Medicine answers to systems beside purely legal, in this case the machinery at work is ethical review and the FDA trial approval process. While allegedly battling paternalistic treatment of patients, the current belief of the system of ethics is that "patients cannot know the true extent of what they consent to lose," so before informed consent is even considered as an option for the patient, you have to establish that your therapy is definitely probably going to work. In disease states that are lethal and have no solid treatment or only expensive treatments like cancer, lines are blurred. In disease states that are cheap and easy to deal with, like allergic rhinitis, lines are blurred. The moment you can say "If you do not take intervention X at this moment in time, there is a Y% chance of the disease progressing into dangerous Z," having a placebo group that receives no treatment at all is impossible, no matter if people would consent to having a fair 50-50 of receiving treatment, which gives you a unique set of problems to deal with. The logic seems obvious, but it makes empirical trials way more difficult to conduct.I'm not too familiar with the legal side, but could a group study be arranged for people who are informed about the intention of the research and willing to sign honest disclaimers to participate? Or would the willingness of the participants to acknowledge that their identity might be a delusion negate the merit of the results (i.e. would that group be too psychologically different from people who believe they're trans without being willing to question what the 'trans feeling' comes from)?
The problem we have run into is that it is clear that transexuality is such a disease, for all the reasons the internet makes fun of it. 41% is a bloody high suicide rate for depression, and that's just one statistic. The fact of the matter is that study of transexuals predates study of treatment for transexuals, and "gender-affirming therapy" was theorycrafted in the time between our post-80s medical ethics and pre-80s medical ethics, so it shut the gate behind it as the "gold standard of care." The fact is, gender-affirming therapy does work, on a number of self-reported metrics. The quality of evidence is shoddy, and the success rate of care is being defined in terms of that shoddy data and not anything about the suicide rate, or how well the person functions in society, etc., it is every problem of psychiatric medicine at once, but you cannot simply deny care because "that is all we have." Yet, as a therapy solution with hormones, gender-affirming therapy necessarily takes years to "prove it works," so any trial with it as a standard of care is bogged way down... it's a daunting task for any clinical investigator. That's the crux of the matter, as much as people want to go after the drug companies profiteering off of the situation as it stands, they aren't the ones blocking any solution to the problem.
The rest of your considerations can honestly be eliminated with careful clinical design or statistical methods. Mostly, a trial involving Pimozide would be "hoping to reduce depressive/psychotic effects of trans comorbidities," on paper, while also very quietly including analysis of which groups have a higher drop-out rate, etc.. The hallmark goal would be to establish that gender-affirming therapy + Pimozide has better outcomes than Gender-affirming therapy alone, because that would be sufficient evidence to speculate that Pimozide alone may be better than gender-affirming therapy alone, and gender-affirming therapy + pimozide if you do it as a three-pronged study. Once any psychoactive substance demonstrates such an effect the floodgates open to ethical experimentation, but until then gender-affirming therapy is going to be a part of it, and it's fucking expensive and slow.
The only other hope would be a meta-analysis comparing outcomes with trans patients on antipsychotics vs those without them, but that's hobbled by the fact there are so few trannies, and the difficulties of documenting them when they insist on being recorded as anonymously their true ~gender~. That particular fad is to blame for a lot of this, too. Between that and the very delayed time to death (5-10 years after therapy starts before suicides tend to coalesce)
For the reasons stated above, Pimozide isn't really an option. It has only barely been explored and recommending anything off-label inappropriately is a death sentence since you have full liability. It's not just Pimozide that hasn't been studied, either; gender non-affirming therapy/same-sex hormones are traditional treatment options, but there simply isn't any data for it that has been formally recorded. Unlike antipsychotics, you cannot , which is the massive barrier to therapy. If anyone can prove that there's a way to budge the massive trans suicide rate and improve their quality of life without or in tandem with gender-affirming therapy, only then can we ethically consider gender non-affirming therapy alone/in combination... unless we just say "fuck it," gut the FDA, and get back to doing medicine the way we used to.Overall, I'm frustrated to see that people are not even told of this option when they start medical transition. Doctors should at the least offer both approaches to people, even if they're not requiring one or the other as a prerequisite to trying the opposite approach. So far, researching this topic leads me to a lot of sources claiming that transitioning is the proven, medical approach -- all while acknowledging that there's only been this one study on the opposite approach. That's not scientific, and the resulting ignorance may be causing unnecessary suffering for a lot of people. Damn.
For disease states people actually care about, that usually means going to Brazil/Eastern Europe/China and doing the challenge trials there. It's ethical if you do it on browns and slavs, you see. Trannies, for all their social relevance, just aren't worth it for anyone, academia or drug companies, to even consider doing that.
To be fair, modern medicine has fought back on SRS for ages, because of the instant and obvious complications. It's only under the crushing burden of opposite-sex hormones being literally useless and suicide rates never budging despite self-reported happy trannies that it's being considered in the states. Hormones have nasty side effects too, but you have to understand that they're seditious, sneaky side effects no one even knew existed until the few special populations that needed hormones started to manifest them, including and especially trannies. I mean, if they're so busy killing themselves, it's kind of hard to track "long-term effects." Every clinician I've ever spoken with has basically been shocked that hormones could do real damage in the way that we're now coming to understand they do after decades of common knowledge that they're "harmless" outside of the (mostly intended) secondary sexual effects.The whole thing is just repulsive isn't it?
"It doesn't matter if our suicide rate is abysmally high"
"It doesn't matter if you have to take foreign hormones and mutilate your body leaving you in pain"
"A pill will never work"
We've said so a million times, but imagine if the treatment for bulimia was giving every one a personal stomach pump. Or anorexia they suction out your visceral fat or give you a lap band. Or schizophrenia they give you mushrooms. Or BPD they tell you everyone does indeed hate you and you should just kill yourself to make everyone's lives better.
Because that's not FUCKING ethical.
Ultimately, the opponents of gender-affirming therapy & SRS are foiled by the fact that gender-affirming therapy got there first, takes overever, and SRS can be adjunct to it, while most reasonable alternatives require the cessation of gender-affirming therapy (because it's making the problem worse). Actually, this thread has given me a lot to think about. There would be remarkable progress in eliminating these practices if someone could hawk antipsychotics as an adjunct therapy for "known comorbidities" of transexuality- and if it "just so happens" that the antipsychotics make the trannies detransition and reveal that it was all a product of gays suffering from fucked up brain chemistry, well, isn't that neat?
AFAIK, no one has tried it yet for all the reasons I've pointed out above, but I think it'd have more luck than simply trying to bring same sex hormones or pimozide alone to trial.