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19th Annual Grammy Awards

The 19th Annual Grammy Awards were held on February 19, 1977, and were broadcast live on American television (CBS). It was the seventh and final year Andy Williams hosted the telecast. The ceremony recognized accomplishments by musicians from the year 1976.

Helen Hayes's win made her the second person to become an EGOT.

Winners and nominees
The following are the winners and nominees of the 19th annual Grammy Awards. Winners appear first and highlighted in bold.

General field
Record of the Year
 * "This Masquerade" - George Benson
 * Tommy LiPuma, producer
 * "If You Leave Me Now" - Chicago
 * James Guercio, producer
 * "I Write the Songs" - Barry Manilow
 * Ron Dante & Barry Manilow, producers
 * "Afternoon Delight" - Starland Vocal Band
 * Milton Okun, producer
 * "50 Ways to Leave Your Lover" - Paul Simon
 * Phil Ramone & Paul Simon, producers

Album of the Year
 * Songs in the Key of Life - Stevie Wonder
 * Stevie Wonder, producer
 * Silk Degrees - Boz Scaggs
 * Joe Wissert, producer
 * Frampton Comes Alive! - Peter Frampton
 * Peter Frampton, producer
 * Chicago X - Chicago
 * James William Guercio, producer
 * Breezin' - George Benson
 * Tommy LiPuma, producer

Song of the Year
 * "I Write the Songs"
 * Bruce Johnston, songwriter (Barry Manilow)
 * "This Masquerade"
 * Leon Russell, songwriter (George Benson)
 * "The Wreck of the Edmund Fitzgerald"
 * Gordon Lightfoot, songwriter (Gordon Lightfoot)
 * "Breaking Up Is Hard to Do"
 * Howard Greenfield & Neil Sedaka, songwriters (Neil Sedaka)
 * "Afternoon Delight"
 * Bill Danoff, songwriter (Starland Vocal Band)

Best New Artist
 * Starland Vocal Band
 * Brothers Johnson
 * Boston
 * Wild Cherry
 * Dr. Buzzard's Original Savannah Band

Children's
Best Recording for Children
 * Prokofiev: Peter and the Wolf/Saint-Saëns: Carnival of the Animals
 * Karl Böhm & Hermione Gingold
 * "Winnie The Pooh For President (Campaign Song)"
 * Larry Groce & Sterling Holloway
 * "The Adventures of Ali and His Gang vs. Mr. Tooth Decay"
 * Muhammad Ali and His Gang
 * "Snow White And The Seven Dwarfs"
 * Various Artists
 * "Dickens' Christmas Carol"
 * Various Artists

Classical
Best Classical Orchestral Performance
 * Strauss: Also Sprach Zarathustra
 * Chicago Symphony Orchestra - Georg Solti (conductor), Raymond Minshull (producer)
 * The Fourth of July! (Ives: Symphony No. 2, Variations On America / Copland: Appalachian Spring / Bernstein: Overture to Candide / Gershwin: An American In Paris)
 * Los Angeles Philharmonic Orchestra
 * Ravel: Daphnis Et Chloe (Complete Ballet)
 * Orchestre de Paris
 * Gershwin: Rhapsody in Blue
 * New York Philharmonic
 * Falla: Three Cornered Hat (Boulez Conducts Falla)
 * New York Philharmonic
 * Elgar: Symphony No. 2 in E Flat Major
 * London Philharmonic
 * Brahms: Symphony No. 1 in C Minor
 * Chicago Symphony Orchestra
 * Berlioz: Symphonie Fantastique
 * Orchestre National de l'ORTF

Best Classical Vocal Soloist Performance
 * Beverly Sills
 * Herbert: Music of Victor Herbert
 * Dietrich Fischer-Dieskau
 * Wolf - Mörike-Lieder
 * Marni Nixon
 * Schoenberg: Nine Early Songs; The Cabaret Songs of Arnold Schoenberg
 * Margaret Price
 * Mozart: Arias (La Clemenza di Tito, Die Entfuhrung aus dem Serail, Nozze di Figaro etc)
 * Janet Baker, James King
 * Mahler: Das Lied von der Erde
 * Jan DeGaetani
 * Ives: Songs
 * Carlo Bergonzi
 * Carlo Bergonzi Sings Verdi
 * Barbra Streisand
 * Classical Barbra

Best Opera Recording
 * Gershwin: Porgy and Bess
 * Cleveland Orchestra - Lorin Maazel (conductor), Michael Woolcock (producer)
 * Verdi: Macbeth
 * La Scala Opera Orchestra & Chorus - Claudio Abbado (conductor), Rainer Brock (producer)
 * Schoenberg: Moses Und Aaron
 * BBC Symphony Orchestra (BBC Symphony Singers & Orpheus Boys Choir) - Pierre Boulez (conductor), Paul Myers (producer)
 * Massenet: Thaïs
 * New Philharmonia Orchestra (John Choir Alldis) - Lorin Maazel (conductor), Christopher Bishop (producer)
 * Joplin: Treemonisha
 * Original Cast Orchestra & Chorus - Gunther Schuller (conductor), Tom Mowrey (producer)
 * Bizet: Carmen
 * London Philharmonic - Georg Solti (conductor), Christopher Raeburn (producer)

Best Choral Performance (other than opera)
 * London Symphony Orchestra & Chorus - André Previn (conductor), Arthur Oldham (choirmaster)
 * Rachmaninoff: The Bells
 * Chorus of La Scala-Milan; Orchestra of La Scala-Milan - Claudio Abbado (conductor), Romano Gandolfi (choir director)
 * Verdi: Opera Choruses
 * BBC Choral Society & BBC Symphony Singers; BBC Symphony Orchestra - Colin Davis (conductor)
 * Tippett: A Child of Our Time
 * Choir of the Monks of Saint-Pierre de Solesmes Abbey - Dom Jean Claire (choir director)
 * Gregorian Chant
 * Netherlands Radio Chorus; Rotterdam Philharmonic - Jean Fournet (conductor), Franz Muller (choir director)
 * Fauré: Requiem
 * London Philharmonic Choir; Orchestra - Sir Adrian Boult (conductor)
 * Elgar: The Kingdom, Op. 51
 * King's College Choir-Cambridge - Phillip Ledger (choir director)
 * Bernstein: Chichester Psalms/Britten: Rejoice in the Lamb
 * Choeurs de Radio France; Orchestre National de France & Orchestre Philharmonique de Radio France - Leonard Bernstein (choir director)
 * Berlioz: Requiem
 * New Philharmonia Chorus and London Philharmonic - Carlo Maria Giulini (conductor), Walter Hagen-Groll (choir director)
 * Beethoven: Missa Solemnis

Best Classical Performance, Instrumental Soloist or Soloists (with orchestra) Best Classical Performance, Instrumental Soloist or Soloists (without orchestra) Best Chamber Music Performance Best Classical Album
 * Daniel Barenboim (conductor), Arthur Rubinstein & the London Philharmonic Orchestra for Beethoven: The Five Piano Concertos
 * Vladimir Horowitz for Horowitz Concerts 1975/76
 * David Munrow (conductor) & the Early Music Consort of London for The Art of Courtly Love
 * Max Wilcox (producer), Daniel Barenboim (conductor), Arthur Rubinstein & the London Philharmonic for Beethoven: The Five Piano Concertos

Comedy
Best Comedy Recording
 * Bicentennial Nigger - Richard Pryor
 * You Gotta Wash Your Ass - Redd Foxx
 * Sleeping Beauty - Cheech & Chong
 * Goodbye Pop - National Lampoon
 * Bill Cosby Is Not Himself These Days - Rat Own, Rat Own, Rat Own - Bill Cosby

Composing and arranging

 * Best Instrumental Composition
 * Chuck Mangione (composer) for Bellavia
 * Album of Best Original Score Written for a Motion Picture or Television Special
 * Norman Whitfield (composer) for Car Wash performed by Rose Royce
 * Best Instrumental Arrangement
 * Chick Corea (arranger) for "Leprechaun's Dream"
 * Best Arrangement Accompanying Vocalist(s)
 * James William Guercio & Jimmie Haskell (arrangers) for "If You Leave Me Now" performed by Chicago
 * Best Arrangement for Voices (duo, group or chorus)
 * Starland Vocal Band (arranger) for "Afternoon Delight"

Country

 * Best Country Vocal Performance, Female
 * Emmylou Harris for Elite Hotel
 * Best Country Vocal Performance, Male
 * Ronnie Milsap for "(I'm a) Stand By My Woman Man"
 * Best Country Vocal Performance by a Duo or Group
 * Amazing Rhythm Aces for "The End Is Not in Sight (The Cowboy Tune)"
 * Best Country Instrumental Performance
 * Chet Atkins & Les Paul for Chester and Lester
 * Best Country Song
 * Larry Gatlin (songwriter) for "Broken Lady"

Folk

 * Best Ethnic or Traditional Recording
 * John Hartford for Mark Twang

Gospel

 * Best Gospel Performance (other than soul gospel)
 * The Oak Ridge Boys for "Where the Soul Never Dies"
 * Best Soul Gospel Performance
 * Mahalia Jackson for How I Got Over
 * Best Inspirational Performance
 * Gary S. Paxton for The Astonishing, Outrageous, Amazing, Incredible, Unbelievable, Different World of Gary S. Paxton

Jazz

 * Best Jazz Performance by a Soloist (Instrumental)
 * Count Basie for Basie & Zoot
 * Best Jazz Performance by a Group
 * Chick Corea for The Leprechaun
 * Best Jazz Performance by a Big Band
 * Duke Ellington for The Ellington Suites
 * Best Jazz Vocal Performance
 * Ella Fitzgerald for Fitzgerald and Pass... Again

Latin

 * Best Latin Recording
 * Eddie Palmieri for Unfinished Masterpiece

Musical show

 * Best Cast Show Album
 * Luigi Creatore & Hugo Peretti (producers) & various artists for Bubbling Brown Sugar

Packaging and notes

 * Best Album Package
 * John Berg (art director) for Chicago X performed by Chicago
 * Best Album Notes
 * Dan Morgenstern (notes writer) for The Changing Face of Harlem, the Savoy Sessions performed by Various Artists

Pop

 * Best Pop Vocal Performance, Female
 * Hasten Down the Wind (album) - Linda Ronstadt
 * Best Pop Vocal Performance, Male
 * Songs in the Key of Life (album) - Stevie Wonder
 * Best Pop Vocal Performance by a Duo, Group or Chorus
 * "If You Leave Me Now" - Chicago
 * Best Pop Instrumental Performance
 * Breezin' - George Benson

Production and engineering

 * Best Engineered Recording, Non-Classical
 * Breezin' - Al Schmitt (engineer)
 * Best Engineered Recording, Classical
 * Gershwin: Rhapsody in Blue - Edward (Bud) T. Graham, Milton Cherin, Ray Moore (engineers)
 * Best Producer of the Year
 * Stevie Wonder

R&B

 * Best R&B Vocal Performance, Female
 * Natalie Cole for "Sophisticated Lady (She's a Different Lady)"
 * Best R&B Vocal Performance, Male
 * Stevie Wonder for "I Wish"
 * Best R&B Vocal Performance by a Duo, Group or Chorus
 * Billy Davis Jr. & Marilyn McCoo for "You Don't Have to Be a Star (To Be in My Show)"
 * Best R&B Instrumental Performance
 * George Benson for "Theme From Good King Bad"
 * Best Rhythm & Blues Song
 * Boz Scaggs & David Paich (songwriters) for "Lowdown" performed by Boz Scaggs

Spoken

 * Best Spoken Word Recording
 * Henry Fonda, Helen Hayes, James Earl Jones & Orson Welles for Great American Documents

title: 19th Annual Grammy Awards


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Pobol y Cwm

Pobol y Cwm (People of the Valley; ) is a Welsh-language soap opera produced by the BBC since October 1974. The longest-running television soap opera produced by the BBC, Pobol y Cwm was originally transmitted on BBC Cymru (now BBC One Wales) and later transferred to the Welsh-language station S4C when it opened in November 1982.

The programme typically centres around the residents of Cwmderi – a fictional, Welsh speaking, agricultural community.

Apart from rugby and football specials, Pobol y Cwm is consistently one of the most watched programmes of the week on S4C, and in 1994 was briefly shown across the whole of the United Kingdom on BBC Two with English subtitles.

On 25 September 2019, the soap hit a significant broadcasting landmark when it aired its 8,000th episode.

In October 2024, the show will celebrate its 50th anniversary.

Setting
The setting for the show is the fictional village of Cwmderi, located in Gwendraeth Valley, which is between Carmarthen and Llanelli in south-west Wales. Whilst much of the show's early activity took place at a nursing home, storylines are currently centred on the village pub, Y Deri, and its adjacent small businesses and houses. Other frequent settings for storylines include the comprehensive school, Ysgol y Mynach, and a local farm, Penrhewl. There are two other fictional villages close to Cwmderi, named Llanarthur and Cwrtmynach.

Originally filmed at Broadcasting House, Cardiff, since 2011 the programme has been filmed at the BBC's drama studios at Roath Lock in Cardiff Bay, other than a few on-location shoots around Cardiff. The exterior outdoor high street of Cwmderi was recreated from scratch, while many interiors are shot inside the Roath Lock Studios.

Broadcast
Three episodes are produced each week, broadcast at 8pm between Tuesdays and Thursdays, a reduction from a fifth episode in 2019, and a reduction from a fourth episode in 2021. In addition, a weekly omnibus with in-vision English subtitles airs on Sunday evenings.

On 18 March 2020 it was announced that filming would be suspended in the light of the spread of COVID-19 until further notice. The number of episodes being broadcast would be also be reduced to two per week "so that we can ensure the audience can continue to enjoy Pobol y Cwm in their homes for as long as possible." The episodes were shown on Tuesdays and Thursdays in the usual time slot. In June 2020, it was announced that Pobol y Cwm would go on a transmission break following the broadcast on 16 June 2020. A behind-the-scenes show, Pobol y Cwm: Y Cymeriadau, aired in the show's place during the transmission break. Every episode featured an exclusive interview with the show's cast, with 12 episodes being shown. The soap also aired a repeat of "iconic" episodes from the past.

Five months later, it was confirmed that there were plans for a return to production. When production recommenced, social distancing measures were utilised and the cast were required to do their own hair and make-up, which is normally done by a make-up artist. Filming recommenced on 10 August 2020, with new episodes airing twice a week from 8 September 2020, increasing to four in January 2021.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Pobol y Cwm


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18th Annual Grammy Awards

The 18th Annual Grammy Awards were held February 28, 1976, and were broadcast live on American television. They recognized accomplishments by musicians from the year 1975.

Award winners

 * Record of the Year
 * "Love Will Keep Us Together" - Captain & Tennille (artist) & Daryl Dragon (producer)
 * Album of the Year
 * Still Crazy After All These Years - Paul Simon (artist) - Phil Ramone & Paul Simon (producers)
 * Song of the Year
 * "Send In the Clowns" - Judy Collins (artist) - Stephen Sondheim (songwriter)
 * Best New Artist
 * Natalie Cole

Children's

 * Best Recording for Children
 * Richard Burton for The Little Prince

Classical

 * Best Classical Performance – Orchestra
 * Pierre Boulez (conductor), the Camarata Singers & the New York Philharmonic for Ravel: Daphnis et Chloé (Complete Ballet)
 * Best Classical Vocal Performance
 * Janet Baker for Mahler: Kindertotenlieder
 * Best Opera Recording
 * Erik Smith (producer), Colin Davis (conductor), Richard van Allan, Janet Baker, Montserrat Caballé, Ileana Cotrubas, Wladimiro Ganzarolli, Nicolai Gedda & the Orchestra of the Royal Opera House for Mozart: Cosi Fan Tutte
 * Best Choral Performance, Classical (other than opera)
 * Michael Tilson Thomas (conductor), Robert Page (choir director) the Cleveland Boys Choir & Cleveland Orchestra Chorus- Orff: Carmina Burana
 * Best Classical Performance Instrumental Soloist or Soloists (with orchestra)
 * Rafael Frühbeck de Burgos (conductor), Alicia de Larrocha & the London Philharmonic for Ravel: Concerto for Left Hand and Concerto for Piano in G/Fauré: Fantaisie for Piano and Orchestra
 * Best Classical Performance Instrumental Soloist or Soloists (without orchestra)
 * Nathan Milstein for Bach: Sonatas and Partitas for Violin Unaccompanied
 * Best Chamber Music Performance
 * Pierre Fournier, Arthur Rubinstein & Henryk Szeryng for Schubert: Trios Nos. 1 in B Flat, Op. 99 and 2 in E Flat, Op. 100 (Piano Trios)
 * Album of the Year, Classical
 * Raymond Minshull (producer), Georg Solti (conductor) & the Chicago Symphony Orchestra for Beethoven: Symphonies (9) Complete

Comedy

 * Best Comedy Recording
 * Richard Pryor for Is It Something I Said?

Composing and arranging

 * Best Instrumental Composition
 * Michel Legrand for Images performed by Michel Legrand & Phil Woods
 * Album of Best Original Score Written for a Motion Picture or a Television Special
 * John Williams (composer) for Jaws
 * Best Instrumental Arrangement
 * Pete Carpenter & Mike Post (arrangers) for "The Rockford Files" performed by Mike Post
 * Best Arrangement Accompanying Vocalist(s)
 * Ray Stevens (arranger) for "Misty"

Country

 * Best Country Vocal Performance, Female
 * Linda Ronstadt for "I Can't Help It (If I'm Still in Love With You)"
 * Best Country Vocal Performance, Male
 * Willie Nelson for "Blue Eyes Crying in the Rain"
 * Best Country Vocal Performance by a Duo or Group
 * Rita Coolidge & Kris Kristofferson for "Lover Please"
 * Best Country Instrumental Performance
 * Chet Atkins for "The Entertainer"
 * Best Country Song
 * Larry Butler & Chips Moman (songwriters) for "(Hey Won't You Play) Another Somebody Done Somebody Wrong Song" performed by B. J. Thomas

Folk

 * Best Ethnic or Traditional Recording
 * Muddy Waters for The Muddy Waters Woodstock Album

Gospel

 * Best Gospel Performance (other than soul gospel)
 * The Imperials for No Shortage
 * Best Soul Gospel Performance
 * Andrae Crouch for Take Me Back performed by Andrae Crouch & the Disciples
 * Best Inspirational Performance
 * The Bill Gaither Trio for Jesus, We Just Want to Thank You

Jazz

 * Best Jazz Performance by a Soloist
 * Dizzy Gillespie for Oscar Peterson and Dizzy Gillespie
 * Best Jazz Performance by a Group
 * Chick Corea & Return to Forever for No Mystery
 * Best Jazz Performance by a Big Band
 * Michel Legrand & Phil Woods for Images

Latin

 * Best Latin Recording
 * Eddie Palmieri for Sun of Latin Music

Musical show

 * Best Cast Show Album
 * Charlie Smalls (composer), Jerry Wexler (producer) & the original cast with Stephanie Mills & Dee Dee Bridgewater for The Wiz

Packaging and notes

 * Best Album Package
 * Jim Ladwig (art director) for Honey performed by the Ohio Players
 * Best Album Notes
 * Pete Hamill (notes writer) for Blood on the Tracks performed by Bob Dylan
 * Best Album Notes – Classical
 * Gunther Schuller (notes writer) for Footlifters performed by Gunther Schuller

Pop

 * Best Pop Vocal Performance, Female
 * "At Seventeen"-Janis Ian
 * Best Pop Vocal Performance, Male
 * "Still Crazy After All These Years"-Paul Simon
 * Best Pop Vocal Performance by a Duo, Group or Chorus
 * "Lyin' Eyes"-The Eagles
 * Best Pop Instrumental Performance
 * "The Hustle"-Van McCoy

Production and engineering

 * Best Engineered Recording, Non-Classical
 * Brooks Arthur, Larry Alexander & Russ Payne for Janis Ian's Between the Lines
 * Best Engineered Recording, Classical
 * Edward (Bud) T. Graham, Milton Cherin, Ray Moore (engineers), Pierre Boulez (conductor), the Camarata Singers & the New York Philharmonic for Ravel: Daphnis et Chloe (Complete Ballet)
 * Producer of the Year, Non-Classical
 * Arif Mardin

R&B

 * Best R&B Vocal Performance, Female
 * Natalie Cole for "This Will Be"
 * Best R&B Vocal Performance, Male
 * Ray Charles for "Living for the City"
 * Best R&B Vocal Performance by a Duo, Group or Chorus
 * Earth, Wind & Fire for "Shining Star"
 * Best R&B Instrumental Performance
 * Silver Convention for "Fly, Robin, Fly"
 * Best Rhythm & Blues Song
 * Harry Wayne Casey, Willie Clarke, Richard Finch & Betty Wright (songwriters) for "Where Is the Love" performed by Betty Wright

Spoken

 * Best Spoken Word Recording
 * James Whitmore for Give 'Em Hell Harry

title: 18th Annual Grammy Awards


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Risperidone

Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions are long-acting and last for 2–4 weeks.

Common side effects include severe depression, movement problems, sleepiness, dizziness, trouble seeing, constipation, and increased weight. Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, as well as neuroleptic malignant syndrome, an increased risk of suicide, and high blood sugar levels. In older people with psychosis as a result of dementia, it may increase the risk of death. It is unknown if it is safe for use in pregnancy. Its mechanism of action is not entirely clear, but is believed to be related to its action as a dopamine and serotonin antagonist.

Study of risperidone began in the late 1980s and it was approved for sale in the United States in 1993. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2021, it was the 138th most commonly prescribed medication in the United States, with more than 4million prescriptions.

Medical uses
Risperidone is mainly used for the treatment of schizophrenia, bipolar disorder, and irritability associated with autism.

Schizophrenia
Risperidone is effective in treating psychogenic polydipsia and the acute exacerbations of schizophrenia.

Studies evaluating the utility of risperidone by mouth for maintenance therapy have reached varying conclusions. A 2012 systematic review concluded that evidence is strong that risperidone is more effective than all first-generation antipsychotics other than haloperidol, but that evidence directly supporting its superiority to placebo is equivocal. A 2011 review concluded that risperidone is more effective in relapse prevention than other first- and second-generation antipsychotics with the exception of olanzapine and clozapine. A 2016 Cochrane review suggests that risperidone reduces the overall symptoms of schizophrenia, but firm conclusions are difficult to make due to very low-quality evidence. Data and information are scarce, poorly reported, and probably biased in favour of risperidone, with about half of the included trials developed by drug companies. The article raises concerns regarding the serious side effects of risperidone, such as parkinsonism. A 2011 Cochrane review compared risperidone with other atypical antipsychotics such as olanzapine for schizophrenia:

Long-acting injectable formulations of antipsychotic drugs provide improved compliance with therapy and reduce relapse rates relative to oral formulations. The efficacy of risperidone long-acting injection appears to be similar to that of long-acting injectable forms of first-generation antipsychotics.

Bipolar disorder
Second-generation antipsychotics, including risperidone, are effective in the treatment of manic symptoms in acute manic or mixed exacerbations of bipolar disorder. In children and adolescents, risperidone may be more effective than lithium or divalproex, but has more metabolic side effects. As maintenance therapy, long-acting injectable risperidone is effective for the prevention of manic episodes but not depressive episodes. The long-acting injectable form of risperidone may be advantageous over long-acting first-generation antipsychotics, as it is better tolerated (fewer extrapyramidal effects) and because long acting injectable formulations of first-generation antipsychotics may increase the risk of depression.

Autism
Compared to placebo, risperidone treatment reduces certain problematic behaviors in autistic children, including aggression toward others, self-injury, challenging behavior, and rapid mood changes. The evidence for its efficacy appears to be greater than that for alternative pharmacological treatments. Weight gain is an important adverse effect. Some authors recommend limiting the use of risperidone and aripiprazole to those with the most challenging behavioral disturbances in order to minimize the risk of drug-induced adverse effects. Evidence for the efficacy of risperidone in autistic adolescents and young adults is less persuasive.

Dementia
While antipsychotic medications such as risperidone have a slight benefit in people with dementia, they have been linked to higher incidence of death and stroke. Because of this increased risk of death, treatment of dementia-related psychosis with risperidone is not FDA approved and carries a black box warning. However, many other jurisdictions regularly use it to control severe aggression and psychosis in those with dementia when other non-pharmacological interventions have failed and their pharmaceutical regulators have approved its use in this population.

Other uses
Risperidone has demonstrated clinical benefit as an augmentation agent in the management of (unipolar) non-psychotic treatment-resistant depression alongside antidepressant treatment. Atypical antipsychotics, such as risperidone, are among the most common augments for antidepressant therapy. Such usage occurs "off-label" in most jurisdictions and the risk of adverse effects (e.g., weight gain, movement disorders) must be carefully weighed against the clinical benefit.

Risperidone has shown promise in treating therapy-resistant obsessive-compulsive disorder, when serotonin reuptake inhibitors alone are not sufficient.

Risperidone has proven to be effective in treatment with attention deficit hyperactivity disorder especially in cases of aggression or with another mental condition.

Risperidone has not demonstrated a benefit in the treatment of eating disorders or personality disorders, except for limited evidence in schizotypal personality disorder.

Forms
Available forms of risperidone include tablet, oral dissolving tablet, oral solution, and powder and solvent for suspension for injection.

Adverse effects
Common side effects include movement problems, sleepiness, dizziness, trouble seeing, constipation, and increased weight. About 9 to 20% of people gained more than 7% of the baseline weight depending on the dose. Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, as well as neuroleptic malignant syndrome, an increased risk of suicide, and high blood sugar levels. In older people with psychosis as a result of dementia, it may increase the risk of death.

While atypical antipsychotics appear to have a lower rate of movement problems as compared to typical antipsychotics, risperidone has a high risk of movement problems among the atypicals. Atypical antipsychotics, however, are associated with a greater amount of weight gain and other metabolic side effects.

Drug interactions

 * Carbamazepine and other enzyme inducers may reduce plasma levels of risperidone. If a person is taking both carbamazepine and risperidone, the dose of risperidone will likely need to be increased. The new dose should not be more than twice the patient's original dose.
 * CYP2D6 inhibitors, such as SSRI medications, may increase plasma levels of risperidone and those medications.
 * Since risperidone can cause hypotension, its use should be monitored closely when a patient is also taking antihypertensive medicines to avoid severe low blood pressure.
 * Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort.

Discontinuation
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse.

Dementia
Older people with dementia-related psychosis are at a higher risk of death.

Pharmacodynamics
Risperidone has been classified as a "qualitatively atypical" antipsychotic agent with a relatively low incidence of extrapyramidal side effects (when given at low doses) that has more pronounced serotonin antagonism than dopamine antagonism. Risperidone contains the functional groups of benzisoxazole and piperidine as part of its molecular structure. Although not a butyrophenone, it was developed with the structures of benperidol and ketanserin as a basis. It has actions at several 5-HT (serotonin) receptor subtypes. These are 5-HT2C, linked to weight gain, 5-HT2A, linked to its antipsychotic action and relief of some of the extrapyramidal side effects experienced with the typical neuroleptics.

It has been found that D -amino acid oxidase, the enzyme that catalyses the breakdown of D -amino acids (e.g.  D -alanine and  D -serine — the neurotransmitters) is inhibited by risperidone.

Risperidone acts on the following receptors:

Dopamine receptors: This drug is an antagonist of the D1 (D1, and D5) as well as the D2 family (D2, D3 and D4) receptors, with 70-fold selectivity for the D2 family. It has "tight binding" properties, which means it has a long half-life. Like other antipsychotics, risperidone blocks the mesolimbic pathway, the prefrontal cortex limbic pathway, and the tuberoinfundibular pathway in the central nervous system. Risperidone may induce extrapyramidal side effects, akathisia and tremors, associated with diminished dopaminergic activity in the striatum. It can also cause sexual side effects, galactorrhoea, infertility, gynecomastia and, with chronic use reduced bone mineral density leading to breaks, all of which are associated with increased prolactin secretion.

Serotonin receptors: Most important pharmalogical function is to compensate dopamine blocking.

Alpha α1 adrenergic receptors: This action accounts for the orthostatic hypotensive effects and perhaps some of the sedating effects of risperidone.

Alpha α2 adrenergic receptors: Risperidone's action at these receptors may cause greater positive, negative, affective, and cognitive symptom control.

Histamine H1 receptors: effects on these receptors account for its sedation and reduction in vigilance. This may also lead to drowsiness and weight gain.

Voltage-gated sodium channels: Because it accumulates in synaptic vesicles, Risperidone inhibits voltage-gated sodium channels at clinically used concentrations.

Pharmacokinetics
Risperidone undergoes hepatic metabolism and renal excretion. Lower doses are recommended for patients with severe liver and kidney disease. The active metabolite of risperidone, paliperidone, is also used as an antipsychotic.

Legal status
Risperidone was approved by the United States Food and Drug Administration (FDA) in 1993 for the treatment of schizophrenia. In 2003, the FDA approved risperidone for the short-term treatment of the mixed and manic states associated with bipolar disorder. In 2006, the FDA approved risperidone for the treatment of irritability in autistic children and adolescents. The FDA's decision was based in part on a study of autistic people with severe and enduring problems of violent meltdowns, aggression, and self-injury; risperidone is not recommended for autistic people with mild aggression and explosive behavior without an enduring pattern. On 22 August 2007, risperidone was approved as the only drug agent available for treatment of schizophrenia in youths, ages 13–17; it was also approved that same day for treatment of bipolar disorder in youths and children, ages 10–17, joining lithium.

On 16 December 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) formally recommended market authorization for Okedi, a long-acting depot injection of risperidone. Okedi was approved for the treatment of schizophrenia in adults for whom the tolerability and effectiveness of risperidone had already been established using an oral formulation. Long-acting depot injectable risperidone was approved for medical use in the European Union in February 2022.

Lawsuits
In April 2012, Johnson & Johnson (J&J) and its subsidiary Janssen Pharmaceuticals Inc. were fined $1.2 billion for downplaying multiple risks associated with risperidone. The verdict was later reversed by the Arkansas state supreme court.

In August 2012, J&J agreed to pay $181 million to 36 US states in order to settle claims that it had promoted risperidone and paliperidone for off-label uses including for dementia, anger management, and anxiety.

In November 2013, J&J was fined $2.2 billion for illegally marketing risperidone for use in people with dementia and paying kickbacks to prescribing physicians and nursing home pharmacies.

In 2015, Steven Brill wrote an investigative journalism piece about J&J in The Huffington Post focused on J&J's marketing of risperidone.

J&J has faced numerous civil lawsuits on behalf of children who were prescribed risperidone who grew breasts (a condition called gynecomastia); as of July 2016 there were about 1,500 cases in Pennsylvania state court in Philadelphia, and there had been a February 2015 verdict against J&J with $2.5 million awarded to a man from Alabama, a $1.75 million verdict against J&J that November, and in 2016 a $70 million verdict against J&J. In October 2019, a jury ordered J&J to pay $8 billion in punitive damages to a Pennsylvania man who had grown breasts during adolescence. This verdict amount chosen by the jury was reduced more than 1,000-fold by a judge in January 2020, with the new punitive damages being $6.8 million. A legal scholar commented that punitive damages which exceed the compensatory damages by a factor of 10 or more in cases of this type are usually found to be legally invalid.

Brand names
Janssen's patent on risperidone expired in December 2003, opening the market for cheaper generic versions from other companies, and Janssen's exclusive marketing rights expired in June 2004 (the result of a pediatric extension). It is available under many brand names worldwide.

Risperidone is available as a tablet, an oral solution, and an ampule, which is a depot injection.

Brand names include Risperdal, Risperdal Consta, Risperdal M-Tab, Risperdal Quicklets, Risperlet, Okedi, and Perseris.

title: Risperidone


text:
User talk:Someone else/talk3

 * User_talk:Someone else/talk1
 * User_talk:Someone_else/talk2

If "Top Cat"'s "close friends get to call him T.C.", do "Boss Cat"'s "close friends get to call him B.C."? -- Someone else

 * Aha! I was just about to complain that the blanking of your talk page would mean that we'd never get to know! To be honest, I can't remember, but maybe someone else... I mean, maybe some other person will know... (Damn it, your name causes such confusion!) -- Oliver P. 22:31 Feb 19, 2003 (UTC)

You are really Someone who makes me surprised, and always seem to have a happy smile. Please spread your humour and everything you know about Hanno (or any other historical pacyderm you have records about ath the wiki I made for EEKMA.

Like here: http://www.eekma.org/cgi-bin/wiki.pl?Famous_elephants

You will feel a sense of history on this site, seeing old UseMod again... :) Dan Koehl 23:12 Feb 19, 2003 (UTC)

Dan, Well, I gave it a shot, I don't know the UseMod, so I hope it saved ok! Let me know what I've done wrong and I may be able to avoid it on other famous elephants! -- Someone else 23:56 Feb 19, 2003 (UTC)

 * Hey great article, thanks. Hope to see you there in the djungle now and then! I dont want to change anything, its so nice with the author name Someone else.

But if you care to change, the historical persons and such can be linked to wikipedia by using WikiPedia:Article_title/name_of_person and the links goes here! Dan Koehl 21:44 Feb 20, 2003 (UTC)

 * Thanx again! Its so nice thet theres Someone else interested in elephants! Dan Koehl 22:31 Feb 20, 2003 (UTC)

 * Well, elephants ARE nice, and people who like animals tend to be nicer that those who don't. I suspect Hanno would have had a longer life if the people taking care of him were a little smarter about elephants (but then human, as well as veterinary, medicine, was pretty primitive in 1514!) Sounds to me like he had some intestinal problem, and they diagnosed angina! -- Someone else 22:37 Feb 20, 2003 (UTC)

 * Yes, I wrote an article on the Swedish wikipedia about Abul-Abbas, Charlemagnes elephant, who arrive to Europe 801 and died (in penuomnia?) after crossing Rhine 804 when he was supposed to be used as war elephant against the danes. Theres along list of historical elephants, with very short life span.Dan Koehl 23:12 Feb 20, 2003 (UTC)

I thought he had more than one, so he could assessorize when needs be. 'Ok! Which one will I pick?' (BAAAD joke!) On a more serious side, keep an eye out for Daeron's 'adaptions. After losing the battle (to common sense) on the Australia page, and the constitutional monarchy page, he suddenly cropped up on the Commonwealth page to insist that a commonwealth is by definition a republic. I had to reword it to be accurate. Then he popped up on the Prime Minister page to assert how Australia had no monarch (which is a logical place to state that nonsense, not!) So God knows where he will pop up next to doctor something next; the page on the Columbia disaster, with a 'Columbia had a few hours earlier flown over the Australian republic' line??? (We also had an anonymous user create a [Republic of Japan] page, which would have come as a bit of a surprise to the Japanese emperor! Is there an outbreak of 'republicanitus' out there?) It is at this stage getting beyond a joke. Making a ludicrous argument and being shot down is one thing. But then 'going secondary' by doctoring other pages to add in the same crap is going too far. If he does it again, I'm tempted to put him on the 'annoying users' page. (I believe there is one, but I don't know where!) {Maybe he'll appear on the papal tiara page next, announcing 'Unlike popes, Australia's head of state (sic) does not wear a crown of any kind!' Weird!} JTD 02:31 Feb 21, 2003 (UTC)

 * I'm inclined to agree that "problem users" is vastly underused - but the annoying ones quickly declare themselves. Sometime's it's useful to take a break from putting out fires and do something more creative for a bit...you can always go back to damage control when it's less annoying.  Me, I'm worried about whether it is proper to describe the President of the United States in Congress assembled as a head of government...  -- Someone else 02:47 Feb 21, 2003 (UTC)  P.S. is it true or urban legend that John Paul II contracted hepatitis C as a result of blood transfusion? I missed it in your list of his ailments (I also should dig out my notes on where removed pope-parts are kept in canopic-like jars).....

OK. I've had enough of Daeron. He went and vandalised the Commonwealth page again, twisting it around to say commonweath = republic, therefore Australia is a republic. (The commonweath page is linked to the Australia one, hence the change.) Where do I find the annoying users page, do you know? JTD 02:50 Feb 21, 2003 (UTC)

 * Click on my "problem users" link! I guess Massachusetts is a republic, then? Defending facts against the lies of determined zealots seems to be a particular sticking-place for Wikipedia :( -- Someone else 02:58 Feb 21, 2003 (UTC)

Re: Hanno -- Everything looks right to me --Ducker 13:05 Feb 23, 2003 (UTC)

About History of elephants in Europe, great!!! (in many form and shapes)

Ill soon have something ready! (Nice with pics of Hanno. Can they be linked from the EEKMA wiki?) Dan Koehl 14:50 Feb 23, 2003 (UTC)

 * I will give it a try, but I needed help to do it here (I'm not too proficient with image manipulation)...we'll see how it works. I do like the top pic of Hanno - Someone else 20:04 Feb 23, 2003 (UTC)
 * is it ok just simply link the images from Wikiedia? Dan Koehl 21:56 Feb 23, 2003 (UTC)
 * Well, it's ok with me. Dunno about Wikipedia's feelings. I am just no good at image syntax! -- Someone else 00:15 Feb 24, 2003 (UTC)

 * Oh, how could you have forgotten the poor mammoths? I've just added them to the page. :) Oh, and that's an impressive list of Spencer-descendants that you've added to the Spencer family page, even if the page is itself a bit of an odd one. Where are these people's descents all documented? -- Oliver P. 15:57 Feb 23, 2003 (UTC)

 * Mammoths! Feh! They're just elephant wanna-be's . You're right that it works better with sentences, too.  I have over 4000 people descended from Henry Spencer in my files, so I left a few of the less-known out - compiled from various places, if there's a particular line you're interested in I'd be happy to share. --- Someone else 20:04 Feb 23, 2003 (UTC)

 * Ah, files! How organised of you. I'm still living in the Dark Ages, and have most of my genealogical notes on random bits of paper hidden in forgotten corners of my room, although I have made a half-hearted attempt to start putting them into my computer... And I've collected a few GEDCOM files that people have left lying around on the Internet, but they all seem so unreliable that I get quite depressed looking through them! What software do you use for genealogical stuff? I quite like GeneWeb - it's free software, you know. I wasn't really asking about any of the lines in particular; just interested in a vague, general way... But I keep getting attacked by my conscience telling me that I should be putting in references for everything in these articles, but then again, putting in every reference needed to confirm a line of descent from a mediaeval person to a modern person would make the list of references fifty times as long as the article itself, so that'd be crazy... Should we just put, "Trust me, I know what I'm talking about," at the bottom of everything? ;) -- Oliver P. 21:42 Feb 23, 2003 (UTC)

 * I agree that anything that one can find ONLY on the internet is at best suspect. I've put a list of the books I've found reasonably reliable at User:Someone else/genealogical bibliography.  Reasonably reliable online sources include: An Online Gotha, the associated site Decendants of King James I/VI, and Brigitte Gastel Lloyd's site with information from Leo van de Pas.  -- Someone else 00:15 Feb 24, 2003 (UTC)

 * Thanks, and that's a nice bibliography! I'll have to get hold of some of those. Well, I've got two of them already. Unfortunately, some of the others are rather out of my price range, and require trips to great big libraries to consult... Is the "Lesbian ancestors" monograph just this webpage, or is there a printed version? And if the latter, does it contain more than the online version? -- Oliver P. 00:25 Feb 24, 2003 (UTC)

 * Dang! I didn't know he'd published it on the web! I think that's the whole thing (it's one of my favorite things to cite: I was familiar only with the microfiche copies deposited at various libraries (My 2nd favorite citation, for the record, is "The Church and Bantu Music"). -- Someone else 00:30 Feb 24, 2003 (UTC)

 * It is a good title, yes. :) But I didn't know that Mr. Willis had a new book out. The Descendants of King George I of Great Britain, eh? Damn, I'm so out of touch. I contacted him to ask about The Descendants of Louis XIII, when that came out, and I could swear he told me that his next project was going to be the descendants of Charles I! Oh well. I bought the Louis XIII one a couple of years ago, via Amazon. It arrived with the cover broken off, so Amazon sent me a free replacement, and soon afterwards the cover fell off that one, too. Grrr. Does the new book suffer from the same problem...? Not that I'm judging the book by its cover, of course... ;) -- Oliver P. 00:40 Feb 24, 2003 (UTC)

 * Short answer: Yes. Longer complaint: Yes, I hate those bindings, yes, the cover fell off George too, no, the bindings never survive, and I'm assuming it's because they use cheap paper for the "mull": in a book that thick, they should use STRONG paper. I can't imagine any of these books surviving a week without being rebound. -- Someone else 00:48 Feb 24, 2003 (UTC)

Seems like a discussion which could be a topic at WikiProject_Genealogy:) Dan Koehl 22:01 Feb 23, 2003 (UTC)

 * The story of Abul-Abbas is there, but suffering from scandinavian english. I hope you or someone else can check the english. :) Dan Koehl 05:45 Feb 24, 2003 (UTC)

 * Excellent! It's already gotten some attention, the English is fine, an odd word here and there and English capitalizes funny. I'm not sure EXACTLY what a trade village is though, I used "trading village" but I'm not sure if there's an exact English equivalent. -- Someone else 05:59 Feb 24, 2003 (UTC)

I wonder if Someone else has an opinion about what the danes are doing with their ancient kings, see http://da.wikipedia.org/wiki/Konger%E6kken. They must have nightmares in their graves now, this cant go on :) Opinions? (see the discussion page, I have stated my absolute and very upset opinion there :) Dan Koehl 23:38 Feb 26, 2003 (UTC)

 * The problem is that they are not interested in history or genelogists, but thay took a lot of material from some encycklopdi. Eventuall someone checked the official royal website and for some verystrangedanish reason roman letters are avoided there. I am trying to save their  from future problems since they will have alot of t work to do. see the king John of Denmark at http://da.wikipedia.org/wiki/Hans. Apart from that they killed a lot of langauge links, but Christian took a lot of time repairing them. (with king 4 numbers)

 * I just thought Ill do what I can can to convince them that this is not vise. But of course its theur decision. But imagine what will happen when the first genealogist starts to contribute, heel go nuts. (or do I really get a little to upset here?) Dan Koehl 01:09 Feb 27, 2003 (UTC)

 * Well, it's easy to get excited, but probably better for you just to take a deep breath and relax...there, see, that's better!.... all you can do is offer your advice, and it's their problem (and it will be!) later... Still as long as it "maps" one to one (6=VI, etc.), it could be worse. At least you can make some sense out of the Danish! -- Someone else 01:13 Feb 27, 2003 (UTC) (P.S. do you know anything about the Stockmar counts? Just a long shot...)  (P.P.S. Some  just cannot be saved!)

Dont have anything myself, while googling I found some baronets (no counts), suppose you honeycombed google for the good old Stockmar´s? Whats the connection anyway? Dan Koehl 02:30 Feb 27, 2003 (UTC)

 * Thanks, yes, I did find a bit. Just idle curiousity, one of their relatives married (well, not so much married really, more like "was involved with") Leopold I of Belgium. I >think< they had Danish ancestry. I'll just file this away for later in case I find more ancestors for her. -- Someone else 02:34 Feb 27, 2003 (UTC)

You removed your links! How am I going to get to your bibliography now? :( -- Oliver P. 14:00 Feb 28, 2003 (UTC) (P.S. - That was a rhetorical question, since I can still find it really, but I was just wondering why you removed the links...)

 * Just entering "read-only" mode, lest I accidentally mention "the nationality that dare not speak its name". --- Someone else 23:52 Feb 28, 2003 (UTC)

 * Oh yes, that. What a strange business it all is. Well, have fun reading! --- Oliver P. 03:03 Mar 1, 2003 (UTC)

Hello someone, I'd appreciate it if you could read over ketone bodies. Thanks, AxelBoldt 08:06 Mar 2, 2003 (UTC)

 * ) Dan Koehl 11:34 Mar 4, 2003 (UTC) Will bring more Eles into the clouds og human history...

 * Hi,Did you see Gaz variety of an ancestor chart at WikiProject_Genealogy? Dan Koehl 10:38 Mar 7, 2003 (UTC)

Thanz, BTW for adding your weight into the Otto of Bavaria 'debate'. STÓD/ÉÍRE 07:31 Mar 9, 2003 (UTC)

 * actually it looks like you won that battle before reinforcements were needed  -- Someone else 07:34 Mar 9, 2003 (UTC)

Thanx. I never thought of that method of moving the page. I'm pretty annoyed over the emperor naming. It is so blatently illogical. If everyone does that and gets away with it, because it is their local manner even though the rest of the world won't be able to make head or tail of it, wikipedia will soon end up an unreadable mess. Everyone I checked with thought it crazy and ludicrous. Between Susan Mason's nutty naming ideas all over the place and the appearance of nonsensical lists all over, I'm pretty pissed off right now. I'm tempted to give up and do something whose standards I can stand over. (Seeing the size of my phone bill after all the time spent on the net, 85% on wiki, hasn't done my mood any better either.) Take care STÓD/ÉÍRE 01:19 Mar 12, 2003 (UTC)

Hi Someone else, I notice you're italicizing scientific names of organisms in various pages. While you're doing it, I'd like to suggest you use the HTML italics rather than the 2-quotes emphasis, i.e. like this, rather than like this. Although they look the same, conceivably the 2-quotes emphasis will change in the future to some other markup, and then the scientific names will be in, say, small caps. The HTML tag guarantees the correct format. I acknowledge I'm being somewhat pedantic; it's not a really big deal (couldn't resist -- that was emphasis).

Zashaw 04:40 Mar 22, 2003 (UTC)

 * Hiya, Zashaw! Actually, believe it or not, I'm not actively following you around madly italicizing, but species' names for some reason really bug me - my analyst says it's harmless.  As for the method of italicization, my understanding was that wiki-style-markup is to be preferred to html-style-markup in cases where there's a choice.  Of course, that may have changed, since I am now used to using it :) - or I may have been completely wrong in my understanding.  At this point, sadly or not, I think  can never stop being italic'', since it's everywhere here! -- Someone else 05:26 Mar 22, 2003 (UTC)

 * Yes,   is preferred over ' (and binomial names should always be italicized). However we still keep ' around because   used to be impossible to nest. But now that USS Langley works the same as USS Langley (both giving USS Langley) I really don't know why we keep ' around. All I know is that when I see   or   I do a find and replace on the text so that '' and  are in the articles instead. --mav

 * Thanks, Mav, good to know! -- Someone else 09:30 Mar 22, 2003 (UTC)

 * I sit corrected. Thanks.  Plus it's nice to know people follow me around :-) Zashaw 21:22 Mar 24, 2003 (UTC)

Hi Someone else, sorry for deleting your edits on Blood pressure, was an accident. Hope I restored the important points, but if you'd care to have another look... Thanks for your helpKosebamse 06:00 Mar 23, 2003 (UTC)

'''Mea culpa. Mea maxima culpa'''. :) Yeah, blame the lateness. I'm having an 'image-full' night. I found a nutty right wing catholic website which has tons of photos (well, a few at least) all copyright free (yippee!) with the explicit instruction go forth and spread, so the graphic designer in mehas come out, I'm go forthing and spreading and I've been plonking in religious images here there and everywhere. I'm current 'doing' Pope John Paul II, done Masses (old & new), papal tiaras, rosary, Pope Paul VI - heh heh. I knew all that catholic stuff I knew would come useful some day. Hell, I'm probably the world's greatest expert on Papal Tiaras right now! Oh well. More religious imagery to spread around! Beats watching the war on Sky News! :) STÓD/ÉÍRE

Hello, I have been working on ethanol and I noticed that nobody explains why ethanol acts as a disinfectant. Do you know? AxelBoldt 19:03 Mar 24, 2003 (UTC)

I think Roxie Hart is good enough, with (movie) attached. We can probably go with Chicago (1927 movie) and Chicago (2002 movie), and probably just Chicago (musical) and discuss all iterations of it in one article. What do you think? -- Zoe

See my comments at User talk:BrianSmithson on Crusader Rabbit. And do you remember his theme song? "Dum-dada-dum, Crusader Rabbit. Dum-dada-dum, Crusader Rabbit ..." :) -- Zoe

Sorry, can't say I remember the Colonel. -- Zoe

Hey, someone. I hope you don't mind, but I redirected the Alma Schindler to Alma Mahler. That is how she is usually known, as far as I know. The article that I wrote there also had more info, including some on her affair with Kokoschka. I kept all of your information and incorporated it. Please check it out and edit/change/correct as you see fit. Danny

Alma was an interesting woman, wasn't she? Danny

 * (butting in)--I just noticed that article - I'd kept meaning to write about her for months, but as usual never got round to it. Her influence on Mahler, and on the perception of Mahler after his death, is worth an article by itself, before you even get onto her--how can I put it--emotional generosity. By the way, Someone, thanks very much for the Paul Wittgenstein link - interesting reading (though I must admit, the thought of yet another Hindemith concerto coming to light doesn't exactly fill me with joy...) --Camembert

Are you getting as sick of trying to keep a lid on this Ptolemaic (Plolemic, whatever) stuff as I am? :p -- John Owens 01:29 Apr 5, 2003 (UTC)

 * OK, now that I'm a sysop, first thing I did was run around and clean up all that stuff; Ptolemaic dynasty is back where it belongs, with its history intact, and most of those other pages he created are no more. Let me know if you find any more (I think I left one redirect alive for now). -- John Owens 09:50 Apr 6, 2003 (UTC)

An Alma Mahler doll? Well, I know what I want for my birthday now! I daresay I'll get round to writing about her influence on Gustav one day, though I should probably write a bit more about Gustav himself first. By the way, which one of those pictures on your user page is of you? --Camembert

 * On a good day, that would be Squeak (the one on the left). The Alma Mahler doll was apparently beheaded by Kokoschka at an orgy, in a vain attempt to exorcise his mad passion.  (I could almost hear bodices ripping when I wrote that last sentence.) Thanks for the Fred II assist. -- Someone else 02:51 Apr 5, 2003 (UTC)

Good job on Vladimir Lenin. I'll do the same for the date pages. -- Zoe

Re: PT Barnum...I'll give it a shot. It will teach me some tricks I should know. Kingturtle 04:56 Apr 8, 2003 (UTC)

Hiya. Finally got around to the Laurent of Belgium issue. The agreed convention was to use {title} {name} of {title/country}. Using {title} of {country/title} isn't workable because
 * many royals have specific titles that don't work in that form; eg, Prince William of Wales isn't Prince of Wales.
 * not including title first creates problems. It is best left for monarchs and royal consorts, meaning that if there is no title we can presume the person is a monarch. If they aren't, a title is stated upfront. Slán. STÓD/ÉÍRE 21:16 Apr 9, 2003 (UTC)

 * Works for me. (P.S. SOMEONE needs to archive his talk page, and it's not me!). I'm so happy not to have Prince Laurent of Belgium at "Laurent Marie" I won't even bring up the Princess Astrid of Belgium vs Archduchess Astrid of Austria issue.  -- Someone else 21:22 Apr 9, 2003 (UTC)

Thanks for sorting out the Pope Pius XII mystery. I suppose having spent a long time staring at that page while rewriting it, I never noticed the spare ]. I think it is a reasonably OK article now. STÓD/ÉÍRE 21:29 Apr 10, 2003 (UTC)
 * You've certainly improved it a lot. (It used to go from birth to him being an antisemite with a mention that he was pope!). And I like the coat of arms pic.  Am I misremembering, or did he experience some kind of Marian vision or locutions?? (P.S. Your talk page is STILL too long!!) -- Someone else 21:33 Apr 10, 2003 (UTC)

Hi. Sorry about the delay in archiving my page. The browser never told me it was that big. (Bad, Bad Browser!) Re the question of Nicolas II's brother; if my memory serves me correctly, from reading Nicholas II's abdication instrument, he named Mikhail as his heir and Mikhail initially agreed then within a short space of time (VERY short) said no, was told 'but you have already accepted. You can't unaccept, Your Majesty!' so unaccepted and abdicated simultaneously to keep everyone happy. I think the best thing to do is that where a monarch abdicated in favour of someone else to say it, even while saying 'they never took up the throne' or whatever. That's why I mentioned that King Farouk abdicated in favour of Faud II - without saying Faud II was the last de facto King of Egypt - whatever about de jure. Similarly a nineteenth century page would mention how Charles X of France abdicated in favour of 'Henry V' but he was immediately deposed by Louis-Philippe. That way you avoid someone coming along and saying - wooa! what about Faud II, Henry V, Mikhail II, etc and changing the page. So the de facto and de jure situations are covered. STÓD/ÉÍRE 01:19 Apr 14, 2003 (UTC)

At least we know Alexis wasn't tsar. Nicholas II's abdication explicitly abdicated in the name of all his heirs, as we was legally entitled to do, rather than setting up a regency. He unambiguously named Mikhail as his successor, and Mikhail accepted, then didn't, then was told he wasn't acceptable to the provisional government, then decided to abdicate. So I would class 'Mikail II' as possibly de jure tsar, certainly not de facto. (Once upon a time I began studying heads of state, presidents, monarchs etc etc. I am now the ultimate anorak on the issue. Though at least it has made me some money, as I've been asked to 'brief' or do reports for two presidents, a possible third one, a monarch and various publications. So an anorak making money from their anoraking. Wow!) STÓD/ÉÍRE 02:00 Apr 14, 2003 (UTC)

BTW I don't know if you are on a Mac :-) or a PC :-( I downloaded the safari browser recently for my mac and it is heaven. Better than Explorer (with less tendency to screw up wiki pages or crawl) and a damn sight nicer looking than Netscape (which I hate!!!). It works well and is VERY fast. If it is compatible with your system I certainly would recommend it. (I downloaded it, Opera and Camino (so I now have 5!!!). I tested them all and found it was far and away the best. Let me know if you want it. The details are somewhere in my last archive page and I can dig them out if necessary. STÓD/ÉÍRE 02:17 Apr 14, 2003 (UTC)

I got an eMac last August and it was well worth it. I cannot believe how good it is. (It is playing Beethoven's Moonlight Sonata on iTunes in the background here on CD, while I am also downloading an MPEG - and doing this.) The graphics are fab, the screen quality first class; it does get a bit of getting used to, and I am someone who has difficulty changing a lightbulb without blacking out all of North Dublin! It regularly tells me when there is a new updated version of something on the hardisk available for free (preferably) on the net. (Now Guns'n'Roses is playing!) I have the old computer sitting nearby under a table and I keep looking over and wondering how the hell did I use that for so long? (Actually I have yet to play a CD-ROM on it (oh good, Eric Clapton's Wonderful Tonight has started!) So go out and buy that new mac a.s.a.p. You won't regret it. And then dump I. Explorer that you'll find it and get safari. Then you'll be on cloud nine. (Oh good. Here comes the Pogues now!!!) STÓD/ÉÍRE

I'd love to hear it myself, though I dread to think what a progy might be. Ugh. --Camembert

Hi Someone! Re: Colin Ferguson -- I tried to be distinct about insane -- that it was claimed that he was insane (directed to mental illness) and that he refused to plead insanity (directed to insanity defense). Did I miss a subtlety? I did consider rewording the sentence so that it said "refused to use the insanity defense", to remove ambiguity, but it seemed to be fairly carefully composed, so I refrained. Suggestions? --Catherine

No, haven't yet been anywhere in New Jersey. We'll have to compare notes sometime. :-) Koyaanis Qatsi

 * Oh, wow. I think that trumps Palatka.  Koyaanis Qatsi

Someone Else, I found Something Else about "sperren". See User talk:Djmutex. -- 2003-04-30

More news on typography. See User talk:Djmutex. Djmutex 22:27 May 1, 2003 (UTC)

Someone else, I got Fraktur news for you. :-) Found an interesting website with tons of high-quality TrueType Fraktur fonts... and they even have the long s on the backslash key. -- Djmutex 15:10 May 2, 2003 (UTC)

 * Excellent! And he has Open-Type fonts too! -- Someone else 19:25 May 2, 2003 (UTC)

I have to go back to work -- can you or somebody else who has the authority continue the fight against Zog and his racism, until one of the programmers gets off his ass and bans all versions of this jerk? -- Zoe

I found lately I was getting into the slice and dice habit too much. I, too, think the article is dubious. But it is fun to take on a project and try to salvage something. I asked J.J. to chime in, since he started the article. But he seems to have left his desk. Kingturtle 04:51 May 8, 2003 (UTC)

Mav- If you're reading this, you can colour me consenting. --Someone else 19:53 May 12, 2003 (UTC)

Kudos on "the White Thaw Nesbit Series"! -- Infrogmation 00:10 May 13, 2003 (UTC)

why do you remove:
 * (perhaps better classified as an excuse)
 * This defense is similar to the excuses of temporary insanity and provocation.

I assume you would have no problem with the first point, if you agreed that black rage was either a form of temporary insanity or provocation; as both of those defenses are forms of excuse.

 * Provocation (as a term of jurisprudence) refers to a possible defense by excuse; via which, a defendant may argue that they should not be held criminally liable for breaking the law, as they were provoked by an aggressor.

I would think it reasonable to conclude that the premise of black rage is that the "black victim" was driven to rage because the actions of "white society" were provocative; for example, if I walked up to a black man and said, "FUCK YOU NIGGAH" he might hit me and successfully argue that I provoked him. Black rage seems 'very similar to provocation.

Likewise, Ferguson certainly acted somewhat "insanely" and it is reasonable to conclude that his lawyers wanted to argue that he had been driven insane by his black rage.
 * There's no need to have the parenthetical phrase there: it's in the innovative defense article, and I find the phrase awkward. It's a VERY busy paragraph. Black rage was explicitly NOT an allegation of insanity, and did not allege provocation. But I ought not be arguing with a banned user. Please do not place me in that position. -- Someone else 00:59 May 13, 2003 (UTC)

-- We are trying to increase the number of people who are Wikipedia Administrators. Until now, we've been relying on users to take the initiative to ask for this access themselves but this has resulted in a slow rate Admin rank expansion. So we've gone ahead and nominated and approved you and several other long-time users for the account upgrade. This means that your fellow Wikipedians feel that you are a responsible, well-known, and fair-minded user.

Agreeing to be an Administrator does not mean that you are expected to do any additional work above and beyond what you do now ; It just means that we trust you to to have certain privileges and responsibilities that can't be entrusted to random users (such as editing the Main Page, protected policy pages, or banning the IPs of vandals).

All we need from you now is your consent. You can either send an email to WikiEN-L (preferred) or simply state "I agree" on the bottom of this page.

-- Daniel Mayer (aka mav)

title: User talk:Someone else/talk3


text:
Quetiapine

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use may not outweigh its undesirable side effects. It is taken orally.

Common side effects include sleepiness, constipation, weight gain, and dry mouth. Other side effects include low blood pressure with standing, seizures, a prolonged erection, high blood sugar, tardive dyskinesia, and neuroleptic malignant syndrome. In older people with dementia, its use increases the risk of death. Use in the third trimester of pregnancy may result in a movement disorder in the baby for some time after birth. Quetiapine is believed to work by blocking a number of receptors, including those for serotonin and dopamine.

Quetiapine was developed in 1985 and approved for medical use in the United States in 1997. It is available as a generic medication. In 2021, it was the 62nd most commonly prescribed medication in the United States, with more than 10million prescriptions. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Quetiapine is primarily used to treat schizophrenia or bipolar disorder. Quetiapine targets both positive and negative symptoms of schizophrenia.

Schizophrenia
A 2013 Cochrane review compared quetiapine to typical antipsychotics:

In a 2013 comparison of 15 antipsychotics in effectiveness in treating schizophrenia, quetiapine demonstrated standard effectiveness. It was 13–16% more effective than ziprasidone, chlorpromazine, and asenapine and approximately as effective as haloperidol and aripiprazole.

There is tentative evidence of the benefit of quetiapine versus placebo in schizophrenia; however, definitive conclusions are not possible due to the high rate of attrition in trials (greater than 50%) and the lack of data on economic outcomes, social functioning, or quality of life.

It is debatable whether, as a class, typical or atypical antipsychotics are more effective. Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages. While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth.

A Cochrane review comparing quetiapine to other atypical antipsychotic agents tentatively concluded that it may be less efficacious than olanzapine and risperidone; produce fewer movement related side effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine; and produce weight gain similar to risperidone, clozapine and aripiprazole. They concluded that it produces suicide attempt, suicide; death; QTc prolongation, low blood pressure; tachycardia; sedation; gynaecomastia; galactorrhoea, menstrual irregularity and white blood cell count at a rate similar to first generation antipsychotics.

Bipolar disorder
In those with bipolar disorder, quetiapine is used to treat depressive episodes; acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium; valproate or lamotrigine); acute mixed episodes; and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).

Major depressive disorder
Quetiapine is effective when used by itself and when used along with other medications in major depressive disorder (MDD). However, sedation is often an undesirable side effect.

In the United States, the United Kingdom and Australia (while not subsidised by the Australian Pharmaceutical Benefits Scheme for treatment of MDD), quetiapine is licensed for use as an add-on treatment in MDD.

Alzheimer's disease
Quetiapine does not decrease agitation among people with Alzheimer's disease. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended.

Others
The use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects. A 2022 network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine did not demonstrate any short-term benefits in sleep quality. Quetiapine, specifically, had an effect size (standardized mean difference) against placebo for treatment of insomnia of 0.05 (95% CI –1.21 to 1.11) at 4weeks of treatment, with the certainty of evidence rated as very low. Doses of quetiapine used for insomnia have ranged from 12.5 to 800mg, with low doses of 25 to 200mg being the most typical. Regardless of the dose used, some of the more serious adverse effects may still possibly occur at the lower dosing ranges, such as dyslipidemia and neutropenia. These safety concerns at low doses are corroborated by Danish observational studies that showed use of specifically low-dose quetiapine (prescriptions filled for tablet strengths >50 mg were excluded) was associated with an increased risk of major cardiovascular events as compared to use of Z-drugs, with most of the risk being driven by cardiovascular death. Laboratory data from an unpublished analysis of the same cohort also support the lack of dose-dependency of metabolic side effects, as new use of low-dose quetiapine was associated with a risk of increased fasting triglycerides at 1-year follow-up.

It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome, musical hallucinations and anxiety disorders.

Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their relatively low extrapyramidal side-effect liability. Owing to the risks associated with clozapine (e.g. agranulocytosis, diabetes mellitus, etc.), clinicians often attempt treatment with quetiapine first, although the evidence to support quetiapine's use for this indication is significantly weaker than that of clozapine.

Adverse effects
Sources for incidence lists:

 * Very common (>10% incidence) adverse effects
 * Dry mouth
 * Dizziness
 * Headache
 * Somnolence (drowsiness; of 15 antipsychotics quetiapine causes the 5th most sedation. Extended release (XR) formulations tend to produce less sedation, dose-by-dose, than the immediate release formulations.)

 * Common (1–10% incidence) adverse effects

 * High blood pressure
 * Orthostatic hypotension
 * High pulse rate
 * High blood cholesterol
 * Elevated serum triglycerides
 * Abdominal pain
 * Constipation
 * Increased appetite
 * Vomiting
 * Increased liver enzymes
 * Backache
 * Asthenia
 * Insomnia
 * Lethargy
 * Tremor
 * Agitation
 * Nasal congestion
 * Pharyngitis
 * Fatigue
 * Pain
 * Dyspepsia (Indigestion)
 * Peripheral oedema
 * Dysphagia

 * Extrapyramidal disease: Quetiapine and clozapine are noted for their relative lack of extrapyramidal side effects.
 * Weight gain: SMD 0.43 kg when compared to placebo. Produces roughly as much weight gain as risperidone, less weight gain than clozapine, olanzapine and zotepine and more weight gain than ziprasidone, lurasidone, aripiprazole and asenapine. As with many other atypical antipsychotics, this action is likely due to its actions at the H1 histamine receptor and 5-HT2C receptor.

 * Rare (<1% incidence) adverse effects

 * Prolonged QT interval (had an odds ratio for prolonging the QT interval over placebo of 0.17)
 * Sudden cardiac death
 * Syncope
 * Diabetic ketoacidosis
 * Restless legs syndrome
 * Hyponatraemia, low blood sodium.
 * Jaundice, yellowing of the eyes, skin and mucous membranes due to an impaired ability of the body to clear bilirubin, a by product of haem breakdown.
 * Pancreatitis, pancreas swelling.
 * Agranulocytosis, a potentially fatal drop in white blood cell count.
 * Leukopenia, a drop in white blood cell count, not as severe as agranulocytosis.
 * Neutropenia, a drop in neutrophils, the cell of the immune cells that defends the body against bacterial infections.
 * Eosinophilia
 * Anaphylaxis, a potentially fatal allergic reaction.
 * Seizure
 * Hypothyroidism, underactive thyroid gland.
 * Myocarditis, swelling of the myocardium.
 * Cardiomyopathy
 * Hepatitis, swelling of the liver.
 * Suicidal ideation
 * Priapism. A prolonged and painful erection.
 * Stevens–Johnson syndrome. A potentially fatal skin reaction.

 * Neuroleptic malignant syndrome a rare and potentially fatal complication of antipsychotic drug treatment. It is characterised by the following symptoms: tremor, rigidity, hyperthermia, tachycardia, mental status changes (e.g. confusion), etc.
 * Tardive dyskinesia. A rare and often irreversible neurological condition characterised by involuntary movements of the face, tongue, lips and rest of the body. Most commonly occurs after prolonged treatment with antipsychotics. It is believed to be particularly uncommon with atypical antipsychotics, especially quetiapine and clozapine

Both typical and atypical antipsychotics can cause tardive dyskinesia. According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%. Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals.

Weight gain can be a problem for some, with quetiapine causing more weight gain than fluphenazine, haloperidol, loxapine, molindone, olanzapine, pimozide, risperidone, thioridazine, thiothixene, trifluoperazine, and ziprasidone, but less than chlorpromazine, clozapine, perphenazine, and sertindole.

As with some other anti-psychotics, quetiapine may lower the seizure threshold, and should be taken with caution in combination with drugs such as bupropion.

Discontinuation
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.

There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.

Pregnancy and lactation
Placental exposure is least for quetiapine compared to other atypical antipsychotics. The evidence is insufficient to rule out any risk to the foetus but available data suggests it is unlikely to result in any major foetal malformations. It is secreted in breast milk and hence quetiapine-treated mothers are advised not to breastfeed.

Abuse potential
In contrast to most other antipsychotic drugs, which tend to be somewhat aversive and often show problems with patient compliance with prescribed medication regimes, quetiapine is sometimes associated with drug misuse and abuse potential, for its hypnotic and sedative effects. It has a limited potential for misuse, usually only in individuals with a history of polysubstance abuse and/or mental illness, and especially in those incarcerated in prisons or secure psychiatric facilities where access to alternative intoxicants is more limited. To a significantly greater extent than other atypical antipsychotic drugs, quetiapine was found to be associated with drug-seeking behaviors, and to have standardised street prices and slang terms associated with it, either by itself or in combination with other drugs (such as "Q-ball" for the intravenous injection of quetiapine mixed with cocaine). The pharmacological basis for this distinction from other second generation antipsychotic drugs is unclear, though it has been suggested that quetiapine's comparatively lower dopamine receptor affinity and strong antihistamine activity might mean it could be regarded as more similar to sedating antihistamines in this context. While these issues have not been regarded as sufficient cause for placing quetiapine under increased legal controls, prescribers have been urged to show caution when prescribing quetiapine to individuals with characteristics that might place them at increased risk for drug misuse.

Overdose
Most instances of acute overdosage result in only sedation, hypotension and tachycardia, but cardiac arrhythmia, coma and death have occurred in adults. Serum or plasma quetiapine concentrations are usually in the 1–10 mg/L range in overdose survivors, while postmortem blood levels of 10–25 mg/L are generally observed in fatal cases. Non-toxic levels in postmortem blood extend to around 0.8 mg/kg, but toxic levels in postmortem blood can begin at 0.35 mg/kg.

Pharmacodynamics
Quetiapine has the following pharmacological actions:

 * Dopamine D1, D2, D3, D4, and D5 receptor antagonist
 * Serotonin 5-HT1A receptor partial agonist, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptor antagonist, and 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F receptor ligand
 * α1- and α2-adrenergic receptor antagonist
 * Histamine H1 receptor antagonist
 * Muscarinic acetylcholine receptor antagonist

This means quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with some anticholinergic properties. Quetiapine binds strongly to serotonin receptors; the drug acts as partial agonist at 5-HT1A receptors. Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor. Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side-effects such as pseudo-parkinsonism as well as elevations in prolactin. Some of the antagonized receptors (serotonin, norepinephrine) are actually autoreceptors whose blockade tends to increase the release of neurotransmitters.

At very low doses, quetiapine acts primarily as a histamine receptor blocker (antihistamine) and α1-adrenergic blocker. When the dose is increased, quetiapine activates the adrenergic system and binds strongly to serotonin receptors and autoreceptors. At high doses, quetiapine starts blocking significant amounts of dopamine receptors. Due to the drug's sedating H1 activity, it is often prescribed at low doses for insomnia. While some feel that low doses of drugs with antihistamine effects like quetiapine and mirtazapine are safer than drugs associated with physical dependency or other risk factors, concern has been raised by some professionals that off-label prescribing has become too widespread due to underappreciated hazards.

When treating schizophrenia, antagonism of D2 receptor by quetiapine in the mesolimbic pathway relieves positive symptoms and antagonism of the 5-HT2A receptor in the frontal cortex of the brain may relieve negative symptoms and reduce severity of psychotic episodes. Quetiapine has fewer extrapyramidal side effects and is less likely to cause hyperprolactinemia when compared to other drugs used to treat schizophrenia, so is used as a first line treatment.

Pharmacokinetics
Peak levels of quetiapine occur 1.5 hours after a dose. The plasma protein binding of quetiapine is 83%. The major active metabolite of quetiapine is norquetiapine (N-desalkylquetiapine). Quetiapine has an elimination half-life of 6 or 7 hours. Its metabolite, norquetiapine, has a half-life of 9 to 12 hours. Quetiapine is excreted primarily via the kidneys (73%) and in feces (20%) after hepatic metabolism, the remainder (1%) is excreted as the drug in its unmetabolized form.

Chemistry
Quetiapine is a tetracyclic compound and is closely related structurally to clozapine, olanzapine, loxapine, and other tetracyclic antipsychotics.

Synthesis
The synthesis of quetiapine begins with a dibenzothiazepinone. The lactam is first treated with phosphoryl chloride to produce a dibenzothiazepine. A nucleophilic substitution is used to introduce the sidechain.

Sustained-release
AstraZeneca submitted a new drug application for a sustained-release version of quetiapine in the United States, Canada, and the European Union in the second half of 2006 for treatment of schizophrenia. AstraZeneca was to retain the exclusive right to market sustained-release quetiapine until 2017. The sustained-release quetiapine is marketed mainly as Seroquel XR. Other marketing names are Seroquel Prolong, Seroquel Depot and Seroquel XL

On 18 May 2007, AstraZeneca announced that the U.S. FDA approved Seroquel XR for acute treatment of schizophrenia. During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007. However, Seroquel XR has become available in U.S. pharmacies only after the FDA approved Seroquel XR for use as maintenance treatment for schizophrenia, in addition to acute treatment of the illness, on 16 November 2007. The company has not provided a reason for the delay of Seroquel XR's launch.

Health Canada approved sale of Seroquel XR on 27 September 2007.

In early October 2008, the FDA approved Seroquel XR for the treatment of bipolar depression and bipolar mania. According to AstraZeneca, Seroquel XR is "the first medication approved by the FDA for the once-daily acute treatment of both depressive and manic episodes associated with bipolar."

On 31 July 2008, Handa Pharmaceuticals, based in Fremont, California, announced that its abbreviated new drug application ("ANDA") for quetiapine fumarate extended-release tablets, the generic version of AstraZeneca's SEROQUEL XR, has been accepted by the FDA.

On 1 December 2008, Biovail announced that the FDA had accepted the company's ANDA to market its own version of sustained-release quetiapine. Biovail's sustained-release tablets will compete with AstraZeneca's Seroquel XR.

On 24 December 2008, AstraZeneca notified shareholders that the FDA had asked for additional information on the company's application to expand the use of sustained-release quetiapine for treatment of depression.

Regulatory status
In the United States, the Food and Drug Administration (FDA) has approved quetiapine for the treatment of schizophrenia and of acute manic episodes associated with bipolar disorder (bipolar mania) and for treatment of bipolar depression. In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder.

Quetiapine received its initial indication from U.S. FDA for treatment of schizophrenia in 1997. In 2004, it received its second indication for the treatment of mania-associated bipolar disorder. In 2007 and 2008, studies were conducted on quetiapine's efficacy in treating generalized anxiety disorder and major depression.

Patent protection for the product ended in 2012; however, in a number of regions, the long-acting version remained under patent until 2017.

Lawsuits
In April 2010, the U. S. Department of Justice fined AstraZeneca $520 million for the company's aggressive marketing of Seroquel for off-label uses. According to the Department of Justice, "the company recruited doctors to serve as authors of articles that were ghostwritten by medical literature companies and about studies the doctors in question did not conduct. AstraZeneca then used those studies and articles as the basis for promotional messages about unapproved uses of Seroquel."

Multiple lawsuits have been filed in relation to quetiapine's side-effects, in particular, diabetes.

Approximately 10,000 lawsuits have been filed against AstraZeneca, alleging that quetiapine caused problems ranging from slurred speech and chronic insomnia to deaths.

Controversy
In 2004, a young man named Dan Markingson committed suicide in a controversial Seroquel clinical trial at the University of Minnesota while under an involuntary commitment order. A group of University of Minnesota bioethicists charged that the trial involved an alarming number of ethical violations.

Nurofen Plus tampering case
In August 2011, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) issued a class-4 drug alert following reports that some batches of Nurofen plus contained Seroquel XL tablets instead.

Following the issue of the Class-4 Drug Alert, Reckitt Benckiser (UK) Ltd received further reports of rogue blister strips in cartons of two additional batches of Nurofen Plus tablets. One of the new batches contained Seroquel XL 50 mg tablets and one contained the Pfizer product Neurontin 100 mg capsules.

Following discussions with the MHRA's Defective Medicines Report Centre (DMRC), Reckitt Benckiser (UK) Ltd decided to recall all remaining unexpired stock of Nurofen Plus tablets in any pack size, leading to a Class-1 Drug Alert. The contamination was later traced to in-store tampering by a customer.

title: Quetiapine


text:
Ziprasidone

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.

Common side effects include dizziness, drowsiness, dry mouth, and twitches. Although it can also cause weight gain, the risk is much lower than for other atypical antipsychotics. How it works is not entirely clear but is believed to involve effects on serotonin and dopamine in the brain.

Ziprasidone was approved for medical use in the United States in 2001. The pills are made up of the hydrochloride salt, ziprasidone hydrochloride. The intramuscular form is the mesylate, ziprasidone mesylate trihydrate, and is provided as a lyophilized powder. In 2020, it was the 282nd most commonly prescribed medication in the United States, with more than 1million prescriptions.

Medical uses
Ziprasidone is approved by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia as well as acute mania and mixed states associated with bipolar disorder. Its intramuscular injection form is approved for acute agitation in schizophrenic patients for whom treatment with just ziprasidone is appropriate.

In a 2013 study in a comparison of 15 antipsychotic drugs in effectiveness in treating schizophrenic symptoms, ziprasidone demonstrated mild-standard effectiveness. Ziprasidone was 15% more effective than lurasidone and iloperidone, approximately as effective as chlorpromazine and asenapine, and 9–13% less effective than haloperidol, quetiapine, and aripiprazole. Ziprasidone is effective in the treatment of schizophrenia, though evidence from the CATIE trials suggests it is less effective than olanzapine, and equally as effective compared to quetiapine. There are higher discontinuation rates for lower doses of ziprasidone, which are also less effective than higher doses.

Adverse effects
Ziprasidone (and all other second generation antipsychotics (SGAs)) received a black box warning due to increased mortality in elderly patients with dementia-related psychosis.

Sleepiness and headache are very common adverse effects (>10%).

Common adverse effects (1–10%), include producing too much saliva or having dry mouth, runny nose, respiratory disorders or coughing, nausea and vomiting, stomach aches, constipation or diarrhea, loss of appetite, weight gain (but the smallest risk for weight gain compared to other antipsychotics ), rashes, fast heart beats, blood pressure falling when standing up quickly, muscle pain, weakness, twitches, dizziness, and anxiety. Extrapyramidal symptoms are also common and include tremor, dystonia (sustained or repetitive muscle contractions), akathisia (the feeling of a need to be in motion), parkinsonism, and muscle rigidity; in a 2013 meta-analysis of 15 antipsychotic drugs, ziprasidone ranked 8th for such side effects.

Ziprasidone is known to trigger mania in some bipolar patients.

This medication can cause birth defects, according to animal studies, although this side effect has not been confirmed in humans.

Recently, the FDA required the manufacturers of some atypical antipsychotics to include a warning about the risk of hyperglycemia and Type II diabetes with atypical antipsychotics. Some evidence suggests that ziprasidone does not cause insulin resistance to the degree of other atypical antipsychotics, such as olanzapine. Weight gain is also less of a concern with ziprasidone compared to other atypical antipsychotics. In fact, in a trial of long term therapy with ziprasidone, overweight patients (BMI > 27) actually had a mean weight loss overall. According to the manufacturer insert, ziprasidone caused an average weight gain of 2.2 kg (4.8 lbs), which is significantly lower than other atypical antipsychotics, making this medication better for patients that are concerned about their weight. In December 2014, the FDA warned that ziprasidone could cause a potentially fatal skin reaction, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), although this was believed to occur only rarely.

Discontinuation
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.

There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely tardive dyskinesia can occur when the medication is stopped.

Correspondence to clinical effects
Ziprasidone mostly affects the receptors of dopamine (D2), serotonin (5-HT2A, partially 5-HT1A, 5-HT2C, and 5-HT1D) and epinephrine/norepinephrine (α1) to a high degree, while of histamine (H1) - moderately. It also somewhat inhibits reuptake of serotonin and norepinephrine, though not dopamine.

Ziprasidone's efficacy in treating the positive symptoms of schizophrenia is believed to be mediated primarily via antagonism of the dopamine receptors, specifically D2. Blockade of the 5-HT2A receptor may also play a role in its effectiveness against positive symptoms, though the significance of this property in antipsychotic drugs is still debated among researchers. Blockade of 5-HT2A and 5-HT2C and activation of 5-HT1A as well as inhibition of the reuptake of serotonin and norepinephrine may all contribute to its ability to alleviate negative symptoms. ; however, its effects on the 5-HT1A receptor may be limited as a study found ziprasidone would likely "produce detectable occupancy [of 5-HT1A receptors] only at higher doses that would produce unacceptable levels of side effects in man, although lower doses are sufficient to produce pharmacological effects." The relatively weak antagonistic actions of ziprasidone on the α1-adrenergic receptor likely in part explains some of its side effects, such as orthostatic hypotension. Unlike many other antipsychotics, ziprasidone has no significant affinity for the mACh receptors, and as such lacks any anticholinergic side effects. Like most other antipsychotics, ziprasidone is sedating due primarily to serotonin and dopamine blockade.

Pharmacokinetics
The systemic bioavailability of ziprasidone is 100% when administered intramuscularly and 60% when administered orally without food.

After a single dose intramuscular administration, the peak serum concentration typically occurs at about 60 minutes after the dose is administered, or earlier. Steady state plasma concentrations are achieved within one to three days. Exposure increases in a dose-related manner and following three days of intramuscular dosing, little accumulation is observed.

The bioavailability of the drug is reduced by approximately 50% if a meal is not eaten before Ziprasidone ingestion.

Ziprasidone is hepatically metabolized by aldehyde oxidase; minor metabolism occurs via cytochrome P450 3A4 (CYP3A4). Medications that induce (e.g. carbamazepine) or inhibit (e.g. ketoconazole) CYP3A4 have been shown to decrease and increase, respectively, blood levels of ziprasidone.

Its biological half-life time is 10 hours at doses of 80–120 milligrams.

History
Ziprasidone is chemically similar to risperidone, of which it is a structural analogue. It was first synthesized in 1987 at the Pfizer central research campus in Groton, Connecticut.

Phase I trials started in 1995. In 1998 ziprasidone was approved in Sweden. After the FDA raised concerns about long QT syndrome, more clinical trials were conducted and submitted to the FDA, which approved the drug on February 5, 2001.

Lawsuit
In September 2009, the U.S. Justice Department announced that Pfizer had been ordered to pay a historic fine of $2.3 billion as a penalty for fraudulent marketing of several drugs, including Geodon. Pfizer had illegally promoted Geodon and submitted false claims to government health care programs for uses that were not medically accepted indications. The civil settlement also resolves allegations that Pfizer paid kickbacks to health care providers to induce them to prescribe Geodon, as well as other drugs. This was the largest civil fraud settlement in history against a pharmaceutical company.

Brand names
In the US, Geodon is marketed by Viatris after Upjohn was spun off from Pfizer.

title: Ziprasidone