Drugs have been used to treat ailments and injuries for thousands of years, as ancient peoples used herbal remedies and plants to care for a variety of conditions and issues. Today, the pharmaceutical business is a multibillion dollar global industry. New and innovative treatments and medications are developed, manufactured, marketed, and distributed around the world on a regular basis.

Prescription drug spending was over $450 billion in 2015 in the United States, and the nation has the highest rate of per capita drug spending in the world.[1], [2] Major pharmaceutical companies reap big profits, and “Big Pharma,” as these industry giants are often collectively called, has been accused of focusing more on profits than on the medical needs of patients and actual healthcare advances. Lawsuits and even criminal charges pepper the industry.

That being said, society as a whole has come a long way from chewing on tree bark for pain relief, and a large part of the advances in healthcare have come out of the research and development of new drugs through the years. The healthcare and pharmaceutical industry serve to improve the overall quality of life of millions of people around the globe by providing vaccines, therapies, treatments, and medications for a wide range of medical conditions, issues, diseases, disorders, and more.

Roots of Pharmacology

Up until the late 18th century, herbal remedies and medicines were used because they were known to be effective; however, medical practitioners largely did not know how or why they worked. In the 1780s, William Withering isolated the active ingredient in the flowering foxglove plant digitalis and was able to formulate more exact dosage recommendations, with fewer negative side effects, for the treatment of cardiac failure.[3] Withering was one of the first people to research and then isolate an active ingredient from an herbal remedy.

In 1796, Edward Jenner discovered and implemented the first vaccine, which protected people from catching the disease smallpox.[4] In 1842, Dr. Crawford Williamson Long first used ether as a general anesthetic for a surgical procedure. In 1846, dentist William T.G. Morton was the first to use it as an inhalation anesthetic, which is generally considered the beginning of the modern anesthesiology practice.[5]

The pharmacology industry continued to slowly inch along over the following century. Oswald Schmiedeberg is generally considered the father of modern pharmacology as he studied the chemical properties of chloral hydrate and chloroform, and in 1878, he published the text, Outline of Pharmacology.[6]

In 1828, Friedrich Wohler was able to produce an organic chemical (urea, a component of urine) from the inorganic compound ammonium cyanate, thus beginning the evolution of modern organic chemistry.[7] Another major contributor to the beginnings of American pharmacology was the isolation and purification of the active chemical naturally occurring in the adrenal medulla region of the brain, which John Jacob Abel named “epinephrin” (the “e” was added later) in 1897.[8] These influential scientific discoveries are considered to have laid the foundation for the pharmaceutical industry, which really began at the end of the 19th century.

Prior to the beginning of the pharmaceutical industry, pharmacists would often manufacture their own medications, and often, medicines were distributed directly from physicians without a prescription. Companies such as Merck, Eli Lilly, and Roche supplied and distributed natural products like strychnine, morphine, and quinine. These companies began undertaking larger scale operations in the mid-19th century. The dyestuff and chemical companies Bayer, Sandoz, and Pfizer began researching medical applications for their products in newly created research labs.[9]

One of the earliest and most influential medications to be synthesized was aspirin in 1897 by Dr. Felix Hoffman, a scientist for Bayer.[10] The active ingredient in aspirin is acetylsalicylic acid, a synthetic form of salicylic acid. Way back in the 5th century, Hippocrates (widely considered the father of modern medicine) was using the bark from the willow tree, which contained salicylic acid, to treat pain and fevers.[11] Aspirin was registered as a trademark in 1899 and became one of the first medicines to be marketed as a tablet. By 1915, it was available without a prescription and quickly became a bestselling drug in the United States.[12] Aspirin is still widely sold and used, and it has many applications today.

Evolution of the Pharmaceutical Industry

Another boon for modern medicine was the introduction of antibiotics, which began with the discovery of penicillin in 1928 by Alexander Fleming. Penicillin has been heralded as one of the biggest advances in therapeutic medicine, as it began the era of antibiotics that brought with it effective treatments for all kinds of bacterial infections that previously had no cure.[13] During World War II, the demand for medications, including penicillin, rose dramatically. Several pharmaceutical companies – including Abbot Laboratories; Merck & Co., Inc.; Lederle Laboratories (now Pfizer, Inc.); Chas. Pfizer & Co., Inc. (now Pfizer, Inc.); and E.R. Squibb & Sons (now Bristol Myers-Squibb Company) – began working on largescale production of the drug.[14]

Insulin was another medical breakthrough around the same time. In 1922, it was discovered and developed to treat high blood glucose levels that accompany diabetes. Frederick Banting, Charles Best, and John Macleod are credited with the discovery and initial human trials for insulin, winning them the Nobel Prize in 1923.[15]

Post-World War II brought many breakthroughs and advances in the pharmacology field. Between 1950 and the 1990s, new analgesics and antibiotics were developed. Novel classes of medications were discovered and manufactured, including oral contraceptives, ACE inhibitors, beta blockers, benzodiazepines, and completely new forms of anti-cancer treatments.[16] The 21st century brings with it even more new scientific and medical developments and discoveries into the global and national pharmaceutical market as technology and biopharmaceuticals advance.

Some notable pharmaceutical achievements include:

  • 1948: Sidney Farber discovers that aminopterin, a folic acid antagonist and chemotherapeutic agent, works to induce remission in children suffering from acute lymphocytic leukemia (ALL).[17] Aminopterin was briefly marketed by Lederle in the early 1950s only to be surpassed by methotrexate (MTX), marketed by Dava Pharmaceuticals, which had fewer toxic side effects. Today, MTX is used for other purposes as well. It is the most popular drug in the world for the treatment of rheumatoid arthritis (RA).[18]
  • 1950s: A freeze-dried and heat-stable version of the smallpox vaccine is developed. In the 1960s, American Home Products (which later became Wyeth) marketed Dryvax (vaccina) in the United States, paving the way for a future of vaccinations.[19]
  • 1952: Chlorpromazine, the first antipsychotic medication, is introduced into the French market by Rhone-Poulenc for the treatment of schizophrenia, starting a new trend in the treatment of mental health disorders and neuropharmacology.[20] Smith Kline & French (now GlaxoSmithKline) market chlorpromazine as Thorazine beginning in 1954.
  • 1955: Dr. Jonas Salk creates and gets the first polio vaccine – inoculated polio virus (IPV) – licensed for commercial use.[21]
  • 1955: McNeil Laboratories introduces Tylenol (acetaminophen) Elixir for children, the first alternative pain reliever to aspirin. A few years later, Johnson & Johnson acquires McNeil Laboratories and the rights to Tylenol. The brand was expanded and made available without a prescription beginning in 1960. By 1976, the Tylenol brand became the bestselling OTC analgesic in the United States.[22]
  • 1958: Fluothane (halothane) becomes the first volatile antithetic that is nonflammable (unlike ether). It rapidly becomes the most popular anesthetic agent in America.[23]
  • 1961: The Boots Group in the UK develops the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen, which is marketed by Wyeth Whitehall Laboratories, which later merged with Pfizer, as Advil beginning in 1974.[24] In 1983, ibuprofen was approved for OTC status, and by 1985, over 100 million people in more than 100 countries had been treated with the drug.[25] Wyeth opened the first automated manufacturing process for Advil in 1987 to keep up with growing demand.
  • 1977: The first “blockbuster” drug is introduced – Tagamet (cimetidine) – by Smith Kline & French (now GlaxoSmithKline or GSK). Tagamet is a medication for ulcers that made over $1 billion in the first decade it was manufactured.[26]
  • 1982: The first biosynthetic form of human insulin, Humulin, becomes commercially available, marketed by Eli Lilly.[27] This is the first recombinant DNA drug on the market, and it really opens up the door for biologic pharmaceuticals.
  • 1987: The first selective serotonin reuptake inhibitor (SSRI), Prozac (fluoxetine), is introduced by Eli Lilly, and it becomes a breakthrough drug for depression.[28]
  • 1987: The first statin drug, which lowers “bad” cholesterol (LDL) to prevent stroke and heart attacks, lovastatin (Mevacor) is FDA-approved and marketed by Merck.[29] A semisynthetic statin, simvastatin (Zocor) is marketed by Merck in 1991. The cholesterol-lowering medication Lipitor (atorvastatin) is developed by Warner-Lambert and marketed in partnership with Pfizer in 1997. It becomes the world’s bestselling drug for the next 15 years, making over $125 billion in sales and at one point netting $12 billion a year.[30], [31] Many other statins, cholesterol-lowering drugs, have had market success, including Crestor (rosuvastatin) by AstraZeneca, which was FDA-approved in 2003.
  • 1989: Astra (now AstraZeneca) releases the first proton pump inhibitor (PPI) Prilosec (omeprazole) for the treatment of stomach acid and ulcers.[32]
  • 1990: The first atypical antipsychotic medication is FDA-approved to treat schizophrenia in the US: Clozaril (clozapine) marketed by Sandoz.[33] Second-generation antipsychotics had fewer extrapyramidal symptoms (EPS). After Clozaril came Risperdal (risperidone) from the Janssen Pharmacuetica division of Johnson & Johnson in 1993; Zyprexa (olanzapine) by Eli Lilly in 1996; Seroquel (quetiapine) by AstraZeneca in 1997; Geodon (ziprasidone) by Pfizer in 2001; and finally, Abilify (aripiprazole) in a joint measure between Osaka America and Bristol Meyers-Squibb in 2002. Prescriptions for these atypical antipsychotic medications tripled between 1995 and 2008, making them some of the most lucrative pharmaceuticals on the market.[34]
  • 1995: Hoffman-La Roche introduces the first protease inhibitor for the treatment of HIV/AIDS, saquinavir (Invirase).[35] Saquinavir was closely followed by ritonavir (Norvir) by AbbVie and indinavir (Crixivan) by Merck, both in 1996.
  • 1997: The blood-thinning drug to treat acute coronary syndrome (ACS), Plavix (clopidogrel), is developed and marketed through a partnership between Bristol Meyers-Squibb and Sanofi-Aventis to become the second-highest grossing prescription medication in America, with annual revenues of $9 billion at its peak.[36]
  • 1997: Genentech and IDEC Pharmaceuticals (now Biogen Idec, Inc.) get approval for Rituxan (rituximab), a biologic for the treatment of non-Hodgkin’s lymphoma.[37]
  • 1998: Amgen’s drug Enbrel (etanercept) becomes the first TNF (tumor necrosis factor) inhibitor treatment to be FDA-approved for autoimmune disorders, such as rheumatoid arthritis (RA) to reduce inflammation and pain.[38]
  • 1998: Remicade (infliximab), manufactured by Schering-Plough Corporation and Mitsubishi Tanabe Pharma Corporation, becomes the first anti-TNF-alpha treatment and rapidly rises to the top of the field, treating Crohn’s disease and RA and helping over 1 million patients worldwide in less than a decade.[39]
  • 1998: The biologic drug made by Genentech, Herceptin (trastuzumab), which is a humanized antibody, is FDA-approved to treat breast cancer.[40]
  • 2001: GlaxoSmithKline (GSK) releases Advair (fluticasone propionate and salmeterol inhalation powder) in the US, a bronchodilator for asthma and chronic obstructive pulmonary disease (COPD).[41] Advair is marketed as Seretide in other countries, and it is one of the top five bestselling drugs on the market in the next decade.[42]
  • 2003: Humira (adalimumab) is launched by Abbot and AbbVie. While it is the third TNF-alpha antibody on the market for RA and other autoimmune disorders, it becomes the first in its class and the bestselling drug, topping $9 billion dollars in sales in 2012.[43]
  • 2003: The first biologic to treat asthma enters the market as Xolair (omalizumab) by Genentech.[44]
  • 2004: The FDA approves the first angiogenesis inhibitors, which block the formation of new blood vessels, for the treatment of metastatic colorectal cancer: Avastin (bevacizumab) by Genentech.[45] Avastin introduces a new way to treat cancer.
  • 2009: Prevnar 13 (pneumococcal polysaccharide conjugate vaccine) by Pfizer, a vaccine to help prevent pneumococcal pneumonia in children, is approved. It becomes the most used pneumococcal conjugate vaccine in the world.[46]

New medications and pharmaceutical products are constantly being developed. In 2015, there were 45 novel medicines approved by the FDA in the United States.[47] Medications can now be made specifically for certain diseases and the way they manifest in specific people- so they can individually target issues. Major pharmaceutical companies are pouring money into research and development, trying to find and harness the next big blockbuster drug.

From Development to the Public: How Medications Are Created and Approved

Pharmaceuticals are big business, and as such, companies are constantly striving to come up with medical and pharmacological breakthroughs. Medications are developed in labs by scientists and researchers. Medicine can be extracted from plants, made from biological materials, or synthesized chemically.

The first stage in developing a medication is experimental, investigational, and research-based, as scientists investigate new ways to use existing chemicals, manufacture new ones, or use new technologies. If a compound is deemed worth investigating further, more tests and research are done as it enters the preclinical stage, which generally includes animal testing and research involving safety of the potential drug.

Researchers perform “in vitro” or “in vivo” testing during the preclinical stage, and they are required to follow good laboratory practices (GLP) which set forth strict regulations and requirements.[48] Preclinical trials do not need to be very large, but they must provide information on dosage and toxicity (potential of the drug to cause harm). If a drug shows promise through clinical trials, researchers will review the findings and possibly approve the drug to be tested in humans – the clinical research phase.

Clinical research involves sanctioned drug testing on groups of people to test the safety and efficacy of a new drug. Before clinical research can begin, researchers and drug developers must submit an application for an Investigational New Drug (IND) and get it approved by the FDA’s Center for Drug Evaluation and Research (CDER). The CDER review team contains scientific experts in various fields. The FDA has 30 days to review an IND before rendering a verdict and allowing it to proceed to the next phase of development: clinical research.

Clinical research has four phases:

  • Phase 1: About 20-100 people, either people with the condition the drug is being tested for or healthy volunteers, are given the drug over a period of several months to test for safety and dosage. About 70 percent of drugs make it past this phase.
  • Phase 2: Several hundred people suffering from the condition or disease are given the drug, over a period of months to up to two years, to test for side effects and efficacy. Around 33 percent of drugs make it through this phase.
  • Phase 3: The testing is expanded to include 300-3,000 people with the condition or disease, and testing continues for 1-4 years to closely monitor adverse reactions and efficacy. About 25-30 percent of drugs make it past this phase.
  • Phase 4: Several thousand volunteers with the condition or disease are tested with the drug to officially determine its safety and efficacy.[49]

After two large and controlled clinical trials are completed, and a drug makes it through all four phases, while submitting research and results to the FDA along the way, the developer may file for a marketing application with a New Drug Application (NDA). The NDA must detail data on the bioavailability and stability of the product, specifications on manufacturing, results of any toxicology studies, packaging and labeling information for both consumer and physicians, and the method of analysis on all dosage forms that will be marketed.[50] The FDA review team has 6-10 months to look over an NDA after it is filed and decide whether to approve the drug.[51] Sometimes, additional information or research is required prior to approval. If the drug is deemed to be safe and effective, then the FDA will work with the NDA applicant to iron out labeling and specific prescribing information. Drugs may then be marketed to the public, and pharmaceutical companies may begin manufacturing and distributing the product.

Much of the time, these companies will also file for patent protection for the drug in order to keep others from being able to make the same thing. These patents give companies proprietary rights for a set period of time. After patents expire, other companies may file applications to manufacture generic forms of these products. Also, if companies wish to alter dosage information or include other uses for the drug, they must file supplemental applications. The FDA also engages in post-market safety monitoring, routinely inspects drug manufacturing plants, and regulates marketing and promotional labeling for the drug. Drugs are not legally allowed to be advertised for purposes other than what they have been approved to treat, and all advertising must be truthful, disclosing potential side effects and efficacy.

Major Legal Issues and Drug Recalls

The pharmaceutical industry has had many legal troubles, lawsuits, and drug recalls. One of the biggest disasters in pharmacology was thalidomide, which was heralded as a sleeping pill and cure for morning sickness in pregnant women all over Europe in the 1950s. Developed by Germany’s Chemie Grunenthal and marketed in the United State by William S. Merrell, thalidomide had a serious problem: It caused birth defects in babies born to mothers who took the drug while pregnant.[52]

In 1960, the FDA denied the request for approval for the drug in the US, citing insufficient evidence research into the drug’s safety by it developer. In late 1961, evidence linking thalidomide to thousands of birth defects became public. By 1962, thalidomide was banned worldwide.

The thalidomide scandal is the reason why regulations on drug approvals are as rigorous as they are in the US – to ensure that the health benefits of new drugs outweigh the risks. Of course, this was not the end of problematic drugs, and several other recalls have occurred over the years.

Some of the most notable drug recalls are outlined below:

  • Tylenol (acetaminophen): In 1982, Johnson & Johnson pulled 31 million bottles of Tylenol from shelves after several people died after ingesting medication that had been altered and laced with cyanide.[53] This was the first major recall of its kind and set the stage for future drug recalls. Tylenol was in the hot seat again in 2010, as Children’s Motrin (ibuprofen) and Infant’s and Children’s Tylenol were recalled again. In 2015, makers of the products, McNeil Consumer Healthcare (of Johnson & Johnson), pled guilty to selling the product despite knowledge that it contained metal bits.[54]
  • FenPhen (fenfluramine/phentermine): This was a common off-label treatment for obesity. American Home Products (AHP) Corporation marketed both Redux and Pondimin, which were found to cause heart valve disease and were recalled in 1997 after close to 25 years on the market.[55] AHP agreed to pay nearly $4 billion in settlements to users of the products, one of the biggest product liability settlements at the time.[56]
  • Vioxx (rofecoxib): A painkiller made by Merck that was supposedly safer on the gastrointestinal system than its predecessor, Vioxx was on the market from 1999 until 2004 when it was pulled after many deaths and heart issues are reported.[57] Merck pays out $4.85 billion – the largest drug settlement as of 2007 – to quell the thousands of lawsuits brought against them. Close to 90,000 people are reported to have suffered heart attacks as a result of taking Vioxx, and more than one-third of them died.
  • Bextra (valdecoxib): This nonsteroidal anti-inflammatory drug (NSAID) made by Pfizer was pulled from the market in 2005 after three years of being marketed as a painkiller due to serious cardiovascular complications.[58]
  • Baycol (cerivastatin): This Bayer product for lowering cholesterol was recalled in 2001 after only three years on the market. Many deaths were reported, and the drug was found to cause life-threatening muscle destruction.[59]

Pharmaceutical companies are regularly involved in lawsuits as well. One company may sue another over patent rights, for example. Pharmaceutical companies have been hit with lawsuits claiming that they used unsavory, and potentially illegal, tactics to bar generic forms of their drugs from hitting the market. Pharmaceutical companies have also been accused of Medicaid fraud, taking kickbacks, inflating profits, and downplaying side effects of a drug. Drugs may be illegally promoted or advertised to treat symptoms or disorders that they are not approved to treat. Oftentimes, pharmaceutical companies agree to pay settlements in order to halt litigation without admitting any wrongdoing.

Examples of massive lawsuits and settlements involving pharmaceuticals include:

  • Abilify (aripiprazole): A schizophrenia medication made by Bristol Meyers-Squibb was marketed for use in children and the elderly; this was not something it was approved for, and the company settled for over $500 million in 2007.[60]
  • Geodon (ziprasidone), Bextra (valdecoxib), Lyrica (pregabalin), Zyvox (linezolid): Pfizer paid out over $2 billion in both criminal fines and settlements with the government over false advertising and off-label promotion of uses for these drugs.[61]
  • Zyprexa (olanzapine): An antipsychotic drug marketed by Eli Lilly was hit with both criminal fines and government settlements due to accusations of false advertisement and off-label uses to the tune of a $1.4 billion settlement.[62]
  • Risperdal (risperidone), Invega (paliperidone), Nesiritide (natrecor): In one of the biggest fraud settlements in healthcare, Johnson & Johnson paid out over $2 billion in 2013 in penalties and settlements for false advertisement over use of these drugs.[63] Resperidal, for example, was advertised to treat dementia when it was only approved to treat schizophrenia.
  • Avandia (rosiglitazone), Paxil (paroxetine), Wellbutrin (bupropion): In 2012, GlaxoSmithKline paid out the largest fraud settlement in healthcare and the largest payout by a drug company for both criminal and civil liability penalties ($3 billion) to date over false marketing, failure to accurately report safety data, and fraudulent price reporting in regard to these drugs and a few others.[64]
  • Celebrex (celecoxib): Pfizer was accused of hiding safety risks associated with both Celebrex (an NSIAD for arthritis pain) and Bextra from its shareholders and agreed to pay out a $486 million settlement in 2016.[65]

Big Pharma’s Role in the Opioid Epidemic

Pharmaceutical companies have faced many charges of fraudulent business practices, downplaying side effects of drugs, promotion of unapproved uses, rushing drugs to market without adequate testing, and other practices to try and raise profits. Perhaps one of the biggest failures of Big Pharma is their involvement in the opioid epidemic.

Rampant opioid abuse, overdose, and high rates of addiction have swept America in recent years. For centuries, people have been aware of the pain-relieving and euphoria-producing effects of the opium poppy plant.

In the early 1800s, Friedrich Serturner is credited with isolating and developing the first opiate drug: morphine.[66] In 1853 the hypodermic needle was invented, giving physicians a much more effective, and quicker, method of getting morphine into the bloodstream, thus increasing its popularity as a painkiller.[67]

In 1898, the Bayer Co. began producing another opioid drug, heroin, on a commercial scale as both a pain reliever and cough suppressant, and it was initially seen as a “wonder drug.”[68] The addictive nature of the drug and deadly side effects were quickly recognized, however. In 1914, the Harrison Narcotics Tax Act began imposing taxes on any product containing opium and on companies manufacturing the drug. By 1924, heroin was considered an illegal drug with no approved medical uses in the United States.[69]

For many years, opioid derivative drugs like Vicodin (hydrocodone/acetaminophen) and Percocet (oxycodone/acetaminophen) were prescribed sparingly and mostly in hospital settings, as medical providers understood them to be highly addictive. The 1990s brought about a change with researchers and doctors beginning to believe the health benefits of narcotic opioids may outweigh the risks, and they began to use these drugs more often to treat chronic pain and terminal illnesses.

OxyContin (oxycodone) entered the drug market in 1996.[70] Purdue Pharma aggressively marketed OxyContin, pouring hundreds of millions of dollars into promoting the long-lasting opioid drug. It quickly became a billion-dollar product and accounted for 30 percent of the painkiller market within a decade of its release.[71]

Purdue Pharma has been accused of misleading the public and prescribers as to the addictiveness of OxyContin, as well as offering kickbacks and sales incentives for pushing the drug. OxyContin abuse spread out beyond licit prescriptions, as it flooded the market and gained the nickname “hillbilly heroin.” In 2007, the state of Kentucky filed suit against Purdue and OxyContin, claiming that the company knowingly allowed addiction to spread by not disclosing how addictive the drug could be. Purdue settled the suit for $24 million in late 2015.[72] In 2007, Purdue Pharma was also forced to pay over $600 million in government fines – one of the largest healthcare fraud settlements ever – for misbranding OxyContin as not being addictive and even being “abuse resistant.”[73]

Purdue Pharma and OxyContin are not off the hook today. In January 2017, the City of Everett, Washington, hit the company with an unprecedented lawsuit.[74] The suit claims that Purdue Pharma knowingly sold OxyContin to “shady” clinics and medical practices often termed “pill mills,” which are basically glorified drug rings. The company may have had knowledge that the drug was being illegally diverted into the black market and did nothing to stop it or notify the proper officials that this was happening. The federal government has yet to charge Purdue Pharma for its sales practices of OxyContin, but city officials in Everett are seeking tens of millions of dollars in retribution.[75]

Today, over 2 million Americans struggle with addiction to prescription opioid drugs. Close to 100 people in the United States die every day as the result of an opioid overdose.[76], [77]

Addiction Medication and Attempts to Stem the Tide

In 2010, in an effort to quell the growing abuse epidemic and scandal surrounding OxyContin and its diversion and abuse, Purdue Pharma rereleased OxyContin in an “abuse-deterrent” form that turns to mush when crushed.[78] This makes it harder to snort, smoke, or inject the drug – popular methods of abuse that bypass the time-release format for a powerful and nearly instant “high.”

While diversion and abuse of OxyContin did drop as a result, many people battling opioid addiction merely switched to a cheaper and more accessible opioid drug: heroin. Heroin abuse continues to rise in the United States across most demographics, and overdose deaths almost quadrupled from 2002 to 2013.[79] Pharmaceutical companies have started marketing new kinds of drug: ones to combat the scourge of addiction.

Treatments for Alcohol Addiction

The first drug approved to treat addiction was designed to treat alcohol dependence. Disulfiram (Antabuse), distributed by Odyssey Pharmaceuticals, works as an aversion therapy.[80] This means that it effectively blocks receptors in the brain from receiving alcohol, thus counteracting any positive effects and making drinking less desirable.

Naltrexone was synthesized in the 1960s by Endo Pharmaceuticals (which was later acquired by DuPont) and branded as Trexan. In 1984, it was FDA-approved to treat opioid addiction. Naltrexone is an opioid antagonist that blocks opioid receptors from receiving drugs like heroin, oxycodone, and morphine.[81] In 1994, DuPont rebranded naltrexone to ReVia, and it was approved to treat alcohol dependence and addiction.[82] Mallinckrodt also markets naltrexone under the brand name Depade, and generic forms are made by other companies as well.

The third drug to treat alcohol dependence was FDA-approved in the United States in 2004 under the name of Campral (made by Merck and distributed in the US by Forest Pharmaceuticals).[83] The active ingredient in Campral is acamprosate, which helps to mitigate alcohol withdrawal side effects and thus curb cravings to drink. Acamprosate, disulfiram, and naltrexone are all approved and widely used to treat alcohol dependence in the United States today.[84]

Cigarette Smoking Cessation Aids

Cigarette smoking has long been a public health epidemic. Prior to the 1990s, nicotine replacement therapy was the only viable answer for medically helping people to quit smoking.

In 1997, bupropion (Zyban and Wellbutrin by GlaxoSmithKline), an antidepressant drug, was approved to treat nicotine dependence, as it was recognized to have anti-smoking properties.[85] In 2006, the novel medication varenicline (Chantix/Champrix by Pfizer) was approved as a new drug for smoking cessation, as it likely has both agonist and antagonist effects.[86] While they work differently in the brain, today, both bupropion and varenicline are FDA-approved medications for smoking cessation.[87]

Opioid Addiction Medications

In 1972, methadone (Dolophine by Roxanne Laboratories and Methadose by Mallinckrodt Pharmaceuticals) was FDA-approved for the treatment of opioid addiction. It serves as a weak analgesic and long-acting opioid that continues to fill opioid receptors, helping to diffuse withdrawal symptoms and cravings.[88] It is still an opioid drug, however, and it therefore has some potential for abuse itself.

In 2002, the novel drug buprenorphine was FDA-approved to treat opioid addiction in two forms: one containing the opioid antagonist naloxone (Suboxone by Reckitt Benckiser) and the other containing merely the agonist buprenorphine (Subutex by Schering-Plough).[89] These medications were approved to be prescribed directly from a doctor’s office, not just from federally regulated clinics like methadone, increasing access to medical opioid addiction treatment options.

Buprenorphine is an opioid agonist like methadone, but unlike its predecessor, it has a weaker agonist effect, and after a certain amount is in the bloodstream, the effects plateau. The addition of the antagonist naloxone acts as an abuse-deterrent. Bunavail (BioDelivery Sciences International), Zubsolv (Orexo), and Suboxone are all buprenorphine/naloxone combination products used to treat opioid addiction and maintain abstinence. Buprenorphine on its own is available in generic form. In 2016, the first buprenorphine implant was FDA-approved for opioid dependence maintenance treatment: Probuphine (Braeburn Pharmaceuticals).[90]

Opioid addiction is best treated with a combination of medical interventions and therapeutic techniques as part of a complete treatment plan.

Ongoing Work in the Pharmaceutical Industry

The pharmaceutical industry is a behemoth in business and profits around the globe. As a multibillion dollar industry, it is no surprise that Big Pharma will undergo large measures to increase revenues. That being said, these companies are working to improve healthcare practices and medical interventions and to turn the table on the chronic and relapsing disease of addiction. New treatments and methods are constantly being researched, tested, and put into practice.

The best thing the general public can do is remain vigilant and educated on the ins and outs of any medical treatments and pharmaceutical products that may be recommended for personal use.

Citations:

[1]Observations on Trends in Prescription Drug Spending.” (Mar. 2016). Office of the Assistant Secretary for Planning and Evaluation (ASPE). Accessed March 7, 2017.

[2] Ellis, Lisa. “Snapshot of the American Pharmaceutical Industry.” (July 2016). Harvard T.H. Chan School of Public Health. Accessed March 7, 2017.

[3] Krikler, Dennis M. MD “The Foxglove, ‘the Old Woman from Shropshire,’ and William Withering.” (May 1985). Journal of the American College of Cardiology. Accessed March 7, 2017.

[4]Smallpox Vaccines.” (2017). World Health Organization (WHO). Accessed March 8, 2017.

[5] Agarwal, Nitin., Chang, Connie Y., Golstien, Elisabeth., Swan, Kenneth G. (Oct. 2015). “Ether in the Developing World: Rethinking an Abandoned Agent.” BMC Anesthesiology. Accessed March 8, 2017.

[6] Taylor, David. “The Pharmaceutical Industry and the Future of Drug Development.” (2015). Pharmaceuticals in the Environment. Accessed March 7, 2017.

[7] Ibid.

[8] Rubin, Ronald, P. (Dec. 2007). “A Brief History of Great Discoveries in Pharmacology: In Celebration of the Centennial of the Anniversary of the Founding of the American Society of Pharmacology and Experimental Therapeutics.” Pharmacological Reviews. Accessed March 8, 2017.

[9] Taylor, David. “The Pharmaceutical Industry and the Future of Drug Development.” (2015). Pharmaceuticals in the Environment. Accessed March 7, 2017

[10]Bayer: Science for a Better Life.” (Oct. 2016). Bayer. Accessed March 7, 2017.

[11] Cohen, Suzy. (June 2000). “From Hippocrates to Hoffman, How Aspirin Got To Be In a Bottle.” Orlando Sentinel. Accessed March 7, 2017.

[12]Bayer: Science for a Better Life.” (Oct. 2016). Bayer. Accessed March 7, 2017.

[13]Discovery and Development of Penicillin.” (1999). American Chemical Society (ACS) International Historic Chemical Landmarks. Accessed March 7, 2017.

[14] Ibid.

[15] Cheick, Isaam, MD, Quianzon, Celeste C. (July 2012). “History of Insulin.” Journal of Community Hospital Internal Medicine Perspectives. Accessed March 7, 2017.

[16] Taylor, David. “The Pharmaceutical Industry and the Future of Drug Development.” (2015). Pharmaceuticals in the Environment. Accessed March 7, 2017.

[17] Weinblatt, Michael E. MD. (2013). “Methotrexate in Rheumatoid Arthritis: A Quarter Century of Development.” Transactions of the American Clinical and Climatological Association. Accessed March 8, 2017.

[18] Ibid.

[19] Belongia, Edward A. MD, Naleway, Allison L. PhD. “Smallpox Vaccine: the Good, the Bad, and the Ugly.” Clinical Medicine & Research (CM & R). Accessed March 8, 2017.

[20] Ban, Thomas A., (Aug. 2007). “Fifty Years Chlorpromazine: A Historical Perspective.” Neuropsychiatric Disease and Treatment. Accessed March 8, 2017.

[21]Polio.” (Feb. 2013). Centers for Disease Control and Prevention (CDC). Accessed March 8, 2017.

[22]Our Story.” (2016). Johnson & Johnson. Accessed March 8, 2017.

[23] AH, Giesecke. (Jul. 2008).”First Use of Halothane in the United States, C. Ronald Stephen, MD. (1916-2006).Bulletin of Anesthesia History. Accessed March 8, 2017.

[24] Dominic (Feb. 2011). “Bodies and Technologies: No More Pain: History of Advil (Ibuprofen).” University of Memphis. Accessed March 8, 2017.

[25] Ibid.

[26]Tagamet: Discovery of H2-Receptor Antagonists.” (1998). American Chemical Society (ACS) International Historic Chemical Landmarks. Accessed March 7, 2017.

[27]The History of a Wonderful Thing We Call Insulin.” (Aug. 2012). American Diabetes Association. Accessed March 8, 2017.

[28] Bymster, FP, Perry, KW, Wong, DT. (Sept. 2005). “Case History: The Discovery of Fluoxetine Hydrochloride (Prozac).Nature Reviews. Drug Discovery. Accessed March 7, 2017.

[29] Endo, Akira. (May 2010). “A Historical Perspective on the Discovery of Statins.” Proceedings of the Japan Academy, Series B Physical and Biological Sciences. Accessed March 8, 2017.

[30]Weekly Dose: Lipitor, the Highest Selling Drug of All Time.” (Mar. 2016). The Conversation. Accessed March 8, 2017.

[31] Taylor, David. “The Pharmaceutical Industry and the Future of Drug Development.” (2015). Pharmaceuticals in the Environment. Accessed March 8, 2017.

[32] Bryan, Jenny. (June 2009). “How the Prescribing of Omeprazole Took Off – and Never Looked Back.” The Pharmaceutical Journal. Accessed March 8, 2017.

[33] Finkel, Rhona (Sept. 2012). “The Atypical History of Atypical Antipsychotics.” Drugsdb.com. Accessed March 8, 2017.

[34] Ibid.

[35]HIV/AIDS Historical Timeline 1995-1999.” (Mar. 2016). U.S. Food and Drug Administration (FDA). Accessed March 8, 2017.

[36]U.S. Approves Sale of Generic Plavix.” (May 2012). Reuters. Accessed March 8, 2017.

[37]A History of Firsts.” (n.d.) Genentech. Accessed March 8, 2017.

[38]History of Enbrel.” (2016). Amgen. Accessed March 8, 2017.

[39] Centocor, Inc. (Nov. 2007). “Remicade Becomes First Anti-TNF Biologic Therapy to Treat 1 Million Patients Worldwide.” EurekAlert. Accessed March 8, 2017.

[40]A History of Firsts.” (n.d.) Genentech. Accessed March 9, 2017.

[41]GSK Launches Advair for Asthma in USA, Major Marketing Push Planned.” (April 2001). The Pharma Letter. Accessed March 8, 2017.

[42] King, Simon. (Jan. 2013). “The Best Selling Drugs of All Time; Humira Joins the Elite.” Forbes. Accessed March 8, 2017.

[43]LaMatinna, John. (May 2012). “Humira Could Have Been a Pfizer Drug.” Forbes. Accessed March 8, 2017.

[44]A History of Firsts.” (n.d.) Genentech. Accessed March 8, 2017.

[45]FDA Approves First Angiogenesis Inhibitor to Treat Colorectal Cancer.” (Feb. 2004). U.S. Food and Drug Administration (FDA). Accessed March 9, 2017.

[46]Pfizer Receives FDA Approval for Prevnar 13 in Adults Age 18 Through 49.” (July 2016). Pfizer. Accessed March 9, 2017.

[47] Mahler, Gustavo. (Jan. 2016). “Advancing Biologics Development and Manufacturing.” American Pharmaceutical Review. Accessed March 9, 2017.

[48]Step 2: Preclinical Research.” (June 2015). U.S. Food and Drug Administration (FDA). Accessed March 9, 2017.

[49]Step 3: Clinical Research.” (Oct. 2016). U.S. Food and Drug Administration (FDA). Accessed March 9, 2017.

[50]How Drugs Are Developed and Approved.” (Aug. 2015). U.S. Food and Drug Administration (FDA). Accessed March 9, 2017.

[51]Step 4: FDA Review.” (June 2015). U.S. Food and Drug Administration (FDA). Accessed March 9, 2017.

[52] Winerip, Michael. (Sept. 2013). “The Death and Afterlife of Thalidomide.” New York Times. Accessed March 9, 2017.

[53] Rehak, Judith and International Herald Tribune. (March 2002). “Tylenol Made a Hero of Johnson & Johnson: The Recall That Started Them All.” New York Times. Accessed March 9, 2017.

[54] Associated Press. (March 2015). “Maker of Children’s Tylenol to Plead Guilty Over Recall.” Fox News. Accessed March 9, 2017.

[55] Morrow, David J. (Oct. 1999). “Fen-Phen Maker to Pay Billions in Settlement of Diet-Injury Cases.” The New York Times. Accessed March 9, 2017.

[56] Ibid.

[57] Prakask, Snigdha. Valentine, Vikki. (Nov. 2007). “Timeline: The Rise and Fall of Vioxx.” NPR. Accessed March 9, 2017.

[58]Bextra (valdecoxib) Apr 2005.” (Aug 2013). U.S. Food and Drug Administration (FDA). Accessed March 9, 2017.

[59] Neergaard, Lauran. (July 2006). “Deaths Spur Cholesterol Drug Recall.” CBS News. Accessed March 9, 2017.

[60] Wilsen, Duff. (Oct. 2010). “Side Effects May Include Lawsuits.” The New York Times. Accessed March 9, 2017.

[61]Ibid.

[62]Ibid.

[63] Valencia, Nick. (Dec. 2016). “Men to Sue Over Drug That Made Them Grow Breasts.” CNN. Accessed March 9, 2017.

[64] Office of Public Affairs. (July 2012). “GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data.” U.S. Department of Justice (DOJ). Accessed March 9, 2017.

[65] Stempel, Jonathan. (Aug. 2016). “Pfizer in $486 Million Settlement of Celebrex, Bextra Litigation.” Reuters. Accessed March 9, 2017.

[66] Mandal, Ananya MD. (Oct. 2013). “Morphine History.” News Medical. Life Sciences. Accessed March 10, 2017.

[67] Ibid.

[68] Moghe, Sonia. (Oct. 2016). “Opioid History: From Wonder Drug to Abuse Epidemic.” CNN. Accessed March 10, 2017.

[69] Ibid.

[70] Mariani, Mike. (March 2015). “How the American Opiate Epidemic Was Started by One Pharmaceutical Company.” The Week. Accessed March 10, 2017.

[71] Ibid.

[72] Associated Press. (Dec. 2015). “Kentucky Settles Lawsuit with OxyContin Maker for $24 Million.” CBS News. Accessed March 10, 2017.

[73] Mariani, Mike. (March 2015). “How the American Opiate Epidemic Was Started by One Pharmaceutical Company.” The Week. Accessed March 10, 2017.

[74] Douglas, David. Gosk, Stephanie. (March 2017). “OxyContin Maker Purdue Pharma Hit with Unprecedented Lawsuit by Washington City.” NBC News. Accessed March 10, 2017.

[75] Ibid.

[76]Opioid Addiction. 2016 Facts & Figures.” (n.d.) American Society of Addiction Medicine (ASAM). Accessed March 10, 2017.

[77]Understanding the Epidemic.” (Dec. 2016). Centers for Disease Control and Prevention (CDC). Accessed March 10, 2017.

[78] Moghe, Sonia. (Oct. 2016). “Opioid History: From Wonder Drug to Abuse Epidemic.” CNN. Accessed March 10, 2017.

[79]Today’s Heroin Epidemic.” (July 2015). Centers for Disease Control and Prevention (CDC). Accessed March 10, 2017.

[80] Substance Abuse and Mental Health Services Administration (SAMHSA). (2009). “Incorporating Alcohol Pharmacotherapies into Medical Practice.” Treatment Improvement Protocol (TIP), Series No. 49. Accessed March 10, 2017.

[81] Ibid.

[82] Ibid.

[83] Ibid.

[84]Treatment Approaches for Drug Addiction.” (July 2016). National Institute on Drug Abuse (NIDA). Accessed March 10, 2017.

[85] Wilkes, Scott. (March 2008). “The Use of Bupropion SR in Cigarette Smoking Cessation.” International Journal of Chronic Obstructive Pulmonary Disease. Accessed March 10, 2017.

[86]FDA Approves Novel Medication for Smoking Cessation.” (May 2006). U.S. Food and Drug Administration (FDA). Accessed March 10, 2017.

[87]Treatment Approaches for Drug Addiction.” (July 2016). National Institute on Drug Abuse (NIDA). Accessed March 10, 2017.

[88] Institute of Medicine. (1995). “Executive Summary.” The National Academies Press. Accessed March 10, 2017.

[89]Buprenorphine.” (n.d.). National Institute on Drug Abuse (NIDA). Accessed March 10, 2017.

[90]Timeline of Selected FDA Activities and Significant Events Addressing Opioid Misuse and Abuse.” (Jan. 2017). U.S. Food and Drug Administration (FDA). Accessed March 10, 2017.