it's a rather large jump to make. Also, Moda and a Benzodiazepine are going to do incredible amounts for the dopaminergic system, as well as lowering social punishment-conditioned fear responses. If someone is borderline manic, that could cause a lot of problems.

Pramipexole is a seriously hardcore drug, I'd encourage you to look into it specifically over other dopamine agonists if you haven't already. I survived one day before deciding it wasn't worth it, personally.

Plus, dopamine agonists can screw some things up about you semi-permanently, so that's a risk, too.

It really feels like a grapeshot cannon from her psychiatrist, to be honest. I don't know her specific situation, but some of the rapid-acting antidepressants have good effects (like Ketamine, which operates I believe on D2, among other things).

Just a few thoughts. I dx' people casually from very little data as a weak point myself (did it today, sorta, in retrospect to be honest), so partially this comment is my internal warning systems triggering on an external comment.

Also, I wanted to put a different opinion so HN readers could get a different potential aide.

I've been tried on lithium and lamotrigine for treatment-resistant depression in the past. It doesn't necessarily indicate bipolar disorder.

I'm floored by the combo of modafinil and xanax. Adding pramipexole to the mix seems insane to me. I'm prescribed modafinil for narcolepsy and depending in the dose, it can sure make you look hypomanic just taken by itself. I had a very productive month after having to go off armodafinil for 2 weeks prior to a sleep study. My exhausted self didn't even think to taper back up to the old dose and went straight back to 250mg. My psych initially diagnosed it as hypomania. Turned out it was just way too high of a dose after losing my tolerance.

I'm no psych, but those 3 meds prescribed together seem like borderline malpractice to me.

Amphetamine and Modafinil have also caused these types of behavior in myself but none moreso than Methylphenidate.

Everyone responds to drugs differently, for me cocaine was relatively mild in its compulsive/forced behaviors compared to methylphenidate.

Compulsion from methylphenidate nearly ruined my life, I’m lucky to have rebuilt somewhat unscathed. I still take Vyvanse every day though, and for the most part the compulsive behaviors aren’t too destructive.

It’s difficult for me to moralize about these because they really do transform so many peoples lives to allow them to function and achieve, but they can be very hazardous in a particularly sinister way.

> Amphetamine and Modafinil have also caused these types of behavior in myself but none moreso than Methylphenidate.

Why is this the case?

I too have been legally prescribed such substances for medical reasons, and I have some of the same issues. The medications do help alleviate some symptoms, but during the initial ramp-up (like shortly after ingestion) I have worse symptoms for about an hour or so. Some of which occasionally include compulsive behaviors.

Very good points, it's scary to me that psychs with access to medications like these (and public trust too) can so casually make what seems to be such an incredibly dangerous decision, but I guess every system will have its bell curve outliers (though I feel many of us suspect that we feel that the tail is much bigger than we would want it to be....)

I have a private pay psychiatrist who is pretty good, something I need because I have a number of conditions and good polypharmacy is possible but hard. I trust him, but I also have a sinking feeling in my gut wondering about how the people going to the psychiatrists/etc that I saw before him are going to be treated. If I'm not in that patient slot, someone else likely will be.

I guess that's one motivator for such rigidity in prescribing medications on some sides of the field. As a lesser sin to prevent this sort of particular madness.

Would you be able to write more about dopamine agonists "screw[ing] some things up about you semi-permanently?"

I was on them for RLS for a while. I had even started taking L-DOPA, when pramipexole/ropinirole/gabapentin/etc. were negatively affecting my quality of life. However, the L-DOPA triggered some very, in-hindsight but unfortunately never during, terrible personality changes. One of which decided that it was prudent to keep upping my L-DOPA dosage, become a severe poly-substance abuser, and all-around just make a huge mess of my life.

I may also be recovering from nerve damage in my legs and feet from this escapade (either from the L-DOPA causing oxidative damage/receptor over-excitement and death -- or from the litany of other substances). I may have also unknowingly "semi-permanently" down-regulated my AAAH (?) enzymes, leading to effects I cannot even imagine.

I omitted the Xanax entirely from my previous post because the polypharmacy here is such a mess, but I agree that it probably factors into disinhibition. I don't personally attribute much relevance to modafinil in this instance; while the wakefulness effects are often described mechanistically through dopamine, I have never seen anyone experience any traditional stimulant or dopamine agonist effects from modafinil.

My only experience with pramipexole and cabergoline are for low dose off-label use in persistent sexual dysfunction after the discontinuation of SSRI medication. The biggest difference I have seen between them is a much higher rate of discontinuation due to side effects (extreme tiredness) for pramipexole.

Modafinil is disruptive to the circadian rhythm, which can exacerbate mania. It won't push dopamine on its own but in combination I'm sure it contributed, especially if, as is common with mania (which this article clearly describes without naming it, which is shameful frankly), she started taking her meds whenever she felt like it, instead of on a schedule.

Modafinil felt far more mild than amphetamine, methylphenidate, or cocaine for me. However, it uniquely (and dramatically) impaired my inhibition for libido compared to the others.

It was a very narrow side effect but also particularly destructive. It was very hard to tell it was the modafinil because it was so mild otherwise, just seemed to “front-load” all my energy and focus for the day into the first six hours of my work day, which worked quite well, and then left me feeling rather normal for the rest of the day (difficulty committing to tasks after it wore off but that is typical after a 6 hour of solid focused work).

I just had extra motivation and capability to flirt with coworkers and strangers and visiting sundry places. I was well-received, but it wasn’t the life choices I would have wanted to make and the workplace romance was self-destructive.

Amphetamine might make me masturbate more but only modafinil caused an impulse to flirt, court, and follow through.

> I have never seen anyone experience any traditional stimulant or dopamine agonist effects from modafinil.

What do you mean by traditional stimulant effects? I mean, modafinil is definitely stimulating, even if Wikipedia says it's an "eugeroic". Combines with caffeine pretty badly.

I meant "stimulant" in the context of traditional dopamine reuptake inhibitors and releasing agents like amphetamine and ritalin which are almost incomparable to less controlled or uncontrolled compounds like modafinil, ephedrine, and caffeine. Even a high dose of caffeine will not produce effects anything like amphetamine. The mechanism of action between amphetamine and caffeine are fundamentally different rather than being a matter of strength. It's unfortunate and misleading that the word stimulant is used for both categories.

Modafinil is a dopamine reuptake inhibitor though, it's just an atypical one. I can't take especially high therapeutic doses of either it or Vyvanse without getting similar physical anxiety.

I assume the reason it's not highly controlled in the US is that it's atypical enough to not be addictive (not that I've ever found Vyvanse to be addictive), but it is controlled in Japan and Russia and it's definitely possible to abuse it. People need their sleep even if it can keep it away for a day.

Interesting. One minor note is Moda a DRI too, albeit a weak one.

> but describes their medication regime as including lithium and lamotrigine which in combination is strongly suggestive of treatment for bipolar depression in particular.

Quite possible, but both medications are actually used in unipolar depression treatment as well. They wouldn’t be first-line treatments, but it’s not uncommon to see one or both of these tried when the patient can’t tolerate SSRIs for some reason. They are also used to augment SSRIs in many cases.

You severely overestimate the quality of care you would receive in a psychiatrist's office when thinking that lithium and lamotrigine wouldn't be prescribed for no reason. Prescription of pramipexole should have given it away.

In general, it would be difficult to tell with an incomplete patient history whether a psychiatrist prescribing pramipexole for depression was making an irresponsible shot in the dark, or a calculated attempt to address something like treatment-resistant anhedonic depression after a few first lines, an MAOI, and referrals to an endocrinologist and a sleep study failed. That being said, I cannot think of any reasonable scenario that leads to simultaneously prescribing pramipexole and mood stabilizers. Perhaps it's too idealistic of me to hope that the pharmacist filling all three of those (plus two controlled substances...) would have called and asked for an explanation.

Probably not no reason, but... yeah.

The article even says later that "[t]he state medical licensing board disciplined the psychiatrist", so I don't understand why people here are critiquing care that was literally censured by the board!

Agree. Even if the behavior was induced by drugs, it's a textbook description of a manic episode. If her psychiatrist had an accurate description of her behavior and praised it (as the article asserts) he was off his rocker.

> If her psychiatrist had an accurate description of her behavior and praised it (as the article asserts) he was off his rocker.

I find people put too much faith in psychs. I'm thankful for the help they have managed to provide people, but it's still the most abstract, nebulous, and least scientific field of medicine. I'm not trying to completely discredit the field by any means, but merely trying to be realistic about it.

From personal experience, it seems like one presents with arbitrary symptoms, and is then given a arbitrary label that cannot be successfully mapped to any underlying biological or physiological cause. Afterwards, one basically proceeds to brute-force n >= 1 medications until something works.

It gets more complicated when one researches the various medications and the underlying mechanisms of how they treat various conditions and their efficacy.

I have ADHD. Data suggests that stimulants are highly effective for ADHD. By why do stimulants work? Good question! To put things in very simple terms, it's hypothesized stimulants work due the effects on the dopaminergic system, but the honest truth is that no one actually knows why stimulants work for ADHD. A similar pattern can be applied to other mental conditions and their respective treatments too.

I feel like you are writing off the whole article with a sentiment along the lines of “this bitch was already psycho”.

I can tell you that I am certainly not bipolar and yet I had similar problems on related drugs, resulting in bankruptcy and violence. I will never, ever again take drugs from a psychiatrist. For all the fake panic about “reefer madness” supposed medical “professionals” can prescribe mind altering drugs that cause violence and bankruptcy.

And then people like you write it off as “oh she was bipolar” with the implication that such reactions can’t happen to “normal” people.

Disappointed but not surprised that all the men here upvoted you, like a circle of bearded 19th century doctors in a mental asylum for “hysterical women”. Lamenting that you can’t get this poor hysterical woman into your institution so you can give her the electrocution “therapy” she desperately needs. Have to make do with these new drugs. Any side effects are clearly due to her frail and mentally weak gender, and not the utterly inappropriate mind altering drugs.

I understand your frustration with the current state of psychiatry, but I think that you may be reading too much of it into my comment. I had no intention of shifting any blame from the wholly inappropriate combination of prescribed drugs or the psychiatrist to the patient, and I used very deliberate wording to intentionally avoid making any reference whatsoever to the gender of the patient. The point of my post was to highlight that this case appeared to be a manic episode which could be triggered by almost any antidepressant, not a rare and unique adverse effect that could only be caused by pramipexole or dopamine agonists.

The article discussed several examples, including men. You stopped reading after making your decision about the one woman.

Agree here. Medications or thyroid issues can absolutely cause bipolar symptoms. A psychiatrist should be screening those out before reaching for a bipolar diagnosis.

Sounds like this behavior change lasted for years though. That is one hell of a manic episode.

(Also, key question, was the art any good?)

There are samples in tfa. Not everyone's taste I'm sure, but pretty impressive for a novice.

Ah so there is, I'm tend to skip over images while reading and I didn't even see them!

> (Also, key question, was the art any good?)

I liked the ones in the article. Dark, unsurprisingly.

Also, she said that the excessive stimulation disappeared after she stopped taking the drug.

These drugs are sometimes prescribed in cases of extreme medication-resistant Anxiety and Depression. My significant other is prescribed lamotrigine precisely for this reason.

Just throwing it out there. I don't disagree with your perception of the article, but there's always edge cases.

Actually the article says Hannah has "depression and anxiety". They mention bipolar briefly in the list of off-label uses for dopamine agonists so presumably wouldn't have mixed it up.

Though, it could have been misdiagnosed.

> It is a rare case of restless legs syndrome that is severe enough to make the risk of prison time or the sex-offender registry look like a reasonable tradeoff.

While I understand the rest of the article, as someone who has been through opioid-withdrawal induced RLS a few times in my life, this is really downplaying how horrible it is.

The RLS alone would stop me from sleeping for a week or more. You lose your mind. It’s horrific. I can understand why someone with a severe case might be willing to take that risk — though from the sounds of it, a lot of prescribers aren’t explaining that risk to their patients.

As an aside, for those who are unaware, RLS is induced by opioid withdrawal because chronic opioid use disorder/abuse down-regulates your dopamine receptors. Our dopamine pathways have wide reaching effects within our bodies and minds.

I’m not an addict but I have suffered from restless leg syndrome in the past, to the severity you describe. Every time you’re on the cusp of sleep, there’s this tickle that travels up your leg to your lower back. But it’s this weird, disembodied tickle. There’s nothing to scratch or press or wrap or anything to alleviate. So you’re now wide awake because of this tickling sensation.

This was ~2016 for me. I read somewhere that restless leg is related to signals in your nervous system, which needs electrolytes to work optimally, and that taking a magnesium supplement would help. I bought some magnesium at Walgreens and took them for about a month. I think I’ve only experienced restless leg once or twice since 2016.

FYI, I hope this helps.

I was prescribed Pramipexole for restless leg syndrome some years ago, and the information leaflet was pretty specific about the impulsive behavior side effects.

The Spanish leaflet lists as "Frequent" (up to 1 out of 10 patients) things like: "Needs to behave in an unusual way", "Hallucinations", "Confusion", "abnormal dreams", "Insomnia"...

I in fact had lots of weird dreams and nightmares.

It also lists as "Less frequent" (up to 1 out of 100) things like: "Paranoia", "Delusion", "Amnesia", "Hyperkinesis", "Fainting", "Concerns", "Inability to resist the impulse, instinct or temptation to take an action that may be harmful to yourself or others, which may include: [buy/gamble/sex/eat]"...

I thankfully had none of that, but 1% looks like a too high probability for me for that kind of effects.

I get mild restless legs if I don't take my daily calcium supplements. I think both calcium and magnesium are helpful, although I have also heard they are meant to work against each other in some way.

It seems to me that issues like this one expose a fundamental flaw with how criminal justice is generally practiced - one that's evident in the term itself.

The focus is on assigning blame and just (fair) punishment. ISTM a better framing might be to determine the desired outcome and how best to achieve it. How likely is someone to re-offend, and what is the best intervention to reduce that likelihood? In the most extreme cases that might mean physically preventing recidivism through imprisonment. In other cases there might be other interventions that could be more beneficial. How likely are others to commit a similar crime, and to what extent, if any, will the outcome of this case affect that (ie deterrence)? And yes, also relevant is how will people - especially victims - feel about the outcome? Does it seem just? However if different norms around the response to crimes were established, feelings would presumably change as well, gradually.

I'm not saying that no one should ever be punished for their crimes, just that the intent of punishment, or of any other intervention, should be to have positive impacts on the future, as opposed to simply an abstract balancing of scales. From that point of view, I expect the handling of cases like these would become significantly simpler.

> The focus is on assigning blame and just (fair) punishment. ISTM a better framing might be to determine the desired outcome and how best to achieve it. How likely is someone to re-offend, and what is the best intervention to reduce that likelihood?

That would be rational, and, especially in the US, our criminal justice system very rarely intersects with rationality. In general, it's based on what will provide the most extreme emotional response among voters.

I think you dramatically underestimate the harshness of a “rational” system. According to one study 63% of violent crimes are committed by 1% of the population (your mileage may vary but the order of magnitudes will be about the same).

This implies that a person that commits any violent crime should be imprisoned for an extremely long time, because the odds are very good that they’ll assault, rape, rob or murder someone else.

Said another way, with the policy of locking people up for a very very long time on a first (violent) offense, you would eliminate nearly half of all violent crime- and that’s not even counting the deterrent effect.

First, to get it out of the way, there are some (serial killers come to mind) that modern psychology is unable to much about.

However, of the 1% you mention, I imagine (without looking at any data to verify) many offenders may suffer from mental health issues or live in harsh socio-economic environment. It seems to me the best thing to do is address these two factors. Then no one need be locked up, and public resources can be put toward things positive for society rather than negative.

As for the serial killer psychopath types.. I’m generally against capital punishment; hate the idea. But like, next to nothing can be done for these people today (I am not an expert, could be way off), and thus they pose a permanent threat to the people they’re around. I can’t think of a solution beyond some kind of exile, which seems silly or difficult to enforce. We could lock them up, but it seems like a waste of resources and overall a miserable way to live. So.. and I reserve the right to change my mind with the availability of more information, but perhaps it makes more sense to simply execute (in the most humane way possible) this very minuscule portion of the population when the offenses occur (specifically more than one near lethal assault or one or more lethal assault) and they are found guilty beyond reasonable doubt?

The disease casually mentioned (https://en.wikipedia.org/wiki/Encephalitis_lethargica) in the article is worth looking into as well - a ?virus? that causes coma, that appeared, wreaked havoc (affected ~1M people and killed half) for a decade or so, then disappeared

Yeah, with the possible connection to the Spanish Flu epidemic this gives one pause when considering long covid and covid's neurological effects in general

Mesmerizing read.

I found it very relatable because as a person trying to manage ADHD those experienced traits and behaviors during treatments are very similar to my untreated ones.

I keep my dark side "on the leash" and maybe it's not as vibrant as ones in story (probably because I was born with it and had chance to adjust over years) but some similarities are uncanny.

With various treatment experiences I had I start to believe that there is no "I" in anyone. It's just an effect of a brain chemistry on which we have very limited effect. Identity that's effect of trauma or treatment is just as real as the one we were born with.

Ethical implications are very interesting, but in reality I doubt anything will change until we have a breakthrough in neurosciences. Even then probably there would be question if we should equalize people different. Feels like a plot for sci-fi movie - there even was one like that: https://www.imdb.com/title/tt0238380/

While reading the article I got the feeling that this article touched on something much deeper than it meant to. In stories there has often been a artistic, dreamy, head in the clouds type that either delights or confuses the more stolid, logical, sensible and practical other character.

Abbot and Costello, Rabbit and Briar Fox, Dexter and Dee-Dee, Billy and Mandy, Drop Dead Fred and everyone else in that movie, (or anyone in a Yahoo Serious movie other than Yahoo Serious) these dualistic Gemini archetypes are littered throughout western culture, and quite possibly others but I don't know them well enough to bring any popular characters to mind.

I wonder how much of that is caused by the fundamental divide between high and low dopamine functioning people?

Wild, zany, brash and in your face manic lifestyle caused primarily by having a lot of dopamine in your brain? With plenty of people around to facilitate the outcome at least in part because of the attention-seeking nature of the effect?

This makes me long to attempt something similar. It makes me wonder who I would be on a long arc dopamine rush. Would I paint? Would I sing? Would I drive my friends and coworkers wild? Or lose everything in a dopamine fueled fumbling towards ecstasy?

Who knows, but it's intriguing! It's as tempting as a siren song. If someone had those pills in front of me right now I don't know if I could resist trying them.

I've actually been taking pramipexole for almost two years now for depression which mostly didn't blink for anything else in the past.

I certainly do behave differently while on it, but not in a way that I think anyone who knew me would claim is inconsistent with my prior personality or behavior, just...less likely to fall into the inertial well that is depression stifling your actions.

A strange anecdote, though - my doctor told me when I was tapering up on it "okay, for some medications they tell you you might feel ill taking it initially, but no, for this, I am going to promise you, you will feel sick, and how well you can tolerate feeling sick is going to be the limiter on how fast we taper this", and he was correct, though it was never that bad during the initial taper up, just mild discomfort...

...then one day, the pharmacy gave me 1x1mg pills instead of 4x0.25mg pills, from the same manufacturer, and suddenly I had horrific nausea if I was in anything moving faster than a brisk walk for hours after taking it, and it went away when I went back to the 4x0.25mg. Which was wild, as I've never had motion sickness from anything before.

(It's also twice a day because the half-life is real short now, which is annoying, but c'est la vie.)

Feel free to ask anything that comes to mind about it, if anecdata interests you.

I read in body building forums that those who are on testosterone take cabergolin to keep their male breast from changing too much.

Some of them said it made them more sexually active than before. They got horny more often and the refractory period was reduced.

When I read about caber, I found out it was given to Parkinson patients and that one of it main side effects was that people were more inclined to gamble and have sex.

Interesting, anecdotally testosterone therapy (even unnaturally super high levels) tends to counteract my ADHD impulsiveness and the obsessive or prurient behaviors driven by dopamine reuptake inhibitors like amphetamine.

Because of the descriptions of dopamine agonists, I suspect pramipexole and cabergolin have a much strong effect than DRI's. But maybe I've just lived with DRI's for so long that I can mitigate/resist the effects somewhat better than a person who just started on them in their middle age.

Based on personal experimentation I also suspect the elevated estrogen from testosterone replacement is largely responsible for the reduction in dopamine-driven behaviors. I tend to do best overall with estradiol on the high side of normal. When estrogens are low I get far more compulsive behaviors shadowing those in TFA, even in the absence of dopamine related pharmaceuticals.

> euthanized her cat on a whim.

this is the scary bit. Killing animals for fun is how many serial killers get started.

It's not really clear how she euthanized her cat. That would seem pretty important.

True. Also whether she previously “felt sorry” for the cat for some reason, maybe it was sick and suffering and the drug just switched her mind.

Slightly off-topic (though related). I think I experience a mild form of the craziness described in the article if I don't get enough sleep the night before. I'm not trying to compare the two in any way, or make it "all about me" - but it's a definite pattern I've observed, and I wondered if anyone else had experienced anything similar.

One possibility is you have always had that craziness but you learned to compensate for it using various strategies. But when you’re low on mental energy, you can’t compensate effectively.

I experience this in an extreme way having bipolar. I learned very young how to function despite a severe disability. Lack of sleep would make everything worse because I couldn’t keep on top of things.

When you’re in the middle of it, it feels normal.

This is not particularly surprising, lack of sleep causes an increase in dopamine (the theory is that the brain tries to "compensate"). There was a very recent episode on the Huberman Lab podcast on using this to "reset" the circadian rhythm and depression (to some extent).

I read this story and… I’m actually terrified that our government has just signed-off on drugs like this. Between that, and the FDA not catching Theranos, it does make me afraid of the FDA’s competence or judgement for allowing such things so loosely.

Here’s a hypothesis that would be interesting to test. As the younger generation continues its obsession with social media technology. Is there some physiological change (perhaps mimicd by the medication in the article) that could be happening simultaneously? Some weird type of brain evolution.

I feel like this is already tested, extensively, by the "video games cause school shootings" crowd.

That particular claim is bullshit but it is true that video games can cause physiological changes and even harm. Like social media, video games today are straight up designed to be addictive. They're essentially Skinner's boxes but the reward lever is the player's credit card.

Not only can addiction of any sort cause physiological changes in the reward center of the brain, video games can also impact physical, social and financial well being by virtue of being an expensive, addictive, sedentary and often isolated activity. Video game addiction is already a recognized medical diagnosis in ICD-11.

https://www.who.int/news/item/14-09-2018-inclusion-of-gaming...

You could rephrase that to "murdered her cat while under the influence of mind-altering prescription drugs used with inadequate supervision". People in states of mental illness have diminished responsibility for their behavior.

You’re actually getting at some of the issues the article explores. The case studies are there to illustrate; they’re not the central point. I almost dismissed the piece based on the headline, but I’m glad I didn’t. You might find it unexpectedly interesting too. If I misjudged whether or not you read the OP, my sincere apologies. No harm intended.

I don't know her but the drug is really known to make some people crazy

The self doesn't exist; the drugs do.