When RxISK launched a Sex Zone, we press released it. We wanted as many people as possible to go to the Zone, explore what was there among the 4.3 million FDA reports we give away for free, and get word out about the site and especially that here was a site that could be used to report about things that doctors rarely report about.
A site with a difference. We intend to put local knowledge in local hands so for instance if a particular sexual fetish on a statin is happening in Madison but not Milwaukee, or exhibitionism on a fluoroquinolone in Cologne but not Frankfurt, our Heatmaps will show this. We think people in Madison and Milwaukee, or Cologne and Frankfurt, faced with these differences are best placed to work out what is going on than regulators, academics from elsewhere or companies.
But in this arena even the innocent use of the word Heatmap for sexual effects on drugs which might include increased libido can be loaded.
Calling some sexual effects of drugs adverse effects is a close to disastrous framing of the issues. If someone on an antidepressant switches from being heterosexual to homosexual and we say that they have had an adverse effect, we risk getting the Gay and Lesbian community up in arms. They might call for a boycott of RxISK. At least this is what we were told. My hunch is the Gay and Lesbian communities will be a lot more relaxed about this than the straight community.
The term adverse effects is plain wrong for other reasons. SSRIs for instance have much clearer, and more consistent and obvious effects on sex than on mood. When they were brought to market in the 1980s it was still impossible to talk about sex. The depression market was a lot bigger, and so they became antidepressants that had side effects on sexual functioning. It is much more accurate to say they have effects on sexual functioning and side effects on mood. It was a boardroom decision by businessmen – not RxISK’s call – that makes any sexual effects into side effects or adverse effects rather than just effects.
So far so academic. But something proverbial hit the fan when the press release included the fact that there were early and consistent reports that antidepressants could change sexual orientation from homosexuality to heterosexuality. Impossible we were told. You will lose all credibility making these claims.
The first report of this effect is tucked away in the very first English language article on the discovery of the antidepressant effects of imipramine by Roland Kuhn. Imipramine we now know is a potent serotonin reuptake inhibitor. Kuhn was a country doctor, more a psychotherapist than a psychopharmacologist. He was conservative in attitude. His explanation for what was going on was that some homosexual behaviors stemmed from depression and relieving this helped “normalize” other behaviors. He didn’t celebrate the issue but he may have been pleased – in line with dominant thinking at that time.
Much more controversially, fifty years later, in 2009 Joseph Nicolosi claimed that Lexapro straightened out a homosexual patient of his. Subject to close scrutiny, this claim fell apart.
The year after that a Nature article on the manipulation of the serotonin system in rats seemed to give some credence to the possibility that tweaking the serotonin system could change orientation.
The RxISK press release said if a change in orientation can happen we have absolutely no reason to believe that antidepressants will only push people one way – from homosexuality to heterosexuality.
We were told stories aren’t evidence. Extraordinary claims need extraordinary evidence. We don’t have any physiological basis for an effect like this.
Let’s back up for a moment. One of the most powerful RxISK stories posted centered on Anne-Marie’s efforts to get to grips with her hunch that the antidepressant she was on was causing her to be “alcoholic”. She was accused of typical alcoholic denial. A confusing switch from one SSRI to another that left the problem in place made it much harder for her to win the argument. Finally she proved her point.
Since her post hundreds of people have posted comments or reported in confirming just what she said – these are really worth reading. We went back to search the academic literature for a basis for her claims and this has led to a peer-reviewed article in press on the issue.
Anne-Marie’s was a compelling story and an extraordinary claim. The conventional wisdom still is that many alcoholics drink because they are depressed. Clear up the mood disorder and you may stop the abusive drinking. Or else their alcohol intake will lead to depression that needs treatment with antidepressants. Very few people buy the idea that the drugs can cause the problem for some.
When Anne-Marie took the “good news” to her AA group she met anger and hostility – you will never be cured while you think like this. When she attempted to post details on alcohol on probation sites she has had her posts taken down and has been threatened with stiffer action.
She is suffering from reverse stigmatization. The stigma of being someone who is cured of something you are not supposed to be cured of or cured in a way that is unsanctioned.
No one it seems likes “simple” complexity. When I was a medical student, we ran a practical where 10 of us took a beta-blocker. We were to monitor blood pressure, heart rate and other variables. They should all have dropped but one woman’s heart rate rose. The group behaved just as the books said. What the books don’t say is these averages may be completely wrong for individuals.
I have seen the same thing over and over again – in neuroendocrine studies, fMRI studies, cognitive function testing, where the processes are not under conscious control and subjects cannot fake the outcomes.
Companies know this well. Lilly used it to counter perceptions of sexual dysfunction on Prozac. An “adverse” effect reported to the company soon after marketing that involved a woman who apparently had an orgasm every time she yawned somehow achieved wide circulation.
It turns out that those saying orientation can’t change fully accept that some heterosexuals come out as homosexuals – they are less clear about the opposite. What’s going on they say is that people use the cover of a pill as an excuse for coming out – they don’t truly change orientation.
A very nuanced interplay between social and biological factors was laid out in response to 50 Shades of Mirtazapine by Ned Shorter. Shorter’s argument brings out an important point. Sexual fetishes were not reported before Leopold von Sader Masoch’s Venus in Furs in 1870, and so this option would not have been available to someone on an SSRI before 1870. The option is likely to be all too available to anyone on an SSRI with the release of Polanski’s movie version of Venus in Furs later this year.
More generally profound changes in the notion of identity took place in the nineteenth century and these changed ideas of sexual orientation in a way we have to take into account when we say a drug could cause a change in orientation.
But the biological changes a drug induces are likely to be the same in an Ancient Greek as a modern New Yorker. The fact that the New Yorker has an outlet in fetishism that the Greek didn’t have – is just that an outlet. Over 50% of Ancient Greeks on an SSRI would have had sexual dysfunction just as 50% of New Yorkers do today. To deny “real” and perhaps fundamental effect on sexual functioning on this basis doesn’t make sense. An Ancient Greek might not have had the example of school shootings to shape his behavior but the agitation the drugs produce would likely still lead to homicide.
In the case of altered sexual behavior, the drugs might disinhibit we are told. They might – and this could give rise to some of the cases reported of female schoolteachers seducing their male pupils. But we have had far more reliably disinhibiting drugs than the SSRIs for decades and nothing comparable has been reported on them. We have had alcohol, benzodiazepines and other drugs with nothing comparable to this. We even have antidepressants that don’t act on the serotonin system – and they don’t generate reports like this.
What we also have are endless social commentaries on the psychopharmacological era that portray the benzodiazepines, mother’s little helpers, as sedating women into suburban prisons. These uniformly fail to take into account the biological reality of these drugs – that they undo conditioned avoidance and may well have done a great deal to upset social hierarchies in the 1960s.
So how might we test these claims about changes in orientation? One suggestion has been that it will need a controlled trial. This is entirely wrong. For complex behaviors such as suicide where drugs can have suicide relieving and suicide provoking effects, controlled trials are worse than useless. The same will be true for complex sexual behaviors (See links).
We can qualitatively interview people – but will the skeptics be any more likely to believe the results of such interviews than alcoholics will believe Anne-Marie?
There is another group of drugs that come into play here – the dopamine agonists – Parlodel, Dostinex, Permax, Mirapex, Requip and Neupro. These are used for Parkinson’s disease – but also for Restless Legs. From soon after the first of these drugs appeared, there were reports of people becoming compulsive gamblers or turning to prostitution or leaving their partners of many years standing, sometimes for members of the opposite sex. Appeals to those affected this way to recognize the effects of the drugs get nowhere. There is something about what happens that is not recognizable to the person taking the pills.
This is not disinhibition. The behaviors in these cases are often stereotyped and compulsive. There is little room here for attributions or social constructions. Messing with the dopamine system disturbs reward hierarchies – and in some cases that can come fairly close to changing who we are, not just changing our sexual orientation.
Twenty years after the first reports, it is now recognized that one in six patients who go on dopamine agonists will have significant changes of behavior in one or other of these domains, and many will have quite disastrous effects. This drug group are widely available on a black market for sexual purposes but astonishingly the FDA data contain vanishingly few reports of any sexual effects on them, even though short of death these are about the most dramatic treatment induced effects there can be.
I routinely see transgender patients in North Wales where many of my colleagues will not. These patients are an astonishingly varied group of people. I have no difficulty in seeing some transgender cases as resulting from a change in how we construct identities since the nineteenth century. But being in a room with a transgender patient and having to make a judgment call on what happens next is an entirely different experience to being in a room with someone who has the rampant promiscuity and change of orientation seen on dopamine agonists and in some cases on SSRIs.
Nor am I averse to a role for some social constructions in adverse events. In my first publication on antidepressants and suicide I made it clear that part of the problem might lie in people making misattributions to what was going on and that warnings and knowledge were important as they could be used to reduce the risk by tackling misattributions.
But the idea that an unexpected drug induced “adverse” event is socially constructed pure and simple seems a contradiction in terms. What’s surprising is that many people seem to know beforehand what in fact is going on – its disinhibition. This sounds all too like the misconstruction of the benzodiazepines. A social account that pays no heed to biology is likely to be wrong.
Is it irresponsible to talk about these issues without nailing the “facts” down? When hundreds of thousands of adolescents are being put on serotonin reuptake inhibiting drugs is it irresponsible not to raise the issue? They are not being put on dopamine agonists but they are being put on the closely related psychostimulants. These drugs are having an impact on them while they are grappling with a sexual maturation process. We have no idea what this means.
Better surely have some place where people can go and access some kind of information on these possibilities than have nothing. Perhaps also those who access RxISK and find they are not alone can teach us all something. Might be fun just to see the Heatmap take shape.