How Everyone Became Depressed

The rise and fall of the nervous breakdown

Benzo Hysteria

The chilling effects of the "addictive" label

This piece began in response to a comment on my May 28 post and is co-written with Susan Bélanger, a member of the History of Medicine Program of the University of Toronto

A reader questioned our comments on the disappearance of the benzodiazepines, given that this drug class still accounts for 3 of the top 10 most commonly prescribed psychiatric medications in the U.S.

OK, here’s the story:

To be sure, Xanax (alprazolam) remains in 1st place with 47.8 million prescriptions, a position it has held since 1988 (Shorter, 2008). Part of its continued strength is attributable to Upjohn’s aggressive marketing campaign for its use in panic disorder, though it is likely that the benzos as a whole are effective for this indication. Also in the top 10 are Ativan (lorazepam), ranked 4th, and Valium (diazepam), ranked 9th.

So it’s true that benzodiazepines are still commonly prescribed, but mainly by family physicians and internists, who use them for a variety of indications. Data on differential prescribing practices by specialty are difficult to come by, yet the few available reports suggest that “psychiatric medications” are being increasingly prescribed by non-psychiatrists.

According to the National Center for Health Statistics (2004), as of 1999/2000, 31.5% of all antianxiety agents were prescribed by specialists, 47.5% by primary-care physicians. The comparative figures for all antidepressants were virtually the same: 43.2% vs. 42.2%.

Here’s another piece of evidence: There are increasing differences in prescribing patterns. In 2006–7, less than a quarter of all U.S. psychotropic prescriptions (23%) were written by psychiatrists. When broken down by drug class, psychiatrists prescribed only 13% of antianxiety agents and only 21% of antidepressants. Psychiatrists’ focus in prescribing has clearly shifted toward mood stabilizers (66%), antipsychotics (49%), and “stimulants” for the treatment of ADHD (34%). Primary-care physicians were responsible for nearly two-thirds (65%) of all anxiolytics, as well as 62% of the antidepressants (Mark et al, 2009). Mark, using 2005 survey data, found that nearly a third of antianxiety drugs (32.3%) were prescribed for non-psychiatric or unspecified conditions, including medical procedures, allergic reactions, and musculoskeletal complaints (Mark, 2010). Among psychiatrists, the move away from benzodiazepines has been very sharp, and the psychopharm listservs are filled with cautionary remarks about their use (“I can’t believe you’re still prescribing benzos!”)

Now, here’s the big news: the prescribing of benzos as a whole has diminished greatly since the heyday of the 1970s. This drug class was the biggest success story in pharmaceutical history before the arrival of the SSRIs. Benzodiazepines were used effectively across the “nervous” spectrum and beyond in the treatment of (non-melancholic) depression and a wide variety of somatic complaints as well as for anxiety.

Librium (chlordiazepoxide), introduced by Hoffmann-LaRoche in March 1960, became an immediate blockbuster, taken by more than 15 million Americans by 1966. Roche’s Valium (diazepam), launched in 1963, was an even bigger hit; between 1964 and 1972, the number of prescriptions written annually swelled from 4 million to over 50 million. In May 1974, a front-page story in the New York Times cited Valium as “the No. 1 prescribed drug in the United States and perhaps the world.” In the previous year it had been taken at one time or another by 10% of Americans aged 18 and over. 1974 represented the high-water mark for Valium, with sales of almost 3 billion tablets. Thereafter the benzodiazepine market became more diversified with the arrival of a host of new compounds including Wyeth’s Ativan (lorazepam) in 1977 and Upjohn’s Xanax (alprazolam) in 1981. By the early 1990s there were over a hundred different benzos on world markets. (Shorter, 2008)

Global manufacture and consumption of diazepam and other benzodiazepines continued to rise in the 1990s and beyond, giving rise to the statistics that our anonymous critic cited.

But the main point is that in the U.S. and Britain this drug class became demonized as addictive. In 1975 the US Department of Justice placed Librium and Valium on schedule IV of its list of controlled substances. Being listed as potential drugs of abuse had a chilling effect on prescribing. In New York State a further drop in use followed the 1989 imposition of restrictive triplicate prescription regulations which mandated state monitoring. A 1991 study reported in JAMA that these regulations led to a 44% decrease in benzodiazepine prescribing between 1987 and 1990 – but also an increase in the use of “less acceptable medications” (barbiturates and other traditional tranquilizers) – as well as the emerging, “more expensive” antidepressants buspirone and Prozac.

The anti-benzo backlash was particularly strong in the U.K. Prescribing there peaked in 1979, with 31 million prescriptions, then began a steady decline in response to government warnings. In 1988, the Committee on Safety of Medicines warned of withdrawal symptoms and dependence “following therapeutic doses given for SHORT periods of time” (its emphasis) and recommended limiting their use for a maximum of 2-4 weeks for “disabling” anxiety or insomnia. These restrictions remain in effect, forcing British doctors to “write fraudulent prescriptions” in order to adequately treat catatonia patients. (Healy, 2013)

After the late 1980s, the initial decline of this useful drug class was completed with the rise of the SSRIs and the shift of psychiatry from anxiety to depression. By the year 2000, so-called “antidepressants” had overtaken all other drug classes not only in psychiatry but in all of medicine. With the exception of nonsteroidal anti-inflammatory analgesics (NSAIDs), antidepressants were prescribed more often than any other drug class. In part industry achieved this by hyping their products as “non-addictive” and free of the troublesome sideeffects of the classic antidepressants.

These tactics worked. Prozac (fluoxetine) hit the market in December 1987, and in 1989 had sales of $350 million, more than had been spent on all antidepressants two years earlier. By 1991, Prozac had been launched in 26 countries and under its influence the world market for psychotropics had more than doubled, from $2 billion in 1986 to $4.4 billion in 1991. A decade later, the new drugs had taken over. In 2001, SSRIs and other second-generation antidepressants had swept the market, accounting for 3 of the top 10 drugs on the American market were SSRIs: Zoloft (sertraline), ranked 6th; Paxil (paroxetine), 7th; and Prozac 9th.. The traditional (and more effective) tricyclics, meanwhile, had shrunk to a tiny 1.2% market share. (Shorter, 2008).

The epidemic anxiety of the 1960s and 70s has now been replaced by an epidemic of depression. According to U.S. government figures, prescriptions for the Prozac-style antidepressants rose from 80 million in 1996 to 192 million a decade later. Between 2005 and 2008, 11% of all Americans over the age of 12 took an antidepressant. More than one in ten! And 25% of women between 40 and 59 did so. (Shorter, 2013)

Whew! Sue and I didn’t think we’d have to write so much. But these changes are of huge importance. The benzos are among the safest and most effective drug classes in the history of psychopharmacology; the SSRI “antidepressants,” a less effective drug class, elbowed them off the roller rink. This is worth knowing.

References

Burt CW, Schappert SM (2004). “Ambulatory Care Visits to Physician Offices, Hospital Outpatient Departments, and Emergency Departments, 1999–2000,” National Center for Health Statistics, Vital and Health Stat 13(157) , table 20, http://www.cdc.gov/nchs/data/series/sr_13/sr13_157.pdf

Committee on Safety of Medicines (1988). Benzodiazepines, Dependence and Withdrawal Symptoms. Current Problems no.21(Jan. 1988),1–2.

Grohol J. (2012), “Top 25 Psychiatric Medication Prescriptions for 2011” PsychCentral, http://psychcentral.com/lib/2012/top-25-psychiatric -medication-prescriptions-for-2012/

Healy D (2013). Catatonia from Kahlbaum to DSM-5. Aust NZ J Psychiatry 47 (5), 412-416, doi: 10.1177/0004867413486584.

Mark, TL etl al. (2009).“Psychotropic Drug Prescriptions by Medical Specialty,” Psychiatric Services 60 (9), 1167, http://ps.psychiatryonline.org/article.aspx?articleid=100738.

Mark TL (2010). “For what diagnoses are psychotropic medications being prescribed?,” CNS Drugs 24 (4), 319–326, http://link.springer.com/article/10.2165/11533120-000000000-00000.

Shorter E (2008). Before Prozac: The Troubled History of Mood Disorders in Psychiatry. (Oxford: Oxford University Press.

Shorter E (2013). How Everyone Became Depressed: The Rise and Fall of the Nervous Breakdown. Oxford: Oxford University Press.

Weintraub M et al (1991). Consequences of the 1989 New York State Triplicate Benzodiazepine Prescription Regulations. J Am Med Assoc 266 (17), 2392-2397.

Edward Shorter, Ph.D., is the Jason A. Hannah Professor in the History of Medicine at the University of Toronto.

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