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Wednesday, May 3, 2023

Mifepristone

From Wikipedia, the free encyclopedia
Mifepristone structure.svg
Mifepristona3D.png
Clinical data
Pronunciation/ˌmɪfəˈprɪˌstn/
Trade namesMifegyne, Mifeprex, Korlym, others
Other namesRU-486; RU-38486; ZK-98296; 11β-[p-(Dimethylamino)phenyl]-17α-(1-propynyl)estra-4,9-dien-17β-ol-3-one
AHFS/Drugs.comMonograph
MedlinePlusa600042
License data
Pregnancy
category
  • Not recommended
Routes of
administration
By mouth
Drug classAntiprogestogen; Antiglucocorticoid

Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of pregnancy. It is also effective in the second trimester of pregnancy. It is taken by mouth.

Common side effects include abdominal pain, feeling tired, and vaginal bleeding. Serious side effects may include heavy vaginal bleeding, bacterial infection, and birth defects if the pregnancy does not end. If used, appropriate follow-up care needs to be available. Mifepristone is an antiprogestogen. It works by blocking the effects of progesterone, making both the cervix and uterine vessels dilate and causing uterine contraction.

Mifepristone was developed in 1980 and came into use in France in 1987. It became available in the United States in 2000. It is on the World Health Organization's List of Essential Medicines. Mifepristone was approved in Canada in January 2017.

Medical uses

Abortion

Mifepristone followed by a prostaglandin analog (misoprostol or gemeprost) is used for medical abortion. Medical organizations have found this combination to be safe and effective. Guidelines from the Royal College of Obstetricians and Gynaecologists describe medication abortion using mifepristone and misoprostol as effective and appropriate at any gestational age. The World Health Organization and the American College of Obstetricians and Gynecologists recommend mifepristone followed by misoprostol for first- and second-trimester medical abortion. Mifepristone alone is less effective, resulting in abortion within 1–2 weeks in anywhere from 54% to 92% of pregnancies, according to review of 13 studies.

Cushing's syndrome

Mifepristone is used for the medical treatment of high blood sugar caused by high cortisol levels in the blood (hypercortisolism) in adults with endogenous Cushing's syndrome who also have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery.

Other

Mifepristone at low doses has been used for emergency contraception. It may also be used together with misoprostol for early pregnancy loss. Mifepristone has also been used to treat symptomatic leiomyoma (uterine fibroids) and endometriosis.

Side effects

Serious complications with mifepristone are rare with about 0.04%–0.9% requiring hospitalization and 0.05% requiring blood transfusion.

Nearly all women using the mifepristone/misoprostol regimen experienced abdominal pain, uterine cramping, and vaginal bleeding or spotting for an average of 9–16 days. For most women, the most severe cramps after use of misoprostol last for less than 6 hours and can generally be managed with ibuprofen. Up to 8% of women experienced some type of bleeding for 30 days or more. Other less common side effects included nausea, vomiting, diarrhea, dizziness, fatigue, and fever. Pelvic inflammatory disease is a very rare but serious complication. Excessive bleeding and incomplete termination of a pregnancy require further intervention by a doctor (such as a repeat dose of misoprostol or a vacuum aspiration). Mifepristone is contraindicated in the presence of adrenal failure, long-term oral corticosteroid therapy (although inhaled and topical steroids are fine), hemorrhagic disorders, inherited porphyria, and hemophilia or anticoagulant use. Women with an intrauterine device in their uterus should remove the IUD prior to medication abortion to avoid unnecessary cramping. Mifepristone is not effective in treating ectopic pregnancy.

A postmarketing summary found, of about 1.52 million women who had received mifepristone until April 2011 in the United States, 14 were reported to have died after application. Eight of these cases were associated with sepsis; the other six had various causes such as drug abuse and suspected murder. Other incidents reported to the FDA included 612 nonlethal hospitalizations, 339 blood transfusions, 48 severe infections, and 2,207 (0.15%) adverse events altogether.

Cancer

No long-term studies to evaluate the carcinogenic potential of mifepristone have been performed. This is in accord with ICH guidelines, which do not require carcinogenicity testing in nongenotoxic drugs intended for administration for less than six months.

Pregnancy

Mifepristone alone results in abortion within 1–2 weeks in 54% to 92% of pregnancies. The effectiveness increases to greater than 90% if misoprostol is given after the mifepristone. There is no evidence that the effects of mifepristone can be reversed, although some anti-abortion groups claim that it can be reversed by giving progesterone. Researchers in the United States initiated a trial of the so-called "reversal" regimen in 2019, but stopped prematurely due to serious safety concerns about using mifepristone without follow-up misoprostol. Giving progesterone has not been shown to halt medication abortion, and not completing the combination regimen of mifepristone and misoprostol may cause serious bleeding.

In those who continue pregnancy after use of mifepristone together with misoprostol for termination, birth defects may occur. Exposure to a single large dose of mifepristone in newborn rats was not associated with any reproductive problems, although chronic low-dose exposure of newborn rats to mifepristone was associated with structural and functional reproductive abnormalities. Studies in mice, rats, and rabbits revealed developmental abnormalities for rabbits, but not rats or mice.

Pharmacology

Pharmacodynamics

Mifepristone is a steroidal antiprogestogen (IC50 = 0.025 nM for the PR), as well as an antiglucocorticoid (IC50 = 2.2 nM for the GR) and antiandrogen (IC50 = 10 nM for the AR) to a much lesser extent. It antagonizes cortisol action competitively at the receptor level.

In the presence of progesterone, mifepristone acts as a competitive progesterone receptor antagonist (in the absence of progesterone, mifepristone acts as a partial agonist). Mifepristone is a 19-nor steroid with a bulky p-(dimethylamino) phenyl substituent above the plane of the molecule at the 11β-position responsible for inducing or stabilizing an inactive receptor conformation and a hydrophobic 1-propynyl substituent below the plane of the molecule at the 17α-position that increases its progesterone receptor binding affinity.

In addition to being an antiprogestogen, mifepristone is also an antiglucocorticoid and a weak antiandrogen. Mifepristone's relative binding affinity at the progesterone receptor is more than twice that of progesterone, its relative binding affinity at the glucocorticoid receptor is more than three times that of dexamethasone and more than ten times that of cortisol. Its relative binding affinity at the androgen receptor is less than one-third that of testosterone, and it does not bind to the estrogen receptor or the mineralocorticoid receptor.

Mifepristone as a regular contraceptive at 2 mg daily prevents ovulation (1 mg daily does not). A single preovulatory 10-mg dose of mifepristone delays ovulation by three to four days and is as effective an emergency contraceptive as a single 1.5-mg dose of the progestin levonorgestrel.

In women, mifepristone at doses greater or equal to 1 mg/kg antagonizes the endometrial and myometrial effects of progesterone. In humans, an antiglucocorticoid effect of mifepristone is manifested at doses greater or equal to 4.5 mg/kg by a compensatory increase in ACTH and cortisol. In animals, a weak antiandrogenic effect is seen with prolonged administration of very high doses of 10 to 100 mg/kg.

In medication abortion regimens, mifepristone blockade of progesterone receptors directly causes endometrial decidual degeneration, cervical softening and dilatation, release of endogenous prostaglandins, and an increase in the sensitivity of the myometrium to the contractile effects of prostaglandins. Mifepristone-induced decidual breakdown indirectly leads to trophoblast detachment, resulting in decreased syncytiotrophoblast production of hCG, which in turn causes decreased production of progesterone by the corpus luteum (pregnancy is dependent on progesterone production by the corpus luteum through the first nine weeks of gestation—until placental progesterone production has increased enough to take the place of corpus luteum progesterone production). When followed sequentially by a prostaglandin, mifepristone 200 mg is (100 mg may be, but 50 mg is not) as effective as 600 mg in producing a medical abortion.

'Contragestion' is a term promoted by Étienne-Émile Baulieu in the context of his advocacy of mifepristone, defining it as inclusive of some hypothesized mechanisms of action of some contraceptives and those of mifepristone to induce abortion. Baulieu's definition of a 'contragestive' included any birth control method that could possibly act after fertilization and before nine-weeks gestational age.

Pharmacokinetics

The elimination half-life is complex; according to the label: "After a distribution phase, elimination is at first slow, the concentration decreasing by a half between about 12 and 72 hours, and then more rapid, giving an elimination half-life of 18 hours. With radio receptor assay techniques, the terminal half-life is of up to 90 hours, including all metabolites of mifepristone able to bind to progesterone receptors." Metapristone is the major metabolite of mifepristone.

Chemistry

Mifepristone, also known as 11β-(4-(dimethylamino)phenyl)-17α-(1-propynyl)estra-4,9-dien-17β-ol-3-one, is a synthetic estrane steroid and a derivative of steroid hormones like progesterone, cortisol, and testosterone. It has substitutions at the C11β and C17α positions and double bonds at the C4(5) and C9(10) positions.

History

1980–1987

In April 1980, as part of a formal research project at the French pharmaceutical company Roussel-Uclaf for the development of glucocorticoid receptor antagonists, endocrinologist Étienne-Émile Baulieu and chemist Georges Teutsch synthesized mifepristone (RU-38486, the 38,486th compound synthesized by Roussel-Uclaf from 1949 to 1980; shortened to RU-486), which was discovered to also be a progesterone receptor antagonist. In October 1981, Étienne-Émile Baulieu, a consultant to Roussel-Uclaf, arranged tests of its use for medical abortion in 11 women in Switzerland by gynecologist Walter Herrmann at the University of Geneva's Cantonal Hospital, with successful results announced on 19 April 1982. On 9 October 1987, following worldwide clinical trials in 20,000 women of mifepristone with a prostaglandin analogue (initially sulprostone or gemeprost, later misoprostol) for medical abortion, Roussel-Uclaf sought approval in France for their use for medical abortion, with approval announced on 23 September 1988.

1988–1990

On 21 October 1988, in response to antiabortion protests and concerns of majority (54.5%) owner Hoechst AG of Germany, Roussel-Uclaf's executives and board of directors voted 16 to 4 to stop distribution of mifepristone, which they announced on 26 October 1988. Two days later, the French government ordered Roussel-Uclaf to distribute mifepristone in the interests of public health. French Health Minister Claude Évin explained: "I could not permit the abortion debate to deprive women of a product that represents medical progress. From the moment Government approval for the drug was granted, RU-486 became the moral property of women, not just the property of a drug company." Following use by 34,000 women in France from April 1988 to February 1990 of mifepristone distributed free of charge, Roussel-Uclaf began selling Mifegyne (mifepristone) to hospitals in France in February 1990 at a price (negotiated with the French government) of US$48 (equivalent to $99.56 in 2021) per 600-mg dose.

1991–1996

Mifegyne was subsequently approved in Great Britain in July 1991, and in Sweden in September 1992, but until his retirement in April 1994, Hoechst AG chairman Wolfgang Hilger, a devout Roman Catholic, blocked any further expansion in availability. On 16 May 1994, Roussel-Uclaf announced it was donating without remuneration all rights for medical uses of mifepristone in the United States to the Population Council, which subsequently licensed mifepristone to Danco Laboratories, a new single-product company immune to antiabortion boycotts, which received approval from the US Food and Drug Administration (FDA) as Mifeprex on 28 September 2000.

1997–1999

On 8 April 1997, after buying the remaining 43.5% of Roussel-Uclaf stock in early 1997, Hoechst AG (US$30 (equivalent to $51.83 in 2021) billion annual revenue) announced the end of its manufacture and sale of Mifegyne (US$3.44 (equivalent to $5.94 in 2021) million annual revenue) and the transfer of all rights for medical uses of mifepristone outside of the United States to Exelgyn S.A., a new single-product company immune to antiabortion boycotts, whose CEO was former Roussel-Uclaf CEO Édouard Sakiz. In 1999, Exelgyn won approval of Mifegyne in 11 additional countries, and in 28 more countries over the following decade.

2000–present

In 2019, the first generic form of mifepristone in the United States became available, manufactured by GenBioPro.

Society and culture

Mifepristone is on the World Health Organization's List of Essential Medicines. Since 2019, it has been included on the core list, with misoprostol, with a special note "where permitted under national law and where culturally acceptable".

Economics

Cost and availability limit access in many parts of the world.

Frequency of use

United States

Medication abortions voluntarily reported by 33 U.S. states to the Centers for Disease Control and Prevention (CDC) have increased as a percentage of total abortions every year since the approval of mifepristone: 1.0% in 2000, 2.9% in 2001, 5.2% in 2002, 7.9% in 2003, 9.3% in 2004, 9.9% in 2005, 10.6% in 2006, and 13.1% in 2007 (20.3% of those at less than 9 weeks gestation).

A Guttmacher Institute survey of abortion providers estimated that medication abortions accounted for 17% of all abortions and slightly over 25% of abortions before 9 weeks gestation in the United States in 2008 (94% of nonhospital medication abortions used mifepristone and misoprostol, 6% used methotrexate and misoprostol). Medication abortions accounted for 32% of first trimester abortions at Planned Parenthood clinics in the United States in 2008. Considering abortions performed in non-hospital facilities, medication abortions accounted for 24% in 2011 and 31% in 2014. In 2014, facilities that provided a relatively small number of abortions (fewer than 400 procedures per year) were more likely to perform them with medication. Medication abortions accounted for 39% of all U.S. abortions in 2017, and 54% in 2020.

Europe

In France, the percentage of medication abortions of all abortions continues to increase: 38% in 2003, 42% in 2004, 44% in 2005, 46% in 2006, 49% in 2007 (vs. 18% in 1996). In England and Wales, 52% of early abortions (less than 9 weeks gestation) in 2009 were medication-based; the percentage of all abortions that are medication-based has increased every year for the past 14 years (from 5% in 1995 to 40% in 2009) and has more than doubled in the last five years. In Scotland, 81.2% of early abortions in 2009 were medication-based (up from 55.8% in 1992 when medication abortion was introduced); the percentage of all abortions that are medication-based has increased every year for the past 17 years (from 16.4% in 1992 to 69.9% in 2009). In Sweden, 85.6% of early abortions and 73.2% of abortions before the end of the 12th week of gestation in 2009 were medication-based; 68.2% of all abortions in 2009 were medication-based. In Great Britain and Sweden, mifepristone is licensed for use with vaginal gemeprost or oral misoprostol. As of 2000, more than 620,000 women in Europe had had medication abortions using a mifepristone regimen. In Denmark, mifepristone was used in between 3,000 and 4,000 of just over 15,000 abortions in 2005.

Legal status

In the United States

Mifepristone was approved for abortion in the United States by the FDA in September 2000. As of 2007, it was legal and available in all 50 states, Washington, D.C., Guam, and Puerto Rico. It is a prescription drug, but was not initially available to the public through pharmacies; its distribution is primarily restricted to specially qualified licensed physicians, sold by Danco Laboratories under the brand name Mifeprex. As of September 2021, in 32 states, the drug could only be provided by a licensed physician, and in 19 states, the prescribing clinician was required to be physically in the room with the patient while they are taking the drug.

Roussel Uclaf did not seek U.S. approval, so in the United States legal availability was not initially possible. The United States banned importation of mifepristone for personal use in 1989, a decision supported by Roussel Uclaf. In 1994, Roussel Uclaf gave the U.S. drug rights to the Population Council in exchange for immunity from any product liability claims. The Population Council sponsored clinical trials in the United States. The drug went on approvable status from 1996. Production was intended to begin through the Danco Group in 1996, but they withdrew briefly in 1997 due to a corrupt business partner, delaying availability again.

In 2016, the US Food and Drug Administration (FDA) approved mifepristone, to end a pregnancy through 70 days gestation (70 days or less since the first day of a woman's last menstrual period). The approved dosing regimen is 200 mg of mifepristone taken by mouth (swallowed).  24 to 48 hours after taking mifepristone, 800 mcg (micrograms) of misoprostol is taken buccally (in the cheek pouch), at a location appropriate for the patient.

Mifepristone tablets have a marketing authorization in the United States for the treatment of high blood sugar caused by high cortisol levels in the blood (hypercortisolism) in adults with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery.

Due to the COVID-19 pandemic, safe access to mifepristone was a concern, and the American College of Obstetricians and Gynecologists among other groups filed a lawsuit to relax the FDA's rule as to allow mifepristone to be acquired from mail-order and retail pharmacies. While the Fourth Circuit had granted a preliminary injunction to allow this distribution, the Supreme Court of the United States issued a stay order in January 2021 to retain the FDA's rule pending the results of the ongoing litigation.

On 16 December 2021, the FDA voluntarily adopted a new rule permanently relaxing the requirement that the pill be obtained in person, allowing it to be sent through the mail. A prescription is still required, so that a doctor can screen for risk factors that would make taking the pill unsafe for the mother. In January 2023, the FDA further relaxed rules, allowing any retail pharmacy to become certified to fill mifepristone prescriptions.

After regulations on abortion early in pregnancy were ruled constitutional by the 2022 decision Dobbs v. Jackson Women's Health Organization, some states enacted restrictions on abortions and abortion pills. In January 2023, the United States Department of Justice issued an interpretation of the Comstock Act that it was legal for United States Postal Service employees to deliver the pills in any state, because they could not know whether the pills would be used for an abortion or other purposes.

In January 2023, GenBioPro filed suit to overturn state laws that prohibit sale of mifepristone, claiming that such laws are invalid because it is a federally approved drug.

In March 2023, Wyoming became the first US state to ban the pill.

In April 2023, during the Alliance for Hippocratic Medicine v. US Food and Drug Administration lawsuit, federal district judge Matthew J. Kacsmaryk issued a preliminary injunction suspending the 2000 approval of mifepristone, which would take effect a week later. The Fifth Circuit reversed parts of Kacsmaryk's injunction, but placing a temporary injunction on the 2016 REMS change to mifepristone. On appeal to the Supreme Court, the Court stayed both injunctions on April 21, 2023, with only Justices Samuel Alito and Clarence Thomas stating their dissent. The stay allowed mifepristone to remain legally available while the lower courts consider the merits of the case.

Also in April 2023, in a lawsuit brought by 17 U.S. states and the District of Columbia, federal district judge Thomas O. Rice issued a temporary injunction that the FDA should not reduce access to mifepristone in these states and the district.

Subsection H

Some drugs are approved by the FDA under subsection H, which has two subparts. The first sets forth ways to rush experimental drugs, such as aggressive HIV and cancer treatments, to market when speedy approval is deemed vital to the health of potential patients. The second part of subsection H applies to drugs that not only must meet restrictions for use due to safety requirements, but also are required to meet postmarketing surveillance to establish that the safety results shown in clinical trials are seconded by use in a much wider population. Until December 2021, Mifepristone was approved under the second part of subsection H. The result is that women could not pick the drug up at a pharmacy, but were required to receive it directly from a doctor. Due to the possibility of adverse reactions such as excessive bleeding, which may require a blood transfusion, and incomplete abortion, which may require surgical intervention, the drug was only considered safe if a physician who is capable of administering a blood transfusion or a surgical abortion is available to the patient in the event of such emergencies. The approval of mifepristone under subsection H included a black box warning.

European Union

Outside the United States, mifepristone is marketed and distributed by Exelgyn Laboratories under the brand name Mifegyne. It was approved for use in France in 1988 (initial marketing in 1989), the United Kingdom in 1991, Sweden in 1992, then Austria, Belgium, Denmark, Finland, Germany, Greece, Luxembourg, the Netherlands, Spain, and Switzerland in 1999. In 2000, it was approved in Norway, Russia and Ukraine. Serbia and Montenegro approved it in 2001, Belarus and Latvia in 2002, Estonia in 2003, Moldova in 2004, Albania and Hungary in 2005, Portugal in 2007, Romania in 2008, Bulgaria, Czech Republic and Slovenia in 2013. In Italy, clinical trials have been constrained by protocols requiring women be hospitalized for three days, but the drug was finally approved on 30 July 2009 (officialized later in the year), despite strong opposition from the Vatican. In Italy, the pill must be prescribed and used in a clinical structure and is not sold at chemists. It was approved in Hungary in 2005, but as of 2005 had not been released on the market yet, and was the target of protests. Mifepristone is licensed in Ireland for use of abortions up to 12 weeks since it was legalised in 2018. Mifepristone is not available in Poland, where abortion is highly restricted.

Mifepristone 200 mg tablets (Mifegyne, Mifepristone Linepharma, Medabon) have marketing authorizations in the European Economic Area from the European Medicines Agency (EMA) for:

  • Early first trimester medication abortion when followed by a prostaglandin analog (misoprostol or gemeprost) through 63 days gestational age
  • Second trimester medication abortion when followed by a prostaglandin analog
  • Cervical softening and dilation prior to first trimester surgical abortion
  • Induction of labor after fetal death in utero when prostaglandin analogs and oxytocin are contraindicated

Other countries

Mifepristone was banned in Australia in 1996. In 2005, a private member's bill was introduced to the Australian Senate to lift the ban and transfer the power of approval to the Therapeutic Goods Administration (TGA). The move caused much debate in the Australian media and among politicians. The bill passed the Senate in February 2006, and mifepristone is legal in Australia. It is provided regularly at several specialized abortion clinics per state. Mifepristone 200 mg tablets have marketing authorizations in Australia from the TGA for early first trimester medication abortion when followed by the prostaglandin analog misoprostol through 63 days gestational age and second trimester medication abortion when followed by a prostaglandin analog.

In New Zealand, pro-abortion rights doctors established an import company, Istar, and submitted a request for approval to Medsafe, the New Zealand pharmaceutical regulatory agency. After a court case brought by Right to Life New Zealand failed, use of mifepristone was permitted.

Mifepristone was approved in Israel in 1999.

Clinical trials of mifepristone in China began in 1985. In October 1988, China became the first country in the world to approve mifepristone. Chinese organizations tried to purchase mifepristone from Roussel Uclaf, which refused to sell it to them, so in 1992 China began its own domestic production of mifepristone. In 2000, the cost of medication abortion with mifepristone was higher than surgical abortion and the percentage of medication abortions varied greatly, ranging from 30% to 70% in cities to being almost nonexistent in rural areas. A report from the United States Embassy in Beijing in 2000 said mifepristone had been widely used in Chinese cities for about two years, and that according to press reports, a black market had developed with many women starting to buy it illegally (without a prescription) from private clinics and drugstores for about US$15 (equivalent to $23.6 in 2021), causing Chinese authorities to worry about medical complications from use without physician supervision.

In 2001, mifepristone was approved in Taiwan. Vietnam included mifepristone in the National Reproductive Health program in 2002.

Mifepristone is approved in only one sub-Saharan African country—South Africa, where it was approved in 2001. It is also approved in one north African country—Tunisia, also in 2001.

Mifepristone was approved for use in India in 2002, where medication abortion is referred to as "medical termination of pregnancy". It is only available under medical supervision, not by prescription, due to adverse reactions such as excessive bleeding, and criminal penalties are given for buying or selling it on the black market or over-the-counter at pharmacies.

Medication induced abortion used to be available in Canada but on a limited basis using methotrexate and misoprostol. Clinical trials were done in 2000 in various Canadian cities comparing methotrexate to mifepristone, after approbation by the federal government. While both drugs had overall similar results, mifepristone was found to act faster. Health Canada gave approval to mifepristone in July 2015. Initially, its use was limited to seven weeks into a pregnancy, but this was changed to nine weeks in 2017. The previous requirement of written consent from the woman was also ended at the same time. It can be dispensed directly to a patient by a pharmacist or a prescribing health professional. Women are required to have an ultrasound to ensure the pregnancy is not ectopic.

Mifepristone was registered for use in Azerbaijan, Georgia, and Uzbekistan in 2002, in Guyana and Moldova in 2004, in Mongolia in 2005, and in Armenia in 2007.

Low dose mifepristone tablets (Bi Yun, Fu Nai Er, Hou Ding Nuo, Hua Dian, Si Mi An) for emergency contraception are available directly from a pharmacist without a prescription and with a prescription in China.

Low dose mifepristone tablets for emergency contraception are available by prescription in Armenia (Gynepriston), Russia (Agesta, Gynepriston, Mifepristone 72, Negele), Ukraine (Gynepriston), and Vietnam (Mifestad 10, Ciel EC).

Controversy

Many anti-abortion groups in the United States actively campaigned against the approval of mifepristone and continue to actively campaign for its withdrawal. They cite either ethical issues with abortion or safety concerns regarding the drug and the adverse reactions associated with it.

Religious and anti-abortion groups outside the United States have also protested mifepristone, especially in Germany and Australia.

A decision by a US appeals court has upheld limited access to the abortion pill [mifepristone]. This ruling is seen as a significant win for advocates of reproductive rights who have been fighting against restrictive abortion laws for years. However, the decision also highlights the ongoing battle over access to abortion and the need for continued advocacy efforts.

Research

The original target for the research group was the discovery and development of compounds with antiglucocorticoid properties. These antiglucocorticoid properties are of great interest in the treatment of severe mood disorders and psychosis, although a review of published articles was inconclusive on their efficacy, and considered the use of these drugs in mood disorders at 'proof of concept' stage.

Use of mifepristone as a cervical ripening agent has been described. The medication has been studied as an antiandrogen in the treatment of prostate cancer. Mifepristone showed no detectable anti-HIV activity in clinical trials.

Mifepristone showed initial promise in psychotic major depression, a difficult-to-treat form of depression, but a phase-III clinical trial was terminated early due to lack of efficacy. It has been studied in bipolar disorder, post traumatic stress disorder, and anorexia nervosa.

American Psychiatric Association

From Wikipedia, the free encyclopedia
 
AbbreviationAPA
FormationOctober 16, 1844; 178 years ago
Founders
Founded atPhiladelphia, Pennsylvania, US
TypeProfessional association
52-2168499
Legal status501(c)(6) organization
HeadquartersWashington, DC, US
Membership
37,400
Vivian B. Pender
President-elect
Rebecca W. Brendel
Chief executive officer
Saul Levin
Subsidiaries
  • American Psychiatric Association Foundation
  • American Psychiatric Political Action Committee
  • American Psychiatric Association Insurance Trust
  • APA Wharf Holdings LLC
Revenue (2016)
$50,557,392
Expenses (2016)$48,736,684
Employees (2016)
236
Volunteers (2016)
850
Websitepsychiatry.org Edit this at Wikidata
Formerly called

The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. It has more than 37,000 members who are involved in psychiatric practice, research, and academia representing a diverse population of patients in more than 100 countries. The association publishes various journals and pamphlets, as well as the Diagnostic and Statistical Manual of Mental Disorders (DSM). The DSM codifies psychiatric conditions and is used mostly in the United States as a guide for diagnosing mental disorders.

The organization has its headquarters in Washington, DC.

History

At a meeting in 1844 in Philadelphia, thirteen superintendents and organizers of insane asylums and hospitals formed the Association of Medical Superintendents of American Institutions for the Insane (AMSAII). The group included Thomas Kirkbride, creator of the asylum model which was used throughout the United States. The group was chartered to focus "primarily on the administration of hospitals and how that affected the care of patients", as opposed to conducting research or promoting the profession.

In 1893, the organization changed its name to the American Medico-Psychological Association. In 1921, the association changed that name to the present American Psychiatric Association. The association was incorporated in 1927.

The cover of the publication Semi-Centennial Proceedings of the American Medical Psychological Association, which the association distributed in 1894 at its 50th annual meeting in Philadelphia, contained the first depiction of the association's official seal. The seal has undergone several changes since that time.

The present seal is a round medallion with a purported likeness of Benjamin Rush's profile and 13 stars over his head to represent the 13 founders of the organization. The outer ring contains the words "American Psychiatric Association 1844." Rush's name and an MD are below the picture.

An association history of the seal states:

The choice of Rush (1746–1813) for the seal reflects his place in history. .... Rush's practice of psychiatry was based on bleeding, purging, and the use of the tranquilizer chair and gyrator. By 1844 these practices were considered erroneous and abandoned. Rush, however, was the first American to study mental disorder in a systematic manner, and he is considered the father of American Psychiatry.

In 2015, the association adopted a new logo that depicts the serpent-entwined Rod of Asclepius superimposed over the image of two hemispheres of a human brain. The logo appears next to the words "American Psychiatric Association", with the word "Psychiatric" in bold type; the tagline "Medical leadership for mind, brain and body" appears below the logo. The association will continue to use the seal bearing Rush's profile for ceremonial purposes and for some internal documents.

Organization and membership

APA is led by the President of the American Psychiatric Association and a board of trustees with an executive committee.

APA reports that its membership is primarily medical specialists who are qualified, or in the process of becoming qualified, as psychiatrists. The basic eligibility requirement is completion of a residency program in psychiatry accredited by the Residency Review Committee for Psychiatry of the Accreditation Council for Graduate Medical Education (ACGME), the Royal College of Physicians and Surgeons of Canada (RCPS[C]), or the American Osteopathic Association (AOA). Applicants for membership must also hold a valid medical license (with the exception of medical students and residents) and provide one reference who is an APA member.

APA holds an annual conference attended by an American and international audience.

APA is made up of some 76 district associations throughout the country.

Foundation

APA operates a non-profit subsidiary called the American Psychiatric Association Foundation (APAF), offering community-based programs and research initiatives intended to better understand and support issues of mental health. Its strategic partners include the Council of State Governments (CSG) Justice Center, Substance Abuse and Mental Health Services Administration (SAMHSA) and the National Association of Counties (NACo).

Corporate Alliance

APAF partners with industry organizations to collaborate on mental health research and development through its Corporate Alliance. Current and recent members of the alliance include:

Donors to the foundation in 2019 include the Austen Riggs Center, BB&T, Cenveo, McLean Hospital, Menninger Foundation, NeuroStar, Newport Academy, NewYork-Presbyterian Hospital, Sheppard Pratt, and Silver Hill Hospital.

Publications and campaigns

APA position statements, clinical practice guidelines, and descriptions of its core diagnostic manual (the DSM) are published.

APA publishes several journals focused on different areas of psychiatry, for example, academic, clinical practice, or news.

Top five Choosing Wisely recommendations

In coordination with the American Board of Internal Medicine, the APA proposes five recommendations for physicians and patients. The list was compiled by members of the Council on Research and Quality Care. The APA places a primary focus on antipsychotic medications due to a rapid increase in sales, from $9.6 billion in 2004 to $18.5 billion in 2011.

  1. Don't prescribe antipsychotic medications to patients for any indication without appropriate initial evaluation and appropriate ongoing monitoring.
  2. Don't routinely prescribe 2 or more antipsychotic medications concurrently.
  3. Don't prescribe antipsychotic medications as a first-line intervention to treat behavioral and psychological symptoms of dementia.
  4. Don't routinely prescribe antipsychotic medications as a first-line intervention for insomnia in adults.
  5. Don't routinely prescribe antipsychotic medications as a first-line intervention for children or adolescents for any diagnosis other than psychotic disorders.

Notable figures

  • Donald Cameron, was president of the American Psychiatric Association from 1952 to 1953. He conducted coercive experiments widely denounced as unethical, including involuntary electroshock therapy, drug administration, and prolonged confinement and sensory deprivation funded as part of the Central Intelligence Agency Project MKUltra.
  • Enoch Callaway, psychiatrist, pioneer in biological psychiatry.
  • Adolf Meyer, former psychiatrist-in-chief at the Johns Hopkins Hospital, was the president of the American Psychiatric Association from 1927 to 1928 and was one of the most influential figures in psychiatry in the first half of the twentieth century.
  • Mark Ragins: American psychiatrist in the recovery movement, founding member of the Village ISA. He won the 1995 van Ameringen Award for his outstanding contribution to the field of psychiatric rehabilitation and was named a Distinguished Fellow of the American Psychiatric Association in 2006.
  • Herb Pardes past president and noted figure in American psychiatry.
  • Robert Spitzer was the chair of the task force of the third edition of the DSM.

Drug company ties

In his book Anatomy of an Epidemic (2010), Robert Whitaker described the partnership that has developed between the APA and pharmaceutical companies since the 1980s. APA has come to depend on pharmaceutical money. The drug companies endowed continuing education and psychiatric "grand rounds" at hospitals. They funded a political action committee in 1982 to lobby Congress. The industry helped to pay for the APA's media training workshops. It was able to turn psychiatrists at top schools into speakers, and although the doctors felt they were independents, they rehearsed their speeches and likely would not be invited back if they discussed drug side effects. "Thought leaders" became the experts quoted in the media. As Marcia Angell wrote in The New England Journal of Medicine (2000), "thought leaders" could agree to be listed as an author of ghostwritten articles, and she cites Thomas Bodenheimer and David Rothman who describe the extent of the drug industry's involvement with doctors. The New York Times published a summary about antipsychotic medications in October 2010.

In 2008, for the first time, Senator Charles Grassley asked the APA to disclose how much of its annual budget came from drug industry funds. The APA said that industry contributed 28 percent of its budget ($14 million at that time), mainly through paid advertising in APA journals and funds for continuing medical education.

The APA receives additional funding from the pharmaceutical industry through its American Psychiatric Association Foundation (APAF), including Boehringer Ingelheim, Janssen Pharmaceuticals, and Takeda Pharmaceutical Company, among others.

Controversies

In the 1964 election, Fact magazine polled American Psychiatric Association members on whether Barry Goldwater was fit to be president and published "The Unconscious of a Conservative: A Special Issue on the Mind of Barry Goldwater". This led to a ban on the diagnosis of a public figure by psychiatrists who have not performed an examination or been authorized to release information by the patient. This became the Goldwater rule.

Supported by various funding sources, the APA and its members have played major roles in examining points of contention in the field and addressing uncertainties about psychiatric illness and its treatment, as well as the relationship of individual mental health concerns to those of the community. Controversies have related to anti-psychiatry and disability rights campaigners, who regularly protest at American Psychiatric Association offices or meetings. In 1971, members of the Gay Liberation Front organization protested the APA conference in San Francisco. In 2003 activists from MindFreedom International staged a 21-day hunger strike, protesting at a perceived unjustified biomedical focus and challenging APA to provide evidence of the widespread claim that mental disorders are due to chemical imbalances in the brain. APA published a position statement in response and the two organizations exchanged views on the evidence.

The APA's DSM came under criticism from autism specialists Tony Attwood and Simon Baron-Cohen for proposing the elimination of Asperger's syndrome as a disorder and replacing it with an autism spectrum severity scale. Roy Richard Grinker wrote a controversial editorial for The New York Times expressing support for the proposal.

The APA president in 2005, Steven Sharfstein, praised the pharmaceutical industry but argued that American psychiatry had "allowed the biopsychosocial model to become the bio-bio-bio model" and accepted "kickbacks and bribes" from pharmaceutical companies leading to the over-use of medication and neglect of other approaches.

In 2008 APA was the focus of congressional investigations on how pharmaceutical industry money shapes the practices of nonprofit organizations that purport to be independent. The drug industry accounted in 2006 for about 30 percent of the association's $62.5 million in financing, half through drug advertisements in its journals and meeting exhibits, and the other half sponsoring fellowships, conferences and industry symposiums at its annual meeting. The APA came under increasing scrutiny and questions about conflicts of interest.

The APA president in 2009–10, Alan Schatzberg, was identified as the principal investigator on a federal study into the drug mifepristone for use as an antidepressant being developed by Corcept Therapeutics, a company Schatzberg had created and in which he had several million dollars' equity.

In 2021, the APA issued an apology for its historical role in perpetuating racism.

Gamblers Anonymous

From Wikipedia, the free encyclopedia

Gamblers Anonymous (GA) founded in 1957 is an international fellowship of people who have a compulsive gambling problem. They meet regularly to share their "experiences, strength and hope", so they can help each other solve the problems compulsive gambling has created in their lives, and to help others recover from the addiction of compulsive gambling. The only requirement for membership is a desire to stop gambling, as stated in the GA Combo book page 2.

Gamblers Anonymous uses the term "Compulsive Gambling" instead of "pathological gambling" or "problem gambling" or a "gambling disorder", terms preferred by clinicians and the American Psychiatric Association (APA).

History

Gamblers Anonymous was founded in 1957 by Jim Willis. Jim W. was an alcoholic who used his experience in Alcoholics Anonymous as the foundation in forming Gamblers Anonymous into a 12 step program.

Due to favorable publicity by the newspaper columnist and TV commentator Paul Coates, of the Los Angeles Mirror, Gamblers Anonymous held its First Group Meeting, on September 13, 1957 in Los Angeles California. 13 people attended the First Gamblers Anonymous meeting. The UPI article also states that 13 people attended the first GA meeting in LA.

The organization began in Los Angeles on September 13, 1957. By 2005 there were over 1000 GA groups in the United States, and groups had been established in:

  • The United States of America, currently in all 50 states, many with multiple Gamblers Anonymous meetings each day.
  • Australia Phillip Sydney the founder of Gamblers Anonymous in Australia, held the first GA meeting in Sydney on November 25, 1961, at the Congregational Church in Surry Hills, with three other compulsive gamblers. Australia then became the second country to successfully establish a GA group in the world. Phillip was a member of Alcoholics Anonymous, which he joined in 1961 prior to starting GA. As of 2005, after Phillip Sydney's death, Australia had 200 GA meetings a week and thousands had achieved abstinence through Gamblers Anonymous Australia.
  • United Kingdom Gordon Moody, The (UK's) Secretary of the Churches' Council of Gambling in 1958, founded Gamblers Anonymous on the 10th July 1964 with the help of Henry and Vivian F. During a business trip to the UK, Henry and Vivian F. members of GA in Brooklyn New York, heard Gordon Moody address a meeting on the subject of gambling at the South Croydon Methodist Church. After which Henry F. approached Gordon Moody and introduced himself as a compulsive gambler and a member of Gamblers Anonymous in the US. Gordon in time learned a great deal from Henry and Vivian, "enough for me to understand – and to be understood" by one seeking help with a gambling problem.
  • Japan GA and Gam-Anon started in Japan in 1989. According to the GA Japan Information Center, in September 2010, GA Japan had 115 groups and GAM-ANON had 93 groups, according to the GAM-ANON Japan Information Center. The annual GA Japan National Conference is held in October, while GAM-ANON Japan holds its National Conference every June. Regional GA and GAM-ANON groups also host smaller conferences annually.
  • Kenya Jackson Okoth is the founder of Gamblers Anonymous in Nairobi Kenya, and the author of Not A Chance. GA Kenya currently lists three meetings, one in Nairobi, and two in Murang'a.
  • Ireland, Scotland, Canada
  • Mexico, South Africa, Brazil, Israel, Uganda, Korea and many other locations throughout the world.

Due to the 2020 COVID-19 pandemic, most GA meetings moved to online platforms such as Zoom, GoToMeetings, telephone conference calls, or a combination of these medium. In person gatherings at physical locations were temporarily suspended due to the COVID-19 Task Force Guidelines, and other regulatory guidelines in other countries throughout the globe.

Symptoms

Gamblers Anonymous members use the 20 Questions as a guide to determine whether they are compulsive gamblers. This is not a definitive evaluation, and only the individual with the aid of their doctor can make the determination as to whether they have a compulsive gambling problem.

The American Psychiatric Association's Diagnosis Criteria of a Gambling Disorder lists the need of a compulsive gambler to increase the amount of money bet, borrowing money to cover loses, lying to conceal the extent of one's gambling, "loss of relationships and jobs", and "frequent thoughts of gambling".

The National Center for Responsible Gaming (NCRG) uses the American Psychiatric Association's DSM-5 to describe the symptoms of a gambling disorder, aka compulsive gambling to be "chasing" loses, inability to stop, cut back or control their gambling. A Gambling disorder is the only non-substance use addiction identified in the American Psychiatric Association's DSM-5.

The Mayo Clinic offers a list of symptoms for compulsive gambling, which include "preoccupation with gambling", "trying to control, cut back or stop", and lying. A compulsive gambler may sell personal property, or engage in illegal activity to finance the gambling addiction.

NOAA lists "Indicators of Compulsive Gambling:", borrowing money, and spending exceedingly long hours gambling. NOAA also lists some of the "Behaviors Observable in the Workplace" of a compulsive gambler.

Treatment

The American Psychiatric Association (APA) suggests counseling can help the compulsive gambler. The APA also offers ""Dos" and "Don'ts" for Partners or Family Members", which include seeking support from GAM-ANON, along with money management strategies.

Gamblers Anonymous offers members a number of suggestions for abstaining from gambling, these include not going near or into a gambling establishment.

Meetings

GA meetings are the core of the fellowship, "Meetings Make It". Participating in GA meetings along with individual psychotherapy, is the preferred form of treatment according to the UCLA gambling studies program. There are a few different meeting formats offered by Gamblers Anonymous:

  • "Closed" (also called "Main") meetings are strictly for those who have or think they have a gambling problem;
  • "Beginners" (also called "Newcomers") meetings are particularly for people new to GA, those who have been in the program under one year. Here the newcomer is introduced to GA's suggestions on how to refrain from gambling, found page 17 of the combo book,. First and foremost Going to lots of meetings in the first 90 days; Staying away from gambling establishments; not associating with people who gamble; getting a sponsor, a more seasoned GA member who can help the newcomer through the first year, and in latter years too; calling other members between meetings; etc...
  • "Mixed" meetings, are gatherings of GA and GAM-ANON members only. During these meetings literature from both GA and GAM-ANON's, 12 step fellowships is read, and members from both fellowships share their experience, strength and hope with each other.
  • "Open" meetings are open to those whose lives have been affected by gambling: the spouses, family and friends of a compulsive gambler.
  • "Step" meetings, in which GA members work specifically on the 12 steps of recovery.
  • "Women's (also known as "Women-Preferred") meetings, are predominantly attend by women.
  • "Modified closed meetings" are held when a group votes to include health professionals or persons from other 12 step fellowships or guest attending with a newcomer to Gamblers Anonymous.
  • Gam-Anon meetings are exclusively for spouses, family, and friends of a compulsive gambler. The compulsive gambler need not be a member of GA for one to attend Gam-Anon meetings.

Gam-Anon

Gam-Anon is the sister 12 step program of Gamblers Anonymous, modeled after Al-Anon/Alateen for spouses, partners, family and friends of a compulsive gambler, who are suffering from the stresses and problems caused by the compulsive gambler's gambling and behaviors. Gam-Anon worldwide was started in NYC by Ruth Sachar, and her husband Irving Sachar started the NYC chapter of Gambler's Anonymous.

Incidence rate and evaluation

Problem gambling is estimated to occur in 1.6% of the adult population in the United States. GA has a list of twenty questions that can be used to self-diagnose compulsive gambling. The results from their instrument have correlated strongly with other tests that screen for compulsive gambling (e.g. the Total Sensation Seeking Scale, Boredom Susceptibility, Experience Seeking, South Oaks Gambling Screen, and Disinhibition subscales).

Effectiveness

Gamblers Anonymous has been compared with other strategies, such as Cognitive-behavioral therapy as efficacy methods of psychotherapies for pathological gambling. Compared to problem gamblers who do not attend GA, GA members tend to have more severe gambling problems, are older, have higher incomes, are less likely to be single, have more years of gambling problems, have larger debts, have more serious family conflicts, and less serious substance use disorders. GA may not be as effective for those who have not had significant gambling problems. GA is effective to prevent "relapses" (inability to remain abstinent from gambling), but not as effective when helping members deal with the consequences of their relapse.

GA spends much of its time and energy counseling members on how to deal with financial and legal problems. GA supports "pressure relief groups" where members take each other to task and encourage them to "get honest" with people in their lives and get their affairs in order. Gamblers who are able to moderate their activity are not likely to continue attending GA meetings. GA members who stopped attending meetings were more likely to consider the sharing at the meetings "meaningless" and were more critical of GA literature. Those who felt particularly elated at their first GA meetings were less likely to continue than those who had a more balanced first impression. GA, therefore, may be most suitable for severe problem gamblers who do not have compounding issues.

Criticism

Attrition

Less than 8% of those who initially attend GA remain in the program and abstain from gambling for over a year. Program participation and abstinence increase if members are involved in additional therapy, or if one or more of their family members are involved in Gam-Anon or Gam-A-Teen.

Gender bias

Among problem gamblers, it has been found that women are more focused on interpersonal issues, and that social issues were more likely to cause them to "relapse". Males more frequently discuss "external concerns" such as jobs and legal problems, and are more likely to relapse because of a substance use disorder. Therefore, it does seem plausible that GA's downplaying of spiritual, interpersonal, and psychoemotional issues, inhibits its effectiveness for women.

Literature

Jim Willis, founder of Gamblers Anonymous (GA), was first a member of Alcoholics Anonymous (AA). GA is modeled after AA’s 12-step program. The first 7 pages of GA’s 17-page Yellow Book borrow almost exclusively from AA’s Big Book. The last page of the yellow book “Gamblers Anonymous” states: “...steps are the basis for the entire GA Program.”

The format of GA's Blue Book (AA's Big Book is also blue) “GA Sharing Recovery Through Gamblers Anonymous” and Red Book “GA a New Beginning” also borrow from AA. GA's Blue Book starts out with a 4-paragraph foreword from a physician. AA's Big Book has a full chapter “The Doctor’s Opinion" that sets the stage of the problem of addiction and the medical field’s failed attempts at fixing it. The concept of a disease beyond the capability of the medical community -- and humans in general -- is borne out of AA's professional opinions and sets the stage for the dependence upon the spiritual solution of the 12 Steps.

One of the most important parts of the steps is that they provide a framework for the continuity of the program itself. If for no other reason that this, it's important that the spiritual foundation of and the reason and actions associated with the 12 steps be emphasized for continuing the program is a spiritual act -- the act of carrying the message is payback by those who have been freely given the gifts of the program.

They must rely on a power greater than themselves.

The AA Big Book and 12 & 12 are widely used as-is by many non-AA 12-step programs.

Literature

Gamblers Anonymous has several approved books used as standard literature in the group. These are some of the most popular examples:

Problem gambling

From Wikipedia, the free encyclopedia
 
Problem gambling
Other namesLudomania, degenerate gambling, gambling addiction, compulsive gambling, gambling disorder
Gambling chips.jpg
SpecialtyPsychiatry, clinical psychology 
SymptomsSpending a lot of money and time in casino/sports betting, Video game addiction
Addiction and dependence glossary
  • addiction – a biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences
  • addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems
  • dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
  • drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
  • drug withdrawal – symptoms that occur upon cessation of repeated drug use
  • physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
  • psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)
  • reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
  • rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
  • sensitization – an amplified response to a stimulus resulting from repeated exposure to it
  • substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress
  • tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose

Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to DSM-5 if certain diagnostic criteria are met. Pathological gambling is a common disorder associated with social and family costs.

The DSM-5 has re-classified the condition as an addictive disorder, with those affected exhibiting many similarities to those with substance addictions. The term gambling addiction has long been used in the recovery movement. Pathological gambling was long considered by the American Psychiatric Association to be an impulse-control disorder rather than an addiction. However, data suggest a closer relationship between pathological gambling and substance use disorders than exists between PG and obsessive–compulsive disorder, mainly because the behaviors in problem gambling and most primary substance use disorders (i.e., those not resulting from a desire to "self-medicate" for another condition such as depression) seek to activate the brain's reward mechanisms while the behaviors characterizing obsessive-compulsive disorder are prompted by overactive and misplaced signals from the brain's fear mechanisms.

Problem gambling is an addictive behavior with a high comorbidity with alcohol problems. A common tendency shared by people who have a gambling addiction is impulsivity.

Signs and symptoms

Research by governments in Australia led to a universal definition for that country which appears to be the only research-based definition not to use diagnostic criteria: "Problem gambling is characterized by many difficulties in limiting money and/or time spent on gambling which leads to adverse consequences for the gambler, others, or for the community." The University of Maryland Medical Center defines pathological gambling as "being unable to resist impulses to gamble, which can lead to severe personal or social consequences".

Most other definitions of problem gambling can usually be simplified to any gambling that causes harm to the gambler or someone else in any way; however, these definitions are usually coupled with descriptions of the type of harm or the use of diagnostic criteria. The DSM-V has since reclassified pathological gambling as gambling disorder and has listed the disorder under substance-related and addictive disorders rather than impulse-control disorders. This is due to the symptomatology of the disorder resembling an addiction not dissimilar to that of a substance use disorder. To be diagnosed, an individual must have at least four of the following symptoms in 12 months:

  • Needs to gamble with increasing amounts of money to achieve the desired excitement
  • Is restless or irritable when attempting to cut down or stop gambling
  • Has made repeated unsuccessful efforts to control, cut back, or stop gambling
  • Is often preoccupied with gambling (e.g., having persistent thoughts of reliving past gambling experiences, handicapping or planning the next venture, thinking of ways to get money with which to gamble)
  • Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed)
  • After losing money gambling, often returns another day to get even ("chasing" one's losses)
  • Lies to conceal the extent of involvement with gambling
  • Has jeopardized or lost a significant relationship, job, education, or career opportunity because of gambling
  • Relies on others to provide money to relieve desperate financial situations caused by gambling

Factors that lead to gambling addiction

Mayo Clinic specialists state that compulsive gambling may result from biological, genetic, and environmental factors, such as:

  • mental health disorders (the presence of substance use disorders, personality disorders, emotional states)
  • age and sex (usually found in youth or middle-aged people, and more common to men than women)
  • impact of family or friends
  • personality traits
  • video games (including any factors that resemble gambling such as slot machines or loot boxes)
  • drugs with rare side-effects (for example, antipsychotic medications or dopamine agonists).

Other studies add the following triggers to the mentioned above:

  • traumatic conditions
  • job-related stress
  • solitude
  • other addictions

If not treated, problem gambling may cause severe and lasting effects on an individual's life:

  • relationship-related issues
  • problems with money, bankruptcy
  • legal problems, imprisonment
  • health problems
  • suicide, including suicidal thoughts and attempts

Suicide rates

A gambler who does not receive treatment for pathological gambling when in a desperation phase may contemplate suicide. Problem gambling is often associated with increased suicidal ideation and attempts compared to the general population.

Early onset of problem gambling may increase the lifetime risk of suicide. Both comorbid substance use and comorbid mental disorders increase the risk of suicide in people with problem gambling. A 2010 Australian hospital study found that 17% of suicidal patients admitted to the Alfred Hospital's emergency department were problem gamblers.

Mechanisms

Biology

According to the Illinois Institute for Addiction Recovery, evidence indicates that pathological gambling is an addiction similar to chemical addiction. It has been observed that some pathological gamblers have lower levels of norepinephrine than normal gamblers. According to a study conducted by Alec Roy, formerly at the National Institute on Alcohol Abuse and Alcoholism, norepinephrine is secreted under stress, arousal, or thrill, so pathological gamblers gamble to make up for their under-dosage.

Studies have compared pathological gamblers to substance addicts, concluding that addicted gamblers display more physical symptoms during withdrawal.

Deficiencies in serotonin might also contribute to compulsive behavior, including a gambling addiction. There are three important points discovered after these antidepressant studies:

  1. Antidepressants can reduce pathological gambling when there is an effect on serotonergic reuptake inhibitors and 5-HT1/5-HT2 receptor antagonists.
  2. Pathological gambling, as part of obsessive-compulsive disorder, requires the higher doses of antidepressants as is usually required for depressive disorders.
  3. In cases where participants do not have or have minimal symptoms of anxiety or depression, antidepressants still have those effect.

A limited study was presented at a conference in Berlin, suggesting opioid release differs in problem gamblers from the general population, but in a very different way from people with a substance use disorder.

The findings in one review indicated the sensitization theory is responsible. Dopamine dysregulation syndrome has been observed in the aforementioned theory in people with regard to such activities as gambling.

Some medical authors suggest that the biomedical model of problem gambling may be unhelpful because it focuses only on individuals. These authors point out that social factors may be a far more important determinant of gambling behavior than brain chemicals, and they suggest that a social model may be more useful in understanding the issue. For example, an apparent increase in problem gambling in the UK may be better understood as a consequence of changes in legislation which came into force in 2007 and enabled casinos, bookmakers, and online betting sites to advertise on TV and radio for the first time and which eased restrictions on the opening of betting shops and online gambling sites.

Pathological gambling is similar to many other impulse-control disorders such as kleptomania. According to evidence from both community- and clinic-based studies, individuals who are pathological gamblers are highly likely to exhibit other psychiatric problems concurrently, including substance use disorders, mood and anxiety disorders, or personality disorders.

Pathological gambling shows several similarities with substance use disorders. There is a partial overlap in diagnostic criteria; pathological gamblers are also likely to have a substance use disorder. The "telescoping phenomenon" reflects the rapid development from initial to problematic behavior in women compared with men. This phenomenon was initially described for alcoholism, but it has also been applied to pathological gambling. Also, biological data support a relationship between pathological gambling and substance use disorder. A comprehensive UK Gambling Commission study from 2018 has also hinted at the link between gambling addiction and a reduction in physical activity, poor diet, and overall well-being. The study links problem gambling to a myriad of issues affecting relationships, and social stability.

Psychological

Several psychological mechanisms are thought to be implicated in the development and maintenance of problem gambling. First, reward processing seems to be less sensitive with problem gamblers. Second, some individuals use problem gambling as an escape from the problems in their lives (an example of negative reinforcement). Third, personality factors such as narcissism, risk-seeking, sensation-seeking, and impulsivity play a role. Fourth, problem gamblers have several cognitive biases, including the illusion of control, unrealistic optimism, overconfidence and the gambler's fallacy (the incorrect belief that a series of random events tends to self-correct so that the absolute frequencies of each of various outcomes balance each other out). Fifth, problem gamblers represent a chronic state of a behavioral spin process, a gambling spin, as described by the criminal spin theory.

Spain's gambling watchdog has updated its 2019–2020 Responsible Gaming Program, classifying problem gambling as a mental disorder.

Diagnosis

The most common instrument used to screen for "probable pathological gambling" behavior is the South Oaks Gambling Screen (SOGS) developed by Lesieur and Blume (1987) at the South Oaks Hospital in New York City. In recent years the use of SOGS has declined due to a number of criticisms, including that it overestimates false positives (Battersby, Tolchard, Thomas & Esterman, 2002).

The DSM-IV diagnostic criteria presented as a checklist is an alternative to SOGS, it focuses on the psychological motivations underpinning problem gambling and was developed by the American Psychiatric Association. It consists of ten diagnostic criteria. One frequently used screening measure based upon the DSM-IV criteria is the National Opinion Research Center DSM Screen for Gambling Problems (NODS). The Canadian Problem Gambling Inventory (CPGI) and the Victorian Gambling Screen (VGS) are newer assessment measures. The Problem Gambling Severity Index, which focuses on the harms associated with problem gambling, is composed of nine items from the longer CPGI. The VGS is also harm based and includes 15 items. The VGS has proven validity and reliability in population studies as well as Adolescents and clinic gamblers.

Treatment

Most treatment for problem gambling involves counseling, step-based programs, self-help, peer-support, medication, or a combination of these. However, no one treatment is considered to be most efficacious and, in the United States, no medications have been approved for the treatment of pathological gambling by the U.S. Food and Drug Administration (FDA).

Gamblers Anonymous (GA) is a commonly used treatment for gambling problems. Modeled after Alcoholics Anonymous, GA is a twelve-step program that emphasizes a mutual-support approach. There are three in-patient treatment centers in North America. One form of counseling, cognitive behavioral therapy (CBT) has been shown to reduce symptoms and gambling-related urges. This type of therapy focuses on the identification of gambling-related thought processes, mood and cognitive distortions that increase one's vulnerability to out-of-control gambling. Additionally, CBT approaches frequently utilize skill-building techniques geared toward relapse prevention, assertiveness and gambling refusal, problem solving and reinforcement of gambling-inconsistent activities and interests.

As to behavioral treatment, some recent research supports the use of both activity scheduling and desensitization in the treatment of gambling problems. In general, behavior analytic research in this area is growing There is evidence that the SSRI paroxetine is efficacious in the treatment of pathological gambling. Additionally, for patients with both pathological gambling and a comorbid bipolar spectrum condition, sustained-release lithium has shown efficacy in a preliminary trial. The opioid antagonist drug nalmefene has also been trialled quite successfully for the treatment of compulsive gambling. Group concepts based on CBT, such as the metacognitive training for problem gambling have also proven effective.

Step-based programs

12 Step–based programs such as Gamblers Anonymous are specific to gambling and generic to healing addiction, creating financial health, and improving mental wellness. Commercial alternatives that are designed for clinical intervention, using the best of health science and applied education practices, have been used as patient-centered tools for intervention since 2007. They include measured efficacy and resulting recovery metrics.

Motivational interviewing

Motivational interviewing is one of the treatments of compulsive gambling. The motivational interviewer's basic goal is promoting readiness to change through thinking and resolving mixed feelings. Avoiding aggressive confrontation, argument, labeling, blaming, and direct persuasion, the interviewer supplies empathy and advice to compulsive gamblers who define their own goal. The focus is on promoting freedom of choice and encouraging confidence in the ability to change.

Peer support

A growing method of treatment is peer support. With the advancement of online gambling, many gamblers experiencing issues use various online peer-support groups to aid their recovery. This protects their anonymity while allowing them to attempt recovery on their own, often without having to disclose their issues to loved ones.

Self-help

Research into self-help for problem gamblers has shown benefits. A study by Wendy Slutske of the University of Missouri concluded one-third of pathological gamblers overcome it by natural recovery.

Pharmaceutical treatments

Numerous pharmaceutical approaches to treating gambling addiction have been suggested including antidepressants, atypical antipsychotic agents, mood stabilizers, and opioid antagonists, however the best approach for treatment, treatment regime including dosage and timing is not clear. There is some evidence to suggest that opioid antagonists, for example, naltrexone or nalmefene, and atypical antipsychotics such as olanzapine, may help reduce the severity of gambling symptoms in the short-term, however it is not clear if these medications are effective at improving other psychological symptoms associated with this disorder or for longer term symptom relief from problem gambling. The evidence suggesting the effectiveness of mood stabilizers is not clear.

Self-exclusion

Gambling self-exclusion (voluntary exclusion) programs are available in the US, the UK, Canada, Australia, South Africa, France, and other countries. They seem to help some (but not all) problem gamblers to gamble less often.

Some experts maintain that casinos in general arrange for self-exclusion programs as a public relations measure without actually helping many of those with problem gambling issues. A campaign of this type merely "deflects attention away from problematic products and industries", according to Natasha Dow Schull, a cultural anthropologist at New York University and author of the book Addiction by Design.

There is also a question as to the effectiveness of such programs, which can be difficult to enforce. In the province of Ontario, Canada, for example, the Self-Exclusion program operated by the government's Ontario Lottery and Gaming Corporation (OLG) is not effective, according to investigation conducted by the television series, revealed in late 2017. |"Gambling addicts ... said that while on the ... self-exclusion list, they entered OLG properties on a regular basis" in spite of the facial recognition technology in place at the casinos, according to the Canadian Broadcasting Corporation. As well, a CBC journalist who tested the system found that he was able to enter Ontario casinos and gamble on four distinct occasions, in spite of having been registered and photographed for the self-exclusion program. An OLG spokesman provided this response when questioned by the CBC: "We provide supports to self-excluders by training our staff, by providing disincentives, by providing facial recognition, by providing our security officers to look for players. No one element is going to be foolproof because it is not designed to be foolproof".

Impact (Australia)

According to the Productivity Commission's 2010 final report into gambling, the social cost of problem gambling is close to 4.7 billion dollars a year. Some of the harms resulting from problem gambling include depression, suicide, lower work productivity, job loss, relationship breakdown, crime and bankruptcy. A survey conducted in 2008 found that the most common motivation for fraud was problem gambling, with each incident averaging a loss of $1.1 million. According to Darren R. Christensen. Nicki A. Dowling, Alun C. Jackson and Shane A. Thomas, a survey done from 1994 to 2008 in Tasmania gave results that gambling participation rates have risen rather than fallen over this period.

Prevalence

Europe

In Europe, the rate of problem gambling is typically 0.5 to 3 percent. The "British Gambling Prevalence Survey 2007", conducted by the United Kingdom Gambling Commission, found approximately 0.6 percent of the adult population had problem gambling issues—the same percentage as in 1999. The highest prevalence of problem gambling was found among those who participated in spread betting (14.7%), fixed odds betting terminals (11.2%), and betting exchanges (9.8%). In Norway, a December 2007 study showed the amount of current problem gamblers was 0.7 percent.

With gambling addiction on the rise worldwide and across Europe in particular, those calling gambling a disease have been gaining grounds. The UK Gambling Commission announced a significant shift in their approach to gambling through their reclassification of gambling as a disease, and therefore that it should be addressed adequately by the NHS.

The World Health Organization has also classified gambling a disease. In its 72nd World Health Assembly held on Saturday, May 25, 2019, ‘gaming disorder’ was recognized as an official illness. The 194-member meet added excessive gaming to a classified list of diseases as it revised its International Statistical Classification of Diseases and Related Health Problems (ICD-11).

North America

Lizbeth García Quevedo, director of the Coordination with Federal Entities (CONADIC), spoke of pathological gambling as a strong addiction in Mexico: "It has very similar behaviors, that is why some experts consider it an addiction because it is similar in the behaviors, in the origins, some risk factors that can trigger pathological gambling, it can also trigger drug consumption". In Mexico there could be between one and three million people addicted to gambling. "They should be aware of what their children are doing, and on the other hand, they should motivate pro-active gambling, healthy gambling", commented Lizbeth García Quevedo. The Ministry of Health document highlights that a study on pathological gambling that analyzed 46 studies carried out in Canada, the United States, Australia, Sweden, Norway, England, Switzerland and Spain, revealed that the prevalence of pathological gambling is relatively higher among adolescents, which shows the continuity of the problem considering that many pathological gamblers state that they started their gambling behavior at an early age.

In the United States, the percentage of pathological gamblers was 0.6 percent, and the percentage of problem gamblers was 2.3 percent in 2008. Studies commissioned by the National Gambling Impact Study Commission Act has shown the prevalence rate ranges from 0.1 percent to 0.6 percent. Nevada has the highest percentage of pathological gambling; a 2002 report estimated 2.2 to 3.6 percent of Nevada residents over the age of 18 could be called problem gamblers. Also, 2.7 to 4.3 percent could be called probable pathological gamblers.

According to a 1997 meta-analysis by Harvard Medical School's division on addictions, 1.1 percent of the adult population of the United States and Canada could be called pathological gamblers. A 1996 study estimated 1.2 to 1.9 percent of adults in Canada were pathological. In Ontario, a 2006 report showed 2.6 percent of residents experienced "moderate gambling problems" and 0.8 percent had "severe gambling problems". In Quebec, an estimated 0.8 percent of the adult population were pathological gamblers in 2002. Although most who gamble do so without harm, approximately 6 million American adults are addicted to gambling.

According to a survey of 11th and 12th graders in Wood County, Ohio found that the percentage who reported being unable to control their gambling rose to 8.3 percent in 2022, up from just 4.2 percent in 2018. The reasons for the increase cited, are the time spent online during the COVID-19 pandemic, gambling-like elements put into video games, and the increased legalization of sports betting in a number of U.S. states.

Signs of a gambling problem include:

  • Using income or savings to gamble while letting bills go unpaid
  • Repeated unsuccessful attempts to stop gambling
  • Chasing losses
  • Losing sleep over thoughts of gambling
  • Arguing with friends or family about gambling behavior
  • Feeling depressed or suicidal because of gambling losses

South America

For Isabel Sánchez Sosa, coordinator of the Compulsive Gamblers Association of Argentina, "gambling addiction is growing a lot in the country because the offer is impressive" and in this sense she asserted that the presence of bingos is a common issue in all neighborhoods. In the province of Buenos Aires there are 46 bingos.

Oceania (Australia)

Casinos and poker machines in pubs and clubs facilitate problem gambling in Australia. The building of new hotels and casinos has been described as "one of the most active construction markets in Australia"; for example, AUD$860 million was allocated to rebuild and expand the Star Complex in Sydney.

A 2010 study, conducted in the Northern Territory by researchers from the Australian National University (ANU) and Southern Cross University (SCU), found that the proximity of a person's residence to a gambling venue is significant in terms of prevalence. Harmful gambling in the study was prevalent among those living within 100 metres of any gambling venue, and was over 50% higher than among those living ten kilometres from a venue. The study's data stated:

Specifically, people who lived 100 metres from their favourite venue visited an estimated average of 3.4 times per month. This compared to an average of 2.8 times per month for people living one kilometre away, and 2.2 times per month for people living ten kilometres away.

According to the Productivity Commission's 2016 report into gambling, 0.5% to 1% (80,000 to 160,000) of the Australian adult population had significant problems resulting from gambling. A further 1.4% to 2.1% (230,000 to 350,000) of the Australian adult population experienced moderate risks making them likely to be vulnerable to problem gambling. Estimates show that problem gamblers account for an average of 41% of the total gaming machine spending.

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