It was Matt Miller’s case that started the ball rolling. The 13 year old had just changed school and was taking time to settle. He was referred to a Dr Geenens, who diagnosed Zoloft. A week later he hung himself in the bathroom between his and his parents’ bedrooms. Zoloft didn’t cause suicide Pfizer’s lawyers argued, it was a case of auto-erotic asphyxiation gone wrong. They sent a detective to scrape the bathroom carpet for seminal stains.
It hit me that either some member of Pfizer’s extended defense team had an interesting sex life or else Pfizer had had reports of auto-erotic asphyxiation on Zoloft. Looking at FDA’s adverse event reports in the RxISK Sex Zone, it is difficult to know how these would have been coded – FDA don’t have a code for auto-erotic asphyxiation. Nor do FDA code the molestation of teenage schoolboys by female school teachers made into great fiction by Zoe Heller in Notes on a Scandal, and a compelling movie, the problem that has led to so many court cases as reported on SSRI stories.
The very first English language paper about antidepressants outlined a case of a homosexual becoming heterosexual on imipramine. It seems that almost no-one in the sexology field thinks this could happen. Whether it can or not, it won’t register as there is no code for this possibility in MedDRA or FDA’s coding system. This is a problem whose name is writ on water.
Sexual addiction made into another compelling movie – Shame starring Michael Fassbender – is also a problem not covered by current codes. It’s a real enough problem though for lots of people to be making money out of it. A new clinic has opened up in Malibu for dual sex and drug addiction. There’s no point, they claim, weaning someone off a drug, when the next sexual act will trigger drug abuse again and vice versa. The drug most linked to this condition is Crystal Meth, the silent star of the hit series Breaking Bad. Truly an end of civilization, life ending drug.
Methamphetamine began life in the 1930s and made its way onto the market in the 1940s as Methidrine. It was used for nerves through to the 1950s when it was eclipsed by the more potent Dexedrine, dexamphetamine, which is now used in huge amounts among children hitting puberty – on prescription only.
When it comes to sex addition, neither Methidrine or Dexedrine can hold a candle, as it were, to GSK’s Ropinirole – ReQuip – originally a treatment for Parkinson’s Disease. The first reports of disturbed sexual behaviors, gambling and other problems with dopamine agonists and related treatments came in the early 1980s. It took 25 years for the problem to be acknowledged and find its way into warnings. Long before that, dopamine agonists had found their way onto the market as much more effective sex aids than Crystal Meth.
No one has ever said “nerves” don’t exist or accused a drug company of conjuring nerves out of nothing. But this is what GSK were accused of when they launched Ropinirole for Restless Legs Syndrome in 2005. RLS and Ropinirole featured as a star turn in PLoS Medicine’s issue on Disease Mongering in 2006. The company were accused of trying to hype up a rare and non-threatening problem into a common and must-treat condition.
Given that Ropinirole and Pramipexole were on the market for Parkinson’s disease and could be used for severe cases of RLS if need be, marketing RLS seemed to be a little more than a way to make more money out of Ropinirole rather than a genuine effort to meet an unmet medical need. The critics of the marketing of RLS might have been a lot more horrified if they knew about the true risks of the treatment.
The FDA reports in the RxISK Sex Zone are fascinating but frustrating. Too many of the most interesting changes have been swept beneath the rubric of paraphilia. Under this heading, which covers klismaphilia, urophilia, zoophilia, necrophilia, sado-masochism, scatologia and sexual deviancy, Pramipexole, Ropinirole, and Levodopa lead the pack – along with two other drugs. Ropinirole is by far the commonest drug reported to enhance sexual fantasies, and along with Pramipexole the most common to enhance libido. These two are essentially the only drugs that have been linked to exhibitionism, and voyeurism.
Among the other drugs featuring as triggering paraphilia is aripiprazole (Abilify). This drug sold as an antipsychotic and mood-stabilizer is a partial dopamine agonist. One of the surprises of surfing the data is how often drugs that have partial effects on the dopamine system, such as buproprion (Wellbutrin – Zyban), enhance libido and cause problems.
But the most intriguing entry for me in the paraphilia area is Zoloft – sertraline. This is up there with Ropinirole and others making it look more likely that Pfizer had reports about erotic asphyxiation or other paraphilias to work on and less likely that their lawyers could tell the rest of us something interesting about sex. Also intriguingly Zoloft rates high for sexual violence – attempted rape or assault – which fits in with the role of SSRIs in generating Notes on a Scandal type problems.
The fact that sertraline has these effects makes sense; back in its early days company scientists and marketers played up its effects on the dopamine system and the interactions between the serotonin and dopamine system in general.
Effexor – Pristiq which is linked to compulsive gambling and sex addiction also has effects on the dopamine system but these effects show up under compulsive gambling rather than sex addiction. If you want to know if your drug has effects on sex, you will likely need to search under terms like gambling also.
Breaking Bad is compelling in the way it shows good people trapped in the system being forced to make increasingly desperate choices and finding themselves turning into people they never expected to be. It shows the impossibility of distinguishing between an efficient criminal and an efficient businessman – all enterprises whether criminal or legitimate have to be run ruthlessly if they are to survive.
All enterprises involving drugs must inevitably have terrible human collateral damage and the Walter Whites and Andrew Wittys have to find a way to manage this. There are far more reports of happily married older men becoming gay sex addicts on Andrew Witty’s Ropinirole than on Walter White’s Crystal Meth. Didier Jambart for instance was last year awarded close to $300,000 for the effects Ropinirole had on his life.
At this point its not clear what fate lies in store for Skyler White, but Marilyn Tobias the wife of the CEO of Lilly ended up on Prozac and committed suicide.
Other groups of drugs can cause changes in orientation and sexual addiction, especially the anticonvulsant drugs, but these have sailed beneath the radar for decades. The anticonvulsants are as likely to cause suicide in people who have no mental illness as antidepressants are in people who are depressed. But where we have a good feel for the agitation, emotional blunting and psychosis that SSRIs trigger that lead on to violence and suicide, we have no idea just what kind of mental changes anticonvulsants produce.
Against this background claims that certain things such as change of orientation can’t be happening or that if they are happening we know what’s going on – it’s just disinhibition – don’t hold water.
A mixture of drugs for instance are linked to reports of gender identity change including testosterone and estradiol, along with the cardiac failure drugs that affect sex steroids, spironolactone and digoxin. Not so surprising perhaps. What is surprising is that citalopram, clozapine, and valproate are linked to many more reports of gender identity change than the sex hormones.
Strangely paroxetine, venlafaxine and duloxetine which are heavily reported as killing libido are reported as enhancing it also. They usually delay ejaculation but are reported to cause premature ejaculation in some. These differences make it clear – there is no such thing as the average individual.
Trazodone is famous for causing priapism so it’s no surprise to find this topping the list of drugs reported to cause this, but its astonishing to find that it only just about beats risperidone and its derivative paliperidone, as causes for this. I’d never have guessed.
Whether you’re a woman or a man it looks like the bisphosphonate group of drugs (used for osteoporosis – alendronate (Fosamax), risedronate (Actonel), pamidronate (Aredia), zoledronic acid (Zometa, Aclasta)) cause problems. They kill lubrication in women.
If you’re a woman you want to be careful of the Mabs – drugs like adalimumab (Humira), natalizumab (Tysabri) and etanercept (Enbrel) used increasingly for everything from arthritis to bowel conditions like Crohns or colitis. These affect menstruation in almost every conceivable way.
Both Mabs and bisphosphonates change vaginal odor, produce dyspareunia, and are reported to cause vaginal infections.
For men, the prostate drugs tamsulosin, finasteride and dutasteride cause erectile problems, reduce seminal volume, cause retrograde ejaculation and other problems.
A woman’s ability to smell a man is likely critical to good heterosexual relations. Her ability to smell him will be affected by Champix, Lyrica, and Zyban, along with almost any nasal sprays. His smell may be affected by bisphosphonates, omega-3, Mabs as well as Champix, and Zyban. Any dopamine blockers like Risperdal, Invega, Fanapt, Seroquel and others used for nerves or as mood-stabilizers will change the oily concentration of skin and are likely to affect his smell as well.
There is no question that drugs acting on dopamine may have profound affects on sexual functioning but lots of questions can be asked about just what is going on. It may have little to do with dopamine as a reward neurotransmitter and much more to do with other subtle things. Until we look closely at these things we aren’t going to know.
Somewhere back around 1870, around the time of the publication of Venus in Furs, the first account of sexual fetishes, sex and our sexual identities began to change. Societal strictures began to feel Victorian and repressive. Leopold von Sacher-Masoch, the author of Venus in Furs, put forward the view that it was only when women were as educated and paid as well as men that sexual relations would work properly.
While sex began to come out of the closet, drug taking went underground. Drug takers began to be policed. In 1914 cocaine and opiate users were restricted to “prescription-only” supplies. In the 1950s this system invented for addicts was extended to the rest of us, and an increasing amount of drug taking activity and knowledge went underground.
It is certain that only a fraction of what happens on treatments is now being reported. This is partly because the coding terms aren’t there, partly because there is no incentive to report. We need you not just to report but to let RxISK and through us MedDRA and FDA know what terms are needed to capture your experience – sexual addiction, change in orientation?
Why? Because its impossible to hide any more that there is a great deal going on in the drug domain. Drugs may treat illnesses, but they also often have much more profound effects on other aspects of our lives from our religious beliefs and political affiliations through to the most intimate areas of our identities. We may have arrived at a cultural watershed comparable to the one a century ago that we can now mark by the publication of works like Venus in Furs, except now that women are better educated than and can beat men at almost everything it might be time to update to Venus in Lycra.