Yesterday, the National Institute for Health and Care Excellence (NICE) announced that Spravato (esketamine) not be recommended for use because of uncertainties over its clinical and cost-effectiveness.
The media picked up on this and many, initially including myself, were happy that such a strong message had been sent out by NICE.
However, there's a big clue in the words 'not recommended'.
Spravato is a nasal spray and according to Janssen, a subsidiary of Johnson & Johnson, the company that market and manufacture it, is indicated for treatment-resistant major depressive disorder in adults.
Treatment-resistant depression, for those who don't know, means, if you've been treated for depression but your symptoms haven't improved, you may have treatment-resistant depression. Big clue in the word 'may'.
In a nutshell, those patients who have been taking antidepressant-type medication, including antipsychotics, to treat their depression may not have needed them in the first place because, it appears, we are now being told that this type of medication has no effect on certain groups of people. Nobody knows who those 'people' are or why antidepressants don't work for them. Pretty much in the same way nobody knows why they work for some people.
One would have thought that investigative research into this was paramount but instead we have a new label, 'treatment-resistant depression' and, wonder of wonders, a new drug that can help this group.
It makes me wonder why a person who takes a product becomes the fault of that product. If I purchased a box of matches and they didn't light when struck, would I be labelled as having some sort of disorder?
I first became aware of ketamine to treat depression back in 2013 when I learned of one of the most bizarre studies I'd ever read. I've read many more bizarre studies since then but this one piqued my interest.
The 2011 study was carried out by Gregory Larkin and Annette Beautrais, the conclusion of which found that the intervention of administering the horse tranquillizer, Ketamine, to patients suffering from depression or displaying suicidal tendencies is "likely to be effective and appropriate for only some subgroups of the depressed and suicidal emergency department population."
The study, carried out on 15 patients, ran over a period of just 10 days and saw patients given a single dose of Ketamine [dose depending on weight] and then monitored over a period of four hours whereby they were given a set of questions using the Montgomery–Åsberg Depression Rating Scale [MADRS]. These ratings were obtained at baseline, and at 40, 80, 120 and 240-minute intervals. Patients were then contacted over a period of 10 days.
There was no control group in this study.
In essence, it appears that the study only lasted 4 hours and the follow-up [10 days] was presumably to follow-up on the 15 patients to see how they were coping [ie; side effects, if depression or suicidal thoughts had returned]
Back in 2013, I laughed off the study, I mean who in their right mind would prescribe a party drug to depressed and suicidal people? It will never take off, I thought.
How wrong was I?
March 5, 2019
Some 8 years after the bizarre study carried out by Larkin and Beautrais, the FDA announced that it was approving Spravato for treatment-resistant depression. Their blurb read:
The U.S. Food and Drug Administration today approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression).The approval came despite mixed results in the esketamine clinical trials. Esketamine improved depression in two late-stage studies compared with placebo. But the drug fared no better than placebo in two others. I'd say that was a 50/50 benefit/risk type of drug, wouldn't you?
Moreover, the FDA seemingly glossed over the adverse events in the clinical trials. Three patients who received the drug died by suicide during clinical trials, compared with none in the control group. This, to me at least, makes the drug more of a 40/60 benefit-risk type of drug.
Two months after FDA approval, the European Medicines Agency (EMA) recommended that it be approved in Europe too. This recommendation was sealed on December 19,2019 when Janssen announced that the European Commission (EC) had approved Spravato nasal spray, in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI), for adults living with treatment-resistant major depressive disorder.
28 January 2020
The NICE website runs with the headline, "Nasal spray medicine for treatment-resistant depression not recommended by NICE"
The statement, if one reads between the lines, seems more about the cost of Spravato more than the concerns about its efficacy and safety. However, one line from the statement is striking. It reads, "...there is uncertainty about the effect of stopping esketamine treatment."
So, what does Janssen make of all this? Well, pulling statements from various media articles it appears they're not happy.
Here's what Janssen-Cilag executive Jennifer Lee had to say:
“...current NICE technology appraisal processes are not fit for purpose in terms of evaluating innovative technologies for complex mental health conditions.”Ouch!
What's complex about someone not benefitting from antidepressant treatment?
It's here we learn that Janssen are now widening their net. They have now applied for an addition to the label stating that Spravato be used for people with major depression considered to be a suicide risk, based on its rapid onset. (Refer back to Larkin & Beautrais)
The publication of the NICE draft guidance kicks off a consultation period until 18 February 2020, with a second appraisal committee meeting expected in March or April to consider the comments received.
In the meantime, Janssen executives will be liaising with NICE officials, no doubt to tell them how wonderful Spravato is and to ignore the three suicides in the clinical trials. Who knows, they may even offer Spravato to the UK along with a subsidizing plan, given that the NICE draft seems to be more focused on its cost than the safety of the patients who take it.
One thing though, if NICE does a U-Turn then they will have to show the public the evidence that suggests the effect of stopping esketamine treatment isn't an issue. Given the shortness of these clinical trials I suspect they will approve it with the caveat, "Patients must be monitored, particularly during withdrawal of esketamine."
Russian Roulette, folks!
Or am I just an old cynic?
Bob Fiddaman
Related
Suicide Prevention and Ketamine - Larkin & Beautrais
No comments: