Monthly Archives: May 2022

Yesterday was the Manager’s Hearing I had been asking for on many occasions as Nearest Relative. You will not be surprised to learn that I was completely ignored as I have been for months on end by the Mental Health Office. It could be that the MHA office are told my only point of contact is as Carers Champion but what right do a MHA office have to ignore you as Nearest Relative who has called for a Manager’s Hearing. A full investigation needs to be undertaken.

I have had another patronising ticking off by the person who is said to be a “carers champion” in that I am supposed to go through her for everything. However this is just like a messenger service where you get no answers and the RC above has been one of 3 who have avoided S17 leave and a junior Dr is then put in charge of a meeting because the RC does not have the time of day for you. Therefore you do not get treated fairly. It is just delaying tactics.

I have found out that a capacity assessment was carried out on Elizabeth without her knowledge by a nurse called G only recently.

Clearly noone wanted me to attend yesterday’s manager’s hearing so what they did was they worked together putting up barriers and perverting the course of justice legally as I as Nearest Relative would be entitled to have a manager’s hearing but instead this was done behind my back and the only reason I knew about it was because Elizabeth told me even down to the time it was taking place and I had been invited by her.

There is such ignorance or blatent disregard to the MHA under Ash Villa it makes this facility not fit for purpose.

The other thing is that Elizabeth has shared with her family her care plan.

From reading this disturbing care plan is revealed the hopelessness of her situation in this dreadful institution – the worst we have ever come across and NHS run. There is no respect for carers and there is no respect for the patient and her life is at risk and I want everyone to know about it as Elizabeth has actually said she is going to die in there.

Time and time again we have asked for CQC intervention at this facility and nothing is ever done. They are due an inspection. I fear that this facility is unsafe. I have now turned to my MP, Victoria Atkins and Healthwatch Lincs. The matter is being passed on to the DoH.

The whole situation has led to me becoming very ill, to the point I cannot visit right now. Thought I had covid but yesterday’s test was negative so it must be flu but this is the effect on you as a carer when you read the care plan that highlights ambulance and fire brigade notified due to her being bariatric and high risk of mortality. They are also missing the point about takeaways – deprived of exercise and meaningful contact with family Elizabeth could be held prisoner under the MHA on the say so of completely unaccountable professionals for years and years on end – a prisoner deprived of all human rights under LINCOLNSHIRE PARTNERSHIP TRUST and what on earth is happening about our complaint? If someone is in bed all day trying to keep out of the way that person is missing meals anyway and if that vulnerable person happens to get up in the night and dares to ask for a drink then they get callously told to get back into bed. I have been subject to severe bullying to the point where a member of staff tried to say I had assaulted a member of staff and in a letter by ward manager accused of threatening behaviour and now I want everything on me under GDPR rules. I have now had to apply for all CCTV footage to clear my name – what could have justified 3 x police cars coming out? I was standing beneath CCTV cameras alone at the time. Not for the first time, this facility whose professionals completely lack communication skills resort in bullying tactics using the police as if they are not busy enough. Anything to blacken your character that is how bad it is and I would welcome a full enquiry.

It was a big mistake coming to this area thinking that MH care would be good and for a long time I kept quiet, not wanting to rock the boat. Right now I couldn’t care less any more as I want something done about the situation before it is all too late now that I have seen the extent of risk to my daughter’s life. There are too many cases of people dying in these institutions who deprive patients of basic human rights and exercise leaving them to go downhill.

What was decided at the Manager’s Hearing was to raise medication to 400 mg near maximum with complete disregard to the fact that Elizabeth is of high risk of mortality and adverse reaction as proven by genetic tests P450 liver enzyme. Even Cygnet respected this certificate but there is no respect at Ash Villa – a hospital that destroys lives.

I am now going to share with you some disturbing but educational information. Elizabeth now said to have no capacity in a capacity assessment conducted by nurse G.

From: b.

sent: Tuesday, May 24, 2022 1:28 pm
To: susanb ; Subject: Re: Managers hearing


You might be interested in the contents of this lecture, especially from slide 38 which explains the duties of Health Informatics Professionals.

As NR and with Elizabeth’s written consent you are entitled view the capacity report which must give full reasons for the decision on capacity.

Capacity is a legal construct and not a medical one.  As Elizabeth’s NR you can challenge the capacity report.  See the Bournewood case (also attached).


From: B
Sent: 24 May 2022 23:37
To: susanb255

Subject: Dosing and P450 metabolism

Very important paper on poor metabolisers

“If a patient on psychotropic medication develops symptoms of delirium or of akathisia, every psychiatry textbook I have been able to identify advises dose reduction or change of medication to one more suited to the patient. The problem occurs on change of dose up or down and has been associated along with other extra pyramidal side effects, as well as sensitivity”

“The half-life of the zuclopenthixol depot preparation is 19 days, so if it is given fortnightly, toxicity will eventually develop”. 

it is clear that Ash Villa staff have no idea about dosage and blood serum levels. they appear to be working on dosing regimes 20 years out of date

Clinical Case Studies and Reports

Clin Case Studie Rep, 2018 doi: 10.15761/CCSR.1000112 Volume 1(2): 1-8

ISSN: 2631-5416

The effect of CYP450 2D6*4 mutation on medication

response: Two cases with different outcomes

Yolande Lucire*

Forensic and medico-legal psychiatry, Pharmacogenomics and Personalized Medicine, Level 5, 203-233 New South Head Road, NSW 2027, Australia


This paper describes different outcomes for genetically similar persons bearing the mutation CYP450 2D6*4. They were treated with the same drugs; their condition

was called “schizophrenia” and in both cases the exclusion criterion essential for that diagnosis was ignored

*Correspondence to: Yolande Lucire, Forensic and medico-legal psychiatry,

Pharmacogenomics and Personalized Medicine, Level 5, 203-233 New South Head

Road, NSW 2027, Australia, Tel: 0411158246, E-mail:

Received: August 07, 2018; Accepted: October 25, 2018; Published: October

31, 2018

Substance/general medical condition exclusion: The disturbance is

not due to the direct physiological effects of a substance (e.g., a drug of

abuse, a medication) or a general medical condition [1].

These cases support the notion that treatment of cannabis-induced

disorders with drugs that have been tested for schizophrenia and

bipolar illness may be counterproductive [2].

The paper highlights a need for doctors to diagnose to the criteria,

and to be aware of (a) the DSM decision tree for the differential

diagnosis of hallucinations, (b) the principles of pharmacogenetics, (c)

the high prevalence of diminished metabolic capability for cytochrome

P450 metabolised drugs, and (d) symptoms of neuroleptic toxicity,

including akathisia [3,4]. It points to the need to seek advice from

pharmacologists and pharmacogeneticists and not from peer clinicians

who may also lack relevant expertise.

Patient C

C, 33, a university graduate, intermittently employed, had mild

brain injury at birth and chicken pox encephalitis at 20. (Brain

injury can cause akathisia and remains a risk factor for akathisia [5].

He smoked cannabis rarely. He was unable to say why he had been

prescribed fluvoxamine by his general practitioner (GP). He soon

developed a variant of erotomania (a side effect of all serotonergic

antidepressants, reported thus in the Physicians’ Desk Reference) in that

he became preoccupied with a former girlfriend, ruminating on what

might have been had he married her. He also harassed a friend of the

former girlfriend, driving in his street and breaking windows [6].

Charged with a stalking offence, he presented for an s32 report

under the NSW Mental Health (Criminal Procedure) Act 1990 that

encourages diversion from the criminal justice system of persons

suffering from a mental illness or condition. He was diagnosed with

“paranoid schizophrenia,” by his account in a 20-minute interview.

Olanzapine was added to fluvoxamine and when he became increasingly

depressed, restless and violently suicidal it was increased to 30 mg

daily while fluvoxamine was increased to 200 mg, and he continued to

deteriorate. Zuclopenthixol depot was added to 200 mg fortnightly and

cigarette smoking increased to 40 a day. There was no improvement

in his behaviour, so he was imprisoned on a certificate that called his

illness schizophrenia but held him responsible for his actions [7].

On release, he continued to drive obsessively in his quarry’s street

(indicative of both organic obsessional disorder and erotomania) and

was about to be imprisoned again on his treating psychiatrist’s certificate

attesting to his intentionality, when he made a suicide attempt and was

hospitalised with deep vein thrombosis [8]. He had 35 mg diazepam

daily added but it gave no relief. Warfarin was added to the above for

the deep vein thrombosis. Zuclopenthixol was suspended in hospital.

The author diagnosed akathisia and erotomania and wrote a Section

32 report, and this avoided his receiving a second prison sentence. Four

years later, fully recovered, on no medication and showing no sign of

schizophrenia and working in three jobs, C described his mental state

at that earlier time:

I figured I had nothing to live for. I was feeling like I had no future

and I did not want 40 more years of this. I thought of hanging myself or

slashing my wrists. I do not know how often. I also thought of crashing

into a truck or jumping in front of a train. I was never suicidal before I

had fluvoxamine. I smoked heaps.

I had the injection because I thought it would keep me out of jail.

I could not sit and read, I could not focus on anything, I was restless,

and I could not sit down. The last five days in jail were hard. I could not

sleep at all, that carried on after I went out of jail. I could not do anything,

could not sit down and watch TV. I had to get up and pace around, a

hundred times a night. After I got out of jail, the world completely

changed. Home to me has always been a haven. For those eight months,

I had hell inside.

On legal advice, the author advised C’s mother that three

psychiatrists, one of whom was a personal friend of C, shared her view

that he had did not have schizophrenia or anything like it. His mother

researched akathisia on the Internet and requested a change of doctor

in view of a total breakdown of the doctor/patient relationship.

Lucire Y (2018) The effect of CYP450 2D6*4 mutation on medication response: Two cases with different outcomes

Clin Case Studie Rep, 2018 doi: 10.15761/CCSR.1000112 Volume 1(2): 2-8

Frustrated by administrative inaction, the mother made a

complaint to the Medical Board of NSW (MBNSW), which declined to

investigate it. However, the Board chose instead to pursue the author for

holding this allegedly minority view through a Professional Standards

Committee (PSC).

The PSC found the author to have “inappropriately” destroyed

the mother’s confidence in the treating doctor, notwithstanding that

the mother gave evidence that she and her son had none. The author

was criticised for having insufficient respect for the diagnoses of her

colleagues and this was based on peer reviews, of peers who did not

acknowledge product information (PI).

The PSC unilaterally, without giving notice, decided to publish its

report where no such PSC matters had ever before been publicised. The

author was publicly humiliated as having “insufficient knowledge” and

as lacking respect for her colleagues’ diagnoses. This decision was based

on the author’s holding what the PSC considered to be a “minority

view” concerning antidepressant side effects and interactions, even

though four files of evidence that antidepressants induced psychosis

and suicide in some people were provided, together with PI and

relevant public health advisories. The MBNSW recommended that the

author seek the counsel of a colleague. The decision was misreported

in The Sun Herald to the effect that the author had been “ordered into

treatment by the Medical Board”.

C was allowed to reduce all his medications slowly. Four years

later, C works in three jobs and shows no signs of schizophrenia. He is

stigmatised by his criminal record and traumatised by the experience of

the painful mental state of some duration, but relieved to know that he

had suffered from a medication side effect rather than a mental illness.

Patient A

While a 16-year-old schoolboy in 2004, smoked cannabis, used

other illicit drugs and experienced hallucinations. He was prescribed

risperidone and deteriorated [11]. Olanzapine was added at both

variable and increasing doses. This produced worsening depression

and continuing hallucinosis. Fluvoxamine was added, and he became

violently suicidal.

Soon added in series and parallel were benztropine, haloperidol,

chlorpromazine, lithium, risperidone and its depot, consta, quetiapine;

previously ineffective treatments were recirculated in escalating doses.

Patient A remained violently akathisic, intensely suicidal,

aggressive and intermittently homicidal. He was seen tramping along

the motorway at night in the rain before he made a homicidal attack on

his stepfather in 2005. He spent four months in an interstate clinic. He

assaulted his psychiatrist in January 2006 and was imprisoned.

He made many suicide attempts and repeatedly complained that

his medication made him feel suicidal. His unremitting death wish was

recorded as “I cannot function on this medication. It makes me want to

kill myself ”. He continued to smoke cannabis, insisting it helped him,

and his tobacco use increased [10].

Zuclopenthixol depot was reinstated in prison at 400mg fortnightly

in the face of his protests and history. After his release it was increased

to 600 mg on one occasion and enforced by a Community Treatment

Order (CTO).

His penultimate suicide attempt from a cliff a day after his release

from hospital on a CTO caused police to return him to hospital where

the diagnosis of schizophrenia was amended to “antisocial personality”.

Two days later and after 4 years of treatment, he was found dead at the

bottom of the same cliff, in December 2006. No root cause analysis was

provided for the relatives.

The coroner gave the author very limited access to clinical records

and treatment sheets and refused permission to make copies. He

determined, on a report from police, that A had not committed suicide

at all but had been “skylarking”. On that basis, he declined to hear expert

evidence prepared for an inquest and did not respond to a suggestion

that genetic testing for CYP450 activity was needed. The issue of the

coroner perhaps having a conflict of interest was raised with both the

Chief Coroner and the Judicial Commission because, as a magistrate,

the coroner had previously been involved with A and because he was

involved with that health service on a daily basis. Both found that no

conflict existed.


CYP450 testing revealed that both patients had a “null” metaboliser

gene 2D6*4 (in the case of A, after exclusion of his parents’ genotypes).

Both had received multiple interacting drugs that compete for

CYP450 2D6, a metabolising resource that is finite and may be limited

by genotype or P450 inhibitors or other health problems. When

a metabolic pathway is already in limited supply, lower doses are

recommended because the drug is likely to reach blood levels above the

“therapeutic window of opportunity’ for each drug” [11].

Both polypharmacy (endemic in Australian psychiatry) and the use

of higher than recommended doses are counterproductive. Akathisia

and other organic neurotoxic states supervene, and patient does not

recover. Standard doses of a single substrate accumulate in diminished

metabolizers and lead to blood levels higher than the therapeutic

window. The concurrent use of Cytochrome P450 inhibitors hastens

that process. More frequent dosing than permitted by the half-life of

each drug results sooner or later in neurotoxic state and hallucinatory


Both C and A were taking, simultaneously, several drugs requiring

the 2D6 pathway, in larger than recommended doses: olanzapine at 30

mg daily is 15 times the normal starting dose, fluvoxamine 200 mg is

4 times, zuclopenthixol injections at 600 mg fortnightly is 8 times the

standard dose. Eli Lilly does not guarantee the safety of olanzapine over

20 mg.

The notion that patients who have not responded to antidepressants

are ultra-rapid metabolizers (UMs) underpins the practice of increasing

a medication or adding another. However, it is many times more

likely that such patients are poor (PMs) or diminished metabolizers

(DMs), and as such need to have the dose decreased. From 5% to 14%

of Caucasians are PMs of 2D6 and a further 20% have diminished

metabolism. PMs may experience potentially lethal side effects within

days, whereas the slower metabolism of intermediate metabolizers

(IMs) causes a slow build-up of blood level while the chemistry of the

brain tries to follow. Rapid changes of psychoactive substances cause

violent mood and behavioural shifts, confusion and delirium in IMs.

UMs comprise only 1-10% of Caucasians [12].

If a patient on psychotropic medication develops symptoms of

delirium or of akathisia, every psychiatry textbook I have been able to

identify advises dose reduction or change of medication to one more

suited to the patient. The problem occurs on change of dose up or down

and has been associated along with other extra pyramidal side effects,

as well as sensitivity.

Lucire Y (2018) The effect of CYP450 2D6*4 mutation on medication response: Two cases with different outcomes

Clin Case Studie Rep, 2018 doi: 10.15761/CCSR.1000112 Volume 1(2): 3-8

Akathisia is a subjective desire to be in constant motion. A

manifestation of drug sensitivity, it may be confused with psychotic

agitation and incorrectly treated by increasing the dose of the offending

medication. The symptom subsides promptly when the offending

medication is discontinued and replaced by another one better tolerated

by the patient [13].

The subjective distress resulting from akathisia is significant and

can lead to non-compliance with neuroleptic treatment. Akathisia may

be associated with dysphoria, irritability, aggression or suicide attempts.

Worsening of psychotic symptoms or behavioral dyscontrol may lead to

an increase in neuroleptic medication dose, which may exacerbate the

problem. Akathisia can develop very rapidly after initiating or increasing

neuroleptic medication [14].

Substrates of 2D6 also include tricyclics, tetracyclics, amphetamines,

chlorpromazine (which has other pathways as well), fluvoxamine,

haloperidol, risperidone, quetiapine and, in part, olanzapine.

Cannabis, involved in both these cases, is metabolised by

cytochromes 3A4, 2B6 and 2C9. It is an inhibitor of 3A4 and induces

1A2. It remains in the body for up to 2 months, depending on the

amount used. Like tobacco, which induces IA2 and caffeine induces the

metabolism of psychiatric drugs as well as producing is own euphoric

neurotoxic state [15,16].


Pharmacogenetic theory and data provide an arena in which

adverse drug reactions can be explored, understood, theorised and

ultimately predicted [17]. The development of pharmacogenetics has

ushered in a paradigm shift of massive proportions in medicine and,

particularly, psychiatry. It is predictable that this shift is resisted [18].

Pharmacogenetics has featured in American textbooks of psychiatry

since 1999, but it has not been taught in Australia until very recently

[19]. Australia is the last of the U.K., Canada and the U.S. to inquire

into the potential of pharmacogenomics, by means of a report that,

unaccountably, expects a lead period of 10 years to full implementation

[20]. “One size does not fit all” appears to be its theme.

Delay in implementing this education will result in more hospital

admissions for adverse drug events, already a major source of costs

in the U.S., as well as prolonged stays, misdiagnoses and unnecessary

deaths and medication-induced suicides and homicides [21-24]. No

psychiatrist can practise safely without this knowledge.

It may be that lack of this knowledge accounts for psychiatry’s

insatiable demand for resources, and for the increasing suicides, suicide

attempts, homicides and violence committed by patients under mental

health care [25,26]. Providing more resources for psychiatry without

questioning the source of this epidemic of seemingly intractable mental

ill health is unlikely to resolve the problem [27,28].

Metabolic pathways

Nearly 90% of drugs are metabolised by the cytochrome CYP450

family of enzymes, 1000 enzymes determined by 40 genes [29]. They

transform “exotoxins” into products that can be metabolised further

(stage II metabolism) and prepared for excretion by the kidney or

liver. Diminished capacity to metabolise drugs results in blood and

brain levels above the sometimes-narrow therapeutic window. These

concentration-dependent adverse effects manifest as neurotoxic

Drug Therapeutic window [31] Metabolism/transport site Enzymes/process inhibited Enzymes Induced/

chlorpromazine 30-300 ng/ml 2D6, 1A2, 3A4, UGT1A4, UGT1A3 2D6a

clomipramine 175-450 ng/ml 1A2, 2C19, 2D6, 3A4 2D6, 1A2, 2C19

cannabis 3A4, 2B6 and 2C9. 3A4 1A2 and 2E1

carbamazepine 6-12 μg/ml 3A4, 2B6, 2C8, 2E1, 2C9, 1A2, UGT2B7,

ABCB1 ?2C19 3A4, 1A2, 2B6, 2C8, 2C9,


clonazepam 20-40 ng/ml 3A4, acetylation

clozapine 350-600 ng/ml 1A2, 3A4, 2D6, 2C9, 2C19, FMO3 2D6c

diazepam 300-400 ng/ml (incl. metabolites) 3C19, 3A4, 2B6, 2C9, glucuronidation

doxepin 50-150 ng/ml 1A2, 2D6, 2C19, 3A4, UGT1A4, UGT1A3 1A2, 2C19, 2D6

fluphenazine 0.5 – 2 ng/ml 2D6a, 1A2 2D6a, 1A2

clopixol >2 ng/ml 2D6

fluvoxamine # 150-300 ngms/ml 2D6, 1A2 1A2a, 2C19a, 2B6b 3A4b, 2D6b, ABCB1

haloperidol 5-17 ng/ml 2D6

lithium 0.5–1.2 mmol/l

lorazepam 10-15 ng/ml UGT2B7, ?other UGTs

olanzapine #

half-life 21-54 mean 30 hrs. 9-25

ngms/ml [32]

100 ngms/ml.

1A2, 1A4 partly by 2D6 and UGT3A4,

UGTs, ABCB1 None known

paliperidone # ? 2D6, 3A4 None known

perphenazine 0.6 – 2.4 ng/ml 2D6, 3A4, 1A2, 2C19 2D6, 1A2

quetiapine # 70-170 ng/ml 3A4, sulfation, ABCB1

risperidone 20-60 ng/ml (including 9-hydroxy) 2D6, 3A4, ABCB1 2D6b

risperidone consta ditto ditto ditto

temazepam UGT2B7,? other UGTs, 2C19, 3A4

valproate 50-100 μg/ml Complex: 2C9, 2C19, 2A6, UGT1A6, 1A9,

2B7 2D6, 2C9, UGTs, 1A4, 1A9, 2B7, 2B15, epoxide

zuclopenthixol 4-50 ngms/ml 2D6 ? 2D6 (European drugs are less well researched than

those used in the U.S.)

Table 1. Drugs metabolic pathways, inducers and inhibitors (of drugs used in these cases) from several sources [30]

a Potent inhibition of enzymatic pathway. b Moderate inhibition c Mild inhibition. Inhibition is also dose-related; mild inhibitors in high doses act as strong inhibitors. # Not licensed for use

in children or adolescents by the United States Food and Drug Administration (FDA) or its Australian equivalent, the Therapeutic Goods Administration, (TGA.

Lucire Y (2018) The effect of CYP450 2D6*4 mutation on medication response: Two cases with different outcomes

Clin Case Studie Rep, 2018 doi: 10.15761/CCSR.1000112 Volume 1(2): 4-8

brain syndromes. Many psychiatric patients are prescribed more than

one drug, with each drug increasing the risk of a pharmacokinetic

interaction. Table 1 shows metabolic pathways inducers and inhibitors,

and it has been brought up to date from primary sources.

There is an argument that patients would benefit from CYP-based

genotyping prior to the prescription of these drugs. Up to 79% of

islanders from around Vanuatu have PM status at 2C19 and around

25% of Caucasians have “diminished metabolism,” at 2D6, and for

them a drug metabolised by that pathway is likely to be or becomes

problematic and might be lethal [33]. East Asians have a 50% prevalence

of the IM gene P2D6*10, as well as up to 35% prevalence of the PM

gene 2C19*2, putting that population at a huge risk from antidepressant

therapy. Testing for CYP450 2D6, 2C19 and 2C9 costs less than $150.

Basic knowledge of the ethnicity-based prevalence of mutations

is essential to counter a common belief among psychiatrists that

worsening depression and suicidality in a patient indicate a lack of

response, and that the patient is therefore a UM. Such reasoning leads

to more and more medication being given. In fact UMs are rare, often

cited in Caucasian populations as 3%.

Most adverse drug reactions occur as a result of simple over-dosing

of genetically normal persons whose cytochrome metabolism has been

inhibited or induced, leading to undesirable bloods levels. There are six

patterns of drug–drug interactions and some are described below [34].

The first effect of making testing available might be to make prescribers

aware that adverse drug events are both explicable and avoidable.

Conditions affecting metabolism include co-prescribed medications

that induce or inhibit the enzymatic pathways, age, nutrition, stress,

liver disease, hormones (natural and extraneous), the sequence in

which medications have been prescribed or taken away, the route of

administration, the range of half-life in any population, the potential for

multiple metabolic pathways, the size of the therapeutic window within

which the drug may be effective and outside of which it is ineffective or

toxic or both, the duration of therapy and duration of inhibition which

may persist after discontinuation [35]. This paper does not deal with the

genetics of transporter and receptor systems.

3A4 is the “workhorse” of the P450 system, which means that

many drugs are substrates of it, and there are many inhibitors and

inducers. There are no PMs but there is 10–30-fold variability in the

efficacy of its functioning. 1A2 metabolises psychiatric drugs and is

induced by tobacco smoking, which also hastens the metabolism of

other psychiatric medicines not known to be metabolised by these

cytochromes. This seems to explain why patients on psychiatric

medications increase their tobacco use: to more quickly metabolise

medicines that have unpleasant or intolerable adverse effects.

Information grows and changes daily. All three are involved in the

metabolism of common antidepressants and antipsychotics [36].

Table 2 is compiled from research done by health insurers Blue

Cross Blue Shield who have found such testing to be cost effective. The

table lists the effects of genetic polymorphisms of CYP450 enzyme genes

on drug metabolism and describes relationships between genotype and

phenotype, as relevant for psychiatric drugs, many of which inhibit the

enzymes required for their metabolism [37-39].

A more useful concept adopted by the Diversity Health Institute

(DHI) at Cumberland Hospital is to describe both PMs and IMs as

having “diminished CYP 450 metabolism”. This is because the inhibition

or absence of one cytochrome may divert into metabolism by others,

which may or may not be available in any given individual. There can

be 1,000% variance in the metabolism of 2D6 drugs between PMs and

UMs and a 30-fold variance in metabolism by the enzyme cytochrome

3A4 [44].

Metaboliser status Metaboliser



status Genotype Phenotype Expected drug effects Prodrug concerns

2D6 2C9 2C19 2D6


(poor) *3, *4,


*5, *6, *7, *8,

*11, *15, *19,

*20, *40


*2 and *3


*2, *3

PM Homozygous or

compound heterozygous

for deficiency alleles.


“Standard” doses may lead

to toxic drug concentrations

and serious adverse reactions,

including suicide and

homicidal behaviours [40].

May not reach therapeutic levels of

active drug, i.e. does not convert

prodrugs into the analgesic morphine, so

they are ineffective. Conversely removal

of a 2D6 inhibitor may lead to rapid

conversion and toxicity and death (the

Heath Ledger phenomenon)

IM (intermediate)

*10, *10XN,

*17, *17XN,

*9, *29, *36,

*41, *41XN


*1 and *2

or *3

or *3/*3


Homozygous for

two reduced activity

enzyme genes alleles

or heterozygous for an

inactive allele and a

reduced activity allele.

These may become PMs or

diminished metabolisers in the

presence of specific inhibitors.

A reduced dose of a single drug

is recommended, and IMs are

unable to metabolise multiple

drugs requiring that pathway.

Higher doses may lead to toxic


May experience some consequences

of PMs.

EM (extensive)

“wild type”

*1, *2, *35


*1, *1


19*17 [41]

Two copies of active

enzyme gene alleles.

Up to 80% of EMs at 2D6

become PMs in the course

of treatment with strong

inhibitors such as paroxetine

[42], fluoxetine and sertraline

and with mild inhibitors in

high doses.

Standard doses lead to

expected drug concentrations

and response.

Expected response to standard dose.

UM (ultra-rapid)

Only 2D6 has




More than two active

copies of active enzyme

gene alleles.

May not reach therapeutic

levels of active drug due to

rapid clearance.

May reach higher than expected

concentrations of active metabolite,

which may cause adverse reactions,

including death from morphine.

Notes: Genotype refers to the genetic makeup of the subject; phenotype refers to the way that the genotype manifests under a variety of conditions [43].

PM = poor metabolizer; IM = intermediate metabolizer; EM = extensive metabolizer; UM = ultrarapid metabolizer. Prodrugs such as tramadol, oxycodone, codeine need to be activated,

i.e. catabolised to morphine by 2D6.

Table 2. Genotypes phenotypes and predictions

Lucire Y (2018) The effect of CYP450 2D6*4 mutation on medication response: Two cases with different outcomes

Clin Case Studie Rep, 2018 doi: 10.15761/CCSR.1000112 Volume 1(2): 5-8

Mutation P450 2D6*4 was found in more than one third of 30

persons tested at the author’s request because they had experienced

severe violent akathisia, suicidal behaviours, homicidal aggression,

behavioural dyscontrol, delirium with hallucinosis, and cognitive

impairment on standard doses of antidepressants (to be reported

elsewhere). The most publicised of these is Melbourne mother and

student Rebekah Beddoe, who published her harrowing account of

three years on antidepressants and antipsychotics, prescribed and coprescribed

by psychiatrists who failed to recognise her problems as side

effects [45].

Drugs relevant to these two cases


Side effects are listed in each drug’s PI, easily accessible through the

website of the U.S. FDA [46]. PI published in the U.S. is substantially

larger and more detailed than that available in Australia. It categorises

“frequent” adverse events as occurring in at least 1/100 patients,

“infrequent” events as occurring in 1/100 to 1/1000 patients and “rare”

events as occurring in less than 1/1000.

By that standard, in clinical trials that were presented to the U.S.

FDA to get olanzapine licensed, death and suicide on olanzapine

occurred at a rate of 1 in 208, which is “rare.” No deaths occurred on

placebo. Khan et al. counted the suicides in antipsychotic trials 2001

but this paper failed to alert the psychiatric community [47].

A rate of 27% akathisia in a trial of olanzapine 10 mg was balanced

by an equally high incidence of akathisia on placebo [49]. This

indicated that Eli Lilly either did not know what they were talking

about (as akathisia is always a medication-induced phenomenon), or

the participants had not fully recovered from whatever they had been

taking before entry to the trial. This been the subject of successful

litigation for fraudulent promotion of olanzapine, such as USA vs. Eli

Lilly which rewarded the whistleblowers with US$800 million [50].

The half-life of olanzapine ranges from 21 to 54 hours (5th to 95th

percentile; mean of 30 hr), and apparent plasma clearance ranges from

12 to 47 L/hr (5th to 95th percentile; mean of 25 L/hr). This means

that sooner or later more than 50% of users will become toxic on it if

the dose is not reduced. The half-life and clearance of olanzapine varies

among individuals on the basis of smoking, status, gender and age.

According to Eli Lilly Australia the therapeutic window of

olanzapine is 9-25 ngm/ml, but other figures are mentioned elsewhere


In drug company terms, “frequent” refers to adverse events affecting

more than 10% of users. The following effects are listed in the 2007

Olanzapine PI. (Olanzapine is licensed for bipolar disorder.)

Nervous System — Frequent: abnormal dreams, amnesia,

delusions, emotional lability, euphoria, manic reaction, paresthesia and

schizophrenic reaction;

Infrequent: akinesia, alcohol misuse, antisocial reaction, ataxia, CNS

stimulation, cogwheel rigidity, delirium, dementia, depersonalization,

dysarthria, facial paralysis, hypesthesia, hypokinesia, hypotonia,

incoordination, libido decreased, libido increased, obsessive compulsive

symptoms, phobias, somatization, stimulant misuse, stupor, stuttering,

tardive dyskinesia, vertigo, and withdrawal syndrome;

Rare: circumoral paresthesia, coma, encephalopathy, neuralgia,

neuropathy, nystagmus, paralysis, subarachnoid hemorrhage, and

tobacco misuse.

Australian PI is incomplete, but it does inform that hallucinations

are “very common” (≥ 10%). That is, they occur in more than 1 in 10


Eli Lilly was fined $US 1.42 billion in the United States for criminal

and fraudulent promotion of the drug, with the judge raising the issue

of racketeering [51]. There are many lawsuits, settled and ongoing,

against Eli Lilly by State Attorneys General, as well as class actions for

suicides. With Eli Lilly reaping US $6 billion annually from olanzapine,

these fines and settlements are apparently insufficient to encourage the

company to change its promotional practices and have made no impact

on the behaviour of the company in Australia.

Four major studies (HGAD, E00, HGAJ and E003) were reviewed by

the U.S. FDA for the purpose of establishing the efficacy of olanzapine in

the treatment of chronic schizophrenia (acute exacerbation). According

to the U.S. FDA reviewers, the studies failed to establish any significant

effectiveness for olanzapine. Two thirds of clinical trial subjects dropped

out without completing 6 weeks. Even after they dropped out, 20 died,

12 by suicide. Concomitant drugs were permitted in these trials.

American PI also discloses that 67 of 3,100 subjects (including

a trial rejected by the U.S. FDA) took overdoses of olanzapine, but it

is silent on whether these patients were considered to be suicidal or

confused. As “only one” died (of the overdose) these numbers are put

forward as evidence of olanzapine safety in overdose. However, a courtordered

investigation of Eli Lilly archives disclosed the deaths and

suicides in the five clinical trials that were presented to the US FDA to

get it licensed [52]. The figures are shown in Tables 3 and 4.

One in every 145 clinical trial subjects for risperidone, olanzapine,

quetiapine, and sertindole died, a total of 36 deaths, most by suicide

[53]. Yet these deaths are not mentioned in the scientific literature nor

in PI. These deaths occurred even though two thirds of the olanzapine

subjects, nearly half of the risperidone subjects and 80% of the

quetiapine subjects did not complete the trials because the drugs were

poorly tolerated [54]. A rate of 27% akathisia in a trial of olanzapine 10

mg was reported, balanced by an equally high incidence of akathisia

on placebo [55]. This indicated that Eli Lilly either did not know what

they were talking about (as akathisia is by definition a medicationinduced

phenomenon), or the participants had not fully recovered

from whatever they had been taking before entry to the trial. Serious

adverse events affected 84 subjects who took risperidone.

None of this information appears in promotional material. Indeed,

47 serious adverse events in 87,000 users of olanzapine injectable in

Drug Number of Trial

Subjects Suicides Suicidal Acts


2500 (5000 started

and did not complete

6-week trials)

12 Not disclosed#

Comparator 810 1 (2) Not disclosed

Placebo 236 0 (1) Not disclosed

# However, U.S. PI (2003) states that 67 subjects out of 3100 overdosed on olanzapine but

does not disclose if these overdoses were due to suicide attempts or delirium, and “only 1


Table 3. Incidence of suicides and suicide attempts in antipsychotic clinical trials drawn

from U.S. FDA license applications [48]

Drug Patient No. Suicides Suicidal Acts

Risperidone 2607 9 43

Comparator 601 1 5

Placebo 195 0 1

Table 4. Antipsychotic Drugs, FDA Trials: Source FDA, David Healy [64]

Lucire Y (2018) The effect of CYP450 2D6*4 mutation on medication response: Two cases with different outcomes

Clin Case Studie Rep, 2018 doi: 10.15761/CCSR.1000112 Volume 1(2): 6-8

clinical trials included eight deaths. We are assured that the deaths

were not related to the olanzapine but, given the number of suicides

and deaths associated with the oral preparation, this seems to be

improbable. The U.S. FDA issued a “black box” warning about sudden

death from the new antipsychotic medications (including quetiapine

and aripiprazole) but only for the elderly, in spite of evidence that all age

groups are adversely affected [56,57].


Fluvoxamine is metabolised by 2D6 and 1A2. 1A2 is induced

by cannabis and tobacco, so smoking both gives relief from toxicity.

Fluvoxamine is best described as a pan inhibitor as it is a potent

inhibitor of 1A2 and 2C19 and a mild to moderate inhibitor of 2B6,

2C9 and 3A4. Fluvoxamine was used in both A and C with olanzapine,

in the face of advice against this combination in PI.

Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of

olanzapine. This results in a mean increase in olanzapine Cmax following

fluvoxamine of 54% in female nonsmokers and 77% in male smokers.

The mean increase in olanzapine Area Under the Curve (AUC) is 52%

and 108%, respectively. Lower doses of olanzapine should be considered in

patients receiving concomitant treatment with fluvoxamine.

Fluvoxamine was the drug prescribed to one of the children

who perpetrated the Columbine High School massacre. Most school

massacres have been perpetrated by children taking prescribed

antidepressants or medications for ADHD [58].

The “atypical” antipsychotics: Risperidone and Consta, its


Risperidone is metabolised by 2D6, has a shorter half-life than

olanzapine and may need twice daily administration. In trials presented

to the U.S. FDA, two thirds of subjects did not complete. Those subjects

have never been mentioned in PI or the scientific literature, but this

information is available at and was summarised

by Grace Jackson for litigation against Eli Lilly in Alaska [59]. None

of the dropout rates, suicides and attempts is disclosed to prescribers

and patients. As a result, treating doctors, not knowing or expecting

these drugs to be poorly tolerated because they were misinformed

about clinical trials, organise for Mental Health Review Tribunals to

enforce them, by injection, to persons who cannot tolerate them orally,

as happened with Patient C. Coroners, if not willing to examine the

activities of hospitals where they are deployed several times a week, can

create a situation where regulatory agencies cannot be made aware of

this epidemic.

The FDA trials and 52 subsequent studies evaluated in 2000, by

John Geddes of Oxford University demonstrated no clear evidence

that atypical antipsychotics were more effective or better tolerated

than conventional antipsychotics [60]. Thirty-six, that being one in

every 145 clinical trial subjects for Risperdal, Zyprexa, Seroquel,) and

Sertindole died; most by suicide, yet these deaths are never mentioned

in scientific literature or prescriber information. These deaths occurred

even though two thirds of Zyprexa, nearly half the Risperdal and 80%

of Seroquel subjects did not complete the trials because the drugs were

poorly tolerated [61]. A rate of 27% akathisia in a trial of Zyprexa 10 mg

was balanced by an equally high incidence of akathisia on placebo [62].

This indicated that Eli Lilly either did not know what they were talking

about (as akathisia events including suicide and homicide are always a

medication-induced adverse drug event or, alternately, the participants

had not fully recovered from whatever they had been taking before

entry to the trial. Serious adverse events affected 84 subjects who took


Zuclopenthixol decanoate

Zuclopenthixol depot has been associated with mental health

homicides, but invariably in combination, with other drugs that are

substrates of 2D6, as in the two cases presented here. The author has

personal experience of admitting patients homicidal on zuclopenthixol,

often co-prescribed with antidepressants and atypical (new generation)

antipsychotics. Several reports of this combination causing violent

attacks and homicidal behaviours were dismissed by the MBNSW, and

her report about patient C was turned into a complaint about her. As

did patients C and A here, many were experiencing akathisia, with

homicidal as well as suicidal ideation and acts [63-65].

The half-life of the zuclopenthixol depot preparation is 19 days, so

if it is given fortnightly, toxicity will eventually develop.


Patients C and A are but two of 48 people from the author’s clinical

and medico legal practice for 2D6, 2C9 and 2C19. Of the people tested,

42 were found to be poor or intermediate metabolizers and the rest

were overmedicated by PI standards. They were tested because they

experienced violent, homicidal and suicidal akathisia on standard

doses of antidepressants; one of them committed suicide, most had

made many attempts and three committed homicide on single doses of

antidepressants after 3 days, 2 weeks and 6 weeks on drugs that genetic

studies showed they could not metabolise; none of these three had a

psychiatric illness before or since, nor any history of violence. Only six

had normal CYP450 cytochromes, but they had either been given large

doses or had inhibitors in play. They had experienced many years of

counterproductive psychiatric treatments.

In the decade a following the introduction of the first of these

drugs, fluoxetine, in 1990, the population under mental health care in

Australia doubled and it has continued to increase. This is reflected in

Australian psychiatry’s vastly increased demands for resources [66].

Many ‘second generation’ drugs have followed this. The treatment of

schizophrenia with new drugs has increased mortality so care needs

to be taken before that diagnosis is applied, along with its remedies

[67-69]. Patients C and A are typical of persons under mental health

care who were not schizophrenic before they used drugs or received

treatment that induced symptoms similar to those of schizophrenia. Yet

testing for CYP450 mutations is available, for $140.00. That is the start

of appropriate personalised medicine.

Cannabis, its metabolites and 2D6

Cannabinols are metabolised by P3A4 and also inhibit it while

inducing 1A2. Sohayla et al. investigated the role of genetic factors in

cannabis dependence (hashish smokers) by CYP 2D6*4 genotyping of

46 habituated volunteers. Their findings suggest that genetic factors may

determine a person’s attraction to the effects of cannabis and other illicit

substances, but the mechanism is not obvious from existing research.

Diminished metaboliser status may cause cannabis to be experienced as

pleasurable, and if so, a propensity to substance-induced mood disorder

is a possibility. Cannabis smokers are said to have a tendency to become

psychotic later in life, but the mechanism is also obscure. Drug clinics

generally yield higher proportions of diminished metabolizers, for

reasons that have not yet been researched.

The common mislabelling of cannabis effects and other toxic

states as schizophrenia mania, major depression or bipolar disorder

Lucire Y (2018) The effect of CYP450 2D6*4 mutation on medication response: Two cases with different outcomes

Clin Case Studie Rep, 2018 doi: 10.15761/CCSR.1000112 Volume 1(2): 7-8

is counterproductive. The diagnostic criteria for all those disorders

contain an exclusion criterion for substance or medication use.

Misdiagnosis of mental and behavioural disorders as being attributable

to psychoactive substance use appears to contribute to the furphy that

cannabis causes schizophrenia.

Clinical prescriptions are available at F10-F19 “Mental and

Behavioural Disorders due to psychoactive substance” of the ICD 10,

still Australia’s official diagnostic system.

Drug clinic and cannabis users

The role of diminished P450 metabolism, specifically 2D6*4,

in cannabis smokers and the prevalence of mutations in drug clinic

populations generally bear further examination. One possibility is

that in diminished metabolism, 2D6 capacity may increase both

the pleasurable effects of cannabis and maybe other drugs and the

tendency to medication-induced psychotic phenomena. It may be that

they are already taking medication and are using cannabis to moderate

it. Suspicion of a high prevalence of diminished metabolizers at 2D6

among cannabis smokers might caution against the use of medicines

demand that substrate.

Misdiagnosis of mental and behavioural disorders due to

psychoactive substance use appears to contribute to the furphy that

cannabis causes schizophrenia.

Although ecological studies report an increase in schizophrenia

and bipolar illness, detailed analysis of such cases suggests that the

population that becomes psychotic on cannabis also develops neurotoxic

syndromes on olanzapine and risperidone, as well as antidepressants,

particularly those metabolised by 2D6.


1. Diagnostic and statistical manual of mental disorders: DSM IV (1992) Washington

DC: American Psychiatric Association 1994. And ICD International Statistical

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World Health Organization.

2. DSM-IV-TR® Handbook of differential diagnosis (2007) Ch. 2. Differential diagnosis

by the trees american psychiatric publishing.

3. De Leon, J Scott, Armstrong Cozza, Kl Med-Psych (2006) Drug-drug interactions

update. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for

CYP450 2D6 and CYP450 2C19 Psychosomatics 47:1.

4. Sachdev P (1995) Akathisia and restless legs, Cambridge University Press. Cambridge.

5. Physicians Desk Reference Oradell New Jersey: Medical Economics Company 2003.

6. Hálfdánarson Ó, Zoëga H, Aagaard L, Bernardo M, Brandt L, et al. (2017)

International trends in antipsychotic use: A study in 16 countries, 2005-2014. Eur

Neuropsychopharmacol 27: 1064-1076. [Crossref]

7. Teicher MH, Glod CA, Cole JO (1993) Antidepressant drugs and the emergence of

suicidal tendencies. Drug Saf 8: 186-212. [Crossref]

8. de Leon J, Susce MT, Pan RM, Fairchild M, Koch WH, et al. (2005) The CYP2D6 poor

metabolizer phenotype may be associated with risperidone adverse drug reactions and

discontinuation. J Clin Psychiatry 66: 15-27. [Crossref]

9. Zullino DF, Delessert D, Eap CB, Preisig M, Baumann P (2002) Tobacco and cannabis

smoking cessation can lead to intoxication with clozapine or olanzapine. Int Clin

Psychopharmacol 17: 141-143. [Crossref]

10. Bauman P, Hiemke C, Ulrich S, Eckermann G, Gaertner I (2004) The ANGP-TDM

expert group consensus guidelines: therapeutic drug monitoring in psychiatry.

Pharmacopsychiatry 37: 243-265. [Crossref]

11. Ingelman-Sundberg M (2005) Genetic polymorphisms of cytochrome P450 2D6

(CYP2D6): clinical consequences, evolutionary aspects and functional diversity.

Review. Pharmacogenomics 5: 6-13.

12. Kaplan HI, Saddock BJ, Freedman AM (1980) Comprehensive textbook of psychiatry.

Baltimore: Wilkins and Wilkins.

13. Diagnostic and statistical manual of mental disorders (DSM-IV) (1994) American

Psychiatric Association. Drug Induced Akathisia.

14. Cannabis is metabolised by 3A4, 2B6 and 2C9. It is an inhibitor of 3A4 and induces

1A2. It remains in the body for up to two years depending on how much was used.

15. Shirley KH, YY Penzak, SR Lam, YWF Spratlin, V Jann MW (2003) Correlation

of cytochrome P450 (CYP) 1A2 activity using caffeine phenotyping and olanzapine

disposition in healthy volunteers. Neuropsychopharmacology 28: 961-966.

16. Cozza KL, Armstrong SC, Oesterheld JR (2003) Drug interaction principles for

medical practice: cytochrome P450s, UGTs, P-Glycoproteins. Arlington, Va, American

Psychiatric Publishing.

17. Refinetti R (1997) Philosophy of science and physiology education. Am J Physiol 272:

S31-35. [Crossref]

18. Hales R, Yudofsky S, Talbot, JA (1999) Textbook of psychiatry. Third ed. Washington

DC: The American Psychiatric Press.

19. Improving the quality use of medicines in Australia: Australian centre for health

research realising the potential of pharmacogenomics (2008).

20. Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse drug reactions in

hospitalized patients: a meta-analysis of prospective studies. JAMA 279: 1200-1205.


21. Schulte JL (1985) Homicide and suicide associated with akathisia and haloperidol.

American Journal of Forensic Psychiatry 6: 3-7.

22. Healy D, Herxheimer A, Menkes DB (2006) Antidepressants and violence: problems at

the interface of medicine and law. PLoS Med 3: e372. [Crossref]

23. Breggin PR (2003) Suicidality, violence, and mania caused by selective serotonin

reuptake inhibitors: A review and analysis. Ethical Human Sciences & Services 5: 225-


24. Yolande Lucire (2005) New Drugs, New Problems. Australian Journal of Forensic

Sciences 37: 19-25.

25. NSW Mental Health Sentinel Events Committee. Tracking Tragedy: A systemic look at

suicides and homicides amongst mental health inpatients (2004).

26. Healy D, Whitaker C (2003) Antidepressants and suicide: risk-benefit conundrums. J

Psychiatry Neurosci 28: 331-337. [Crossref]

27. Whitaker R (2005) Anatomy of an epidemic: psychiatric drugs and the astonishing

rise of mental illness in America. Ethical human psychology and psychiatry. An

International Journal of Critical Inquiry 7: 23-35.

28. Tanaka E, Hisawa S (1999) Clinically significant pharmacokinetic drug interactions

with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450

system. Journal of Clinical Pharmacy & Therapeutics 24: 7-16.

29. Oesterheld, JR Cozza, K Armstrong SC, Neil B Sandson (2007) Drug-drug interactions:

a compendium of case vignettes for the practicing clinician. American Psychiatric


30. Letter from Eli Lilly Australia, cf Bauman, opp cit.

31. Communiqué: mayo reference services. Cytochrome P450 enzyme genotyping:

optimizing patient care through pharmacogentics. September 2005.

32. Armstrong SC, Cozza KL, Sandson NB (2003) Six patterns of drug-drug interactions.

Psychosomatics 44: 255-258. [Crossref]

33.; and

34. Sandson NB (2007) Drug-drug interactions primer. A compendium of vignettes for the

practicing clinician. American Psychiatric Press.

35. Blue Cross Blue Shield Association (2004) Special report: genotyping for cytochrome

P450 polymorphisms to determine drug-metabolizer status. Technology Assessment

Program 19: 1-34.



38. Cassidy vs. Eli Lilly also http://www.

39. Wynn GH, Oesterheld, JR Cozza, K, Armstrong SC (2009) Clinical Manual of Drug

Interaction Principles for Medical Practice. American Psychiatric Publishing Inc.

40. Zourkova A, Hadasova E (2003) Paroxetine-induced conversion of cytochrome P450

2D6 phenotype and occurence of adverse effects. General Physiology & Biophysics

22: 103-113.

Lucire Y (2018) The effect of CYP450 2D6*4 mutation on medication response: Two cases with different outcomes

Clin Case Studie Rep, 2018 doi: 10.15761/CCSR.1000112 Volume 1(2): 8-8

To: ZB
Subject: FW: Endocrinologist

Dear Z

Being deprived of meaningful contact with my daughter through her not having any section 17 leave which has been avoided for months on end – there is no greater punishment than that.  It is in effect having a drastic effect on my physical health.

Knowing my daughter is getting no better and never will under Ash Villa and held a prisoner in bed most of the day is heartbreaking.

It is hard knowing the true reality that we should never ever have come to this area where I wanted so much to provide the right living accommodation and support in the community.   That clearly is not happening and never will because it costs £4000 thereabouts to hold my daughter under Ash Villa a prisoner.   She will never get off the section whilst staff write negatively and constantly do so and all the time my daughter is lying there in bed during the day and becoming weaker and weaker physically.  Mentally she has capacity and is sharing information with me which I then share with the rest of the family in accordance with her wishes.

I do not expect a penny or any support from this area.   Such restrictive punishment in deprival of Section 17 leave is not conducive to recovery and is having a knock-on effect to my physical health and is of great upset to all my family.

My daughter was not seen as a risk to others in the former area otherwise she would not have been released without a Section in place.  She was also complying with treatment.


Susan Bevis

From: ZB
Sent: 19 May 2022 16:00
To: susan bevis
Subject: Meeting Points.

Hi Susan

Please see meeting notes from todays meeting.

  • S17 leave has not changed and remains at 2 x 30 minutes ground leave escorted by 2 members of staff.
  • Risk was explained regarding why E …… is escorted by 2 x members of staff.
  • Nursing advised that Elizabeth does see her advocate on a one to one basis however Elizabeth has refused from time to time.
  • Dr S advised the a consultant would be available next week to be involved in the meetings.
  • We discussed Takeaways and how these are becoming more frequent.
  • That you would like some inclusion.
  • You was offered invitations to Carers support groups and you refused these.
  • You would like to continue with the weekly meeting with a consultant.
  • You wish to visit on a Saturday @14.00

I will look at booking next weeks appointment and forwards to you in due course.

Kind regards


Ash Villa


NG34 8QA


Working hours Monday to Friday 09.00-17.00 pm

From: B
Sent: 16 May 2022 18:05
To: susanb255

Subject: Re: stress induced psychosis


They recognise that Elizabeth has stress induced psychosis but signally fail to recognise that they are the cause of much of the stress.  Do they not realise that being deprived of liberty is about as stressful as it gets.

Oh, and nasty tastes are an effect of the anticholinergic effects of the drugs.  Odd they don’t recognise that either.



Ask for a detailed explanation of why Elizabeth cannot be given s.17 leave.  Including a full appraisal of her current state of mind.not some utterly inadequate reference to outdated diagnostic criteria.  Section 17 leave is part of the rehabilitation programme and patients do not get better permanently locked up in a bizarre setting with hostile staff.

It is patently obvious that if Elizabeth does not want to engage with the staff in Ash Villa that they need to make better arrangements.  She clearly needs one to one psychotherapy with someone she can trust and who can break through the barrier that these mental health professionals themselves create.

No amount of incarceration in a locked ‘rehabilitation’ ward will improve her quality of life and all it will do is make her more determined to reject their interventions.  The idea that rehabilitation can be achieved in a lock-up is bloody ridiculous in any case.

As for schizophrenia I would suggest that the nurse needs to do some CME training.  Virtually no-one considers this an organic condition anymore and even where it is recognised as a disorder it is syndromal and not a condition with either aetiology or prognosis.  Thousands of those accused of being schizophrenics recover if properly treated.  Millions of others are simply drugged and locked up for convenience.  

I think that Elizabeth would show signs of recovery if she was given seven days leave and later attended as a voluntary patient.  If they cannot see that her defiance will not subside after this length of time they need to reconsider their chosen professions.


From: : ZB 24 May 2022 10:12
To: susan bevis
Subject: RE: Managers hearing

Good morning Susan

I hope your well.

As advised on many occasions I am your single point of access, others will not reply but I will seek to gain the relevant answers and feed them back to you.

You will not be sent the link to the managers meeting today, Elizabeth has not given verbal consent to any member of staff although we have tried to gain this on many occasions.

Elizabeth has not been deemed to have Capacity to consent to your request on this occasion.

Kind regards


Ash Villa


NG34 8QA

Email: ZB Friday 09.00-17.00 pm

From: ZB
Sent: 10 May 2022 11:45
To: susan bevis
Subject: RE: EB

Good afternoon susan

To be clear Elizabeth does not have unlimited ground leave  ground leave is 2 x 30 minutes a week

However we have a locked garden which elizabeth can access this does not fall under leave.

Hope this clarifies for you.

Kind regards


Ash Villa


NG34 8QA

Email: ZB Working hours Monday to Friday 09.00-17.00 pm

From: ZB
Sent: 09 May 2022 16:22
To: susan bevis
Subject: EB

Hi Susan

Thank you for your email.

To be clear on the garden, we have a private garden on the grounds and Elizabeth has full use of them when ever she wishes to have some fresh air.

This has been mentions on a couple of occasions.

As you are aware Elizabeth is held on a section 3, this went to tribunal and was upheld.

The professionals in the meeting have agreed this is the right things for Elizabeth at this point in her recovery.

All next possible steps will be considered for Elizabeth moving forwards.

Kind regards


Ash Villa


NG34 8QA

Email: ZB

Working hours Monday to Friday 09.00-17.00 pm

From: B Sent: Saturday, May 7, 2022 8:21:34 PM
To: susanb
Subject: Re: Negligence


There is no tangible reason why Elizabeth cannot be given s.17 leave and the refusal to allow her some respite form permenant confinement is positively detrimental to her mental health.

In a nutshell they are institutionalising her by stealth.  This is a human rights issue and not one for half-assed tribunals.  I am quite prepared to help you put together a case if Elizabeth agrees.  The matter needs taking to the High Court on the grounds they are acting ultra vires.

This circumvents the institutional bias of the tribunals and involved decisions based on well establish law rather than the convenience of the staff at Ash Villa.  It is utterly absurd that she has not had some home leave in eight months. Even a restricted patient would have been allowed some leave.


—–Original Message—–
From: susan bevis <susanb
To: B
Sent: Sat, 7 May 2022 18:32
Subject: RE: Negligence

I will try and do that tomorrow but doubt this will be allowed.  They are totally avoiding the issue of leave.  One doctor after another.  I am not racist but they seem to be and do not seem to care one bit.  I have not spoken to elizabeth for several days.  Cannot get through on the phone.

What they are trying to do is isolate and keep her away from her family as they have their own agenda clearly and none of us agree with that.  Why should my daughter have to go to another locked prison instead of coming home in accordance with her wishes.

This area is an absolute disgrace when it comes to mental health and the facilities are not fit for purpose.

I thought Enfield was bad enough.  Elizabeth has been held now a prisoner deprived of contact and leave now since September.




PTSD and Complex PTSD can seriously affect the default mode network in the brain and cause faulty neuronal connections that can lead to psychotic symptoms.  The failure to perceive this as an injury rather than a disease causes bio-psychiatrists to employ medications that cause further injury to this complex structure of inter brain communication, which consequently causes cognitive dysfunction and psychosis.  

Bob Johnson has focused on this and the concomitant decreases in oxygenated blood in the brain.  

Neuroleptics will not treat PTSD but merely depress the more florid symptoms of it.  The problem is that they also cause the disruption in the DMN to get worse.

Bob’s comments on the effects in Broca’s area of the brain is fascinating.  This is the centre for language processing and damage there might account for the word fixation that is seen in some patients incorrectly diagnosed as psychotic.  

“Dr Richard Ngomba and I are also looking into disruptions in the mesocortical pathways potentially caused by brain inflammation.”  Decreases in oxygenated blood may well cause the triggering of inflammation in the temporal horn.    We saw in Martin Harrow’s study that neuroleptics have caused a marked decrease in cognitive function in patients prescribed these drugs long term.   Precisely what you would expect in patients with damage to neural pathways (mesocortical pathways) 

Professor Roderick Orner, who is an international authority on complex PTSD is in our research group.  

Subject: What is complex PTSD? – Mind

Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD).

My work has focussed on trauma recall.
This is blocked 100% in severe, untreated cases.
If the DMN is “autonomic’, then it is less significant clinically, than
voluntary, or insight driven cerebral

DMN abnormalities in patients with severe PTSD symptoms
are characterized by decreased overall inter connections.
Absolutely – but especially, as mentioned in Broca’s area, and the
frontal cortex. Decrease is an understatement – the blank look on the
faces is underpinned by Kolk’s PET scans when trauma tapes are played.

Those decreased interconnections are another potential reason why
patients incorrectly diagnosed with psychosis who are actually suffering
from PTSD are treatment refractive.
2 points –(1) beneath every psychotic symptom I have examined, there is a
fiercely blocked trauma. In one transcribed dialogue a 40 year old
verbalises the difficulty she has thinking. PTSD in spades.
(2) If the treatment envisaged is neuroleptics, then, as Harrow showed,
it makes things worse. In my view it does this by blocking even the
beginnings of reactivation of frontal cortical blockage, which is intimately
linked to Broca. Drug induced zombies cannot begin to pull themselves

The decreased interactions will interfere with the uptake of psychopharmaceutical medications by creating an effective block in neurotransmitter receptors in the mesocortical pathways.
Is the assumption here that better uptake is clinically beneficial? Clinical
evidence does not support this, though bio-psychiatrists swear by it.
And, yes, the blockages noted by Kolk were arterial, oxygen supply related, I
imagine, which implies the whole frontal area shows decreased activity.
DR Bob Johnson Page 2 of 2 Your 6 points – 1MAY22

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