In an interview on Biotech Nation, Gary Cupit made an offhand remark about why so many drugs list headache as a possible side-effect: clinical trial participants are often asked to abstain from coffee during the trial. That also explains why those who receive placebo often complain of headache as well.
Cupit’s company Somnus Therapeutics makes a sleep medication for people who have no trouble going to sleep but do have trouble staying asleep. The medication has a timed-release so that it is active only in the middle of the night when needed. One of the criteria by which the drug is evaluated is whether there is a lingering effect the next morning. Obviously researchers would like to eliminate coffee consumption as a confounding variable. But this contributes to the litany of side-effects that announcers must mumble in television commercials.
Related: Adaptive clinical trial design
Kind of makes sense.
Great nugget! Just a thought: if both the placebo and test groups report the same side effect, wouldn’t they consider removing that side effect from the list of official ones?
I’m not a regulatory expert, but I think drug companies have to report every side effect someone experienced. However, they also report the placebo side effects. So I’ve seen where a drug insert will say something like 20% reported headache but 15% on placebo also reported headache.
Note that insomnia trial subjects are particularly likely to be asked to abstain from coffee! And any side effect seen in trials will end up on the final list, even if it is seen in placebo subjects.
Interesting piece of information, John. Thanks for mentioning it.
So why not solicit test subjects who are not caffeine addicts of any kind and, in that way, researchers can get a truer picture of the actual side effects of the drug?
Moya: Maybe, as Ellen Martin suggested, insomniacs are likely coffee drinkers.
Clinical trials are messy. Coffee is a minor complication. You’d like a homogeneous group to test, but the more homogeneous, the smaller the pool, and the harder to recruit enough subjects.
Moya, I second John’s comment. It’s hard enough to recruit subjects for clinical trials without eliminating the majority of Americans who drink coffee daily (50-80% according to various sources), not to mention tea or other caffeinated beverages.
But I think John misinterpreted my comment–it’s not that insomnia patients are more likely to consume caffeine (although that may well be true), but that concomitant caffeine consumption would mess up the PK measurements in studies of sleep drugs.
Ellen: I misunderstood your first comment, but I also agree with your clarification that caffeine particularly like to mess up the analysis of tests of sleep drugs.
Bit weird: if all due to caffeine withdrawal, they’ll rarely find a significant difference in headache reports between placebo and treatment group… How do they measure that – would also be interesting.
Is there a policy of listing side-effects also found in the placebo group, just in case? Or did this quote come from someone who doesn’t understand experimental designs?
This makes no sense in general. Real people take coffee. Asking people to behave differently throws the realism of the test out.
Regarding drug testing, especially large scale tests for generics, I wonder how good the data actually are. Study participants are compensated, but only as long as they are in the study. Adverse events like passing out lead to one being removed from the study due to health and safety concerns. So there is considerable incentive for the participants to hide or minimize such adverse side effects.
I had a friend who lived in Austin, Texas. At that time he was working as a bar back and also looking to earn extra money as a drug trial participant. He went to the recruiting station but the drug they were recruiting for that day was for lowering serum cholesterol (probably a statin) and he had low serum cholesterol, so he was excluded. The recruiter suggested he go eat some pizza and cheeseburgers and come back.
Another place where caffeine withdrawal is a problem is in hospitals. I’ve heard anecdotal reports that heavy coffee drinkers coming out of anesthesia after surgery often have horrible headaches from caffeine withdrawal. Also, during the observation period at mental hospitals to assess mental health they don’t allow caffeine, which can make it miserable.
I wonder how receptive the medical personnel would be to a request that they add caffeine to one’s IV some time before the anesthetic wears off?
As a couple of side notes about medical uses of caffeine, Spalding Gray said that on a trip to the USSR he had been tipped off to bring his own coffee. Sure enough, the only coffee available was decaffeinated — all of the caffeine had been extracted for medical use.
Also, my daughter was born prematurely and stayed in the NICU for a while. One issue was keeping her heart rate up, but without interfering with her sleep. The prescribed medicine was oral caffeine, which would stimulate her heart without interfereing with REM sleep like other heart stimulating drugs did. At first she got oral theobromine, because the caffeine was out of stock. After she came home I had to go to a specialty pharmacy to fill her prescription, although I can’t think of any drug which is more widely available albeit in different forms. Talk about a miracle drug!
“I’ve heard anecdotal reports that heavy coffee drinkers coming out of anesthesia after surgery often have horrible headaches from caffeine withdrawal. … I wonder how receptive the medical personnel would be to a request that they add caffeine to one’s IV some time before the anesthetic wears off?”
Before my double surgery back in 1995, I told both my docs: “A study has found that the post-surgery headache, usually attributed to an aftereffect of the anesthesia, only occurs in coffee addicts. I am a coffee addict. Unless y’all have a darned good reason why I shouldn’t, I’m going to have a friend bring me my morning coffee later in the morning after surgery.” They had no objections. She brought my coffee. I had no post-surgery headache!
I’ve even seen “headache” listed as a common side effect for a drug that had *fewer* reported headaches in the treatment group cf. placebo.
The family statistician tells me that the pharmaceutical business can be rather too dishonest for comfort. He wonders if publishing this sort of trivial side-effect is done to bury more serious issues. Or if it is intended to lend verisimilitude to an otherwise bald and unconvincing narrative–“I get a headache, it must be doing something.”
When an insomnia drug is released, it will be prescribed for patients who will probably also be instructed to avoid caffeine as part of their treatment regime. Thus headache is to be expected, even if not as a result of the medication.
Subjects are also often required to refrain from food and drink, except water, for at least 8 (often 12) hours prior to blood draws on one or more occasions during a trial. Fasting may bring on headaches for reasons unrelated to caffeine withdrawal, eg, low blood sugar or dehydration.