Posts

On This Day … 08 December

Published on by Andrew MarshallLeave a comment

People (Births)

  • 1928 – Ulric Neisser, German-American psychologist, neuroscientist, and academic (d. 2012).
  • 1949 – Robert Sternberg, American psychologist and academic.

Ulric Neisser

Ulric Richard Gustav Neisser (08 December 1928 to 17 February 2012) was a German-American psychologist and member of the US National Academy of Sciences.

He has been referred to as the “father of cognitive psychology”. Neisser researched and wrote about perception and memory. He posited that a person’s mental processes could be measured and subsequently analysed. In 1967, Neisser published Cognitive Psychology, which he later said was considered an attack on behaviourist psychological paradigms. Cognitive Psychology brought Neisser instant fame and recognition in the field of psychology. While Cognitive Psychology was considered unconventional, it was Neisser’s Cognition and Reality that contained some of his most controversial ideas. A main theme in Cognition and Reality is Neisser’s advocacy for experiments on perception occurring in natural (“ecologically valid”) settings. Neisser postulated that memory is, largely, reconstructed and not a snap shot of the moment. Neisser illustrated this during one of his highly publicised studies on people’s memories of the Challenger explosion.

In his later career, he summed up current research on human intelligence and edited the first major scholarly monograph on the Flynn effect. A Review of General Psychology survey, published in 2002, ranked Neisser as the 32nd most cited psychologist of the 20th century.

Robert Sternberg

Robert J. Sternberg (born 08 December 1949) is an American psychologist and psychometrician. He is Professor of Human Development at Cornell University.

Prior to joining Cornell, Sternberg was president of the University of Wyoming for 5 months. He has been Provost and Professor at Oklahoma State University, Dean of Arts and Sciences at Tufts University, IBM Professor of Psychology and Education at Yale University. He is a member of the editorial boards of numerous journals, including American Psychologist. He is the past President for the American Psychological Association.

Sternberg has a BA from Yale University and a PhD from Stanford University, under advisor Gordon Bower. He holds thirteen honorary doctorates from two North American, one South American, one Asian, and nine European universities, and additionally holds an honorary professorship at the University of Heidelberg, in Germany. He is a Distinguished Associate of the Psychometrics Centre at the University of Cambridge.

Among his major contributions to psychology are the triarchic theory of intelligence and several influential theories related to creativity, wisdom, thinking styles, love, hate, and leadership. A Review of General Psychology survey, published in 2002, ranked Sternberg as the 60th most cited psychologist of the 20th century. Sternberg has acquired over $20 million in grants and contracts for his research and has conducted research on five continents. The central focus of his research is on intelligence, creativity, and wisdom. He has also studied close relationships, love, and hatred. He has authored or co-authored over 1,500 publications, including articles, book chapters, and books. His work has been critiqued due to excessive self-citation and self-plagiarism. In 2018 he resigned as the editor of Perspectives on Psychological Science in response to these claims.

Robert Sternberg is married to Karin Sternberg, a German psychologist, with whom he has a set of triplets, consisting of a boy and two girls. Sternberg and his first wife had a son and a daughter.

On This Day … 06 December

Published on by Andrew MarshallLeave a comment

People (Births)

  • 1890 – Dion Fortune, Welsh occultist, psychologist, and author (d. 1946).

People (Deaths)

  • 1961 – Frantz Fanon, Martinique-French psychiatrist and author (b. 1925).

Dion Fortune

Dion Fortune (born Violet Mary Firth, 06 December 1890 to 06 January 1946) was a British occultist, ceremonial magician, novelist and author. She was a co-founder of the Fraternity of the Inner Light, an occult organisation that promoted philosophies which she claimed had been taught to her by spiritual entities known as the Ascended Masters. A prolific writer, she produced a large number of articles and books on her occult ideas and also authored seven novels, several of which expound occult themes.

Fortune was born in Llandudno, Caernarfonshire, North Wales, to a wealthy upper middle-class English family, although little is known of her early life. By her teenage years she was living in England’s West Country, where she wrote two books of poetry. After time spent at a horticultural college she began studying psychology and psychoanalysis at the University of London before working as a counsellor in a psychotherapy clinic. During the First World War she joined the Women’s Land Army and established a company selling soy milk products. She became interested in esotericism through the teachings of the Theosophical Society, before joining an occult lodge led by Theodore Moriarty and then the Alpha et Omega occult organisation.

She came to believe that she was being contacted by the Ascended Masters, including “the Master Jesus”, and underwent trance mediumship to channel the Masters’ messages. In 1922 Fortune and Charles Loveday claimed that during one of these ceremonies they were contacted by Masters who provided them with a text, The Cosmic Doctrine. Although she became the president of the Christian Mystic Lodge of the Theosophical Society, she believed the society to be uninterested in Christianity, and split from it to form the Community of the Inner Light, a group later renamed the Fraternity of the Inner Light. With Loveday she established bases in both Glastonbury and Bayswater, London, began issuing a magazine, gave public lectures, and promoted the growth of their society. During the Second World War she organised a project of meditations and visualisations designed to protect Britain. She began planning for what she believed was a coming post-war Age of Aquarius, although she died of leukaemia shortly after the war’s end.

Fortune is recognised as one of the most significant occultists and ceremonial magicians of the early 20th century. The Fraternity she founded survived her and in later decades spawned a variety of related groups based upon her teachings. Her novels in particular proved an influence on later occult and modern Pagan groups such as Wicca.

Frantz Fanon

Frantz Omar Fanon (20 July 1925 to 6 December 1961), also known as Ibrahim Frantz Fanon, was a French West Indian psychiatrist and political philosopher from the French colony of Martinique (today a French department).

His works have become influential in the fields of post-colonial studies, critical theory and Marxism. As well as being an intellectual, Fanon was a political radical, Pan-Africanist, and Marxist humanist concerned with the psychopathology of colonisation and the human, social, and cultural consequences of decolonisation.

In the course of his work as a physician and psychiatrist, Fanon supported Algeria’s War of independence from France and was a member of the Algerian National Liberation Front.

For more than five decades, the life and works of Frantz Fanon have inspired national-liberation movements and other radical political organisations in Palestine, Sri Lanka, South Africa, and the United States. He formulated a model for community psychology, believing that many mental-health patients would do better if they were integrated into their family and community instead of being treated with institutionalised care. He also helped found the field of institutional psychotherapy while working at Saint-Alban under Francois Tosquelles and Jean Oury.

Fanon published numerous books, including The Wretched of the Earth (1961). This influential work focuses on what he believed is the necessary role of violence by activists in conducting decolonisation struggles.

On This Day … 05 December

Published on by Andrew MarshallLeave a comment

People (Births)

  • 1901 – Milton H. Erickson, American psychiatrist and author (d. 1980).

Milton H. Erickson

Milton Hyland Erickson (05 December 1901 to 25 March 1980) was an American psychiatrist and psychologist specialising in medical hypnosis and family therapy.

He was founding president of the American Society for Clinical Hypnosis and a fellow of the American Psychiatric Association, the American Psychological Association, and the American Psychopathological Association. He is noted for his approach to the unconscious mind as creative and solution-generating.

He is also noted for influencing brief therapy, strategic family therapy, family systems therapy, solution focused brief therapy, and neuro-linguistic programming.

On This Day … 04 December

Published on by Andrew MarshallLeave a comment

People (Births)

  • 1882 – Constance Davey, Australian psychologist (d. 1963).

People (Deaths)

  • 1963 – Constance Davey, Australian psychologist (b. 1882).
  • 1981 – Jeanne Block, American psychologist (b. 1923).

Constance Davey

Constance Muriel Davey OBE (04 December 1882 to 04 December 1963) was an Australian psychologist who worked in the South Australian Department of Education, where she introduced the state’s first special education classes.

Davey was born in 1882 in Nuriootpa, South Australia, to Emily Mary (née Roberts) and Stephen Henry Davey. She began teaching at a Port Adelaide private school in 1908 and at St Peter’s Collegiate Girls’ School in 1909. She attended the University of Adelaide as a part-time student, completing a B.A. in philosophy in 1915 and an M.A. in 1918. In 1921 she won a Catherine Helen Spence Memorial Scholarship which allowed her to undertake a doctorate at the University of London; her main area of research was “mental efficiency and deficiency” in children. She received her doctorate in 1924 and visited the United States and Canada to observe the teaching of intellectually disabled and delinquent children before returning to Australia.

In November 1924 Davey was hired as the first psychologist in the South Australian Department of Education, where she was tasked with examining and organising classes for “backward, retarded and problem” school students. She examined and performed intelligence tests on all educationally delayed children, and established South Australia’s first “opportunity class” for these children in 1925. She set up a course which educated teachers on working with intellectually disabled children in 1931. She began lecturing in psychology at the University of Adelaide in 1927, continuing until 1950, and in 1938 she helped to set up a new university course for training social workers. She resigned from the Department of Education in 1942, by which point there were 700 children in the opportunity classes she had introduced.

Davey was a member of the Women’s Non-Party Political Association for 30 years and served as the organisation’s president from 1943 to 1947. She became a fellow of the British Psychological Society in 1950 and was appointed an Officer of the Order of the British Empire (OBE) in 1955. In 1956 she published Children and Their Law-makers, a historical study of South Australian law as it pertained to children, which she had begun in 1945 as a senior research fellow at the University of Adelaide. Davey died of thyroid cancer on her 81st birthday in 1963.

Jeanne Block

Jeanne Lavonne Humphrey Block (17 July 1923 to 04 December 1981) was an American psychologist and expert on child development. She conducted research into sex-role socialisation and, with her husband Jack Block, created a person-centred personality framework. Block was a fellow of the American Association for the Advancement of Science and conducted her research with the National Institute of Mental Health and the University of California, Berkeley. She was an active researcher when she was diagnosed with cancer in 1981.

Early Life and Education

Block was born in 1923 in Tulsa, Oklahoma. She was raised in a small town in Oregon. After graduating from high school, she entered Oregon State University as a home economics major, but she was dissatisfied with her education. She joined SPARS, the women’s branch of the United States Coast Guard, in 1944. While serving in World War II, Block was badly burned and nearly died. She was treated with skin grafts, and she was able to return to military service until 1946.

In 1947, after completing a psychology degree at Reed College, she attended graduate school at Stanford University. At Stanford, Block met two mentors, Ernest Hilgard and Maud Merrill James. Hilgard wrote a popular general psychology textbook and co-wrote a textbook on learning theories, and he became president of the American Psychological Association. James had been an associate of intelligence researcher Lewis Terman. Block also met her future husband and research collaborator, Jack Block, during her time at Stanford.

Career

Pregnant at the time she finished her Ph.D. at Stanford in 1951, Block worked mostly part-time in the 1950s while she raised four children. Block and her husband created a person-centred personality theory that became popular among personality researchers. The theory examined personality in terms of two variables, ego-resiliency (the ability to respond flexibly to changing situations) and ego-control (the ability to suppress impulses). In 1963, she was awarded a National Institute of Mental Health fellowship and she moved with her family to Norway for a year. She joined the faculty as a research psychologist at the University of California, Berkeley’s Institute of Human Development in 1965. She became a professor-in-residence in the department of psychology in 1979.

In the 1970s, Block published an analysis the sex-role socialization occurring in several groups of children in the United States and Northern Europe. Even across countries, boys were typically raised to be independent, high-achieving and unemotional, and girls were generally encouraged to express feelings, to foster close relationships and to pursue typical feminine ideals.

Block was made a fellow of the American Association for the Advancement of Science in 1980 and received the Lester N. Hofheimer Prize for outstanding psychiatric research from the American Psychological Association (APA) in 1979. She was elected president of the APA Division of Developmental Psychology.

In 1984 her book, Sex Role Identity and Ego Development was published posthumously.[4]

Death

Block died at the Alta Bates Hospital in Berkeley on 04 December 1981. She had been diagnosed with cancer earlier that year. She was survived by her husband, Jack, who died in 2010, four children, her brother and mother.

What is Alprazolam?

Published on by Andrew Marshall8 Comments

Introduction

Alprazolam, sold under the brand name Xanax, among others, is a fast-acting tranquiliser of medium duration in the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring.

It is most commonly used in short-term management of anxiety disorders, specifically panic disorder or generalised anxiety disorder (GAD). Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is generally taken by mouth.

Common side effects include sleepiness, depression, headaches, feeling tired, dry mouth, and memory problems. Some of the sedation and tiredness may improve within a few days. Due to concerns about misuse, some do not recommend alprazolam as an initial treatment for panic disorder. Withdrawal or rebound symptoms may occur if use is suddenly decreased; gradually decreasing the dose over weeks or months may be required. Other rare risks include suicide, and a two fold increased risk of all cause mortality. Alprazolam, like other benzodiazepines, acts through the GABAA receptor.

Alprazolam was patented in 1971 and approved for medical use in the United States in 1981. Alprazolam is a Schedule IV controlled substance and is a common drug of abuse. It is available as a generic medication. In 2019, it was the 41st most commonly prescribed medication in the United States, with more than 17 million prescriptions.

Medical Uses

Alprazolam is mostly used in short term management of anxiety disorders, panic disorders, and nausea due to chemotherapy. Alprazolam may also be indicated for the treatment of GAD, as well as for the treatment of anxiety conditions with co-morbid depression. The US Food and Drug Administration (FDA) label advises that the physician should periodically reassess the usefulness of the drug.

Panic Disorder

Alprazolam is effective in the relief of moderate to severe anxiety and panic attacks. However, it is not a first line treatment since the development of selective serotonin reuptake inhibitors. Alprazolam is no longer recommended in Australia for the treatment of panic disorder due to concerns regarding tolerance, dependence, and abuse. Most evidence shows that the benefits of alprazolam in treating panic disorder last only 4 to 10 weeks. However, people with panic disorder have been treated on an open basis for up to 8 months without apparent loss of benefit.

In the United States, alprazolam is FDA-approved for the treatment of panic disorder with or without agoraphobia. Alprazolam is recommended by the World Federation of Societies of Biological Psychiatry (WFSBP) for treatment-resistant cases of panic disorder where there is no history of tolerance or dependence.

Anxiety Disorders

Anxiety associated with depression is responsive to alprazolam. Clinical studies have shown that the effectiveness is limited to 4 months for anxiety disorders. However, the research into antidepressant properties of alprazolam is poor and has only assessed its short-term effects against depression. In one study, some long term, high-dosage users of alprazolam developed reversible depression. In the US, alprazolam is FDA-approved for the management of anxiety disorders (a condition corresponding most closely to the Diagnostic and Statistical Manual DSM-IV-TR diagnosis of generalized anxiety disorder) or the short-term relief of symptoms of anxiety. In the UK, alprazolam is recommended for the short-term treatment (2-4 weeks) of severe acute anxiety.

Nausea due to Chemotherapy

Alprazolam may be used in combination with other medications for chemotherapy-induced nausea and vomiting.

Contraindications

Benzodiazepines require special precaution if used in children and in alcohol- or drug-dependent individuals. Particular care should be taken in pregnant or elderly people, people with substance use disorder history (particularly alcohol dependence), and people with comorbid psychiatric disorders. The use of alprazolam should be avoided or carefully monitored by medical professionals in individuals with: myasthenia gravis, acute narrow-angle glaucoma, severe liver deficiencies (e.g. cirrhosis), severe sleep apnoea, pre-existing respiratory depression, marked neuromuscular respiratory, acute pulmonary insufficiency, chronic psychosis, hypersensitivity or allergy to alprazolam or other benzodiazepines, and borderline personality disorder (where it may induce suicidality and dyscontrol).

Like all central nervous system depressants, alprazolam in larger-than-normal doses can cause significant deterioration in alertness and increase drowsiness, especially in those unaccustomed to the drug’s effects.

Elderly individuals should be cautious in the use of alprazolam due to the possibility of increased susceptibility to side-effects, especially loss of coordination and drowsiness.

Side Effects

Sedative drugs, including alprazolam, have been associated with an increased risk of death.

Possible side effects include:

  • Anterograde amnesia and concentration problems.
  • Ataxia, slurred speech.
  • Disinhibition.
  • Drowsiness, dizziness, lightheadedness, fatigue, unsteadiness, and impaired coordination, vertigo.
  • Dry mouth (infrequent).
  • Hallucinations (rare).
  • Jaundice (very rare).
  • Seizures (less common).
  • Skin rash, respiratory depression, constipation.
  • Suicidal ideation or suicide.
  • Urinary retention (infrequent).
  • Muscle weakness.

In September 2020, the FDA required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.

Paradoxical Reactions

Although unusual, the following paradoxical reactions have been shown to occur:

  • Aggression.
  • Mania, agitation, hyperactivity, and restlessness.
  • Rage, hostility.
  • Twitches and tremor.

Food and Drug Interactions

Alprazolam is primarily metabolised via CYP3A4. Combining CYP3A4 inhibitors such as cimetidine, erythromycin, norfluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene, and ritonavir delay the hepatic clearance of alprazolam, which may result in its accumulation and increased severity of its side effects.

Imipramine and desipramine have been reported to increase an average of 31% and 20% respectively by the concomitant administration of alprazolam tablets. Combined oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation.

Alcohol is one of the most common interactions; alcohol and alprazolam taken in combination have a synergistic effect on one another, which can cause severe sedation, behavioural changes, and intoxication. The more alcohol and alprazolam taken, the worse the interaction. Combination of alprazolam with the herb kava can result in the development of a semi-comatose state. Plants in the genus Hypericum (including St. John’s wort) conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.

Pregnancy and Breastfeeding

Benzodiazepines cross the placenta, enter the foetus, and are also excreted in breast milk. Chronic administration of diazepam, another benzodiazepine, to nursing mothers has been reported to cause their infants to become lethargic and to lose weight.

The use of alprazolam during pregnancy is associated with congenital abnormalities, and use in the last trimester may cause foetal drug dependence and withdrawal symptoms in the post-natal period as well as neonatal flaccidity and respiratory problems. However, in long-term users of benzodiazepines, abrupt discontinuation due to concerns of teratogenesis has a high risk of causing extreme withdrawal symptoms and a severe rebound effect of the underlying mental health disorder. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications, including benzodiazepines.

Overdose

Refer to Benzodiazepine Overdose.

The maximum recommended daily dose is 10 milligrams per day.

Overdoses of alprazolam can be mild to severe depending on the quantity ingested and if other drugs are taken in combination.

Alprazolam overdoses cause excess central nervous system (CNS) depression and may include one or more of the following symptoms:

  • Coma and death if alprazolam is combined with other substances.
  • Fainting.
  • Hypotension (low blood pressure).
  • Hypoventilation (shallow breathing).
  • Impaired motor functions.
  • Dizziness.
  • Impaired balance.
  • Impaired or absent reflexes.
  • Muscle weakness.
  • Orthostatic hypotension (fainting while standing up too quickly).
  • Somnolence (drowsiness).

Dependence and Withdrawal

Refer to Benzodiazepine Dependence and Benzodiazepine Withdrawal Syndrome.

The potential for misuse among those taking it for medical reasons is controversial, with some expert reviews stating that the risk is low and similar to that of other benzodiazepine drugs. Others state that there is a substantial risk of misuse and dependence in both patients and non-medical users and that the short half-life and rapid onset of action may increase the risk of misuse. Compared to the large number of prescriptions, relatively few individuals increase their dose on their own initiative or engage in drug-seeking behaviour.

Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA (gamma-aminobutyric acid) receptor. When bound to these sites, which are referred to as benzodiazepine receptors, it modulates the effect of GABAA receptors and, thus, of GABAergic neurons. Long-term use causes adaptive changes in the benzodiazepine receptors, making them less sensitive to stimulation and thus making the drugs less potent.

Withdrawal and rebound symptoms commonly occur and necessitate a gradual reduction in dosage to minimise withdrawal effects when discontinuing.

Not all withdrawal effects are evidence of true dependence or withdrawal. Recurrence of symptoms such as anxiety may simply indicate that the drug was having its expected anti-anxiety effect and that, in the absence of the drug, the symptom has returned to pre-treatment levels. If the symptoms are more severe or frequent, the person may be experiencing a rebound effect due to the removal of the drug. Either of these can occur without the person actually being drug dependent.

Alprazolam and other benzodiazepines may also cause the development of physical dependence, tolerance, and benzodiazepine withdrawal symptoms during rapid dose reduction or cessation of therapy after long-term treatment. There is a higher chance of withdrawal reactions if the drug is administered in a higher dosage than recommended, or if a person stops taking the medication altogether without slowly allowing the body to adjust to a lower-dosage regimen.

In 1992, Romach and colleagues reported that dose escalation is not a characteristic of long-term alprazolam users and that the majority of long-term alprazolam users change their initial pattern of regular use to one of symptom control only when required.

Some common symptoms of alprazolam discontinuation include malaise, weakness, insomnia, tachycardia, lightheadedness, and dizziness.

Those taking more than 4 mg per day have an increased potential for dependence. This medication may cause withdrawal symptoms upon abrupt withdrawal or rapid tapering, which in some cases have been known to cause seizures, as well as marked delirium similar to that produced by the anticholinergic tropane alkaloids of Datura (scopolamine and atropine). The discontinuation of this medication may also cause a reaction called rebound anxiety.

In a 1983 study, only 5% of patients who had abruptly stopped taking long-acting benzodiazepines after less than 8 months demonstrated withdrawal symptoms, but 43% of those who had been taking them for more than 8 months did. With alprazolam – a short-acting benzodiazepine – taken for 8 weeks, 65% of patients experienced significant rebound anxiety. To some degree, these older benzodiazepines are self-tapering.

The benzodiazepines diazepam and oxazepam have been found to produce fewer withdrawal reactions than alprazolam, temazepam, or lorazepam. Factors that determine the risk of psychological dependence or physical dependence and the severity of the benzodiazepine withdrawal symptoms during dose reduction of alprazolam include: dosage used, length of use, frequency of dosing, personality characteristics of the individual, previous use of cross-dependent/cross-tolerant drugs (alcohol or other sedative-hypnotic drugs), current use of cross-dependent/-tolerant drugs, use of other short-acting, high-potency benzodiazepines, and method of discontinuation.

Pharmacology

Alprazolam is a positive allosteric modulator of the GABA type A receptor. When it binds to the receptor, effects of GABA are enhanced leading to inhibition of neurones in the brain. This results in effects including reduced anxiety, muscle relaxant, antidepressant and anticonvulsant activity. The activity of alprazolam in the central nervous system is dose dependent.

Mechanism of Action

Alprazolam is classed as a high-potency triazolobenzodiazepine: a benzodiazepine with a triazole ring attached to its structure. As a benzodiazepine, alprazolam produces a variety of therapeutic and adverse effects by binding to the GABAA benzodiazepine receptor site and modulating its function; GABA receptors are the most prolific inhibitory receptor within the brain. The GABA chemical and receptor system mediates inhibitory or calming effects of alprazolam on the nervous system. Binding of alprazolam to the GABAA receptor, a chloride ion channel, enhances the effects of GABA, a neurotransmitter. When GABA binds the GABAA receptor the channel opens and chloride enters the cell which makes it more resistant to depolarisation. Therefore, alprazolam has a depressant effect on synaptic transmission to reduce anxiety.

The GABAA receptor is made up of 5 subunits out of a possible 19, and GABAA receptors made up of different combinations of subunits have different properties, different locations within the brain, and, importantly, different activities with regard to benzodiazepines. Alprazolam and other triazolobenzodiazepines such as triazolam that have a triazole ring fused to their diazepine ring appear to have antidepressant properties. This is perhaps due to the similarities shared with tricyclic antidepressants, as they have two benzene rings fused to a diazepine ring. Alprazolam causes a marked suppression of the hypothalamic-pituitary-adrenal axis. The therapeutic properties of alprazolam are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic and amnesic; however, it is used mainly as an anxiolytic.

Giving alprazolam, as compared to lorazepam, has been demonstrated to elicit a statistically significant increase in extracellular dopamine D1 and D2 concentrations in the striatum.

Pharmacokinetics

Alprazolam is taken orally, and is absorbed well – 80% of alprazolam binds to proteins in the serum (the majority binding to albumin). The concentration of alprazolam peaks after one to two hours.

Alprazolam is metabolised in the liver, mostly by the enzyme cytochrome P450 3A4 (CYP3A4). Two major metabolites are produced: 4-hydroxyalprazolam and α-hydroxyalprazolam, as well as an inactive benzophenone. The low concentrations and low potencies of 4-hydroxyalprazolam and α-hydroxyalprazolam indicate that they have little to no contribution to the effects of alprazolam.

The metabolites, as well as some unmetabolised alprazolam, are filtered out by the kidneys and are excreted in the urine.

Chemistry

Physical Properties

Alprazolam is a triazole and benzodiazepine derivative substituted with a phenyl group at position 6, with a chlorine atom at position 8 and with a methyl group at position 1. It is an analogue of triazolam, the difference between them being the absence of a chlorine atom in the ‘ortho’ position of the phenyl ring. It is slightly soluble in chloroform, soluble in alcohol, slightly soluble in acetone and insoluble in water. It has a melting point in the temperature range 228-229.5 °C.

Synthesis

For the synthesis of alprazolam the same method can be used as for triazolam, excepting that it starts from 2-amino-5-chlorobenzophenone. However, an alternative easier synthesis starting with 2,6-dichloro-4-phenylquinoline has been suggested, in which it reacts with hydrazine giving 6-chloro-2-hydrazino-4-phenylquinoline. Boiling the mixture with triethyl orthoacetate results in cyclization with the formation of the triazole ring. The product undergoes oxidative degradation in the presence of periodate and ruthenium dioxide in acetone solution, giving 2-[4-(3′-methyl-1,2,4-triazolo)]-5-chlorobenzophenone. Oxy-methylation with formaldehyde results in a product that is treated with phosphorus tribromide, when 2-[4-(3′-methyl-5′-bromomethyl-1,2,4-triazolo)]-5-chlorobenzophenone is obtained. By substituting the bromine atom with an amino group conferred by ammonia, it forms alprazolam triazolobenzophenone, following which an intermolecular heterocyclisation takes place to obtain alprazolam.

Detection

Quantification of alprazolam in blood and plasma samples may be necessary to confirm a diagnosis of intoxication in hospitalised patients, or to provide evidence in the case of crimes e.g., impaired driving arrest, or to assist in a thorough forensic investigation, e.g. in a medicolegal death investigation. Blood or plasma alprazolam concentrations are usually in a range of 10-100 μg/L in persons receiving the drug therapeutically, 100-300 μg/L in those arrested for impaired driving, and 300–2000 μg/L in victims of acute overdosage. Most of the commercial immunoassays used for the benzodiazepine class of drugs cross-react with alprazolam, but confirmation and quantitative determination are usually done by chromatographic techniques.

Forms of Alprazolam

Alprazolam regular release and orally disintegrating tablets are available as 0.25 mg, 0.5 mg, 1 mg, and 2 mg tablets, while extended release tablets are available as 0.5 mg, 1 mg, 2 mg, and 3 mg. Liquid alprazolam is available in a 1 mg/mL oral concentrate. Inactive ingredients in alprazolam tablets and solutions include microcrystalline cellulose, corn starch, docusate sodium, povidone, sodium starch glycollate, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, and sodium benzoate. In addition, the 0.25 mg tablet contains D&C Yellow No. 10 and the 0.5 mg tablet contains FD&C Yellow No. 6 and D&C Yellow No. 10.

Society and Culture

Patent

Alprazolam is covered under US Patent 3,987,052, which was filed on 29 October 1969, granted on 19 October 1976, and expired in September 1993.

Recreational Use

Refer to Benzodiazepine Use Disorder.

There is a risk of misuse and dependence in both patients and non-medical users of alprazolam; alprazolam’s high affinity binding, high potency, and rapid onset increase its abuse potential. The physical dependence and withdrawal syndrome of alprazolam also add to its addictive nature. In the small subgroup of individuals who escalate their doses there is usually a history of alcohol or other substance use disorders. Despite this, most prescribed alprazolam users do not use their medication recreationally, and the long-term use of benzodiazepines does not generally correlate with the need for dose escalation. However, based on US findings from the Treatment Episode Data Set (TEDS), an annual compilation of patient characteristics in substance abuse treatment facilities in the United States, admissions due to “primary tranquiliser” (including, but not limited to, benzodiazepine-type) drug use increased 79% from 1992 to 2002, suggesting that misuse of benzodiazepines may be on the rise. In 2011, The New York Times reported, “The Centres for Disease Control and Prevention last year reported an 89 percent increase in emergency room visits nationwide related to nonmedical benzodiazepine use between 2004 and 2008.”

Alprazolam is one of the most commonly prescribed and misused benzodiazepines in the United States. A large-scale nationwide US government study conducted by SAMHSA found that, in the US, benzodiazepines are recreationally the most frequently used pharmaceuticals due to their widespread availability, accounting for 35% of all drug-related visits to hospital emergency and urgent care facilities. Men and women are equally likely to use benzodiazepines recreationally. The report found that alprazolam is the most common benzodiazepine for recreational use, followed by clonazepam, lorazepam, and diazepam. The number of emergency department visits due to benzodiazepines increased by 36% between 2004 and 2006.

Regarding the significant increases detected, it is worthwhile to consider that the number of pharmaceuticals dispensed for legitimate therapeutic uses may be increasing over time, and DAWN estimates are not adjusted to take such increases into account. Nor do DAWN estimates take into account the increases in the population or in ED use between 2004 and 2006.

Those at a particularly high risk for misuse and dependence are people with a history of alcoholism or drug abuse and/or dependence and people with borderline personality disorder.

Alprazolam, along with other benzodiazepines, is often used with other recreational drugs. These uses include aids to relieve the panic or distress of dysphoric (“bad trip”) reactions to psychedelic drugs, such as LSD, and the drug-induced agitation and insomnia in the “comedown” stages of stimulant use, such as amphetamine, cocaine, and MDMA allowing sleep. Alprazolam may also be used with other depressant drugs, such as ethanol, heroin, and other opioids, in an attempt to enhance their psychological effects. Alprazolam may be used in conjunction with cannabis, with users citing a synergistic effect achieved after consuming the combination.

The poly-drug use of powerful depressant drugs poses the highest level of health concerns due to a significant increase in the likelihood of experiencing an overdose, which may cause fatal respiratory depression.

A 1990 study found that diazepam has a higher misuse potential relative to many other benzodiazepines and that some data suggest that alprazolam and lorazepam resemble diazepam in this respect.

Anecdotally, injection of alprazolam has been reported, causing dangerous damage to blood vessels, closure of blood vessels (embolisation) and decay of muscle tissue (rhabdomyolysis). Alprazolam is not very soluble in water – when crushed in water it does not fully dissolve (40 µg/ml of H2O at pH 7). There have also been anecdotal reports of alprazolam being snorted.[111] Due to the low weight of a dose, alprazolam, in one case, was distributed on blotter paper in a manner similar to LSD.

Slang terms for alprazolam vary from place to place. Some of the more common terms are modified versions of the trade name “Xanax”, such as Xannies (or Xanies) and the phonetic equivalent of Zannies; references to their drug classes, such as benzos or downers; or remark upon their shape or colour (most commonly a straight, perforated tablet or an oval-shaped pill): bars, ladders, Xanbars, Xans, Z-bars, handle bars, beans, footballs, planks, poles, sticks, blues, or blue footballs.

Availability

Alprazolam is available in English-speaking countries under the following brand names:

  • Alprax, Alprocontin, Alzam, Alzolam, Anzilum, Apo-Alpraz, Helex, Kalma, Mylan-Alprazolam, Niravam, Novo-Alprazol, Nu-Alpraz, Pacyl, Restyl, Tranax, Trika, Xycalm, Xanax, Xanor, Zolam, Zopax.

In December 2013, in anticipation of the rescheduling of alprazolam to Schedule 8 in Australia, Pfizer Australia announced they would be discontinuing the Xanax brand in Australia as it was no longer commercially viable.

Alprazolam has varied legal status depending on jurisdiction:

  • In the United States, alprazolam is a prescription drug and is assigned to Schedule IV of the Controlled Substances Act by the Drug Enforcement Administration.
  • Under the UK drug misuse classification system, benzodiazepines are Class C drugs (Schedule 4).
    • In the UK, alprazolam is not available on the NHS and can only be obtained on a private prescription.
  • In Ireland, alprazolam is a Schedule 4 medicine.
  • In Sweden, alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).
  • In the Netherlands, alprazolam is a List 2 substance of the Opium Law and is available for prescription.
  • In Germany, alprazolam can be prescribed normally in doses up to 1 mg.
    • Higher doses are scheduled as Anlage III drugs and require a special prescription form.
  • In Australia, alprazolam was originally a Schedule 4 (Prescription Only) medication; however, as of February 2014, it has become a Schedule 8 medication, subjecting it to more rigorous prescribing requirements.
  • In the Philippines, alprazolam is legally classified as a “dangerous drug” under the Comprehensive Dangerous Drugs Act of 2002, along with other schedule drugs listed in the 1971 Convention on Psychotropic Substances.
    • The importation of dangerous drugs including alprazolam, requires authorisation from the Philippine Drug Enforcement Agency.
  • Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.

What is Triazolobenzodiazepine?

Published on by Andrew Marshall7 Comments

Introduction

Triazolobenzodiazepines (TBZD) are a class of benzodiazepine (BZD) derivative pharmaceutical drugs. Chemically, they differ from other benzodiazepines by having an additional fused triazole ring.

Examples include:

  • Adinazolam.
  • Alprazolam.
  • Bromazolam.
  • Clonazolam.
  • Estazolam.
  • Flualprazolam.
  • Flubromazolam.
  • Flunitrazolam.
  • Nitrazolam.
  • Pyrazolam.
  • Triazolam.
  • Zapizolam.

Synthesis

Synthesis of 1-methyltriazolobenzodiazepines (alprazolam type) is possible by heating 1,4-benzodiazepin-2-thiones with hydrazine and acetic acid in n-butanol under reflux.

What is Seproxetine?

Published on by Andrew MarshallLeave a comment

Introduction

Seproxetine, also known as (S)-norfluoxetine, is a selective serotonin reuptake inhibitor (SSRI).

Background

It is the S enantiomer of norfluoxetine, the main active metabolite of the widely used antidepressant fluoxetine; but little is known about its pharmacological actions. Seproxetine was being investigated by Eli Lilly and Company as an antidepressant; however, cardiac side effects were discovered and development was discontinued.

What is Alloplastic Adaptation?

Published on by Andrew MarshallLeave a comment

Introduction

Alloplastic adaptation (from the Greek word “allos”, meaning “other”) is a form of adaptation where the subject attempts to change the environment when faced with a difficult situation. Criminality, mental illness, and activism can all be classified as categories of alloplastic adaptation.

The concept of alloplastic adaptation was developed by Sigmund Freud, Sándor Ferenczi, and Franz Alexander. They proposed that when an individual was presented with a stressful situation, they could react in one of two ways:

  • Autoplastic adaptation: The subject tries to change themselves, i.e. the internal environment.
  • Alloplastic adaptation: The subject tries to change the situation, i.e. the external environment.

Origins and Development

These terms are possibly due to Ferenczi, who used them in a paper on “The Phenomenon of Hysterical Materialization” (1919,24). But he there appears to attribute them to Freud (who may have used them previously in private correspondence or conversation). Ferenczi linked the purely “autoplastic” tricks of the hysteric…[to] the bodily performances of “artists” and actors.

Freud’s only public use of the terms was in his paper “The Loss of Reality in Neurosis and Psychosis” (1924), where he points out that “expedient, normal behaviour leads to work being carried out on the external world; it does not stop, as in psychosis, at effecting internal changes. It is no longer autoplastic but alloplastic”.

A few years later, in his paper on “The Neurotic Character” (1930), Alexander described “a type of neurosis in which…the patient’s entire life consists of actions not adapted to reality but rather aimed at relieving unconscious tensions”. Alexander considered that “neurotic characters of this type are more easily accessible to psychoanalysis than patients with symptom neuroses…[due] to the fact that in the latter the patient has regressed from alloplasticity to autoplasticity; after successful analysis he must pluck up courage to take action in real life”.

Otto Fenichel however took issue with Alexander on this point, maintaining that “The pseudo-alloplastic attitude of the neurotic character cannot be changed into a healthy alloplastic one except by first being transformed, for a time, into a neurotic autoplastic attitude, which can then be treated like an ordinary symptom neurosis”.

Human Evolution

Alloplasticity has also been used to describe humanity’s cultural “evolution”. Man’s “evolution by culture…is through alloplastic experiment with objects outside his own body….Unlike autoplastic experiments, alloplastic ones are both replicable and reversible”.

In particular, “advanced technological societies…are generally characterized by “alloplastic” relations with the environment, involving the manipulation of the environment itself”.

On This Day … 03 December

Published on by Andrew MarshallLeave a comment

People (Births)

  • 1895 – Anna Freud, Austrian-English psychologist and psychoanalyst (d. 1982).
  • 1943 – J. Philippe Rushton, English-Canadian psychologist and academic (d. 2012).

People (Deaths)

  • 2008 – Robert Zajonc, Polish-American psychologist and author (b. 1923).
  • 2014 – Nathaniel Branden, Canadian-American psychotherapist and author (b. 1930).

Anna Freud

Anna Freud (03 December 1895 o 09 October 1982) was a British psychoanalyst of Austrian-Jewish descent. She was born in Vienna, the sixth and youngest child of Sigmund Freud and Martha Bernays. She followed the path of her father and contributed to the field of psychoanalysis. Alongside Hermine Hug-Hellmuth and Melanie Klein, she may be considered the founder of psychoanalytic child psychology.

Compared to her father, her work emphasized the importance of the ego and its normal “developmental lines” as well as incorporating a distinctive emphasis on collaborative work across a range of analytical and observational contexts.

After the Freud family were forced to leave Vienna in 1938 with the advent of the Nazi regime in Austria, she resumed her psychoanalytic practice and her pioneering work in child psychology in London, establishing the Hampstead Child Therapy Course and Clinic in 1952 (now the Anna Freud National Centre for Children and Families) as a centre for therapy, training and research work.

J. Philippe Rushton

John Philippe Rushton (03 December 1943 to 02 October 2012) was a Canadian psychologist and author. He taught at the University of Western Ontario and became known to the general public during the 1980s and 1990s for research on race and intelligence, race and crime, and other purported racial correlations.

Rushton’s work was heavily criticised by the scientific community for the questionable quality of its research, with many academics arguing that it was conducted under a racist agenda. From 2002 until his death, he served as the head of the Pioneer Fund, an organization that was founded in 1937 to promote eugenics and that in its early years supported Nazi ideology, for example, by funding the distribution in US churches and schools of a Nazi propaganda film about eugenics. The Pioneer Fund has been described as a white supremacist organisation and designated as a hate group by the Southern Poverty Law Centre.

Rushton was a Fellow of the Canadian Psychological Association and a onetime Fellow of the John Simon Guggenheim Memorial Foundation. In 2020 the Department of Psychology of the University of Western Ontario released a statement stating that “much of his research was racist” and his work was “deeply flawed from a scientific standpoint”. As of 2021, Rushton has had six research publications retracted.

Robert Zajonc

Robert Bolesław Zajonc (23 November 1923 to 03 December 2008) was a Polish-born American social psychologist who is known for his decades of work on a wide range of social and cognitive processes.

One of his most important contributions to social psychology is the mere-exposure effect. Zajonc also conducted research in the areas of social facilitation, and theories of emotion, such as the affective neuroscience hypothesis. He also made contributions to comparative psychology. He argued that studying the social behaviour of humans alongside the behaviour of other species, is essential to our understanding of the general laws of social behaviour. An example of his viewpoint is his work with cockroaches that demonstrated social facilitation, evidence that this phenomenon is displayed regardless of species. A Review of General Psychology survey, published in 2002, ranked Zajonc as the 35th most cited psychologist of the 20th century.

He died of pancreatic cancer on 03 December 2008 in Palo Alto, California.

Nathaniel Branden

Nathaniel Branden (born Nathan Blumenthal; 09 April 1930 to 03 December 2014) was a Canadian-American psychotherapist and writer known for his work in the psychology of self-esteem. A former associate and romantic partner of Ayn Rand, Branden also played a prominent role in the 1960s in promoting Rand’s philosophy, Objectivism. Rand and Branden split acrimoniously in 1968, after which Branden focused on developing his own psychological theories and modes of therapy.

What is the Toronto Alexithymia Scale?

Published on by Andrew Marshall1 Comment

Introduction

The Toronto Alexithymia Scale is a measure of deficiency in understanding, processing, or describing emotions.

Background

It was developed in 1986 and later revised, removing some of the items.

The current version has twenty statements rated on a five-point Likert scale.

The reliability and validity of the TAS-20 was established by a series of articles by Bagby and colleagues (1994).

Reference

Bagby, R.M., Parker, J.D.A. & Taylor, G.J. (1994) The Twenty-Item Toronto Alexithymia Scale—I. Item Selection and Cross-Validation of the Factor Structure. Journal of Psychosomatic Research. 38(1), pp.23-32.