Metformin

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https://en.wikipedia.org/wiki/Metformin

 

Metformin

Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, and is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotic medication. It has been shown to inhibit inflammation, and is not associated with weight gain. Metformin is taken by mouth.

Metformin is generally well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain. It has a small risk of causing low blood sugar. High blood lactic acid level (acidosis) is a concern if the medication is used in overly large doses or prescribed in people with severe kidney problems.

Metformin is a biguanide anti-hyperglycemic agent. It works by decreasing glucose production in the liver, increasing the insulin sensitivity of body tissues, and increasing GDF15 secretion, which reduces appetite and caloric intake.

Metformin was first described in the scientific literature in 1922 by Emil Werner and James Bell. French physician Jean Sterne began the study in humans in the 1950s. It was introduced as a medication in France in 1957. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2022, it was the second most commonly prescribed medication in the United States, with more than 86 million prescriptions. In Australia, it was one of the top 10 most prescribed medications between 2017 and 2023.

Medical uses

Metformin is used to lower the blood glucose in those with type 2 diabetes. It is also used as a second-line agent for infertility in those with polycystic ovary syndrome.

Type 2 diabetes

The American Diabetes Association and the American College of Physicians both recommend metformin as a first-line agent to treat type 2 diabetes. It is as effective as repaglinide and more effective than all other oral drugs for type 2 diabetes.

Efficacy

Treatment guidelines for major professional associations, including the European Association for the Study of Diabetes, the European Society for Cardiology, and the American Diabetes Association, describe evidence for the cardiovascular benefits of metformin as equivocal. A 2020 Cochrane systematic review did not find enough evidence of reduction of cardiovascular mortality, non-fatal myocardial infarction or non-fatal stroke when comparing metformin monotherapy to other glucose-lowering drugs, behavior change interventions, placebo or no intervention.

The use of metformin reduces body weight in people with type 2 diabetes in contrast to sulfonylureas, which are associated with weight gain. Some evidence shows that metformin is associated with weight loss in obesity in the absence of diabetes. Metformin has a lower risk of hypoglycemia than the sulfonylureas, although hypoglycemia has uncommonly occurred during intense exercise, calorie deficit, or when used with other agents to lower blood glucose. Metformin modestly reduces low density lipoprotein and triglyceride levels.

In individuals with prediabetes, a 2019 systematic review comparing the effects of metformin with other interventions in the reduction of risk of developing type 2 diabetes found moderate-quality evidence that metformin reduced the risk of developing type 2 diabetes when compared to diet and exercise or a placebo. However, when comparing metformin to intensive diet or exercise, moderate-quality evidence was found that metformin did not reduce risk of developing type 2 diabetes and very low-quality evidence was found that adding metformin to intensive diet or exercise did not show any advantage or disadvantage in reducing risk of type 2 diabetes when compared to intensive exercise and diet alone. The same review also found one suitable trial comparing the effects of metformin and sulfonylurea in reducing the risk of developing type 2 diabetes in prediabetic individuals, however, this trial did not report any patient-relevant outcomes.

Polycystic ovary syndrome

In those with polycystic ovary syndrome (PCOS), tentative evidence shows that metformin use increases the rate of live births. This includes those who have not been able to get pregnant with clomiphene. Metformin does not appear to change the risk of miscarriage. A number of other benefits have also been found both during pregnancy and in nonpregnant women with PCOS. In an updated Cochrane (2020) review on metformin versus placebo/no treatment before or during IVF/ICSI in women with PCOS no conclusive evidence of improved live birth rates was found. In long GnRH-agonist protocols there was uncertainty in the evidence of improved live birth rates but there could be increases in clinical pregnancy rate. In short GnRH-antagonist protocols metformin may reduce live birth rates with uncertainty on its effect on clinical pregnancy rate. Metformin may result in a reduction of OHSS but could come with a greater frequency of side effects. There was uncertainty as to metformin's impact on miscarriage. The evidence does not support general use during pregnancy for improving maternal and infant outcomes in obese women.

The United Kingdom's National Institute for Health and Clinical Excellence recommended in 2004 that women with PCOS and a body mass index above 25 be given metformin for anovulation and infertility when other therapies fail to produce results. UK and international clinical practice guidelines do not recommend metformin as a first-line treatment or do not recommend it at all, except for women with glucose intolerance. The guidelines suggest clomiphene as the first medication option and emphasize lifestyle modification independently from medical treatment. Metformin treatment decreases the risk of developing type 2 diabetes in women with PCOS who exhibited impaired glucose tolerance at baseline.

Diabetes and pregnancy

A total review of metformin use during pregnancy compared to insulin alone found good short-term safety for both the mother and baby, but safety in the longer term is unclear. Several observational studies and randomized controlled trials found metformin to be as effective and safe as insulin for the management of gestational diabetes. Nonetheless, several concerns have been raised and evidence on the long-term safety of metformin for both mother and child is lacking. Compared with insulin, women with gestational diabetes treated with metformin gain less weight and are less likely to develop pre-eclampsia during pregnancy. Babies born to women treated with metformin have less visceral fat, and this may make them less prone to insulin resistance in later life. The use of metformin for gestational diabetes resulted in smaller babies compared to treatment with insulin. However, despite initially lower birth weight, children exposed to metformin during pregnancy had accelerated growth after birth, and were heavier by mid-childhood than those exposed to insulin during pregnancy. This pattern of initial low birth weight followed by catch-up growth that surpasses comparative children has been associated with long-term cardiometabolic disease.

A systematic review and meta-analysis of metformin, published in 2024, found that it is safe and effective in managing gestational diabetes or diabetes in pregnancy with no adverse impact on the mother or the child after eleven years of childbirth.

Weight change

Metformin use is typically associated with weight loss. It appears to be safe and effective in counteracting the weight gain caused by the antipsychotic medications olanzapine and clozapine. Although modest reversal of clozapine-associated weight gain is found with metformin, primary prevention of weight gain is more valuable.

Use with insulin

Metformin may reduce the insulin requirement in type 1 diabetes, albeit with an increased risk of hypoglycemia.

Contraindications

Metformin is contraindicated in people with:

• Severe renal impairment (estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m²)
• Known hypersensitivity to metformin
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis (from uncontrolled diabetes), with or without coma

Adverse effects

The most common adverse effect of metformin is gastrointestinal irritation, including diarrhea, cramps, nausea, vomiting, and increased flatulence. Metformin is more commonly associated with gastrointestinal adverse effects than most other antidiabetic medications. The most serious potential adverse effect of metformin is lactic acidosis; this complication is rare, and seems to be related to impaired liver or kidney function. Metformin is not approved for use in those with severe kidney disease, but may still be used at lower doses in those with kidney problems.

Gastrointestinal

Gastrointestinal upset can cause severe discomfort; it is most common when metformin is first administered, or when the dose is increased. The discomfort can often be avoided by beginning at a low dose (1.0 to 1.7 g/day) and increasing the dose gradually, but even with low doses, 5% of people may be unable to tolerate metformin. Use of slow or extended-release preparations may improve tolerability.

Long-term use of metformin has been associated with increased homocysteine levels and malabsorption of vitamin B₁₂. Higher doses and prolonged use are associated with increased incidence of vitamin B₁₂ deficiency, and some researchers recommend screening or prevention strategies.

Vitamin B₁₂

Metformin treatment has been associated with reductions in vitamin B₁₂ in certain people. Left untreated, vitamin B12 deficiencies can lead to serious health problems including neurological problems and anemia. Although more research is needed to understand the mechanisms of this association, it is suggested that people who take metformin monitor their vitamin B12 levels and if low, begin supplementation. In most cases of deficiencies if the person's deficiency can be corrected with exogenous administration of vitamin B12, they can continue their metformin treatment under the supervision of their doctor.

Lactic acidosis

Lactic acidosis rarely occurs with metformin exposure during routine medical care. Rates of metformin-associated lactic acidosis are about nine per 100,000 persons/year, which is similar to the background rate of lactic acidosis in the general population. A systematic review concluded no data exists to definitively link metformin to lactic acidosis.

Metformin is generally safe in people with mild to moderate chronic kidney disease, with a proportional reduction of metformin dose according to severity of estimated glomerular filtration rate (eGFR) and with periodic assessment of kidney function, (e.g., periodic plasma creatinine measurement). The US Food and Drug Administration (FDA) recommends avoiding the use of metformin in more severe chronic kidney disease, below the eGFR cutoff of 30 mL/minute/1.73 m². Lactate uptake by the liver is diminished with metformin use because lactate is a substrate for hepatic gluconeogenesis, a process that metformin inhibits. In healthy individuals, this slight excess is cleared by other mechanisms (including uptake by unimpaired kidneys), and no significant elevation in blood levels of lactate occurs. Given severely impaired kidney function, clearance of metformin and lactate is reduced, increasing levels of both, and possibly causing lactic acid buildup. Because metformin decreases liver uptake of lactate, any condition that may precipitate lactic acidosis is a contraindication. Common causes include alcoholism (due to depletion of NAD+ stores), heart failure, and respiratory disease (due to inadequate tissue oxygenation); the most common cause is kidney disease.

Metformin-associated lactate production may also take place in the large intestine, which could potentially contribute to lactic acidosis in those with risk factors. The clinical significance of this is unknown, though, and the risk of metformin-associated lactic acidosis is most commonly attributed to decreased hepatic uptake rather than increased intestinal production.

Overdose

The most common symptoms following an overdose include vomiting, diarrhea, abdominal pain, tachycardia, drowsiness, and rarely, hypoglycemia or hyperglycemia. Treatment of metformin overdose is generally supportive, as no specific antidote is known. Extracorporeal treatments are recommended in severe overdoses. Due to metformin's low molecular weight and lack of plasma protein binding, these techniques have the benefit of removing metformin from the blood plasma, preventing further lactate overproduction.

Metformin may be quantified in blood, plasma, or serum to monitor therapy, confirm a diagnosis of poisoning, or assist in a forensic death investigation. Blood or plasma metformin concentrations are usually in a range of 1–4 mg/L in persons receiving therapeutic doses, 40–120 mg/L in victims of acute overdosage, and 80–200 mg/L in fatalities. Chromatographic techniques are commonly employed.

The risk of metformin-associated lactic acidosis is also increased by a massive overdose of metformin, although even quite large doses are often not fatal.

Interactions

The H₂-receptor antagonist cimetidine causes an increase in the plasma concentration of metformin by reducing clearance of metformin by the kidneys; both metformin and cimetidine are cleared from the body by tubular secretion, and both, particularly the cationic (positively charged) form of cimetidine, may compete for the same transport mechanism. A small double-blind, randomized study found the antibiotic cephalexin to also increase metformin concentrations by a similar mechanism; theoretically, other cationic medications may produce the same effect.

Metformin also interacts with anticholinergic medications, due to their effect on gastric motility. Anticholinergic drugs reduce gastric motility, prolonging the time drugs spend in the gastrointestinal tract. This impairment may lead to more metformin being absorbed than without the presence of an anticholinergic drug, thereby increasing the concentration of metformin in the plasma and increasing the risk for adverse effects.

Pharmacology

Mechanism of action

The molecular mechanism of metformin is not completely understood. Multiple potential mechanisms of action have been proposed: inhibition of the mitochondrial respiratory chain (complex I), activation of AMP-activated protein kinase (AMPK), inhibition of glucagon-induced elevation of cyclic adenosine monophosphate (cAMP) with reduced activation of protein kinase A (PKA), complex IV–mediated inhibition of the GPD2 variant of mitochondrial glycerol-3-phosphate dehydrogenase (thereby reducing the contribution of glycerol to hepatic gluconeogenesis), and an effect on gut microbiota.

Metformin exerts an anorexiant effect in most people, decreasing caloric intake. Metformin decreases gluconeogenesis (glucose production) in the liver. Metformin inhibits basal secretion from the pituitary gland of growth hormone, adrenocorticotropic hormone, follicle stimulating hormone, and expression of proopiomelanocortin, which in part accounts for its insulin-sensitizing effect with multiple actions on tissues including the liver, skeletal muscle, endothelium, adipose tissue, and the ovaries. The average person with type 2 diabetes has three times the normal rate of gluconeogenesis; metformin treatment reduces this by over one-third.

Activation of AMPK was required for metformin's inhibitory effect on liver glucose production. AMPK is an enzyme that plays an important role in insulin signaling, whole-body energy balance, and the metabolism of glucose and fats. AMPK activation is required for an increase in the expression of small heterodimer partner, which in turn inhibited the expression of the hepatic gluconeogenic genes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase. Metformin is frequently used in research along with AICA ribonucleotide as an AMPK agonist. The mechanism by which biguanides increase the activity of AMPK remains uncertain: metformin increases the concentration of cytosolic adenosine monophosphate (AMP) (as opposed to a change in total AMP or total AMP/adenosine triphosphate) which could activate AMPK allosterically at high levels; a newer theory involves binding to PEN-2. Metformin inhibits cyclic AMP production, blocking the action of glucagon, and thereby reducing fasting glucose levels. Metformin also induces a profound shift in the faecal microbial community profile in diabetic mice, and this may contribute to its mode of action possibly through an effect on glucagon-like peptide-1 secretion.

In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake (by inducing the phosphorylation of GLUT4 enhancer factor), decreases insulin-induced suppression of fatty acid oxidation, and decreases the absorption of glucose from the gastrointestinal tract. Increased peripheral use of glucose may be due to improved insulin binding to insulin receptors. The increase in insulin binding after metformin treatment has also been demonstrated in patients with type 2 diabetes.

AMPK probably also plays a role in increased peripheral insulin sensitivity, as metformin administration increases AMPK activity in skeletal muscle. AMPK is known to cause GLUT4 deployment to the plasma membrane, resulting in insulin-independent glucose uptake. Some metabolic actions of metformin do appear to occur by AMPK-independent mechanisms, however, AMPK likely has a modest overall effect and its activity is not likely to directly decrease gluconeogenesis in the liver.

Metformin has indirect antiandrogenic effects in women with insulin resistance, such as those with PCOS, due to its beneficial effects on insulin sensitivity. It may reduce testosterone levels in such women by as much as 50%. A Cochrane review, though, found that metformin was only slightly effective for decreasing androgen levels in women with PCOS.

Metformin also has significant effects on the gut microbiome, such as its effect on increasing agmatine production by gut bacteria, but the relative importance of this mechanism compared to other mechanisms is uncertain.

Due to its effect on GLUT4 and AMPK, metformin has been described as an exercise mimetic.

Pharmacokinetics

Metformin has an oral bioavailability of 50–60% under fasting conditions, and is absorbed slowly. Peak plasma concentrations (C_max) are reached within 1–3 hours of taking immediate-release metformin and 4–8 hours with extended-release formulations. The plasma protein binding of metformin is negligible, as reflected by its very high apparent volume of distribution (300–1000 L after a single dose). Steady state is usually reached in 1–2 days.

Metformin has acid dissociation constant values (pK_a) of 2.8 and 11.5, so it exists very largely as the hydrophilic cationic species at physiological pH values. The metformin pK_a values make it a stronger base than most other basic medications with less than 0.01% nonionized in blood. Furthermore, the lipid solubility of the nonionized species is slight as shown by its low logP value (log(10) of the distribution coefficient of the nonionized form between octanol and water) of −1.43. These chemical parameters indicate low lipophilicity and, consequently, rapid passive diffusion of metformin through cell membranes is unlikely. As a result of its low lipid solubility, it requires the transporter SLC22A1 for it to enter cells. The logP of metformin is less than that of phenformin (−0.84) because two methyl substituents on metformin impart lesser lipophilicity than the larger phenylethyl side chain in phenformin. More lipophilic derivatives of metformin are presently under investigation to produce prodrugs with superior oral absorption than metformin.

Metformin is not metabolized. It is cleared from the body by tubular secretion and excreted unchanged in the urine; it is undetectable in blood plasma within 24 hours of a single oral dose. The average elimination half-life in plasma is 6.2 hours. Metformin is distributed to (and appears to accumulate in) red blood cells, with a much longer elimination half-life: 17.6 hours (reported as ranging from 18.5 to 31.5 hours in a single-dose study of nondiabetics).

Some evidence indicates that liver concentrations of metformin in humans may be two to three times higher than plasma concentrations, due to portal vein absorption and first-pass uptake by the liver in oral administration.

Chemistry

Metformin hydrochloride (1,1-dimethylbiguanide hydrochloride) is freely soluble in water, slightly soluble in ethanol, but almost insoluble in acetone, ether, or chloroform. The pK_a of metformin is 12.4. The usual synthesis of metformin, originally described in 1922, involves the one-pot reaction of dimethylamine hydrochloride and 2-cyanoguanidine over heat.

According to the procedure described in the 1975 Aron patent, and the Pharmaceutical Manufacturing Encyclopedia, equimolar amounts of dimethylamine and 2-cyanoguanidine are dissolved in toluene with cooling to make a concentrated solution, and an equimolar amount of hydrogen chloride is slowly added. The mixture begins to boil on its own, and after cooling, metformin hydrochloride precipitates with a 96% yield.

Impurities

See also: Ranitidine § impurities

In December 2019, the US Food and Drug Administration (FDA) announced that it learned that some metformin medicines manufactured outside the United States might contain a nitrosamine impurity called N-nitrosodimethylamine (NDMA), classified as a probable human carcinogen, at low levels. Health Canada announced that it was assessing NDMA levels in metformin. The European Medicines Agency provided an update on NDMA in metformin.

In February 2020, the FDA found NDMA levels in some tested metformin samples that did not exceed the acceptable daily intake.

In February 2020, Health Canada announced a recall of Apotex immediate-release metformin, followed in March by recalls of Ranbaxy metformin and in March by Jamp metformin.

In May 2020, the FDA asked five companies to voluntarily recall their sustained-release metformin products. The five companies were not named, but they were revealed to be Amneal Pharmaceuticals, Actavis Pharma, Apotex Corp, Lupin Pharma, and Marksans Pharma Limited in a letter sent to Valisure, the pharmacy that had first alerted the FDA to this contaminant in metformin via a Citizen Petition.

In June 2020, the FDA posted its laboratory results showing NDMA amounts in metformin products it tested. It found NDMA in certain lots of ER metformin and is recommending companies recall lots with levels of NDMA above the acceptable intake limit of 96 nanograms per day. The FDA is also collaborating with international regulators to share testing results for metformin.

In July 2020, Lupin Pharmaceuticals pulled all lots (batches) of metformin after discovering unacceptably high levels of NDMA in tested samples.

In August 2020, Bayshore Pharmaceuticals recalled two lots of tablets.

The FDA issued revised guidelines about nitrosamine impurities in September 2024.

History

Galega officinalis is a natural source of galegine.

The biguanide class of antidiabetic medications, which also includes the withdrawn agents phenformin and buformin, originates from the plant Goat's rue (Galega officinalis) also known as Galega, French lilac, Italian fitch, Spanish sainfoin, Pestilenzkraut, or Professor-weed. (The plant should not be confused with plants in the genus Tephrosia which are highly toxic and sometimes also called Goat's rue.) Galega officinalis has been used in folk medicine for several centuries. G. officinalis itself does not contain biguanide medications which are chemically synthesized compounds composed of two guanidine molecules and designed to be less toxic than the plant-derived parent compounds guanidine and galegine (isoamylene guanidine).

Metformin was first described in the scientific literature in 1922, by Emil Werner and James Bell, as a product in the synthesis of N,N-dimethylguanidine. In 1929, Slotta and Tschesche discovered its sugar-lowering action in rabbits, finding it the most potent biguanide analog they studied. This result was ignored, as other guanidine analogs such as the synthalins, took over and were themselves soon overshadowed by insulin.

Interest in metformin resumed at the end of the 1940s. In 1950, metformin, unlike some other similar compounds, was found not to decrease blood pressure and heart rate in animals. That year, Filipino physician Eusebio Y. Garcia used metformin (he named it Fluamine) to treat influenza; he noted the medication "lowered the blood sugar to minimum physiological limit" and was not toxic. Garcia believed metformin to have bacteriostatic, antiviral, antimalarial, antipyretic, and analgesic actions. In a series of articles in 1954, Polish pharmacologist Janusz Supniewski was unable to confirm most of these effects, including lowered blood sugar. Instead, he observed antiviral effects in humans.

French diabetologist Jean Sterne studied the antihyperglycemic properties of galegine, an alkaloid isolated from G. officinalis, which is related in structure to metformin, and had seen brief use as an antidiabetic before the synthalins were developed. Later, working at Laboratoires Aron in Paris, he was prompted by Garcia's report to reinvestigate the blood sugar-lowering activity of metformin and several biguanide analogs. Sterne was the first to try metformin on humans for the treatment of diabetes; he coined the name "Glucophage" (glucose eater) for the medication and published his results in 1957.

It was introduced as a medication in France in 1957. Metformin became available in the British National Formulary in 1958. It was sold in the UK by a small Aron subsidiary called Rona.

Broad interest in metformin was not rekindled until the withdrawal of the other biguanides in the 1970s. Metformin was approved in Canada in 1972, but did not receive approval by the U.S. Food and Drug Administration (FDA) for type 2 diabetes until 1994. Produced under license by Bristol-Myers Squibb, Glucophage was the first branded formulation of metformin to be marketed in the U.S., beginning on 3 March 1995. Generic formulations are available in several countries.

The US FDA granted the application for metformin orphan drug designation. The European Medicines Agency granted orphan drug status to metformin.

Society and culture

Environmental impact

Metformin and its major transformation product guanylurea [de] are present in wastewater treatment plant effluents and regularly detected in surface waters. Guanylurea concentrations above 200 μg/L have been measured in the German river Erpe, which are amongst the highest reported for pharmaceutical transformation products in aquatic environments.

Formulations

Generic metformin 500-mg tablets, as sold in the United Kingdom

Metformin is the British Approved Name (BAN), the United States Adopted Name (USAN), and the International Nonproprietary Name (INN). It is sold under several brand names. Common brand names include Glucophage, Riomet, Fortamet, and Glumetza in the US. In other areas of the world, there is also Obimet, Gluformin, Dianben, Diabex, Diaformin, Metsol, Siofor, Metfogamma and Glifor. There are several formulations of metformin available on the market, and all but the liquid form have generic equivalents.

Combination with other medications

When used for type 2 diabetes, metformin is often prescribed in combination with other medications. Several medications are available as fixed-dose combinations, with the potential to reduce pill burden, decrease cost, and simplify administration.

Thiazolidinediones (glitazones)

Rosiglitazone

A combination of metformin and rosiglitazone was released in 2002, and sold as Avandamet by GlaxoSmithKline, or as a generic medication. Formulations are 500/1, 500/2, 500/4, 1000/2, and 1000 mg/4 mg of metformin/rosiglitazone.

In 2009, it was the most popular metformin combination.

In 2005, the stock of Avandamet was removed from the market, after inspections showed the factory where it was produced was violating good manufacturing practices. The medication pair continued to be prescribed separately, and Avandamet was again available by the end of that year. A generic formulation of metformin/rosiglitazone from Teva received tentative approval from the FDA and reached the market in early 2012.

However, following a meta-analysis in 2007, that linked the medication's use to an increased risk of heart attack, concerns were raised over the safety of medicines containing rosiglitazone. In September 2010, the European Medicines Agency recommended that the medication be suspended from the European market because the benefits of rosiglitazone no longer outweighed the risks.

It was withdrawn from the market in the UK and India in 2010, and in New Zealand and South Africa in 2011. From November 2011 until November 2013 the FDA did not allow rosiglitazone or metformin/rosiglitazone to be sold without a prescription; moreover, makers were required to notify patients of the risks associated with its use, and the drug had to be purchased by mail order through specified pharmacies.

In November 2013, the FDA lifted its earlier restrictions on rosiglitazone after reviewing the results of the 2009 RECORD clinical trial (a six-year, open-label randomized control trial), which failed to show elevated risk of heart attack or death associated with the medication.

Pioglitazone

The combination of metformin and pioglitazone (Actoplus Met, Piomet, Politor, Glubrava) is available in the US and the European Union.

DPP-4 inhibitors

See also: GLP-1 receptor agonist

Dipeptidyl peptidase-4 inhibitors inhibit dipeptidyl peptidase-4 and thus reduce glucagon and blood glucose levels.

DPP-4 inhibitors combined with metformin include a sitagliptin/metformin combination (Janumet), a saxagliptin/metformin combination (Kombiglyze XR, Komboglyze), and an alogliptin/metformin combination (Kazano, Vipdomet).

Linagliptin combined with metformin hydrochloride is sold under the brand name Jentadueto. As of August 2021, linagliptin/metformin is available as a generic medicine in the US.

SGLT2 inhibitors

There are combinations of metformin with the SGLT2 inhibitors dapagliflozin, empagliflozin, and canagliflozin.

Sulfonylureas

Sulfonylureas act by increasing insulin release from the beta cells in the pancreas.

A 2019 systematic review suggested that there is limited evidence if the combined use of metformin with sulfonylurea compared to the combination of metformin plus another glucose-lowering intervention, provides benefit or harm in mortality, severe adverse events, macrovascular and microvascular complications. Combined metformin and sulfonylurea therapy did appear to lead to a higher risk of hypoglycemia.

Metformin is available combined with the sulfonylureas glipizide (Metaglip) and glibenclamide (US: glyburide) (Glucovance). Generic formulations of metformin/glipizide and metformin/glibenclamide are available (the latter is more popular).

Meglitinide

Meglitinides are similar to sulfonylureas, as they bind to beta cells in the pancreas, but differ by the site of binding to the intended receptor and the drugs' affinities to the receptor. As a result, they have a shorter duration of action compared to sulfonylureas and require higher blood glucose levels to begin to secrete insulin. Both meglitinides, known as nateglinide and repanglinide, are sold in formulations combined with metformin. A repaglinide/metformin combination is sold as Prandimet, or as its generic equivalent.

Triple combination

The combination of metformin with dapagliflozin and saxagliptin is available in the United States as Qternmet XR.

The combination of metformin with pioglitazone and glibenclamide is available in India as Accuglim-MP, Adglim MP, and Alnamet-GP; and in the Philippines as Tri-Senza.

The combination of metformin with pioglitazone and lipoic acid is available in Turkey as Pional.

Research

Metformin is a pleiotropic drug, with extensive off-target activity beyond its antidiabetic effect. Much of this has been attributed to its action on AMP-activated protein kinase (AMPK), although other mechanisms have been proposed. Metformin has been studied for its effects on multiple other conditions, including:

• Non-alcoholic fatty liver disease
• Premature puberty
• Cancer
• Cardiovascular disease in people with diabetes
• Aging

Aging and life extension

Metformin is under investigation that it may be an agent that delays aging; it may increase longevity in some animal models (e.g., C. elegans and crickets). This effect may be mediated by insulin and carbohydrate regulation, similar to its effects on diabetes. Whether metformin may help extend life, even in otherwise healthy people, remains unknown; a 2021 review of the literature found it is likely to improve healthspan, i.e., the number of years spent in good health, rather than lifespan overall.

A 2017 review found that people with diabetes who were taking metformin had lower all-cause mortality. They also had reduced cancer and cardiovascular disease compared with those on other therapies. In people without diabetes, metformin does not appear to reduce the risk of cancer and cardiovascular disease.

Cancer

The potential anti-cancer effects of metformin are believed to be mediated through multiple pathways, particularly involving AMP-activated protein kinase (AMPK) activation and IGF-1R modulation. Research has focused particularly on stomach cancer, with evidence of protective impact (reducing the risk of cancer) and improving survival rates among patients in whom cancer has already developed. Despite promising findings, evidence is still preliminary and there is no consensus on its preventive and therapeutic role.

COVID-19

A study found a benefit using metformin to reduce the occurrence of long COVID.

It is unclear if there is a reduced risk of death using metformin to treat people with COVID-19.

Neurological and neurodegenerative disorders

There has been extensive research into the potential neuroprotective effects of metformin in developmental and neurodegenerative diseases, including Alzheimer's disease and other dementias, Parkinson's disease, Huntington's disease, certain types of epilepsy, and fragile X syndrome, with mixed results.

Preliminary studies have examined whether metformin can reduce the risk of Alzheimer's disease and whether there is a correlation between type 2 diabetes and the risk of Alzheimer's disease.

While metformin may reduce body weight in persons with fragile X syndrome, whether it improves neurological or psychiatric symptoms is uncertain.

Derivatives

A derivative HL156A, also known as IM156, is a potential new drug for medical use.

Neuropsychological assessment

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Neuropsychological_assessment

Over the past three millennia, scholars have attempted to establish connections between localized brain damage and corresponding behavioral changes. A significant advancement in this area occurred between 1942 and 1948, when Soviet neuropsychologist Alexander Luria developed the first systematic neuropsychological assessment, comprising a battery of behavioral tasks designed to evaluate specific aspects of behavioral regulation. During and following the Second World War, Luria conducted extensive research with large cohorts of brain-injured Russian soldiers.

Among his most influential contributions was the identification of the critical role played by the frontal lobes of the cerebral cortex in neuroplasticity, behavioral initiation, planning, and organization. To assess these functions, Luria developed a range of tasks—such as the Go/no-go task, "count by 7," hands-clutching, clock-drawing task, repetitive pattern drawing, word associations, and category recall—which have since become standard elements in neuropsychological evaluations and mental status examinations.

Due to the breadth and originality of his methodological contributions, Luria is widely regarded as a foundational figure in the field of neuropsychological assessment. His neuropsychological test battery was later adapted in the United States as the Luria-Nebraska neuropsychological battery during the 1970s. Many of the tasks from this battery were subsequently incorporated into contemporary neuropsychological assessments, including the Mini–mental state examination (MMSE), which is commonly used for dementia screening.

History

Neuropsychological assessment has traditionally been employed to evaluate the degree of impairment in specific cognitive or functional abilities and to assist in identifying potential areas of brain damage resulting from brain injury or neurological illness. With the development of advanced neuroimaging techniques, the precise localization of space-occupying lesions can now be achieved with greater accuracy, thereby shifting the focus of neuropsychological assessment toward the evaluation of cognitive and behavioral functioning. This includes the systematic examination of the impact of brain injury or other neuropathological processes on an individual.

A central component of neuropsychological assessment involves the administration of standardized neuropsychological tests, which provide a structured means of evaluating cognitive abilities. However, neuropsychological assessment encompasses more than the mere administration and scoring of these tests and screening instruments. It is critical that such assessments also incorporate an evaluation of the individual's mental status, particularly in cases involving suspected Alzheimer's disease or other types of dementia.

Cognitive domains typically assessed include orientation, memory and new learning, general intellectual functioning, language abilities, visuoperceptual skills, and executive function. Nevertheless, comprehensive clinical neuropsychological assessment extends beyond cognitive evaluation to consider psychological factors, personality characteristics, interpersonal relationships, and the broader contextual and environmental circumstances relevant to the individual.

Assessment may be carried out for a variety of reasons, such as:

• Clinical evaluation, to understand the pattern of cognitive strengths as well as any difficulties a person may have, and to aid decision making for use in a medical or rehabilitation environment.
• Scientific investigation, to examine a hypothesis about the structure and function of cognition to be tested, or to provide information that allows experimental testing to be seen in context of a wider cognitive profile.
• Medico-legal assessment, to be used in a court of law as evidence in a legal claim or criminal investigation.

Miller outlined three broad goals of neuropsychological assessment. Firstly, diagnosis, to determine the nature of the underlying problem. Secondly, to understand the nature of any brain injury or resulting cognitive problem (see neurocognitive deficit) and its impact on the individual, as a means of devising a rehabilitation programme or offering advice as to an individual's ability to carry out certain tasks (for example, fitness to drive, or returning to work). And lastly, assessments may be undertaken to measure change in functioning over time, such as to determine the consequences of a surgical procedure or the impact of a rehabilitation programme over time.

Diagnosis of a neuropsychological disorder

Certain types of damage to the brain will cause behavioral and cognitive difficulties. Psychologists can start screening for these problems by using either one of the following techniques or all of these combined:

History taking

This includes gathering medical history of the patient and their family, presence or absence of developmental milestones, psychosocial history, and character, severity, and progress of any history of complaints. The psychologist can then gauge how to treat the patient and determine if there are any historical determinants for his or her behavior.

Interviewing

Psychologists use structured interviews in order to determine what kind of neurological problem the patient might be experiencing. There are a number of specific interviews, including the Short Portable Mental Status Questionnaire, Neuropsychological Impairment Scale, Patient's Assessment of Own Functioning, and Structured Interview for the Diagnosis of Dementia.

Test-taking

Scores on standardized tests of adequate predictive validity predictor well current and/or future problems. Standardized tests allow psychologists to compare a person's results with other people's because it has the same components and is given in the same way. It is therefore representative of the person's's behavior and cognition. The results of a standardized test are only part of the jigsaw. Further, multidisciplinary investigations (e.g. neuroimaging, neurological) are typically needed to officially diagnose a brain-injured patient.

Intelligence testing

Testing one's intelligence can also give a clue to whether there is a problem in the brain-behavior connection. The Wechsler Scales are the tests most often used to determine level of intelligence. The variety of scales available, the nature of the tasks, as well as a wide gap in verbal and performance scores can give clues to whether there is a learning disability or damage to a certain area of the brain.

Testing other areas

Other areas are also tested when a patient goes through neuropsychological assessment. These can include sensory perception, motor functions, attention, memory, auditory and visual processing, language, problem solving, planning, organization, speed of processing, and many others. Neuropsychological assessment can test many areas of cognitive and executive functioning to determine whether a patient's difficulty in function and behavior has a neuropsychological basis.

Information gathered from assessment

Tsatsanis and Volkmar assert that neuropsychological assessment can yield valuable insights into the specific nature of a psychological or neurological disorder, thereby informing the development of an appropriate treatment plan. Such assessments assist in clarifying the characteristics of the disorder and in evaluating the cognitive functioning associated with it. Furthermore, neuropsychological evaluations can help clinicians monitor the developmental trajectory of a disorder, enabling the prediction of potential future complications and the formulation of comprehensive treatment strategies.

Various forms of assessment may also be utilized to identify an individual's risk for developing specific conditions. However, a single assessment at one point in time may not provide sufficient information for long-term treatment planning, given the potential variability in behavioral and cognitive functioning. Consequently, repeated assessments are often necessary to determine whether the current treatment approach remains appropriate. Through neuropsychological testing, researchers can identify specific brain regions that may be impaired, based on observed cognitive and behavioral patterns.

Benefits of assessment

Neuropsychological assessment serves as a valuable tool in providing an accurate diagnosis, particularly in cases where the clinical presentation is unclear. Such assessments enable psychologists to identify the specific disorder affecting the patient, thereby informing more targeted and effective treatment strategies. These evaluations also assist in determining the severity of cognitive or neurological deficits, facilitating informed decision-making for both clinicians and patients. Additionally, neuropsychological assessments are useful in monitoring the progression of degenerative conditions through repeated evaluations over time.

These assessments also have important applications in the field of forensic psychology, particularly in cases where a defendant's mental competency is under scrutiny due to suspected brain injury or neurological impairment. In such contexts, neuropsychological testing may reveal cognitive deficits that are not detected through neuroimaging. Moreover, it can aid in the identification of malingering, wherein an individual may be feigning symptoms to obtain a reduced sentence.

Typically, the administration of neuropsychological tests requires between 6 and 12 hours, depending on the scope and complexity of the evaluation. This timeframe does not include the additional tasks performed by the psychologist, such as scoring, interpretation of results, case formulation, and the preparation of a comprehensive written report.

Qualifications for conducting assessments

Neuropsychological assessments are typically conducted by doctoral-level psychologists (Ph.D. or Psy.D.) who have received specialized training in neuropsychology. These professionals are referred to as clinical neuropsychologists. The qualifications, training requirements, and scope of practice for clinical neuropsychologists are defined by the widely recognized Houston Conference Guidelines. These individuals typically complete postdoctoral training in areas such as neuropsychology, neuroanatomy, and brain function. The majority are licensed psychologists practicing within their respective jurisdictions.

Advancements in the field have enabled certain tasks, such as the administration of specific neuropsychological instruments, to be performed by trained professionals known as psychometrists. However, the interpretation of test results and the formulation of clinical conclusions remain under the purview of the supervising clinical neuropsychologist.

Psychological evaluation

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Psychological_evaluation

Psychological evaluation is a method to assess an individual's behavior, personality, cognitive abilities, and several other domains. A common reason for a psychological evaluation is to identify psychological factors that may be inhibiting a person's ability to think, behave, or regulate emotion functionally or constructively. It is the mental equivalent of physical examination. Other psychological evaluations seek to better understand the individual's unique characteristics or personality to predict things like workplace performance or customer relationship management.

History

Modern psychological evaluation has been around for roughly 200 years, with roots that stem as far back as 2200 B.C. It started in China, and many psychologists throughout Europe worked to develop methods of testing into the 1900s. The first tests focused on aptitude. Eventually scientists tried to gauge mental processes in patients with brain damage, then children with special needs.

Ancient psychological evaluation

Earliest accounts of evaluation are seen as far back as 2200 B.C. when Chinese emperors were assessed to determine their fitness for office. These rudimentary tests were developed over time until 1370 A.D. when an understanding of classical Confucianism was introduced as a testing mechanism. As a preliminary evaluation for anyone seeking public office, candidates were required to spend one day and one night in a small space composing essays and writing poetry over assigned topics. Only the top 1% to 7% were selected for higher evaluations, which required three separate session of three days and three nights performing the same tasks. This process continued for one more round until a final group emerged, comprising less than 1% of the original group, became eligible for public office. The Chinese failure to validate their selection procedures, along with widespread discontent over such grueling processes, resulted in the eventual abolishment of the practice by royal decree.

Development of psychological evaluation in 1800-1900-s

In the 1800s, Hubert von Grashey developed a battery to determine the abilities of brain-damaged patients. This test was also not favorable, as it took over 100 hours to administer. However, this influenced Wilhelm Wundt, who had the first psychological laboratory in Germany. His tests were shorter, but used similar techniques. Wundt also measured mental processes and acknowledged the fact that there are individual differences between people.

Francis Galton established the first tests in London for measuring IQ. He tested thousands of people, examining their physical characteristics as a basis for his results and many of the records remain today. James Cattell studied with him, and eventually worked on his own with brass instruments for evaluation. His studies led to his paper "Mental Tests and Measurements", one of the most famous writings on psychological evaluation. He also coined the term "mental test" in this paper.

As the 1900s began, Alfred Binet was also studying evaluation. However, he was more interested in distinguishing children with special needs from their peers after he could not prove in his other research that magnets could cure hysteria. He did his research in France, with the help of Theodore Simon. They created a list of questions that were used to determine if children would receive regular instruction, or would participate in special education programs. Their battery was continually revised and developed, until 1911 when the Binet-Simon questionnaire was finalized for different age levels.

After Binet's death, intelligence testing was further studied by Charles Spearman. He theorized that intelligence was made up of several different subcategories, which were all interrelated. He combined all the factors together to form a general intelligence, which he abbreviated as "g". This led to William Stern's idea of an intelligence quotient. He believed that children of different ages should be compared to their peers to determine their mental age in relation to their chronological age. Lewis Terman combined the Binet-Simon questionnaire with the intelligence quotient and the result was the standard test we use today, with an average score of 100.

The large influx of non-English speaking immigrants into the US brought about a change in psychological testing that relied heavily on verbal skills for subjects that were not literate in English, or had speech/hearing difficulties. In 1913, R.H. Sylvester standardized the first non-verbal psychological test. In this particular test, participants fit different shaped blocks into their respective slots on a Seguin form board. From this test, Knox developed a series of non-verbal psychological tests that he used while working at the Ellis Island immigrant station in 1914. In his tests, were a simple wooden puzzle as well as digit-symbol substitution test where each participant saw digits paired up with a particular symbol, they were then shown the digits and had to write in the symbol that was associated with it.

When the United States moved into World War I, Robert M. Yerkes convinced the government that they should be testing all of the recruits they were receiving into the Army. The results of the tests could be used to make sure that the "mentally incompetent" and "mentally exceptional" were assigned to appropriate jobs. Yerkes and his colleagues developed the Army Alpha and Army Beta tests to use on all new recruits. These tests set a precedent for the development of psychological testing for the next several decades.

After seeing the success of the Army standardized tests, college administration quickly picked up on the idea of group testing to decide entrance into their institutions. The College Entrance Examination Board was created to test applicants to colleges across the nation. In 1925, they developed tests that were no longer essay tests that were very open to interpretation, but now were objective tests that were also the first to be scored by machine. These early tests evolved into modern day College Board tests, like the Scholastic Assessment Test, Graduate Record Examination, and the Law School Admissions Test.

Formal and informal evaluation

Formal psychological evaluation consists of standardized batteries of tests and highly structured clinician-run interviews, while informal evaluation takes on a completely different tone. In informal evaluation, assessments are based on unstructured, free-flowing interviews or observations that allow both the patient and the clinician to guide the content. Both of these methods have their pros and cons. A highly unstructured interview and informal observations provide key findings about the patient that are both efficient and effective. A potential issue with an unstructured, informal approach is the clinician may overlook certain areas of functioning or not notice them at all. Or they might focus too much on presenting complaints. The highly structured interview, although very precise, can cause the clinician to make the mistake of focusing a specific answer to a specific question without considering the response in terms of a broader scope or life context. They may fail to recognize how the patient's answers all fit together.

There are many ways that the issues associated with the interview process can be mitigated. The benefits to more formal standardized evaluation types such as batteries and tests are many. First, they measure a large number of characteristics simultaneously. These include personality, cognitive, or neuropsychological characteristics. Second, these tests provide empirically quantified information. The obvious benefit to this is that we can more precisely measure patient characteristics as compared to any kind of structured or unstructured interview. Third, all of these tests have a standardized way of being scored and being administered. Each patient is presented a standardized stimulus that serves as a benchmark that can be used to determine their characteristics. These types of tests eliminate any possibility of bias and produce results that could be harmful to the patient and cause legal and ethical issues. Fourth, tests are normed. This means that patients can be assessed not only based on their comparison to a "normal" individual, but how they compare to the rest of their peers who may have the same psychological issues that they face. Normed tests allow the clinician to make a more individualized assessment of the patient. Fifth, standardized tests that we commonly use today are both valid and reliable. We know what specific scores mean, how reliable they are, and how the results will affect the patient.

Most clinicians agree that a balanced battery of tests is the most effective way of helping patients. Clinicians should not become victims of blind adherence to any one particular method. A balanced battery of tests allows there to be a mix of formal testing processes that allow the clinician to start making their assessment, while conducting more informal, unstructured interviews with the same patient may help the clinician to make more individualized evaluations and help piece together what could potentially be a very complex, unique-to-the-individual kind of issue or problem .

Modern uses

Psychological assessment is most often used in the psychiatric, medical, legal, educational, or psychological clinic settings. The types of assessments and the purposes for them differ among these settings.

In the psychiatric setting, the common needs for assessment are to determine risks, whether a person should be admitted or discharged, the location the patients should be held, as well as what therapy the patient should be receiving. Within this setting, the psychologists need to be aware of the legal responsibilities that what they can legally do in each situation.

Within a medical setting, psychological assessment is used to find a possible underlying psychological disorder, emotional factors that may be associated with medical complaints, assessment for neuropsychological deficit, psychological treatment for chronic pain, and the treatment of chemical dependency. There has been greater importance placed on the patient's neuropsychological status as neuropsychologists are becoming more concerned with the functioning of the brain.

Psychological assessment also has a role in the legal setting. Psychologists might be asked to assess the reliability of a witness, the quality of the testimony a witness gives, the competency of an accused person, or determine what might have happened during a crime. They also may help support a plea of insanity or to discount a plea. Judges may use the psychologist's report to change the sentence of a convicted person, and parole officers work with psychologists to create a program for the rehabilitation of a parolee. Problematic areas for psychologists include predicting how dangerous a person will be. The predictive accuracy of these assessments is debated; however, there is often a need for this prediction to prevent dangerous people from returning to society.

Psychologists may also be called on to assess a variety of things within an education setting. They may be asked to assess strengths and weaknesses of children who are having difficulty in the school systems, assess behavioral difficulties, assess a child's responsiveness to an intervention, or to help create an educational plan for a child. The assessment of children also allows for the psychologists to determine if the child will be willing to use the resources that may be provided.

In a psychological clinic setting, psychological assessment can be used to determine characteristics of the client that can be useful for developing a treatment plan. Within this setting, psychologists often are working with clients who may have medical or legal problems or sometimes students who were referred to this setting from their school psychologist.

Some psychological assessments have been validated for use when administered via computer or the Internet. However, caution must be applied to these test results, as it is possible to fake in electronically mediated assessment. Many electronic assessments do not truly measure what is claimed, such as the Meyers-Briggs personality test. Although one of the most well known personality assessments, it has been found both invalid and unreliable by many psychological researches, and should be used with caution.

Within clinical psychology, the "clinical method" is an approach to understanding and treating mental disorders that begins with a particular individual's personal history and is designed around that individual's psychological needs. It is sometimes posed as an alternative approach to the experimental method which focuses on the importance of conducting experiments in learning how to treat mental disorders, and the differential method which sorts patients by class (gender, race, income, age, etc.) and designs treatment plans based around broad social categories.

Taking a personal history along with clinical examination allow the health practitioners to fully establish a clinical diagnosis. A medical history of a patient provides insights into diagnostic possibilities as well as the patient's experiences with illnesses. The patients will be asked about current illness and the history of it, past medical history and family history, other drugs or dietary supplements being taken, lifestyle, and allergies. The inquiry includes obtaining information about relevant diseases or conditions of other people in their family. Self-reporting methods may be used, including questionnaires, structured interviews and rating scales.

Personality Assessment

Personality traits are an individual's enduring manner of perceiving, feeling, evaluating, reacting, and interacting with other people specifically, and with their environment more generally. Because reliable and valid personality inventories give a relatively accurate representation of a person's characteristics, they are beneficial in the clinical setting as supplementary material to standard initial assessment procedures such as a clinical interview; review of collateral information, e.g., reports from family members; and review of psychological and medical treatment records.

Main article: Minnesota Multiphasic Personality Inventory

MMPI

History

Developed by Starke R. Hathaway, PhD, and J. C. McKinley, MD, The Minnesota Multiphasic Personality Inventory (MMPI) is a personality inventory used to investigate not only personality, but also psychopathology. The MMPI was developed using an empirical, atheoretical approach. This means that it was not developed using any of the frequently changing theories about psychodynamics at the time. There are two variations of the MMPI administered to adults, the MMPI-2 and the MMPI-2-RF, and two variations administered to teenagers, the MMPI-A and MMPI-A-RF. This inventory's validity has been confirmed by Hiller, Rosenthal, Bornstein, and Berry in their 1999 meta-analysis. Throughout history the MMPI in its various forms has been routinely administered in hospitals, clinical settings, prisons, and military settings.

MMPI-2

The MMPI-2 consists of 567 true or false questions aimed at measuring the reporting person's psychological wellbeing. The MMPI-2 is commonly used in clinical settings and occupational health settings. There is a revised version of the MMPI-2 called the MMPI-2-RF (MMPI-2 Restructured Form). The MMPI-2-RF is not intended to be a replacement for the MMPI-2, but is used to assess patients using the most current models of psychopathology and personality.

MMPI-2 and MMPI-2-RF Scales

Version	Number of Items	Number of Scales	Scale Categories
MMPI-2	567	120	Validity Indicators, Superlative Self-Presentation Subscales, Clinical Scales, Restructured Clinical (RC) Scales, Content Scales, Content Component Scales, Supplementary Scales, Clinical Subscales (Harris-Lingoes and Social Introversion Subscales)
MMPI-2-RF	338	51	Validity, Higher-Order (H-O), Restructured Clinical (RC), Somatic, Cognitive, Internalizing, Externalizing, Interpersonal, Interest, Personality Psychopathology Five (PSY-5)

MMPI-A

The MMPI-A was published in 1992 and consists of 478 true or false questions. This version of the MMPI is similar to the MMPI-2 but used for adolescents (age 14–18) rather than for adults. The restructured form of the MMPI-A, the MMPI-A-RF, was published in 2016 and consists of 241 true or false questions that can understood with a sixth grade reading level. Both the MMPI-A and MMPI-A-RF are used to assess adolescents for personality and psychological disorders, as well as to evaluate cognitive processes.

MMPI-A and MMPI-A-RF Scales

Verson	Number of Items	Number of Scales	Scale Categories
MMPI-A	478	105	Validity Indicators, Clinical Scales, Clinical Subscales (Harris-Lingoes and Social Introversion Subscales), Content Scales, Content Component Scales, Supplementary Scales
MMPI-A-RF	241	48	Validity, Higher-Order (H-O), Restructured Clinical (RC), Somatic/Cognitive, Internalizing, Externalizing, Interpersonal, Personality Psychopathology Five (PSY-5)

NEO Personality Inventory

The NEO Personality Inventory was developed by Paul Costa Jr. and Robert R. McCrae in 1978. When initially created, it only measured three of the Big Five personality traits: Neuroticism, Openness to Experience, and Extroversion. The inventory was then renamed as the Neuroticism-Extroversion-Openness Inventory (NEO-I). It was not until 1985 that Agreeableness and Conscientiousness were added to the personality assessment. With all Big Five personality traits being assessed, it was then renamed as the NEO Personality Inventory. Research for the NEO-PI continued over the next few years until a revised manual with six facets for each Big Five trait was published in 1992. In the 1990s, now called the NEO PI-R, issues were found with the personality inventory. The developers of the assessment found it to be too difficult for younger people, and another revision was done to create the NEO PI-3.

The NEO Personality Inventory is administered in two forms: self-report and observer report. It consists of 240 personality items and a validity item. It can be administered in roughly 35–45 minutes. Every item is answered on a Likert scale, widely known as a scale from Strongly Disagree to Strongly Agree. If more than 40 items are missing or more than 150 responses or less than 50 responses are Strongly Agree/Disagree, the assessment should be viewed with great caution and has the potential to be invalid. In the NEO report, each trait's T score is recorded along with the percentile they rank on compared to all data recorded for the assessment. Then, each trait is broken up into their six facets along with raw score, individual T-scores, and percentile. The next page goes on to list what each score means in words as well as what each facet entails. The exact responses to questions are given in a list as well as the validity response and amount of missing responses.

When an individual is given their NEO report, it is important to understand specifically what the facets are and what the corresponding scores mean.

• Neuroticism
  • Anxiety
    • High scores suggest nervousness, tenseness, and fearfulness. Low scores suggest feeling relaxed and calm.
  • Angry Hostility
    • High scores suggest feeling anger and frustration often. Low scores suggest being easy-going.
  • Depression
    • High scores suggest feeling guilty, sad, hopeless, and lonely. Low scores suggest less feeling of that of someone who scores highly, but not necessarily being light-hearted and cheerful.
  • Self-consciousness
    • High scores suggest shame, embarrassment, and sensitivity. Low scores suggest being less affected by others' opinions, but not necessarily having good social skills or poise.
  • Impulsiveness
    • High scores suggest the inability to control cravings and urges. Low scores suggest easy resistance to such urges.
  • Vulnerability
    • High scores suggest inability to cope with stress, being dependent, and feeling panicked in high stress situations. Low scores suggest capability to handle stressful situations.
• Extraversion
  • Warmth
    • High scores suggest friendliness and affectionate behavior. Low scores suggest being more formal, reserved, and distant. A low score does not necessarily mean being hostile or lacking compassion.
  • Gregariousness
    • High scores suggest wanting the company of others. Low scores tend to be from those who avoid social stimulation.
  • Assertiveness
    • High scores suggest a forceful and dominant person who lacks hesitation. Low scores suggest are more passive and try not to stand out in a crowd.
  • Activity
    • High scores suggest a more energetic and upbeat personality and lead a quicker paced lifestyle. Low scores suggest the person is more leisurely, but does not imply being lazy or slow.
  • Excitement-Seeking
    • High scores suggest a person who seeks and craves excitement and is similar to those with high sensation seeking. Low scores seek a less exciting lifestyle and come off more boring.
  • Positive Emotions
    • High scores suggest the tendency to feel happier, laugh more, and are optimistic. Low scorers are not necessarily unhappy, but more so are less high-spirited and are more pessimistic.

• Openness to Experience
  • Fantasy
    • Those who score high in fantasy have a more creative imagination and daydream frequently. Low scores suggest a person who lives more in the moment.
  • Aesthetics
    • High scores suggest a love and appreciation for art and physical beauty. These people are more emotionally attached to music, artwork, and poetry. Low scorers have a lack of interest in the arts.
  • Feelings
    • High scorers have a deeper ability to experience emotion and see their emotions as more important than those who score low on this facet. Low scorers are less expressive.
  • Actions
    • High scores suggest a more open-mindedness to traveling and experiencing new things. These people prefer novelty over a routine life. Low scorers prefer a scheduled life and dislike change.
  • Ideas
    • Active pursuit of knowledge, high curiosity, and the enjoyment of brain teasers and philosophical are common of those who score high on this facet. Those who score lower are not necessarily less intelligent, nor does a high score imply high intelligence. However, those who score lower are more narrow in their interests and have low curiosity.
  • Values
    • High scorers are more investigative of political, social, and religious values. Those who score lower and more accepting of authority and honor more traditional values. High scorers are more typically liberal while lower scorers are more typically conservative.
• Agreeableness
  • Trust
    • High scores are more trusting of others and believe others are honest and have good intentions. Low scorers are more skeptical, cynical, and assumes others are dishonest and/or dangerous.
  • Straightforwardness
    • Those who score high in this facet are more sincere and frank. Low scorers are more deceitful and more willing to manipulate others, but this does not mean they should be labeled as a dishonest or manipulative person.
  • Altruism
    • High scores suggest a person concerned with the well-being of others and show it through generosity, willingness to help others, and volunteering for those less fortunate. Low scores suggest a more self-centered person who is less willing to go out of their way to help others.
  • Compliance
    • High scorers are more inclined to avoid conflict and tend to forgive easily. Low scores suggest a more aggressive personality and a love for competition.
  • Modesty
    • High scorers are more humble, but not necessarily lacking in self-esteem or confidence. Low scorers believe they're more superior than others and may come off as more conceited.
  • Tender-Mindedness
    • This facet scales one's concern for others and their ability to empathize. High scorers are more moved by others' emotions, while low scorers are more hardheaded and typically consider themselves realists.

• Conscientiousness
  • Competence
    • High scores suggest one is capable, sensible, prudent, effective, and are well-prepared to deal with whatever happens in life. Low scores suggest a potential lower self-esteem and are often unprepared.
  • Order
    • High scorers are more neat and tidy, while low scorers lack organization and are unmethodical.
  • Dutifulness
    • Those who score highly in this facet are more strict about their ethical principles and are more dependable. Low scorers are less reliable and are more casual about their morals.
  • Achievement Striving
    • Those who score highly in this facet have higher aspirations and work harder to achieve their goals. However, they may be too invested in their work and become a workaholic. Low scorers are much less ambitious and perhaps even lazy. They are often content with their lack of goal-seeking.
  • Self-Discipline
    • High scorers complete whatever task is assigned to them and are self-motivated. Low scorers often procrastinate and are easily discouraged.
  • Deliberation
    • High scorers tend to think more than low scorers before acting. High scorers are more cautious and deliberate while low scorers are more hasty and act without considering the consequences.

HEXACO-PI

The HEXACO-PI, developed by Lee and Ashton in the early 2000s, is a personality inventory used to measure six different dimensions of personality which have been found in lexical studies across various cultures. There are two versions of the HEXACO: the HEXACO-PI and the HEXACO-PI-R which are examined with either self reports or observer reports. The HEXACO-PI-R has forms of three lengths: 200 items, 100 items, and 60 items. Items from each form are grouped to measure scales of more narrow personality traits, which are them grouped into broad scales of the six dimensions: honesty & humility (H), emotionality (E), Extraversion (X), agreeableness (A), conscientiousness (C), and openness to experience (O).The HEXACO-PI-R includes various traits associated with neuroticism and can be used to help identify trait tendencies. One table which give examples of typically high loaded adjectives on the six factors of HEXACO can be found in Ashton's book "Individual Differences and Personality"

Adjective relating to the six factors within the HEXACO structure

Personality Factor	Narrow Personality Traits	Related Adjectives
Honesty-Humility	Sincerity, fairness, greed-avoidance, modesty	Sincere, honest, faithful/loyal, modest/unassuming, fair-minded versus sly, deceitful, greedy, pretentious, hypocritical, boastful, pompous
Emotionality	Fearfulness, anxiety, depenence, sentimentality	Emotional, oversensitive, sentimental, fearful, anxious, vulnerable versus brave, tough, independent, self-assured, stable
Extraversion	Social self-esteem, social boldness, sociability, liveliness	Outgoing, lively, extraverted, sociable, talkative, cheerful, active versus shy, passive, withdrawn, introverted, quiet, reserved
Agreeableness	Forgivingness, gentleness, flexibility, patience	Patient, tolerant, peaceful, mild, agreeable, lenient, gentle versus ill-tempered, quarrelsome, stubborn, choleric
Conscientiousness	Organization, diligence, perfectionism, prudence	Organized, disciplined, diligent, careful, thorough, precise verus sloppy, negligent, reckless, lazy, irresponsible, absent-minded
Openness to Experience	Aesthetic appreciation, inquisitiveness, creativity, unconventionality	Intellectual, creative, unconventional, innovative, ironic versus shallow, unimaginative, conventional

One benefit of using the HEXACO is that of the facet of neuroticism within the factor of emotionality: trait neuroticism has been shown to have a moderate positive correlation with people with anxiety and depression. The identification of trait neuroticism on a scale, paired with anxiety, and/or depression is beneficial in a clinical setting for introductory screenings some personality disorders. Because the HEXACO has facets which help identify traits of neuroticism, it is also a helpful indicator of the dark triad.

Temperament Assessment

In contrast to personality, i.e. the concept that relates to culturally- and socially-influenced behaviour and cognition, the concept of temperament' refers to biologically and neurochemically-based individual differences in behaviour. Unlike personality, temperament is relatively independent of learning, system of values, national, religious and gender identity and attitudes. There are multiple tests for evaluation of temperament traits (reviewed, for example, in, majority of which were developed arbitrarily from opinions of early psychologists and psychiatrists but not from biological sciences. There are only two temperament tests that were based on neurochemical hypotheses: The Temperament and Character Inventory (TCI) and the Trofimova's Structure of Temperament Questionnaire-Compact (STQ-77). The STQ-77 is based on the neurochemical framework Functional Ensemble of Temperament that summarizes the contribution of main neurochemical (neurotransmitter, hormonal and opioid) systems to behavioural regulation. The STQ-77 assesses 12 temperament traits linked to the neurochemical components of the FET. The STQ-77 is freely available for non-commercial use in 24 languages for testing in adults and several language versions for testing children

Pseudopsychology (pop psychology) in assessment

Although there have been many great advancements in the field of psychological evaluation, some issues have also developed. One of the main problems in the field is pseudopsychology, also called pop psychology. Psychological evaluation is one of the biggest aspects in pop psychology. In a clinical setting, patients are not aware that they are not receiving correct psychological treatment, and that belief is one of the main foundations of pseudopsychology. It is largely based upon the testimonies of previous patients, the avoidance of peer review (a critical aspect of any science), and poorly set up tests, which can include confusing language or conditions that are left up to interpretation.

Pseudopsychology can also occur when people claim to be psychologists, but lack qualifications. A prime example of this is found in quizzes that can lead to a variety of false conclusions. These can be found in magazines, online, or just about anywhere accessible to the public. They usually consist of a small number of questions designed to tell the participant things about themselves. These often have no research or evidence to back up any claims made by the quizzes.

Ethics

Concerns about privacy, cultural biases, tests that have not been validated, and inappropriate contexts have led groups such as the American Educational Research Association (AERA) and the American Psychological Association (APA) to publish guidelines for examiners in regards to assessment. The American Psychological Association states that a client must give permission to release any of the information that may come from a psychologist. The only exceptions to this are in the case of minors, when the clients are a danger to themselves or others, or if they are applying for a job that requires this information. Also, the issue of privacy occurs during the assessment itself. The client has the right to say as much or little as they would like, however they may feel the need to say more than they want or even may accidentally reveal information they would like to keep private.

Guidelines have been put in place to ensure the psychologist giving the assessments maintains a professional relationship with the client since their relationship can impact the outcomes of the assessment. The examiner's expectations may also influence the client's performance in the assessments.

The validity and reliability of the tests being used also can affect the outcomes of the assessments being used. When psychologists are choosing which assessments they are going to use, they should pick one that will be most effective for what they are looking at. Also, it is important for the psychologists are aware of the possibility of the client, either consciously or unconsciously, faking answers and consider use of tests that have validity scales within them.