This blog post has first been published on the RxISK.org website and can be viewed here.
In RxISK Stories, we regularly take you to dark places where few would wish to go. We have perhaps become too used to the horrific consequences of medicines going wrong that we fail to appreciate how off-putting this sequence of posts can be. It is like a doctor taking a friend into an operating theater just when the surgeon is sawing through the breastbone failing to appreciate that the friend is likely to faint away.
We want you to give us some good news stories – about new uses for drugs, or discoveries about how to manage side effects. The supporters of drugs classically say that critics fail to take into account all the lives that would be lost if the drug were not used – nowhere more so than in the case of the antidepressants where warnings they argue will deter people from seeking and getting the benefits of treatment. But the efforts to persuade doctors to prescribe and the rest of us to take antidepressants went hand in hand with efforts to persuade doctors to stop prescribing and the rest of us to stop taking benzodiazepines. And this gives rise to deaths also.
Cora was 18 and beautiful. Slim, with long blond hair, about average height. She had just finished high school, where she had been the homecoming queen. She was set to attend college, though she wasn’t certain what direction to take there. She had a boyfriend but was worried he might want to leave her, while at the same time knowing her parents didn’t approve of him.
At a rock festival with her boyfriend, she got lost and, trying to find him, had taken a fall and injured her arm. She was admitted to a local hospital for treatment and sent home from there. Several days later, in a state of perplexity she was brought to the psychiatric unit where I have inpatient beds.
Had she been traumatized or abused in some way? Had she been taking drugs and had a trip gone awry? Had her boyfriend left her? Her mental state was quite unstable, but despite having input from the many people involved in looking after someone in hospital I couldn’t make a diagnosis. Cora was not hearing voices, did not have delusional beliefs, and was not consistently depressed, elated or anxious. But she was volatile. At times in the ensuing weeks, apparently improved, I gave her leave to go out with her parents, but she was typically brought back severely confused again – sometimes only minutes after having walked out through the hospital doors. At other times she was almost completely unresponsive and inaccessible. I could see no reason to give her an antidepressant or an antipsychotic. On occasion when she seemed particularly agitated I wrote her up for a minor tranquilizer – a benzodiazepine.
Finally after about 6 weeks she went on weekend leave with her parents, held her own, and did not come back. I was happy to file her case as diagnosis unknown. I heard she was doing well at college and was still dating the same boyfriend.
I saw her again a year later – 8½ months pregnant. She was clearly too unwell to be managed at home. But where she had been mute and inaccessible previously, now she was over-active, manipulative, and attention-seeking while still seeming confused; her actions did not seem fully under her own control. She looked as though she might go into labor at any moment, so I held off medication.
After the birth, I sent her to a hospital that had a mother and baby facility. The psychiatric team that took over her care there, I learned, thought she had schizophrenia. She was put on regular antipsychotics, but apparently was not making much progress and the baby was taken from her. Some months later, I heard she had been given weekend leave; one evening of that weekend, having told her parents she was going out for a walk, she laid her neck on the track in the face of an oncoming express train.
Looking back at Cora’s confusion, emotional lability, and switches between immobility and overactivity, I came to see that she had a textbook case of uncomplicated catatonia. Few readers of this blog will know what catatonia is, as it has supposedly vanished, even though 50 years ago up to 15% of patients in asylums were estimated to suffer from it, and it was one of the most horrifying mental illnesses, with a much greater fatality rate than any other disorder except General Paralysis of the Insane (tertiary syphilis). While mental health professionals are aware catatonia is listed in the DSM, few would spot a case if faced with it.
If Cora had a rare condition that doctors do not now need to recognize, if she was the exception that proves the rule of medical progress, she would have been unfortunate. But in fact up to 10% of patients going through mental health units in America and worldwide still have the features of catatonia – if they are looked for (Chalasani et al). Sometimes the only condition they have is catatonia; other times catatonic features complicate another disorder and resolving the catatonia may make it easier to clear whatever other problem is present. But almost no-one thinks of catatonia and so, like me, they miss the diagnosis. Cora was given antipsychotics, which are liable to make a catatonia worse. She died when a few days’ consistent treatment with a benzodiazepine would almost certainly have restored her to normal, making her death scandalous rather than accidental.
But the benzodiazepines are a group of drugs that are no longer on patent, and no company has thus any incentive to help doctors see what might be in front of their eyes when it comes to a disease like catatonia. Instead, all of the pharmaceutical exhortations are to attend to diseases for which on-patent drugs are designed, even if this means conjuring diseases out of thin air—disease mongering—such as fibromyalgia, to market on-patent medications such as Pfizer’s Lyrica, or restless legs syndrome, a disorder conjured up as a target for GlaxoSmithKline’s Requip (ropinirole).
Catatonia and other vanishing diseases are part of the “opportunity cost” of disease mongering, lost in the chatter about disorders that match up with on-patent drugs.
No one has any idea how many versions of Cora’s story play out in daily clinical practice — versions in which the diagnosis of a treatable disease goes unnoticed by doctors pleased with themselves for making a fashionable diagnosis like fibromyalgia and who, even in the face of treatment failure, will add ever more on-patent drugs to a patient’s treatment regimen rather than go back to the drawing board and look more closely at the patient in front of them. Once upon a time the height of medical art lay in being able to go back and look at cases afresh and match the profile of symptoms against less fashionable or apparently uncommon disorders – no longer.
Studies this week in BMJ and BMJ Open linked benzodiazepines to an increased risk of developing dementia and early death. For many the benzodiazepines like Valium remain much darker drugs than Prozac, Cymbalta, Pristiq and other drugs. The risks of getting diagnosed with dementia are quite likely to turn out to be much higher in those given an antidepressant than in those given benzodiazepines and the risks of suicide and premature death are certainly greater on antidepressants. The antidepressants are in many ways much darker drugs than the benzodiazepines. We need to find a way to bear this in mind while still holding on to the idea that for the right person either of these drug groups could be life-saving.
Cora’s story can be found in Pharmageddon which was written as a tribute to many who have died like her and especially to the people, mostly women, who have campaigned to make treatment safer for all of us.