If you were among the 12.6 million viewers who tuned in for the Nov. 1 episode of CBS's "The Big Bang Theory," you may have noticed a brief commercial that aired at about the midway point. Featuring a determined-looking middle-aged woman who hops out of a cab that's been stymied by afternoon Brooklyn traffic, the 15-second spot is for Eli Lilly's new cancer drug, Verzenio.

Within the context of the episode's rapid-fire jokes about Amish barn-raisings, toddlers wearing soiled diapers on their heads and the perils of academic grant allocations, the Verzenio ad is somewhat jarring. "Metastatic breast cancer is trying to stop me—but not today," the actress intones as she rushes to collect her granddaughter from school. The short spot ends with a call to action, prompting interested viewers to seek out additional information about the drug at TreatMBC.com, which redirects to Lilly's Verzenio page.

Verzenio is hardly an outlier. Among the pharmaceutical products that have bought time this season in TV's most-watched comedy are the rheumatoid arthritis drugs Enbrel and Xeljanz; Lyrica, a remedy prescribed for the treatment of neuropathy; and Trulicity, a once-weekly dose designed to combat type 2 diabetes.

When no one was looking, sitcoms became repositories for some of the most dire and depressing pharma ads imaginable, and the opportunity to chuckle along at the multi-cam antics of your favorite comedy stars has been complicated by some some real dark-night-of-the-soul advertising. Pharma ads have become so prevalent in broadcast comedies that sitting down to watch "The Big Bang Theory" on a Thursday night is like rifling through your eldest neighbor's medicine cabinet in search of giggle pills, only to be confronted by the Reaper with the 1,000-mg stare. The journey from laugh track to lymphoma often takes mere seconds.

No laughing matter

According to iSpot.tv estimates, pharma accounted for 12 percent of the 2017-18 "Big Bang" ad spend, with treatments for diabetes/blood disorders, stroke/cholesterol/heart disease and psoriasis leading the pack. Through the first seven episodes of this season, pharma buys have added up to nearly $4 million, or about 17 percent of the show's current take.

Among the other network comedies cleaning up on drug dollars: CBS's reboot of "Murphy Brown," which has accommodated ads for products used to treat osteoporosis, COPD, cancer, psoriasis, stroke and heart disease, has generated 24 percent of its ad revenue from pharma, while "Big Bang" spinoff/prequel "Young Sheldon" can thank drug companies for approximately 13 percent of its overall ad sales haul.

Which is not to suggest that CBS has cornered the market on drug-fueled comedy. ABC's "The Conners," a show that launched with the off-screen death of the family matriarch (Roseanne overdoses on prescription opioids), sees 12 percent of its ad sales revenue channeled through pharma brands, while 11 percent of the ad load in Fox's "Last Man Standing" is derived from drug spend. Hipper, less-trafficked sitcoms like NBC's "The Good Place" are far less reliant on pharma bucks; per iSpot data, a mere 4 percent of the ensemble comedy's sales are linked to potions and palliatives.

If presenting sitcom viewers with commercial messages freighted with bodily decrepitude, disease, death and anxieties of all stripes appears wildly counterintuitive, there is a method to this pharmaceutical madness. For starters, these sort of buys make perfect sense from a demographics standpoint; given that so many of the meds advertised are used to treat maladies that tend to visit older Americans, what better place to advertise than in a show with an audience that skews likewise? Per Nielsen, the median age of "Big Bang" viewers is currently 59.3 years old, while the "Murphy Brown" crowd is grayer still (61.5 years). Fish where the fish are.

Everybody hurts

But the logic informing the proliferation of drug spots in network comedy goes far beyond mere demo targeting. According to a recent Kantar Media study, pharma brands who buy time in "Big Bang" seem to have a particularly firm grasp on the show's fanbase, and that understanding has made for smarter marketing investments.

In studying the back half of Season 11 of "Big Bang," Kantar discovered that the show's viewers were 44 percent more likely to suffer from arthritis than the general public, which jibes nicely with the program's client roster. Per Kantar, arthritis medication accounted for 23 percent of the $22.5 million in total pharma advertising allocated to "Big Bang" during the period. In terms of categorical spend, that 23 percent share makes arthritis drugs the show's primary pharma segment, topping pain relievers/central nervous system medications (16 percent), dermatological cure-alls (11 percent) and coronary disease remedies (11 percent).

Among the arthritis medications that have bought time in "Big Bang" this season are Amgen's Enbrel, Pfizer's Xeljanz and Lilly's Taltz. Given how the show's fan base over-indexes on arthritic diagnoses and the sheer size of the audience—"Big Bang's" average draw of 4.22 million adults 25-54 per episode is greater than the overall viewership totals for 39 other broadcast series—these brands are securing time in an environment that resonates with the people who may be most in need of their products.

A similar dynamic can be found among diabetic "Big Bang" enthusiasts. According to Kantar, fans of the Nerd Herd are 34 percent more likely to suffer from the kind of neuropathy associated with diabetes, which suggests that the audience may be especially receptive to commercials for big spenders like Pfizer's Lyrica, which is used to mitigate diabetic nerve pain. Per Kantar, Lyrica last season accounted for 16 percent of the "Big Bang" pharma spend. In terms of individual brand investment in the show, Lyrica was the second biggest spender behind only Subaru, according to iSpot data.

Through a glass, darkly

Among the pharma categories that may want to reconsider their current targeting strategy are antidepressants and sedatives. Much like the high-strung characters themselves, viewers of "Big Bang" are 31 percent more likely to suffer from social anxiety, and yet not a single ad for a selective serotonin re-uptake inhibitor or benzodiazepine has appeared in the show since the season began. (In the latter half of last season, antidepressants accounted for 9 percent of all "Big Bang" pharma buys.)

If mood disorders, diabetic nerve pain and rheumatoid arthritis are nothing to chortle at, at least some of the minor complaints reported by many "Big Bang" watchers seem to match the comedic tone of the series. For example, Kantar's research suggests that the show's audience is 38 percent more likely to suffer from an overactive bladder, which aligns nicely with the show's obsession with urine. A Google search for "Big Bang Theory" + "pee" turns up no fewer than 922,000 results, many of which involve a character's overwhelming need to micturate. (In one episode from way back in Season 5, the character Howard—who also happens to suffer from transient idiopathic arrhythmia—complains that he is dehydrated after a recent adventure in the wilderness. "My pee is like toothpaste," he says, to the howls of the studio audience.)

The little metatextual riffs are everywhere if you know what to look for. In that regard, Michele Deutschman, VP of strategic partnerships and business development at Kantar Media notes, points to one ailment in particular: "Viewers are 40 percent more likely to have been diagnosed with 'Low T,'" she says, referring in shorthand to low testosterone, a disorder that can lead to reduced energy levels and a lowering of the sex drive. "So not only do they have a lot in common with Sheldon, Howard and Raj, but they may be predisposed to pay more attention to commercials for drugs in that category."

Unfortunately for manufacturers of androgens and other treatments designed to boost flagging testosterone levels, they've long been shut out of the sort of marketing opportunity inherent in buying time in "Big Bang." Manufacturers for testosterone therapy drugs effectively vanished from broadcast prime back in 2014, when the U.S. Food and Drug Administration responded to a boom in the off-label use of Low T drugs by warning that their use led to a possible increased risk of heart attack or stroke. Brands like AndroGel, which in 2013 had spent $67.9 million on direct-to-consumer ads, thereupon suspended their buys and have not spent a dime on TV inventory since.

This is your TV on drugs

Not that the networks seem to miss the testosterone cash. According to Kantar, direct-to-consumer pharma spend on TV jumped 11 percent in the first half of the year to $2.29 billion. TV took in 73 percent of all DTC dollars from Jan. 1 through June 30, while magazines (17 percent) and digital (7 percent) lagged far behind. Of those TV dollars, 55 percent, or around $1.26 billion, were spent on broadcast inventory, while cable accounted for a quarter ($572 million) and syndication 18 percent ($411.8 million).

Per Kantar, Pfizer was by far the top-spending DTC advertiser in the first half of the year, as the manufacturer of Lyrica, Eliquis, Chantix, Eucrisa and other highly marketable compounds invested $489 million in TV time. Runner-up AbbVie plunked down $199.3 million for its TV inventory, much of it devoted to its arthritis medication Humira and a non-specific endometriosis campaign meant to pave the way for its newly-approved Orilissa, while Lilly put up $186 million in DTC spots.

DTC ads boast a significant efficiency rate, which is one of the reasons you're seeing so many pharma ads in primetime. (According to Kantar, no category in the last five years has boosted its TV spend more than pharma.) Speaking last month in Jersey City at the DTC Forum on TV and Print, Deutschman noted that 39 percent of viewers who had watched a televised pharma spot had taken some kind of action as a result of that exposure. By way of comparison, the click-through rate on banner ads is less than 1 percent. Direct mail campaigns on average scratch out a 2 percent response rate.

While Deutschman hasn't advanced a theory as to why pharma spots (no matter how dire the affliction) seem to perform well in the context of network comedy, the Kantar data would seem to indicate that the drug manufacturers find an unequivocal value in the genre. In the first half of the year, pharma spend in broadcast sitcoms added up to $102.5 million, making comedy the fourth most popular programming environment behind news ($325.6 million), drama ($215.1 million) and reality ($113.2 million). Drugs to combat heart disease, regulate blood pressure and cholesterol and treat arthritis were the biggest buyers of comedy, with spending on blood and bone treatments adding up to just under $30 million.

Curiously, one pharma category that hasn't really staked out a serious comedy claim is antidepressants, as happy pills in the first six months of 2018 accounted for just 9 percent of drug spend in network sitcoms. Then again, if laughter truly is the best medicine, perhaps an SSRI spot in a comedic environment is simply redundant.