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On This Day … 21 September [2022]

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People (Births)

  • 1946 – Mart Siimann, Estonian psychologist and politician, 12th Prime Minister of Estonia.

Mart Siimann

Mart Siimann (born 21 September 1946) was the Prime Minister of Estonia from 1997 to 1999, representing the liberal/centrist Estonian Coalition Party. He was the president of the Estonian Olympic Committee from 2001 to 2012.

Born at Kilingi-Nõmme, Siimann studied at the University of Tartu from 1965 to 1971. In 1971, he graduated as a philologist-psychologist. From 1989 to 1992, he was the director of the Estonian Television and from 1992 to 1995, Managing Director of Advertising Television Co. He was a member of the Estonian Parliament from 1995 to 1997 and from 1999 to 2003, elected as a Coalition Party member (but since 2001 served as the chairman of the centre-left/social democratic association “Mõistuse ja Südamega” (“With Reason and Heart”).

On This Day … 20 September [2022]

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People (Births)

  • 1847 – Susanna Rubinstein, Austrian psychologist (d. 1914).

Susanna Rubinstein

Susanna or Susanne Rubinstein (20 September 1847 to 29 March 1914) was an Austrian psychologist and the first woman to earn a doctorate from the University of Bern in Switzerland.

Rubinstein was born in Czernowitz (then part of Austria-Hungary, now Chernivtsi, Ukraine) into the Jewish family of the banker and parliamentarian Isak Rubinstein (c. 1804-1878). Her mother died when she was young.

She and her three siblings were greatly encouraged to pursue their education, even though this was a time when girls were often denied that opportunity. (A high school for girls was eventually opened in Czernowitz in1898 and a girls’ grammar school was established only during the years just before the First World War).

At first, her father arranged for Rubinstein to take private lessons but, when it came time to finish high school, she was unable to take the necessary examinations from tutors, so she did so before an academic committee from a boys’ high school.

Rubinstein went on to study psychology and German literature at the University of Prague, in the spring of 1870, and then at the Leipzig University three years later. After being denied admission to the doctoral program in Basel, Switzerland, she enrolled at the University of Bern and there she gained a Ph.D. in 1874 in psychology and German literature. By doing so, she became the first woman to receive a doctorate in Bern. Her thesis was “Uber die sensoriellen und sensitiven Sinne” (“About the sensory and sensitive senses”).

With the completion of her doctorate, Rubinstein spent a year in Germany visiting Leipzig, Heidelberg and Munich.

Her 1878 work “Psychologisch-Asthetische Essays” (“Psychological-Aesthetic Essays”) has been described as “a major contribution to the study of human emotions”. It was reprinted in 2012 (Nabu Press, ISBN 978-1277814729).

Susanna Rubinstein died 29 March 1914 in Würzburg, Germany.

What is Amoxapine?

Published on by Andrew Marshall1 Comment

Introduction

Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCAs). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 years after most of the other TCAs were introduced in the United States).

Medical Uses

Moxapine is used in the treatment of major depressive disorder (MDD). Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days. In excess of 80% of patients that do respond to amoxapine are reported to respond within two weeks of the beginning of treatment. It also has properties similar to those of the atypical antipsychotics, and may behave as one and may be used in the treatment of schizophrenia off-label. Despite its apparent lack of extrapyramidal side effects in patients with schizophrenia it has been found to exacerbate motor symptoms in patients with Parkinson’s disease and psychosis.

Contraindications

As with all US Food and Drug Administration (FDA)-approved antidepressants it carries a black-box warning about the potential of an increase in suicidal thoughts or behaviour in children, adolescents and young adults under the age of 25. Its use is also advised against in individuals with known hypersensitivities to either amoxapine or other ingredients in its oral formulations. Its use is also recommended against in the following disease states:

  • Severe cardiovascular disorders (potential of cardiotoxic adverse effects such as QT interval prolongation).
  • Uncorrected narrow angle glaucoma.
  • Acute recovery post-myocardial infarction.

Its use is also advised against in individuals concurrently on monoamine oxidase inhibitors or if they have been on one in the past 14 days and in individuals on drugs that are known to prolong the QT interval (e.g. ondansetron, citalopram, pimozide, sertindole, ziprasidone, haloperidol, chlorpromazine, thioridazine, etc.).

Lactation

Its use in breastfeeding mothers not recommended as it is excreted in breast milk and the concentration found in breast milk is approximately a quarter that of the maternal serum level.

Side Effects

Very Common (>10% Incidence) Adverse Effects Include:

  • Constipation.
  • Dry mouth.
  • Sedation.

Common (1–10% Incidence) Adverse Effects Include:

  • Anxiety.
  • Ataxia.
  • Blurred vision.
  • Confusion.
  • Dizziness.
  • Headache.
  • Fatigue.
  • Nausea.
  • Nervousness/restlessness.
  • Excessive appetite.
  • Rash.
  • Increased perspiration (sweating).
  • Tremor.
  • Palpitations.
  • Nightmares.
  • Excitement.
  • Weakness.
  • ECG changes.
  • Oedema.
    • An abnormal accumulation of fluids in the tissues of the body leading to swelling.
  • Prolactin levels increased.
    • Prolactin is a hormone that regulates the generation of breast milk.
    • Prolactin elevation is not as significant as with risperidone or haloperidol.

Uncommon/Rare (<1% Incidence) Adverse Effects Include:

  • Diarrhoea.
  • Flatulence.
  • Hypertension (high blood pressure).
  • Hypotension (low blood pressure).
  • Syncope (fainting).
  • Tachycardia (high heart rate).
  • Menstrual irregularity.
  • Disturbance of accommodation.
  • Mydriasis (pupil dilation).
  • Orthostatic hypotension (a drop in blood pressure that occurs upon standing up).
  • Seizure.
  • Urinary retention (being unable to pass urine).
  • Urticaria (hives).
  • Vomiting.
  • Nasal congestion.
  • Photosensitisation
  • Hypomania (a dangerously elated/irritable mood).
  • Tingling.
  • Paresthaesias of the extremities.
  • Tinnitus.
  • Disorientation.
  • Numbness.
  • Incoordination.
  • Disturbed concentration.
  • Epigastric distress.
  • Peculiar taste in the mouth.
  • Increased or decreased libido.
  • Impotence (difficulty achieving an erection).
  • Painful ejaculation.
  • Lacrimation (crying without an emotional cause).
  • Weight gain.
  • Altered liver function.
  • Breast enlargement.
  • Drug fever.
  • Pruritus (itchiness).
  • Vasculitis a disorder where blood vessels are destroyed by inflammation.
    • Can be life-threatening if it affects the right blood vessels.
  • Galactorrhoea:
    • Lactation that is not associated with pregnancy or breast feeding.
  • Delayed micturition:
    • That is, delays in urination from when a conscious effort to urinate is made.
  • Hyperthermia:
    • Elevation of body temperature; its seriousness depends on the extent of the hyperthermia.
  • Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) this is basically when the body’s level of the hormone, antidiuretic hormone, which regulates the conservation of water and the restriction of blood vessels, is elevated.
    • This is potentially fatal as it can cause electrolyte abnormalities including hyponatraemia (low blood sodium), hypokalaemia (low blood potassium) and hypocalcaemia (low blood calcium) which can be life-threatening.
  • Agranulocytosis a drop in white blood cell counts.
    • The white blood cells are the cells of the immune system that fight off foreign invaders.
    • Hence agranulocytosis leaves an individual open to life-threatening infections.
  • Leukopaenia the same as agranulocytosis but less severe.
  • Neuroleptic malignant syndrome (a potentially fatal reaction to antidopaminergic agents, most often antipsychotics.
    • It is characterised by hyperthermia, diarrhoea, tachycardia, mental status changes [e.g. confusion], rigidity, extrapyramidal side effects)
  • Tardive dyskinesia a most often irreversible neurologic reaction to antidopaminergic treatment, characterised by involuntary movements of facial muscles, tongue, lips, and other muscles.
    • It develops most often only after prolonged (months, years or even decades) exposure to antidopaminergics.
  • Extrapyramidal side effects.
    • Motor symptoms such as tremor, parkinsonism, involuntary movements, reduced ability to move one’s voluntary muscles, etc.

Unknown Incidence or Relationship to Drug Treatment Adverse Effects Include:

  • Paralytic ileus (paralysed bowel).
  • Atrial arrhythmias including atrial fibrillation.
  • Myocardial infarction (heart attack).
  • Stroke.
  • Heart block.
  • Hallucinations.
  • Purpura.
  • Petechiae.
  • Parotid swelling.
  • Changes in blood glucose levels.
  • Pancreatitis swelling of the pancreas.
  • Hepatitis swelling of the liver.
  • Urinary frequency.
  • Testicular swelling.
  • Anorexia (weight loss).
  • Alopecia (hair loss).
  • Thrombocytopenia:
    • A significant drop in platelet count that leaves one open to life-threatening bleeds.
  • Eosinophilia an elevated level of the eosinophils of the body.
    • Eosinophils are the type of immune cell that’s job is to fight off parasitic invaders.
  • Jaundice:
    • yellowing of the skin, eyes and mucous membranes due to an impaired ability of the body to clear the by product of haem breakdown, bilirubin, most often the result of liver damage as it is the liver’s responsibility to clear bilirubin.

It tends to produce less anticholinergic effects, sedation and weight gain than some of the earlier TCAs (e.g. amitriptyline, clomipramine, doxepin, imipramine, trimipramine). It may also be less cardiotoxic than its predecessors.

Overdose

Refer to Tricyclic Antidepressant Overdose.

It is considered particularly toxic in overdose, with a high rate of renal failure (which usually takes 2-5 days), rhabdomyolysis, coma, seizures and even status epilepticus. Some believe it to be less cardiotoxic than other TCAs in overdose, although reports of cardiotoxic overdoses have been made.

Pharmacology

Pharmacodynamics

Amoxapine possesses a wide array of pharmacological effects. It is a moderate and strong reuptake inhibitor of serotonin and norepinephrine, respectively, and binds to the 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, 5-HT7, D2, α1-adrenergic, D3, D4, and H1 receptors with varying but significant affinity, where it acts as an antagonist (or inverse agonist depending on the receptor in question) at all sites. It has weak but negligible affinity for the dopamine transporter and the 5-HT1A, 5-HT1B, D1, α2-adrenergic, H4, mACh, and GABAA receptors, and no affinity for the β-adrenergic receptors or the allosteric benzodiazepine site on the GABAA receptor. Amoxapine is also a weak GlyT2 blocker, as well as a weak (Ki = 2.5 μM, EC50 = 0.98 μM) δ-opioid receptor partial agonist.

7-Hydroxyamoxapine, a major active metabolite of amoxapine, is a more potent dopamine receptor antagonist and contributes to its neuroleptic efficacy, whereas 8-hydroxyamoxapine is a norepinephrine reuptake inhibitor but a stronger serotonin reuptake inhibitor and helps to balance amoxapine’s ratio of serotonin to norepinephrine transporter blockade

Pharmacokinetics

Amoxapine is metabolised into two main active metabolites: 7-hydroxyamoxapine and 8-hydroxyamoxapine.

Society and Culture

Brand Names

Brand names for amoxapine include (where † denotes discontinued brands):

  • Adisen (KR).
  • Amolife (IN).
  • Amoxan (JP).
  • Asendin† (previously marketed in CA, NZ, US).
  • Asendis† (previously marketed in IE, UK).
  • Défanyl (FR).
  • Demolox (DK†, IN, ES†).
  • Oxamine (IN).
  • Oxcap.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Amoxapine >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

On This Day … 19 September [2022]

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People (Births)

  • 1913 – Frances Farmer, American actress (d. 1970).
  • 1954 – Adam Phillips, Welsh psychotherapist and author.

Frances Farmer

Frances Elena Farmer (19 September 1913 to 01 August 1970) was an American actress and television hostess. She appeared in over a dozen feature films over the course of her career, though she garnered notoriety for the various sensationalised accounts of her life, especially her involuntary commitment to psychiatric hospitals and subsequent mental health struggles.

A native of Seattle, Washington, Farmer began acting in stage productions while a student at the University of Washington. After graduating, she began performing in stock theatre before signing a film contract with Paramount Pictures on her 22nd birthday in September 1935. She made her film debut in the B film Too Many Parents (1936), followed by another B picture, Border Flight, before being given the lead role opposite Bing Crosby in the musical Western Rhythm on the Range (1936). Unhappy with the opportunities the studio gave her, Farmer returned to stock theatre in 1937 before being cast in the original Broadway production of Clifford Odets’s Golden Boy, staged by New York City’s Group Theatre. She followed this with two Broadway productions directed by Elia Kazan in 1939, but a battle with depression and binge drinking caused her to drop out of a subsequent Ernest Hemingway stage adaptation.

Farmer returned to Los Angeles, earning supporting roles in the comedy World Premiere (1941) and the film noir Among the Living (1941). In 1942, publicity of her reportedly erratic behaviour began to surface and, after several arrests and committals to psychiatric institutions, Farmer was diagnosed with paranoid schizophrenia. At the request of her family, particularly her mother, she was committed to an institution in her home state of Washington, where she remained a patient until 1950. Farmer attempted an acting comeback, mainly appearing as a television host in Indianapolis on her own series, Frances Farmer Presents. Her final film role was in the 1958 drama The Party Crashers, after which she spent the majority of the 1960s occasionally performing in local theatre productions staged by Purdue University. In the spring of 1970, she was diagnosed with oesophageal cancer, from which she died on 01 August 1970, aged 56.

Farmer has been the subject of various works, including two feature films and several books, many of which focus on her time spent institutionalised, during which she claimed to have been subject to various systemic abuses. Her posthumously released, ghostwritten, and widely discredited autobiography, Will There Really Be a Morning? (1972), details these claims, but has been exposed as a largely fictional work by a friend of Farmer’s to clear debts. Another discredited 1978 biography of her life, Shadowland, alleged that Farmer underwent a transorbital lobotomy during her institutionalisation, but the author has since stated in court that he fabricated this incident and several other aspects of the book. A 1982 biographical film based on this book depicted these events as true, resulting in renewed interest in her life and career.

Adam Phillips

Adam Phillips (born 19 September 1954) is a British psychoanalytic psychotherapist and essayist.

Since 2003 he has been the general editor of the new Penguin Modern Classics translations of Sigmund Freud. He is also a regular contributor to the London Review of Books.

Joan Acocella, writing in The New Yorker, described Phillips as “Britain’s foremost psychoanalytic writer”,[2] an opinion echoed by historian Élisabeth Roudinesco in Le Monde.

On This Day … 18 September [2022]

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People (Births)

  • 1888 – Toni Wolff, Swiss psychologist and author (d. 1953).
  • 1954 – Steven Pinker, Canadian-American psychologist, linguist, and author.

Toni Wolff

Toni Anna Wolff (18 September 1888 to 21 March 1953) was a Swiss Jungian analyst and a close collaborator of Carl Jung. During her analytic career Wolff published relatively little under her own name, but she helped Jung identify, define, and name some of his best-known concepts, including anima, animus, and persona, as well as the theory of the psychological types. Her best-known paper is an essay on four “types” or aspects of the feminine psyche: the Amazon, the Mother, the Hetaira, and the Medial (or mediumistic) Woman.

Steven Pinker

Steven Arthur Pinker (born 18 September 1954) is a Canadian-American cognitive psychologist, psycholinguist, popular science author and public intellectual. He is an advocate of evolutionary psychology and the computational theory of mind.

On This Day … 16 September [2022]

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People (Deaths)

  • 1980 – Jean Piaget, Swiss psychologist and philosopher (b. 1896).

Jean Piaget

Jean William Fritz Piaget (09 August 1896 to 16 September 1980) was a Swiss psychologist known for his work on child development. Piaget’s theory of cognitive development and epistemological view are together called “genetic epistemology”.

Piaget placed great importance on the education of children. As the Director of the International Bureau of Education, he declared in 1934 that “only education is capable of saving our societies from possible collapse, whether violent, or gradual”. His theory of child development is studied in pre-service education programs. Educators continue to incorporate constructivist-based strategies.

Piaget created the International Centre for Genetic Epistemology in Geneva in 1955 while on the faculty of the University of Geneva, and directed the centre until his death in 1980. The number of collaborations that its founding made possible, and their impact, ultimately led to the Centre being referred to in the scholarly literature as “Piaget’s factory”.

According to Ernst von Glasersfeld, Piaget was “the great pioneer of the constructivist theory of knowing”. However, his ideas did not become widely popularised until the 1960s. This then led to the emergence of the study of development as a major sub-discipline in psychology. By the end of the 20th century, Piaget was second only to B.F. Skinner as the most-cited psychologist of that era.

On This Day … 15 September [2022]

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People (Deaths)

Jurg Schubiger

Jürg Schubiger (14 October 1936 to 15 September 2014) was a Swiss psychotherapist and writer of children’s books. He won the Deutscher Jugendliteraturpreis (German Youth Literature Award) in 1996 for Als die Welt noch jung war.

For his “lasting contribution” as a children’s writer Schubiger received the biennial Hans Christian Andersen Medal in 2008. The award conferred by the International Board on Books for Young People is the highest recognition available to a writer or illustrator of children’s books.

A Brief Overview of Advocacy in Fife (Scotland)?

Published on by Andrew Marshall1 Comment

Introduction

This short article aims to introduce key concepts about advocacy in Fife, Scotland, including:

  • The importance of advocacy;
  • The principles and standards;
  • Types of advocacy; and
  • The services available for children, younger people, adults and older people in Fife.

Read in conjunction with What is Advocacy?.

What is Advocacy?

Advocacy IS:

  • Supporting people to speak about issues important to them;
  • A safeguarding role;
  • Supporting people to make their own choices and decisions;
  • Supporting people to have their views heard and increase their self-confidence; and
  • Representing the views of people when they are unable to do so for themselves.

Advocacy IS NOT:

  • Counselling;
  • Mediation;
  • Care/support;
  • Telling somebody what to do; or
  • Befriending.

What are the Two Types of Advocate?

  • Citizen Advocates:
    • Are volunteers from all walks of life who want to help others in their community.
    • They are a friend, an ally and a spokesperson and they take time out of their busy lives to support people who may not otherwise be able to put their own interests forward.
    • Advocates may help their partner with practical support and advice, or just be someone to turn to for moral support.
  • Advocacy Partners:
    • Are vulnerable adults looking for support and someone to speak up for them.
    • Partners are generally people with learning disabilities or other issues that mean they may risk isolation, social exclusion or unfair treatment.
    • Partners may also have a mental health need, physical disability or long-term (chronic) health condition that means they are at risk of being unable to safeguard their rights.
    • Partners may be people living independently, in long-term care or in supported housing.

What is an Advocacy Relationship?

  • An advocacy relationship is a mutual partnership in which the advocate’s sole loyalty is to their partner.
  • It is not a service provided to the person with a disability but a relationship of friendship and support between two individuals.

What is the Importance of Advocacy?

Independent advocacy services are critical to safeguarding and empowering those people who are most vulnerable and at risk be enabling them to express their views and to have their voice heard.

Advocacy has to main themes:

  • Safeguarding people who are in situations where they are vulnerable; and
  • Speaking up for and with people who are not being heard, helping them to express their views and make their own decisions and contributions.

What are the Principles and Standards of Independent Advocacy?

Independent advocacy should be provided by an organisation whose sole role is independent advocacy, or whose other tasks either compliment or do not conflict with the provision of independent advocacy. If the service or advocate has a conflict of interest, they should withdraw from acting for the person.

  • Listening:
    • Ensures people are listened to and their views are taken into account.
    • Recognises and safeguards everyone’s right to be heard.
    • Reduces the barriers people face in having their voice head because of communication, capacity, the political, social, economic and personal interests.
  • Loyalty:
    • Is loyal to the people it supports, and stands by their views and wishes.
    • Provides no others services, has no other interests, ties or links other than delivery, promotion, support and defence of independent advocacy.
    • Must be able to evidence and demonstrate its structural, financial, and psychological independence from others.
    • Follows the agenda of the people supported, regardless of the views, interest and agendas of others.
  • Upholding Rights:
    • Stands up to injustice, discrimination and disempowerment.
    • Enables people to have greater control and influence.
    • Challenges discrimination and promotes equality and human rights.
    • Recognises power imbalances, or the barriers people face, and takes steps to address these.

What are the Types of Independent Advocacy?

Below are some of the most common types of independent advocacy services:

  • Individual Advocacy:
    • Professional, or issue-based advocacy, involves a professional advocate providing expert and specialist knowledge to help resolve a particular issue. The relationship is normally short-term.
    • Citizen advocacy is a person-based service that usually, but not always, takes place on a longer-term basis The advocate is usually an unpaid volunteer, who builds a trusting relationship with a person, and supports them to resolve any issues they have. This ensures that individuals have an active life within the community.
  • Non-Instructed Advocacy:
    • Can be provided by professional or citizen advocates. It happens when a person cannot tell an advocate what they want. This may be because the person has complex needs, and/or limited communication, which prevent them from clearly stating their wished and desires.
    • The advocate observes the person, tries different ways of communicating with them, and will speak to significant others in the person’s life.
  • Group Advocacy:
    • Group advocacy, or collective self-advocacy, is designed to allow people with the same concerns, issues or experiences to provide support to each other and highlight issues or campaign for improvement. The groups are run by members, for members, and are supported by a development worker.
  • Peer Advocacy:
    • This is provided by an individual who has gone through similar experiences. This arrangement can help to reassure the person, who is be advocated for, that the individual providing the advocacy understands them and their situation.
  • Children’s Rights Services:
    • The nature of Children’s Right Services is very similar to professional advocacy. It aims to ensure that a child’s rights are fully taken into account when decisions are made about them. Generally, this service is focussed on providing support for children and young people who have been in the care system, or who are subject to a child protection case conference.
    • The service supports the child or young person at reviews and other complex meetings, helping them to express their views and wishes in all decisions affecting them. This advocacy allows children and young people to contribute to statutory child’s plans.

What are the Adult Eligibility Criteria?

Within Fife, Scotland, the eligibility criteria for adults and older people includes:

  • People in Fife aged 16 or over;
  • People affected by disability;
  • People affected by chronic illness;
  • People with dementia or mental disorder (including mental illness, learning disability or personality disorder); and
  • Individuals who are unable to safeguard their own well-being, rights, care, or other interests.

What are the Professional Advocacy Services for Available for Adults and Older People in Fife?

  • Fife Women’s Aid (FWA):
  • Fife Forum:
    • A voluntary sector advice and information agency.
    • Established in 1990 as the Fife Elderly Forum Executive.
    • Provides advocacy for people over 65 who are in community hospitals, residential homes, or nursing care homes.
    • http://www.fifeforum.org.uk.
  • Fife Carers Centre:
  • Kindred:
  • Circles Network:
  • Fife Advocacy Forum (FVA):
    • Provides professional advocacy to children subject to compulsory measures under the Mental Health (Care and Treatment) (Scotland) Act 2003.
    • http://www.fifeadvocacyforum.org.uk.

What are the Citizen Advocacy Services for Adults and Older People in Fife?

  • Citizen advocates are unpaid and independent of service providers and families.
  • They are members of the local community.
  • Fife has three (3) citizen advocacy organisations who provide support on a longer term basis for people aged 16-65.
  • Shorter term advocacy is also available when someone would benefit from a citizen advocacy relationship to resolve a specific issue.

Organisations include:

What are the Group/Peer Advocacy Services for Adults and Older People in Fife?

  • People First (Scotland) work to support people with learning difficulties to have more choice and control over their lives.
  • Peer advocacy refers to one-to-one support provided by advocates with a similar disability or experience to a person using the service(s).
  • Trained and supported volunteers often provide peer advocacy as part of a coordinated project.
  • They facilitate seventeen (17) local advocacy groups in Fife, including two (2) women only groups and two (2) men only groups.
  • People First workers will support individuals to find a suitable local group for their needs.
  • http://peoplefirstscotland.org/.

What are the Advocacy Services for Children and Young People in Fife?

  • Who Cares? Scotland:
    • Provides professional advocacy for young people up to the age of 25.
    • These young people will either have been, or will be, resident in Fife’s residential homes.
    • http://www.whocaresscotland.org/.
  • Kindred:
  • Fife Young Carers:
  • Circles Network:
    • Provides professional advocacy to children subject to compulsory measures under the Mental Health (Care and Treatment) Act 2003.
    • http://circlesnetwork.org.uk/.
  • Believe in Children (Barnardo’s):
    • Provides a children’s rights and advocacy service to children and young people in secure or purchased residential placements.
    • Children looked after at home, in kinship care, foster care, or children and young people who are subject to multi-agency statutory child’s plans can also access advocacy through Barnardo’s.
    • http://www.barnardos.org.uk/fifeservices/.

Further Reading

  • Fife Advocacy Strategy 2018-2021.
  • Carers Strategy for Fife 2018-2021.
  • Advocacy in Fife (Information Leaflet).
  • Fife Adult Support and Protection (webpage).
  • Fife Health and Social Care Strategic Plan 2016-2019.

What is Amitriptyline?

Published on by Andrew Marshall10 Comments

Introduction

Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant (TCA) primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder (MDD) and a variety of pain syndromes from neuropathic pain to fibromyalgia to migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.

The most common side effects are dry mouth, drowsiness, dizziness, constipation, and weight gain. Of note is sexual dysfunction, observed primarily in males. Glaucoma, liver toxicity and abnormal heart rhythms are rare but serious side effects. Blood levels of amitriptyline vary significantly from one person to another, and amitriptyline interacts with many other medications potentially aggravating its side effects.

Amitriptyline was discovered in the late 1950s by scientists at Merck and approved by the US Food and Drug Administration (FDA) in 1961. It is on the World Health Organisation’s List of Essential Medicines. It is available as a generic medication. In 2019, it was the 94th most commonly prescribed medication in the United States, with more than 8 million prescriptions.

Brief History

Amitriptyline was first developed by the American pharmaceutical company Merck in the late 1950s. In 1958, Merck approached a number of clinical investigators proposing to conduct clinical trials of amitriptyline for schizophrenia. One of these researchers, Frank Ayd, instead, suggested using amitriptyline for depression. Ayd treated 130 patients and, in 1960, reported that amitriptyline had antidepressant properties similar to another, and the only known at the time, tricyclic antidepressant imipramine. Following this, the FDA approved amitriptyline for depression in 1961.

In Europe, due to a quirk of the patent law at the time allowing patents only on the chemical synthesis but not on the drug itself, Roche and Lundbeck were able to independently develop and market amitriptyline in the early 1960s.

According to research by the historian of psychopharmacology David Healy, amitriptyline became a much bigger selling drug than its precursor imipramine because of two factors. First, amitriptyline has much stronger anxiolytic effect. Second, Merck conducted a marketing campaign raising clinicians’ awareness of depression as a clinical entity.

Medical Uses

Amitriptyline is indicated for the treatment of major depressive disorder and neuropathic pain and for the prevention of migraine and chronic tension headache. It can be used for the treatment of nocturnal enuresis in children older than 6 after other treatments have failed.

Depression

Amitriptyline is effective for depression, but it is rarely used as a first-line antidepressant due to its higher toxicity in overdose and generally poorer tolerability. It can be tried for depression as a second-line therapy, after the failure of other treatments. For treatment-resistant adolescent depression or for cancer-related depression amitriptyline is no better than placebo. It is sometimes used for the treatment of depression in Parkinson’s disease, but supporting evidence for that is lacking.

Pain

Amitriptyline alleviates painful diabetic neuropathy. It is recommended by a variety of guidelines as a first or second line treatment. It is as effective for this indication as gabapentin or pregabalin but less well tolerated.

Low doses of amitriptyline moderately improve sleep disturbances and reduce pain and fatigue associated with fibromyalgia. It is recommended for fibromyalgia accompanied by depression by Association of the Scientific Medical Societies in Germany and as a second-line option for fibromyalgia, with exercise being the first line option, by European League Against Rheumatism. Combinations of amitriptyline and fluoxetine or melatonin may reduce fibromyalgia pain better than either medication alone.

There is some (low-quality) evidence that amitriptyline may reduce pain in cancer patients. It is recommended only as a second line therapy for non-chemotherapy-induced neuropathic or mixed neuropathic pain, if opioids did not provide the desired effect.

Moderate evidence exists in favour of amitriptyline use for atypical facial pain. Amitriptyline is ineffective for HIV-associated neuropathy.

Headache

Amitriptyline is probably effective for the prevention of periodic migraine in adults. Amitriptyline is similar in efficacy to venlafaxine and topiramate but carries a higher burden of adverse effects than topiramate. For many patients, even very small doses of amitriptyline are helpful, which may allow for minimization of side effects. Amitriptyline is not significantly different from placebo when used for the prevention of migraine in children.

Amitriptyline may reduce the frequency and duration of chronic tension headache, but it is associated with worse adverse effects than mirtazapine. Overall, amitriptyline is recommended for tension headache prophylaxis, along with lifestyle advice, which should include avoidance of analgesia and caffeine.

Other Indications

Amitriptyline is effective for the treatment of irritable bowel syndrome; however, because of its side effects, it should be reserved for select patients for whom other agents do not work. There is insufficient evidence to support its use for abdominal pain in children with functional gastrointestinal disorders.

Tricyclic antidepressants decrease the frequency, severity, and duration of cyclic vomiting syndrome episodes. Amitriptyline, as the most commonly used of them, is recommended as a first-line agent for its therapy.

Amitriptyline may improve pain and urgency intensity associated with bladder pain syndrome and can be used in the management of this syndrome. Amitriptyline can be used in the treatment of nocturnal enuresis in children. However, its effect is not sustained after the treatment ends. Alarm therapy gives better short- and long-term results.

In the US, amitriptyline is commonly used in children with ADHD as an adjunct to stimulant medications without any evidence or guideline supporting this practice. Many physicians in the UK (and the US also) commonly prescribe amitriptyline for insomnia; however, Cochrane reviewers were not able to find any randomised controlled studies that would support or refute this practice.

Contraindications and Precautions

The known contraindications of amitriptyline are:

  • History of myocardial infarction.
  • History of arrhythmias, particularly any degree of heart block.
  • Coronary artery disease.
  • Porphyria.
  • Severe liver disease (such as cirrhosis).
  • Being under six years of age.
  • Patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken them within the last 14 days.

Amitriptyline should be used with caution in patients with epilepsy, impaired liver function, pheochromocytoma, urinary retention, prostate enlargement, hyperthyroidism, and pyloric stenosis.

In patients with the rare condition of shallow anterior chamber of eyeball and narrow anterior chamber angle, amitriptyline may provoke attacks of acute glaucoma due to dilation of the pupil. It may aggravate psychosis, if used for depression with schizophrenia, or precipitate the switch to mania in those with bipolar disorder.

CYP2D6 poor metabolisers should avoid amitriptyline due to increased side effects. If it is necessary to use it, half dose is recommended. Amitriptyline can be used during pregnancy and lactation, in the cases when SSRI do not work.

Side Effects

The most frequent side effects, occurring in 20% or more of users, are dry mouth, drowsiness, dizziness, constipation, and weight gain (on average 1.8 kg). Other common side effects (in 10% or more) are vision problems (amblyopia, blurred vision), tachycardia, increased appetite, tremor, fatigue/asthenia/feeling slowed down, and dyspepsia.

A literature review about abnormal movements and amitriptyline found that this drug is associated with various movement disorders, particularly dyskinesia, dystonia, and myoclonus. Stuttering and restless legs syndrome are some of the less common associations.

A less common side effect of amitriptyline is urination problems (8.7%).

Amitriptyline-associated sexual dysfunction (occurring at a frequency of 6.9%) seems to be mostly confined to males with depression and is expressed predominantly as erectile dysfunction and low libido disorder, with lesser frequency of ejaculatory and orgasmic problems. The rate of sexual dysfunction in males treated for indications other than depression and in females is not significantly different from placebo.

Liver tests abnormalities occur in 10-12% of patients on amitriptyline, but are usually mild, asymptomatic and transient, with consistently elevated alanine transaminase in 3% of all patients. The increases of the enzymes above the 3-fold threshold of liver toxicity are uncommon, and cases of clinically apparent liver toxicity are rare; nevertheless, amitriptyline is placed in the group of antidepressants with greater risks of hepatic toxicity.

Amitriptyline prolongs the QT interval. This prolongation is relatively small at therapeutic doses but becomes severe in overdose.

Overdose

Refer to Tricyclic Antidepressant Overdose.

The symptoms and the treatment of an overdose are largely the same as for the other TCAs, including the presentation of serotonin syndrome and adverse cardiac effects. The British National Formulary notes that amitriptyline can be particularly dangerous in overdose, thus it and other TCAs are no longer recommended as first-line therapy for depression. The treatment of overdose is mostly supportive as no specific antidote for amitriptyline overdose is available. Activated charcoal may reduce absorption if given within 1-2 hours of ingestion. If the affected person is unconscious or has an impaired gag reflex, a nasogastric tube may be used to deliver the activated charcoal into the stomach. ECG monitoring for cardiac conduction abnormalities is essential and if one is found close monitoring of cardiac function is advised. Body temperature should be regulated with measures such as heating blankets if necessary. Cardiac monitoring is advised for at least five days after the overdose. Benzodiazepines are recommended to control seizures. Dialysis is of no use due to the high degree of protein binding with amitriptyline.

Interactions

Since amitriptyline and its active metabolite nortriptyline are primarily metabolised by cytochromes CYP2D6 and CYP2C19, the inhibitors of these enzymes are expected to exhibit pharmacokinetic interactions with amitriptyline. According to the prescribing information, the interaction with CYP2D6 inhibitors may increase the plasma level of amitriptyline. However, the results in the other literature are inconsistent: the co-administration of amitriptyline with a potent CYP2D6 inhibitor paroxetine does increase the plasma levels of amitriptyline two-fold and of the main active metabolite nortriptyline 1.5-fold, but combination with less potent CYP2D6 inhibitors thioridazine or levomepromazine does not affect the levels of amitriptyline and increases nortriptyline by about 1.5-fold; a moderate CYP2D6 inhibitor fluoxetine does not seem to have a significant effect on the levels of amitriptyline or nortriptyline. A case of clinically significant interaction with potent CYP2D6 inhibitor terbinafine has been reported.

A potent inhibitor of CYP2C19 and other cytochromes fluvoxamine increases the level of amitriptyline two-fold while slightly decreasing the level of nortriptyline. Similar changes occur with a moderate inhibitor of CYP2C19 and other cytochromes cimetidine: amitriptyline level increases by about 70%, while nortriptyline decreases by 50%. CYP3A4 inhibitor ketoconazole elevates amitriptyline level by about a quarter. On the other hand, cytochrome P450 inducers such as carbamazepine and St. John’s Wort decrease the levels of both amitriptyline and nortriptyline.

Oral contraceptives may increase the blood level of amitriptyline by as high as 90%. Valproate moderately increases the levels of amitriptyline and nortriptyline through an unclear mechanism.

The prescribing information warns that the combination of amitriptyline with monoamine oxidase inhibitors may cause potentially lethal serotonin syndrome; however, this has been disputed. The prescribing information cautions that some patients may experience a large increase in amitriptyline concentration in the presence of topiramate. However, other literature states that there is little or no interaction: in a pharmacokinetic study topiramate only increased the level of amitriptyline by 20% and nortriptyline by 33%.

Amitriptiline counteracts the antihypertensive action of guanethidine. When given with amitriptyline, other anticholinergic agents may result in hyperpyrexia or paralytic ileus. Co-administration of amitriptyline and disulfiram is not recommended due to the potential for the development of toxic delirium. Amitriptyline causes an unusual type of interaction with the anticoagulant phenprocoumon during which great fluctuations of the prothrombin time have been observed.

Pharmacology

Pharmacodynamics

Amitriptyline inhibits serotonin transporter (SERT) and norepinephrine transporter (NET). It is metabolised to nortriptyline, a stronger norepinephrine reuptake inhibitor, further augmenting amitriptyline’s effects on norepinephrine reuptake.

Amitriptyline additionally acts as a potent inhibitor of the serotonin 5-HT2A, 5-HT2C, the α1A-adrenergic, the histamine H1 and the M1-M5 muscarinic acetylcholine receptors.

Amitriptyline is a non-selective blocker of multiple ion channels, in particular, voltage-gated sodium channels Nav1.3, Nav1.5, Nav1.6, Nav1.7, and Nav1.8, voltage-gated potassium channels Kv7.2/ Kv7.3, Kv7.1, Kv7.1/KCNE1, and hERG.

Mechanism of Action

Inhibition of serotonin and norepinephrine transporters by amitriptyline results in interference with neuronal reuptake of serotonin and norepinephrine. Since the reuptake process is important physiologically in terminating transmitting activity, this action may potentiate or prolong activity of serotonergic and adrenergic neurons and is believed to underlie the antidepressant activity of amitriptyline.

Inhibition of norepinephrine reuptake leading to increased concentration of norepinephrine in the posterior grey column of the spinal cord appears to be mostly responsible for the analgesic action of amitriptyline. Increased level of norepinephrine increases the basal activity of alpha-2 adrenergic receptors, which mediate an analgesic effect by increasing gamma-aminobutyric acid transmission among spinal interneurons. The blocking effect of amitriptyline on sodium channels may also contribute to its efficacy in pain conditions.

Pharmacokinetics

Amitriptyline is readily absorbed from the gastrointestinal tract (90-95%). Absorption is gradual with the peak concentration in blood plasma reached after about 4 hours. Extensive metabolism on the first pass through the liver leads to average bioavailability of about 50% (45%-53%). Amitriptyline is metabolized mostly by CYP2C19 into nortriptyline and by CYP2D6 leading to a variety of hydroxylated metabolites, with the principal one among them being (E)-10-hydroxynortriptyline, and to a lesser degree, by CYP3A4.

Nortriptyline, the main active metabolite of amitriptyline, is an antidepressant on its own right. Nortriptyline reaches 10% higher level in the blood plasma than the parent drug amitriptyline and 40% greater area under the curve, and its action is an important part of the overall action of amitriptyline.

Another active metabolite is (E)-10-hydroxynortriptyline, which is a norepinephrine uptake inhibitor four times weaker than nortriptyline. (E)-10-hydroxynortiptyline blood level is comparable to that of nortriptyline, but its cerebrospinal fluid level, which is a close proxy of the brain concentration of a drug, is twice higher than nortriptyline’s. Based on this, (E)-10-hydroxynortriptyline was suggested to significantly contribute to antidepressant effects of amitriptyline.

Blood levels of amitriptyline and nortriptyline and pharmacokinetics of amitriptyline in general, with clearance difference of up to 10-fold, vary widely between individuals. Variability of the area under the curve in steady state is also high, which makes a slow upward titration of the dose necessary.

In the blood, amitriptyline is 96% bound to plasma proteins; nortriptyline is 93-95% bound, and (E)-10-hydroxynortiptyline is about 60% bound. Amitriptyline has an elimination half life of 21 hours, nortriptyline – 23-31 hours, and (E)-10-hydroxynortiptyline – 8-10 hours. Within 48 hours, 12-80% of amitriptyline is eliminated in the urine, mostly as metabolites. 2% of the unchanged drug is excreted in the urine. Elimination in the faeces, apparently, have not been studied.

Therapeutic levels of amitriptyline range from 75 to 175 ng/mL (270-631 nM), or 80-250 ng/mL of both amitriptyline and its metabolite nortriptyline.

Pharmacogenetics

Since amitriptyline is primarily metabolised by CYP2D6 and CYP2C19, genetic variations within the genes coding for these enzymes can affect its metabolism, leading to changes in the concentrations of the drug in the body. Increased concentrations of amitriptyline may increase the risk for side effects, including anticholinergic and nervous system adverse effects, while decreased concentrations may reduce the drug’s efficacy.

Individuals can be categorised into different types of CYP2D6 or CYP2C19 metabolisers depending on which genetic variations they carry. These metaboliser types include poor, intermediate, extensive, and ultrarapid metabolisers. Most individuals (about 77-92%) are extensive metabolisers, and have “normal” metabolism of amitriptyline. Poor and intermediate metabolisers have reduced metabolism of the drug as compared to extensive metabolisers; patients with these metaboliser types may have an increased probability of experiencing side effects. Ultrarapid metabolisers use amitriptyline much faster than extensive metabolisers; patients with this metaboliser type may have a greater chance of experiencing pharmacological failure.

The Clinical Pharmacogenetics Implementation Consortium recommends avoiding amitriptyline in patients who are CYP2D6 ultrarapid or poor metabolizers, due to the risk for a lack of efficacy and side effects, respectively. The consortium also recommends considering an alternative drug not metabolised by CYP2C19 in patients who are CYP2C19 ultrarapid metabolisers. A reduction in starting dose is recommended for patients who are CYP2D6 intermediate metabolisers and CYP2C19 poor metabolisers. If use of amitriptyline is warranted, therapeutic drug monitoring is recommended to guide dose adjustments. The Dutch Pharmacogenetics Working Group also recommends selecting an alternative drug or monitoring plasma concentrations of amitriptyline in patients who are CYP2D6 poor or ultrarapid metabolisers, and selecting an alternative drug or reducing initial dose in patients who are CYP2D6 intermediate metabolisers.

Chemistry

Amitriptyline is a highly lipophilic molecule having an octanol-water partition coefficient (pH 7.4) of 3.0, while the log P of the free base was reported as 4.92. Solubility of the free base amitriptyline in water is 14 mg/L. Amitriptyline is prepared by reacting dibenzosuberone with 3-(dimethylamino)propylmagnesium chloride and then heating the resulting intermediate product with hydrochloric acid to eliminate water.

Society and Culture

English folk singer Nick Drake died from an overdose of Tryptizol in 1974.

Senteni Masango, wife of Swaziland King Mswati, died on 6 April 2018 after committing suicide by overdosing on amytriptyline capsules.

In the 2021 film The Many Saints of Newark, amitriptyline (referred to by the brand name Elavil) is part of the plot line of the movie.

Generic Names

Amitriptyline is the English and French generic name of the drug and its INN, BAN, and DCF, while amitriptyline hydrochloride is its USAN, USP, BANM, and JAN. Its generic name in Spanish and Italian and its DCIT are amitriptilina, in German is Amitriptylin, and in Latin is amitriptylinum. The embonate salt is known as amitriptyline embonate, which is its BANM, or as amitriptyline pamoate unofficially.

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On This Day … 13 September [2022]

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People (Deaths)

  • 1999 – Benjamin Bloom, American psychologist and academic (b. 1913).

Benjamin Bloom

Benjamin Samuel Bloom (21 February 1913 to 13 September 13, 1999) was an American educational psychologist who made contributions to the classification of educational objectives and to the theory of mastery learning.

He is particularly noted for leading educational psychologists to develop the comprehensive system of describing and assessing educational outcomes in the mid-1950s. He has influenced the practices and philosophies of educators around the world from the latter part of the twentieth century.