Is Big Pharma Over-Selling Depression?

If you watch late-night television you’ve probably seen the ads for a new antidepressant drug called “Rexulti.”  It’s billed as a break-through cure for people who’ve already been treated for depression but are still experiencing its symptoms.   The manufacturer, Otsuka, is heavily promoting Rexulti just as it did its earlier controversial anti-depressant known as “Abilify.”

It’s all part of a new push by Big Pharma to sell “treatment-resistant” depression as a major new public health threat.

But there’s little real evidence that it is.

It turns out that Big Pharma has been sponsoring research on treatment-resistant depression for some time.  And despite only mixed supporting evidence from clinical trials, they’ve managed to foist new drugs on unsuspecting consumers that exhibit a host of side effects, some of them potentially dangerous.

Much of the current emphasis on treatment-resistant depression can be traced to a 2007 study which noted that some depression patients were failing to achieve “remission” after “two adequate trials of anti-depression therapy” – a period of about 6 weeks.

What was missing?  A 2012 study found that some patients being treated for depression still suffered from “functional impairment, poor quality of life, suicide ideation and attempts, self-injurious behavior, and a high relapse rate.”

At the time of these early studies, estimates of those suffering from “treatment-resistant” depression were fairly low — in the 10% range, but with speculation that it might be as high as 30%.  That seemed vaguely reassuring – after all, antidepressants on the market were working for most people, it seemed.

But it wasn’t long before physicians were reporting that as many as 70% of depression patients weren’t achieving “remission.”  Amazingly, despite a two decades push by Eli Lilly on Prozac, the new depression wonder drug wasn’t actually working for most people.

That might have – indeed, should have — given the medical establishment pause. They might have consulted a number of studies suggesting there were other non-pharmaceutical techniques — from talk therapy to brain massage and yes, more humane versions of EST — that might augment – or simply substitute for – the depression meds.

Instead, drug companies like Japan-based Otsuka seized upon the problems with Prozac and its competitors to start developing a brand new class of drugs.

From the beginning, this effort has been controversial.  For one thing, the new medications are considered “anti-psychotics,” not “antidepressants.”  While drugs like Prozac work on the brain’s neuro-transmitters, specifically its ability to transfer serotonin, the science behind the anti-psychotics turns out to be as cloudy as the disease it seeks to treat.

Rexulti – and its predecessor, Abilify, also produced by Otsuka – is supposed to treat conditions as diverse as depression, schizophrenia and bipolar disorder – in other words, close to the entire range of major mental disorders.  In theory, that’s good news.  Many depression sufferers do, in fact, have “co-occurring” mental illnesses, especially bipolar disorder, which features bouts of mania or hypomania – mood “highs” that alternate with depression’s “low”.

But Otsuka’s claims for Abilify have never been independently verified.  The company conducted a limited clinical trial, without the usual protocols, and went to the FDA seeking approval.  And for reasons that remain unknown, the FDA granted its approval.   Distribution and use of the new drug in the US market soon became widespread.  And the results proved disastrous.  Not only was Abilify not providing effective treatment for bipolar disorder, it was displacing other more established and effective drugs that did.

It should have been a major medical scandal, but it wasn’t.  To this day the FDA has never really explained how this might have occurred.  But it probably didn’t hurt that Otsuka had decided to partner with Bristol Meyer-Squibb, an American pharmaceutical giant with enormous lobbying influence, to promote its new product in the US market.  Apparently, the FDA, long accustomed to acceding to corporate lobbying influence from Big Pharma, simply looked the other way.

Still, there was considerable fall-out, mainly from physicians who refused to prescribe Abilify.  And that’s basically how Rexulti got on the market.  Otsuka, without accepting blame for the way it had foisted Abilify on consumers, set about creating a new and improved version of the drug, promising much the same results.

Is Rexulti working?  No one knows for sure, but skepticism is growing.  Last month, the FDA, in response to consumer complaints, released the results of its own agency testing on the drug. To no one’s surprise, the agency found Otsuka’s claim that Rexulti reduced depression in current sufferers by 62% “overstated.”  In the FDA’s three tests, the Rexulti reduced depression by at most

As is so often the case, the FDA waited three years to look into the matter, after taking Otsuka’s claims at face value and rubber-stamping its approval.  During that time, Otsuak ran its ads on late night TV almost every night, often 3-4 times an hour, hammering home the message that there is fresh relief for depression sufferers.

And amazingly, Otsuka’s ads weren’t shy about listing possible side effects –  everything from minor annoyances like nausea, constipation and a stuffy nose to “weight gain,” “distress,” “agitation” and “seizures.”  The ads described these side effects as “common.” And that’s not to mention the possibility of heart attacks and strokes, especially among the elderly or those with pre-existing conditions.

It’s a formidable list, and makes any sane person wonder:  Even if Rexulti works, is it really worth the risk?

Another issue is cost.  You can get a free sample of Rexulti, but advertisements don’t tell you that a monthly prescription could cost you anywhere from $600 to $1,000 dollars.  Right now, there’s no generic, so Otsuka and its collaborators are poised to rake in big profits from a drug that doesn’t even work as claimed – with debilitating side effects to boot.

For a company with such a dubious track record, this hardly seems like consumer protection at its best.

Science has come a long way in its understanding of brain chemistry and depression, but the medical establishment is reluctant to admit that it’s still fumbling around in the dark, experimenting with new drugs, just hoping their drugs will prove effective, while limiting the harm.

Depression is big business now.  Eli Lilly made billions off of Prozac during the early depression “boom” years of the 1990s – $1 billion in 2001 alone, a third of its profits that year. The Indiana-based pharmaceutical giant promised to make a debilitating disease treatable in new and more effective ways, and in fact, some of the stigma surrounding the disease did begin to subside.

But it’s also helped make Americans more pill-dependent than ever.  You won’t find pharmaceutical companies asking the tough questions about why depression persists – and whether other lifestyle conditions, from diet and exercise to substance abuse, work addiction and a loss of intimacy and community, are partly to blame.   Addressing the issue this way might open up a brand new discussion about the quality of American life and about the deeper changes needed to make ourselves feel truly happy and healthy.

Americans, it seems, want a quick fix for everything.  And the Squibbs and Otsukas of the world – and their powerful allies in Big Pharma – are here to make sure they get it, regardless of who they harm.

Stewart Lawrence is a long-time Washington, DC-based policy consultant.  He can be reached at