After struggling with Multiple Systems Atrophy, sadly Steve recently passed away.
We will always remember Steve for his great musical talents.
Rest in Peace Steve.
Campaigning for fairer & compassionate mental health care since 2007. Humane therapy, not DRUGS tyranny! Working together GREATER results can be achieved! Join us :)
Friday, 20 November 2015
R.I.P. Steve Morgan
After struggling with Multiple Systems Atrophy, sadly Steve recently passed away.
We will always remember Steve for his great musical talents.
Rest in Peace Steve.
November Newsletter
Dear Friends,
We wish to thank the amazing speakers Cristian Montenegro, Rodrigo Fredes, Paula Peters and Dave Skull for their presentation at our Human Rights event at the Kingsley Hall last week.
As days are colder and shorter we received many apologies, however we were very pleased with the few but good participants that came along in support of the event. Specially delighted to see several Mad Pride members (please see details for event on 20th Nov below the page).
We were very pleased to hear the manifesto contained in the brand new Mental Health Manual of Human Rights presented by Rodrigo, which was recently presented in Europe, at the International Hearing Voices convention in Madrid. We look forward to see the English translated book soon. In the meantime the Spanish version is available to be purchased; please contact Rodrigo directly for more details on locospornuestrosderechos@gmail.com
Notes from the event are now available to be shared. Send us an email if you wish to have a copy.
F.E.E.L. is now 8 years old. This week, at our monthly meeting at LARC, we have discussed the work we have done in these past years, run entirely by complete volunteer initiative. Although externally for some people might have not meant much, for ourselves it has been of amazing benefit. We have now decided to have a sabbatical to take care of ourselves, possibly resuming the monthly meetings around February 2016. There probably won't be much action online either, as it's a much needed time for some media and social media detox, although we will do our best to support fellow campaigners events, when energy will allow us.
On a personal level, looking at the likeness of the figure 8 with the infinity symbol
, there is a feeling of completion of what F.E.E.L. has served for ourselves and the community. Our message is out there, repeated infinitus, not only by fellow survivors, but from a large range of professionals around the world. Most of these, which might have first hand experience of mental illness themselves, have their own stories, their own evidence to share that match our own. Some people might have seen us as extremist, but probably those don't know, nor understand what we are talking about.
I have not got around sharing my personal story as I wish it to see imprinted; yet I am proud of being free from the damaging pshyco-drugs for over two years now. Nevertheless I am dependent to other meds that keep me alive and cannot incriminate Big Pharma from all angles. Nor I wish to encourage or push people to come off their meds; everyone needs to be free to make their own choices, responsible of the self and own life. Only suggestion is to stay informed!
My early (unedited!) blog posts still hold the strong feelings that have fuelled my involvement in F.E.E.L., which has been a great support in maintaining sanity in this crazy world. Thank you comrades!
Concluding, wishing you all to find strength and courage to go thought difficulties; always remember that either good or bad things never last forever. Make the most of your favourite ones!
--------------------------------
MENTAL HEALTH RESISTANCE NETWORK Event Friday 20th November
As part of MHRN's series of "SolidariTea" events at the Field in New Cross, on Friday from 7.30pm we will be hosting a Survivors Poetry performance with music and poetry from Dave Russell, Frank Bangay, Razz, King Miserable, C.T. and floor spots. Free crisps. All welcome. This will be preceded by a MHRN action-planning meeting.
--------------------------------
Tangled Up in Laing: Reading R. D. Laing
Host: Adrian Chapman. Venue: Arcola Theatre 24 Ashwin St, London E8 3DL
Date: Sat 21 November. Time: 12.30pm-2pm FREE To book: drop in
This discussion-based event introduces Laing, the radical Scottish psychiatrist, author and sixties counter-cultural figure (who played a part in the original anti-university of London). We’ll focus especially on Laing’s conception of alienation. Attention will be paid, too, to his influence and the ways in which he might be relevant today.
No prior knowledge of Laing is required. Brief photocopies of his work, on which discussion will be based, will be handed out. Why not make an afternoon of it? Book a ticket to see a performance of The Divided Laing following this discussion in the same venue. Adrian Chapman, who teaches English Literature and writing at American universities based in London, has published on Laing and anti-psychiatry and will take up a Wellcome Trust-funded research fellowship next year at University of Glasgow, where he will be researching in the R. D. Laing Archive.
www.antiuniversity.org/Tangled-Up-in-Laing-Reading-R-D-Laing
The Divided Laing. The play by Patrick Marmion is currently showing at the Arcola Theatre in Hackney, until the 12th of December
https://www.arcolatheatre.com/production/arcola/the-divided-laing
--------------------------------
The Survivors History Group London Meeting
The next Survivors History Group meeting is taking place on Wednesday 25th November. As usual the meeting will be happening at the mezzanine at Together, 12 Old Street, London, EC1V 9BE from 1pm to 4.30pm ish. Refreshments will be provided and everyone is very welcome.
--------------------------------
Mad about Poetry Books Launch 2
Thursday 26th November
Venue: Tea House Theater 139 Vauxhall Walk SE11 5HL. Door open 19:30
The most amazing evening coming to South London A magical evening of fun laughter and performance poetry with international poets. Never before and probably never again 17 of London's finest poets come together in one evening supporting 8 new title from W.C.H. Publishing , covering a range of emotion heartfelt express as only people who know. Their books take you on a journey of human hart string pluck to express the many different emotions. £3 entry, free for performers.
londonpoetrybooks.com/poetry/books-launch/
--------------------------------
William Blake's 258th Birthday Celebration
Sat 28th November, from 1pm
All are welcome to the William Blake Congregation's annual Celebration of Blake's Birthday at the Tate Britain, in the Blake room,(Turner wing) Millbank, SW1P 4RG. Free to attend. Bring Poetry, Music, Dance to celebrate William Blake 258th! Cake & Cava in the garden afterwards!
--------------------------------
Spark London Open Mic
Spark London has been called Britain’s first true storytelling club. Everyone is welcome to sit back and listen, or you can get stuck into the action and tell your own story. There are only three rules at Spark:
1) It must be true
2) It must be your own story, and
3) It must be under five minutes long.
With a different theme each time, you'll soon find yourself talking to friends and strangers about moments from each other's lives. Our aim is always to connect people through true stories. There are regular storytelling nights at the Hackney Attic and Upstairs at the Ritzy, and we put on a monthly show at the Canal Café Theatre featuring all the best stories plus special guest storytellers.
WORKSHOP: We run regular storytelling workshops to help you find and develop your stories. If there are no workshops listed on our events page then please email Joanna@sparklondon.com or join our mailing list so we can let you know what is happening when. www.sparklondon.com/attend.php
--------------------------------
***HEALING WAVE***
Sacred Cacao Lotus Love Journey @ Kingsley Hall, Bromley - by- Bow
Saturday 12th December 7 -11pm
5 Elements Meditation and Dance Sound Journey Sacred Cacao Ceremony with 5 element dance with the energy of AIR, with EARTH, with FIRE, with WATER. sacredcacaolotuslovejourney.brownpapertickets.com/
***Low income Online tickets £15
***Normal wages Online tickets £20
***At the door £25
We wish to thank the amazing speakers Cristian Montenegro, Rodrigo Fredes, Paula Peters and Dave Skull for their presentation at our Human Rights event at the Kingsley Hall last week.
As days are colder and shorter we received many apologies, however we were very pleased with the few but good participants that came along in support of the event. Specially delighted to see several Mad Pride members (please see details for event on 20th Nov below the page).
We were very pleased to hear the manifesto contained in the brand new Mental Health Manual of Human Rights presented by Rodrigo, which was recently presented in Europe, at the International Hearing Voices convention in Madrid. We look forward to see the English translated book soon. In the meantime the Spanish version is available to be purchased; please contact Rodrigo directly for more details on locospornuestrosderechos@gmail.com
Notes from the event are now available to be shared. Send us an email if you wish to have a copy.
F.E.E.L. is now 8 years old. This week, at our monthly meeting at LARC, we have discussed the work we have done in these past years, run entirely by complete volunteer initiative. Although externally for some people might have not meant much, for ourselves it has been of amazing benefit. We have now decided to have a sabbatical to take care of ourselves, possibly resuming the monthly meetings around February 2016. There probably won't be much action online either, as it's a much needed time for some media and social media detox, although we will do our best to support fellow campaigners events, when energy will allow us.
On a personal level, looking at the likeness of the figure 8 with the infinity symbol
, there is a feeling of completion of what F.E.E.L. has served for ourselves and the community. Our message is out there, repeated infinitus, not only by fellow survivors, but from a large range of professionals around the world. Most of these, which might have first hand experience of mental illness themselves, have their own stories, their own evidence to share that match our own. Some people might have seen us as extremist, but probably those don't know, nor understand what we are talking about. I have not got around sharing my personal story as I wish it to see imprinted; yet I am proud of being free from the damaging pshyco-drugs for over two years now. Nevertheless I am dependent to other meds that keep me alive and cannot incriminate Big Pharma from all angles. Nor I wish to encourage or push people to come off their meds; everyone needs to be free to make their own choices, responsible of the self and own life. Only suggestion is to stay informed!
My early (unedited!) blog posts still hold the strong feelings that have fuelled my involvement in F.E.E.L., which has been a great support in maintaining sanity in this crazy world. Thank you comrades!
Concluding, wishing you all to find strength and courage to go thought difficulties; always remember that either good or bad things never last forever. Make the most of your favourite ones!
--------------------------------
MENTAL HEALTH RESISTANCE NETWORK Event Friday 20th November
As part of MHRN's series of "SolidariTea" events at the Field in New Cross, on Friday from 7.30pm we will be hosting a Survivors Poetry performance with music and poetry from Dave Russell, Frank Bangay, Razz, King Miserable, C.T. and floor spots. Free crisps. All welcome. This will be preceded by a MHRN action-planning meeting.
--------------------------------
Tangled Up in Laing: Reading R. D. Laing
Host: Adrian Chapman. Venue: Arcola Theatre 24 Ashwin St, London E8 3DL
Date: Sat 21 November. Time: 12.30pm-2pm FREE To book: drop in
This discussion-based event introduces Laing, the radical Scottish psychiatrist, author and sixties counter-cultural figure (who played a part in the original anti-university of London). We’ll focus especially on Laing’s conception of alienation. Attention will be paid, too, to his influence and the ways in which he might be relevant today.
No prior knowledge of Laing is required. Brief photocopies of his work, on which discussion will be based, will be handed out. Why not make an afternoon of it? Book a ticket to see a performance of The Divided Laing following this discussion in the same venue. Adrian Chapman, who teaches English Literature and writing at American universities based in London, has published on Laing and anti-psychiatry and will take up a Wellcome Trust-funded research fellowship next year at University of Glasgow, where he will be researching in the R. D. Laing Archive.
www.antiuniversity.org/Tangled-Up-in-Laing-Reading-R-D-Laing
The Divided Laing. The play by Patrick Marmion is currently showing at the Arcola Theatre in Hackney, until the 12th of December
https://www.arcolatheatre.com/production/arcola/the-divided-laing
--------------------------------
The Survivors History Group London Meeting
The next Survivors History Group meeting is taking place on Wednesday 25th November. As usual the meeting will be happening at the mezzanine at Together, 12 Old Street, London, EC1V 9BE from 1pm to 4.30pm ish. Refreshments will be provided and everyone is very welcome.
--------------------------------
Mad about Poetry Books Launch 2
Thursday 26th November
Venue: Tea House Theater 139 Vauxhall Walk SE11 5HL. Door open 19:30
The most amazing evening coming to South London A magical evening of fun laughter and performance poetry with international poets. Never before and probably never again 17 of London's finest poets come together in one evening supporting 8 new title from W.C.H. Publishing , covering a range of emotion heartfelt express as only people who know. Their books take you on a journey of human hart string pluck to express the many different emotions. £3 entry, free for performers.
londonpoetrybooks.com/poetry/books-launch/
--------------------------------
William Blake's 258th Birthday Celebration
Sat 28th November, from 1pm
All are welcome to the William Blake Congregation's annual Celebration of Blake's Birthday at the Tate Britain, in the Blake room,(Turner wing) Millbank, SW1P 4RG. Free to attend. Bring Poetry, Music, Dance to celebrate William Blake 258th! Cake & Cava in the garden afterwards!
--------------------------------
Spark London Open Mic
Spark London has been called Britain’s first true storytelling club. Everyone is welcome to sit back and listen, or you can get stuck into the action and tell your own story. There are only three rules at Spark:
1) It must be true
2) It must be your own story, and
3) It must be under five minutes long.
With a different theme each time, you'll soon find yourself talking to friends and strangers about moments from each other's lives. Our aim is always to connect people through true stories. There are regular storytelling nights at the Hackney Attic and Upstairs at the Ritzy, and we put on a monthly show at the Canal Café Theatre featuring all the best stories plus special guest storytellers.
WORKSHOP: We run regular storytelling workshops to help you find and develop your stories. If there are no workshops listed on our events page then please email Joanna@sparklondon.com or join our mailing list so we can let you know what is happening when. www.sparklondon.com/attend.php
--------------------------------
***HEALING WAVE***
Sacred Cacao Lotus Love Journey @ Kingsley Hall, Bromley - by- Bow
Saturday 12th December 7 -11pm
5 Elements Meditation and Dance Sound Journey Sacred Cacao Ceremony with 5 element dance with the energy of AIR, with EARTH, with FIRE, with WATER. sacredcacaolotuslovejourney.brownpapertickets.com/
***Low income Online tickets £15
***Normal wages Online tickets £20
***At the door £25
Sunday, 15 November 2015
Monday, 2 November 2015
Mental Health, Psychiatric Drugs and Metabolism
We are pleased to publicate this article about the effects of psychiatric medication on metabolism recently written by Catherine Clarke SRN, SCM, MSSCH, MBChA and Jan Evans MCSP. Grad Dip Phys.
There is plenty of evidence about these type of studies and researches. Since the pharmaceutical industry has no interest in circulating them it is OUR responsibility, being at the receiving end, to share them and stay informed.
Previous articles by Clarke shedding light on the ill-effect of psychiatric drugs and consequential patient violence were publicised on the Asylum Magazine ( Nos 17.2, 17.3 and 20.3).
The fully referenced and detailed article can be obtained requesting it directly to the author : cclarke@post.com
Catherine Clarke SRN, SCM, MSSCH, MBChA
Jan Evans MCSP. Grad Dip Phys
28th September 2015
Mental health disorders are predominantly treated with psychiatric medications, which are licensed psychoactive drugs. This document focuses primarily on psychiatric drug induced mood changing side effects in relation to metabolisation. Metabolism is defined as an ability of the body to break down medications. Individual inability to break down medications efficiently causes toxicity, resulting in side effects. This enlightening information falls outside the remit of mental health mainstream literature. Although ‘side effects’ is common terminology, Adverse Drug Reactions (ADRs) is the more accurate term as it reflects drug induced toxicities and is referred to throughout this document. The term antipsychotic is definitively replaced by neuroleptic, which means literally to ‘seize the nerve’.
Psychiatric Medications Adverse Drug Reactions
Many individuals treated with psychiatric medications experience severe ADRs, without any effective drug response. Whilst antidepressant and neuroleptic drugs can cause iatrogenic physical ADRs, it is not widely known that psychiatric medications can induce mood changing neurotoxic behavioural ADRs. SSRIs for depression can precipitate deepening depression, suicidal ideation, suicide, homicidal ideation, homicide, akathisia and agitation, mania and delirium, severe anxiety, bizarre thinking and reasoning psychosis, and hallucinations. Neuroleptics, used to treat psychosis, are linked with violence, suicidal and homicidal behaviour leading to completed suicide and homicide.
So why do some individuals respond well to drugs and others not?
A major factor for varied drug responses is due to individuals’ differing genetic makeup, known as pharmacogenetics or drug metabolism. Although there are many metabolising systems in the body, the major metabolising systems for psychiatric medications are the CYP450 enzyme system, principally in the liver, and the serotonergic system. Both systems have an important role in the outcome of treatment, ADRs and efficacy.
450CYP Enzyme System
75% of psychiatric drugs including antidepressant and neuroleptic medications, are metabolised through CYP2D6, which is one of the most variable metabolizing enzyme pathways known. Other pathways that metabolise antidepressants and neuroleptic drugs include CYPC19, CYPC9, CYP1A2, CYP 3A4 and CYPA5.Genetic variations, known as alleles, classify individuals as either being Poor Metaboliser (PM), Intermediate Metaboliser (IM), Extensive Metaboliser (EM) or Ultra Metaboliser (UM) genotypes. PMs have two non-functional alleles and IMs have one non-functional allele plus one diminished allele or two diminished alleles or two partially active alleles. UMs have more than two active gene copies on the same allele, or increased expression of a single allele. EMs have one or at the most two functional alleles with ‘normal ‘activity.Genetic variability affects psychiatric medication outcomes. PMs and IMs incur neurotoxicities leading to violent acts, as do UMs with prodrug use. EM individuals are likely to have a therapeutic response without neurotoxic ADRs.EMs determine the window of opportunity for a drug therapeutic level and sets the recommended drug dosage. This is important, as drug companies do not specify drug dosage for UMs, IMs and PMs, which explains why these individuals do not respond well to standard drug doses.
Combined PM and IM frequency via CYP450 2D6:
· 26% Caucasians
· 40-50% African-Americans
· 50% Africans
Statistically, Black Minority and Ethnic (BME) populations have greater difficulty metabolising psychiatric medications compared with White and Asian population, due to the higher frequency of lower metabolism at CYP 2D6. BME groups are four times more likely to experience psychosis than Caucasians, with African Caribbean people three to five times more likely than any other group, of being diagnosed with schizophrenia and admitted to hospital.
Serotonergic System
Antidepressants and neuroleptics are regulated through the serotonergic system. The serotonin system consists of the Serotonin Transporter Gene and serotonin receptors (5-HT). As with the CYP450 system, the serotonergic system has genetic variations that affect outcomes.
Serotonin Transporter Gene and Antidepressants
Genetic variations in the promoter region of the Serotonin Transporter Gene (5HTT-LPR) are coded as L/L (2 long alleles), L/S (a long and a short allele) or S/S (2 short alleles). Those individuals with the L/L code have a ‘normal’ gene activity and respond well to antidepressant medications. In contrast individuals with the short allele have slower gene activity, resulting in a reduction of serotonin transmission. Both L/S and S/S individuals treated with antidepressants have poor outcomes, and a ‘powerfully predicted non response’. Emerging antidepressant ADRs are inevitable for individuals with the short allele.
Individual response to neuroleptic medication is also affected by 5HTT-LPR variations. 50% of individuals coded L/L receiving neuroleptic treatment with haloperidol experienced parkinsonian side effects; however the incidence of parkinsonian side effects for L/S and S/S allele individuals rose to 62.2% and 83.1% respectively.
What is the frequency of 5HTT-LPR Gene Variants?
Population Frequency of 5HTT-LPR Variations
Individuals coded with (S/S) and (S/L) genotype:
Caucasians S/S (39%)
Caucasians S/L (52%)
East Asians S/S (49–74%)
Native Americans S/S (42%)
African Americans S/S (7–17%)
Individuals coded with L/L genotype:
Caucasians (29–43%)
African Americans (45–56%)
Native American (10–14%)
East Asian samples (1–13%)
Serotonin Receptors
There are 14 types of 5-HT receptors that can be targeted by antidepressants and neuroleptics. However the 5-HT 2A serotonin receptor variant, in particular, is associated with individual poor response and increased risk of ADRs when treated with antidepressant selective serotonin reuptake inhibitors. This same receptor variant has been linked to poor response from some individuals having neuroleptic treatment.
Genotype Testing
CYP450, 5HTT-LPR and 5-HT receptor genotype testing can determine individual status for metabolizing psychiatric medications. Prescribers do not currently conduct genotype testing prior to treatment and take no account of whether or not individuals are able to efficiently metabolise medication. The current practice is to work on a crude trial and error basis when treating individuals with psychiatric medication.
Genotype testing of an individual prior psychiatric medication treatment would enable assessment and prediction of the potential for neurotoxic behavioural ADRs in line with genotype status as depicted in the table above. The genotype test is a simple blood or swab test and in 2013 the standard cost of a test was £30. Retrospective genotyping for psychiatric drugs has demonstrated that there would have been a significant reduction in the financial outlay/cost based on the use of inappropriate medication and subsequent unnecessary healthcare costs.
Genotype testing is used by pharmaceutical companies during medication trials (stages II - 1V), to de-select individuals who are PMs and potentially liable to suffer severe ADRs. This practice includes trials with psychiatric medication and is done for reasons of safety, and also to show medication in its best light.
Discussion
Neurotoxic behavioural ADRs are not understood in psychiatry. When individuals respond violently to psychiatric medication the practice in psychiatry is to increase the dose and/or polypharmacy. This practice is completely futile as further medications increase neurotoxicities. Individuals are theoretically being overdosed, albeit unwittingly by prescribers. Prescribing of psychiatric medications is done on a crude trial end error basis. Individual suffering is immense. This needs to change.
There is plenty of evidence about these type of studies and researches. Since the pharmaceutical industry has no interest in circulating them it is OUR responsibility, being at the receiving end, to share them and stay informed.
Previous articles by Clarke shedding light on the ill-effect of psychiatric drugs and consequential patient violence were publicised on the Asylum Magazine ( Nos 17.2, 17.3 and 20.3).
The fully referenced and detailed article can be obtained requesting it directly to the author : cclarke@post.com
Catherine Clarke SRN, SCM, MSSCH, MBChA
Jan Evans MCSP. Grad Dip Phys
28th September 2015
Mental health disorders are predominantly treated with psychiatric medications, which are licensed psychoactive drugs. This document focuses primarily on psychiatric drug induced mood changing side effects in relation to metabolisation. Metabolism is defined as an ability of the body to break down medications. Individual inability to break down medications efficiently causes toxicity, resulting in side effects. This enlightening information falls outside the remit of mental health mainstream literature. Although ‘side effects’ is common terminology, Adverse Drug Reactions (ADRs) is the more accurate term as it reflects drug induced toxicities and is referred to throughout this document. The term antipsychotic is definitively replaced by neuroleptic, which means literally to ‘seize the nerve’.
Psychiatric Medications Adverse Drug Reactions
Many individuals treated with psychiatric medications experience severe ADRs, without any effective drug response. Whilst antidepressant and neuroleptic drugs can cause iatrogenic physical ADRs, it is not widely known that psychiatric medications can induce mood changing neurotoxic behavioural ADRs. SSRIs for depression can precipitate deepening depression, suicidal ideation, suicide, homicidal ideation, homicide, akathisia and agitation, mania and delirium, severe anxiety, bizarre thinking and reasoning psychosis, and hallucinations. Neuroleptics, used to treat psychosis, are linked with violence, suicidal and homicidal behaviour leading to completed suicide and homicide.
So why do some individuals respond well to drugs and others not?
A major factor for varied drug responses is due to individuals’ differing genetic makeup, known as pharmacogenetics or drug metabolism. Although there are many metabolising systems in the body, the major metabolising systems for psychiatric medications are the CYP450 enzyme system, principally in the liver, and the serotonergic system. Both systems have an important role in the outcome of treatment, ADRs and efficacy.
450CYP Enzyme System
75% of psychiatric drugs including antidepressant and neuroleptic medications, are metabolised through CYP2D6, which is one of the most variable metabolizing enzyme pathways known. Other pathways that metabolise antidepressants and neuroleptic drugs include CYPC19, CYPC9, CYP1A2, CYP 3A4 and CYPA5.Genetic variations, known as alleles, classify individuals as either being Poor Metaboliser (PM), Intermediate Metaboliser (IM), Extensive Metaboliser (EM) or Ultra Metaboliser (UM) genotypes. PMs have two non-functional alleles and IMs have one non-functional allele plus one diminished allele or two diminished alleles or two partially active alleles. UMs have more than two active gene copies on the same allele, or increased expression of a single allele. EMs have one or at the most two functional alleles with ‘normal ‘activity.Genetic variability affects psychiatric medication outcomes. PMs and IMs incur neurotoxicities leading to violent acts, as do UMs with prodrug use. EM individuals are likely to have a therapeutic response without neurotoxic ADRs.EMs determine the window of opportunity for a drug therapeutic level and sets the recommended drug dosage. This is important, as drug companies do not specify drug dosage for UMs, IMs and PMs, which explains why these individuals do not respond well to standard drug doses.
Combined PM and IM frequency via CYP450 2D6:
· 26% Caucasians
· 40-50% African-Americans
· 50% Africans
Statistically, Black Minority and Ethnic (BME) populations have greater difficulty metabolising psychiatric medications compared with White and Asian population, due to the higher frequency of lower metabolism at CYP 2D6. BME groups are four times more likely to experience psychosis than Caucasians, with African Caribbean people three to five times more likely than any other group, of being diagnosed with schizophrenia and admitted to hospital.
Serotonergic System
Antidepressants and neuroleptics are regulated through the serotonergic system. The serotonin system consists of the Serotonin Transporter Gene and serotonin receptors (5-HT). As with the CYP450 system, the serotonergic system has genetic variations that affect outcomes.
Serotonin Transporter Gene and Antidepressants
Genetic variations in the promoter region of the Serotonin Transporter Gene (5HTT-LPR) are coded as L/L (2 long alleles), L/S (a long and a short allele) or S/S (2 short alleles). Those individuals with the L/L code have a ‘normal’ gene activity and respond well to antidepressant medications. In contrast individuals with the short allele have slower gene activity, resulting in a reduction of serotonin transmission. Both L/S and S/S individuals treated with antidepressants have poor outcomes, and a ‘powerfully predicted non response’. Emerging antidepressant ADRs are inevitable for individuals with the short allele.
Individual response to neuroleptic medication is also affected by 5HTT-LPR variations. 50% of individuals coded L/L receiving neuroleptic treatment with haloperidol experienced parkinsonian side effects; however the incidence of parkinsonian side effects for L/S and S/S allele individuals rose to 62.2% and 83.1% respectively.
What is the frequency of 5HTT-LPR Gene Variants?
Population Frequency of 5HTT-LPR Variations
Individuals coded with (S/S) and (S/L) genotype:
Caucasians S/S (39%)
Caucasians S/L (52%)
East Asians S/S (49–74%)
Native Americans S/S (42%)
African Americans S/S (7–17%)
Individuals coded with L/L genotype:
Caucasians (29–43%)
African Americans (45–56%)
Native American (10–14%)
East Asian samples (1–13%)
Serotonin Receptors
There are 14 types of 5-HT receptors that can be targeted by antidepressants and neuroleptics. However the 5-HT 2A serotonin receptor variant, in particular, is associated with individual poor response and increased risk of ADRs when treated with antidepressant selective serotonin reuptake inhibitors. This same receptor variant has been linked to poor response from some individuals having neuroleptic treatment.
Genotype Testing
CYP450, 5HTT-LPR and 5-HT receptor genotype testing can determine individual status for metabolizing psychiatric medications. Prescribers do not currently conduct genotype testing prior to treatment and take no account of whether or not individuals are able to efficiently metabolise medication. The current practice is to work on a crude trial and error basis when treating individuals with psychiatric medication.
Genotype testing of an individual prior psychiatric medication treatment would enable assessment and prediction of the potential for neurotoxic behavioural ADRs in line with genotype status as depicted in the table above. The genotype test is a simple blood or swab test and in 2013 the standard cost of a test was £30. Retrospective genotyping for psychiatric drugs has demonstrated that there would have been a significant reduction in the financial outlay/cost based on the use of inappropriate medication and subsequent unnecessary healthcare costs.
Genotype testing is used by pharmaceutical companies during medication trials (stages II - 1V), to de-select individuals who are PMs and potentially liable to suffer severe ADRs. This practice includes trials with psychiatric medication and is done for reasons of safety, and also to show medication in its best light.
Discussion
Neurotoxic behavioural ADRs are not understood in psychiatry. When individuals respond violently to psychiatric medication the practice in psychiatry is to increase the dose and/or polypharmacy. This practice is completely futile as further medications increase neurotoxicities. Individuals are theoretically being overdosed, albeit unwittingly by prescribers. Prescribing of psychiatric medications is done on a crude trial end error basis. Individual suffering is immense. This needs to change.
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