Thomas Kingston

Medicines & Healthcare products
Regulatory Agency

10 South Colonnade
Canary Wharf
London

E14 4PU

United Kingdom
gov.uk/mhra

Ms K Skerrett

His Majesty's Senior Coroner for Gloucestershire
Gloucestershire Coroners Court

By Email:

Reference: Ss

12 February 2025
Dear Ms Skerrett,

Regulation 28 Report into the death of Thomas Henry Robin Kingston

Thank you for your Regulation 28 Report relating to the death of Thomas Henry Robin
Kingston. | would like to offer my sincere condolences to Mr Kingston’s family on their tragic
loss.

In the Matters of Concern section of the report relating to Mr Kingston you ask the Medicines
and Healthcare products Regulatory Agency (MHRA) whether there is adequate
communication about the risks of suicide associated with the Selective Serotonin Reuptake
inhibitor (SSRI) medicines and whether the current guidance to persist with SSRI medicine
or switch to an alternative SSRI is appropriate when no benefit has been achieved and/ or
especially when any adverse side effects are being experienced.

May | start by outlining the current information with SSRI antidepressant medicines
regarding the risk of suicidal behaviour. The product information for all SSRI medicines
contains warnings about the risk of suicidal behaviour. These warnings were introduced
following UK and European reviews of the evidence of such a risk which were started in
2003 and concluded that the risk of suicidal acts and behaviour is increased with the use of
sertraline, citalopram, escitalopram, paroxetine, venlafaxine, and mirtazapine in young

patients (under 25 years of age).

The product information for all SSRIs warns that the risk of suicidal behaviour is considered
to be greatest in the early stages of antidepressant treatment. This is likely to be related to
antidepressants being effective only after a few weeks of taking the medicine and
depression itself being associated with an increased risk of suicidal behaviour.

There are no marked differences in suicidal risk between the different antidepressants within
the SSRI class of medicines. The product information for all SSRIs recommends that close
supervision of patients and particularly those at high risk should accompany drug therapy
especially in early treatment and following dose changes. Patients (and caregivers of
patients) should be alerted about the need to monitor for any clinical worsening, suicidal
behaviour or thoughts and unusual changes in behaviour and to seek medical advice
immediately if these symptoms present.

The current warnings in the SSRI medicines’ Patient Information Leaflets (PILs), including
citalopram and sertraline, were subject to user testing and section two contains a bold
headline on “Thoughts of suicide and worsening of your depression or anxiety
disorder’. Use of emboldened text and bullet points are used throughout the PIL to highlight
key safety information and action for people who experience thoughts of self-harm. There is
also advice in the PIL to inform family and friends about a diagnosis of depression or anxiety
as it is recognised people with depression may not have insight into their own behaviour and
in some patients leaflets this is emboldened.

To supplement this information, the MHRA has informed healthcare professionals in the UK
about the risk of suicidal behaviour associated with antidepressants via articles in the
MHR&’s bulletin Drug Safety Update in April 2008' and published guidance for prescribers
on the MHRA website in December 2014 to summarise key safety messages’.

The British National Formulary (BNF) states, “the use of antidepressants has been linked
with suicidal thoughts and behaviour; children, young adults, and patients with a history of
suicidal behaviour are particularly at risk. Where necessary patients should be monitored for
suicidal behaviour, self-harm, or hostility, particularly at the beginning of treatment or if the
dose is changed.” The information in the product information and the BNF should form the
basis of a discussion between the doctor and patient when deciding on the most appropriate
medicine for them.

Despite all the currently available information about the risk and benefits of SSRI
antidepressants designed to supplement and support the clinical conversation and
monitoring of patients by the healthcare professionals prescribing antidepressants, the
MHRA is aware that some patients and families have ongoing concerns about the
effectiveness of the current warnings in the patient information leaflets.

In 2022, the MHRA sought the advice of the Commission on Human Medicines (CHM) on
the need to convene an Expert Working Group (EWG) to review how the risk of suicidal
behaviours is communicated in the patient leaflets to establish if this can be improved or if it
would be more helpful for patients to receive this information in different formats within the
regulatory framework. The first meeting of the EWG was held on 4 July 2024. Round table
meetings involving patient charities and families of those bereaved by suicide will be held in

March 2025. The membership and remit of the EWG can be found here Commission on
Human Medicines - GOV.UK.

1 https://www.gov.uk/drug-safety-update/a ntidepressants-suicidal-thoughts-and-behaviour

2 https:/Avww.gov.uk/government/ ublications/ssris-and-snris-use-and-safety/selective-
serotonin-reu take-inhibitors-ssris-and-serotonin-and-noradrenaline-reu take-inhibitors-

snris-use-and-safety

The considerations of the EWG are anticipated to complete in 2025. We will communicate to
healthcare professionals, patient groups and relevant voluntary organisations any updates
on how the risk of suicidal behaviours associated with antidepressants is presented in the
antidepressant PILs following the conclusions of the EWG and subsequent CHM advice.

Secondly in your letter you also ask about the guidance around the use of SSRIs,
particularly if no benefit has been seen or adverse reactions have been reported. Clinical
guidance issued by the National Institute for Health and Care Excellence (NICE) (Clinical
Guideline NG222) on depression in adults recommends that if a person with depression is
started on antidepressants and is considered to be an increased suicide risk or is between
18 and 25 years (because of the potential increased prevalence of suicidal thoughts in the
early stages of antidepressant treatment for this group) they should be reviewed after one
week of starting antidepressants or after increasing the dose and again after this as often as
needed, but no later than four weeks after the appointment at which the antidepressant was
started.

Clinical Guideline 90 advises prescribers to follow a stepped-care model in which to organise
the provision of services and supports patients, carers and practitioners in identifying and
accessing the most effective interventions; the least intrusive and most effective intervention
is provided first. More details of this stepped-care model can be found at
httos:/Awww.nice.org.uk/quidance/cg90/resources/de! ression-in-adults-recognition-and-

management-pdf-975742636741

NICE guidelines advise healthcare professionals that if a person's depression has had no or
a limited response to treatment with antidepressant medication alone, and no obvious cause
can be found and resolved, to discuss further treatment options with the person and make a
shared decision on how to proceed based on their clinical need and preferences.

Finally | should add that your report of Mr Kingston's adverse reaction to SSRI medicines
has been added to the Yellow Card database (reference number ADR 34440796), which is
the UK's system for collecting and monitoring information on suspected Adverse Drug
Reactions.

| ™ " _ have -_ further = please do not hesitate to contact my office:

Yours sincerely

Chief Executive
Medicines and Healthcare products Regulatory Agency
E:

NI Cc National Institute for 3rd floor
Health and Care Excellence 3 Piccadilly Place

Manchester
M1 3BN
United Kingdom

+44 (0)300 323 0140
31 January 2025

Ms Katy Skerrett

HM Area Coroner
Gloucestershire Coroners Court
Corinium Avenue

Barnwood

Gloucestershire

GL4 3DJ

Sent via em: IRD

Our reference:

Dear Ms Skerrett

Re: Regulation 28 Prevention of Future Deaths Report (Thomas Henry Robin Kingston)

| write in response to your regulation 28 report dated 7 January 2025 regarding the very sad
death of Thomas Henry Robin Kingston. | would like to express my sincere condolences to
Thomas's family.

Our patient safety leads at NICE have discussed the contents of your report and the summary
information given relating to the death of Mr Kingston, while considering the relevant published

NICE guidance on this topic, in this case depression in adults: treatment and management
(NG222).

Given that the matters of concern relate to the side effects and safety of medication, specifically
selective serotonin reuptake inhibitors (SSRIs), we believe that the key issues raised are best
addressed in the first instance by the Medicines and Healthcare products Regulatory Agency
(MHRA), and | note that your report has also been sent to them.

Therefore, we are currently working collaboratively with the MHRA on this issue. The outcome
of that work will inform any action NICE may need to take in respect of its recommendations.

Please consider this our initial reply. We will write to you again as soon as possible with further
information once our work with the MHRA has concluded. Please note that given the complex
nature of the MHRA work, our final response is unlikely to be submitted by the original response
date required by your report.

| hope this is an acceptable way forward and would like to assure you that | will send my further
reply as soon as possible.

Yours sincerely,

De
NICE nice.org.uk | nice@nice.org.uk

Chief Executive

{Insert footer here] 2 of 2

RC Royal College of
ee General Practitioners

Honorary Secretary of Council

Ms K Skerrett
His Majesty’s Seqj for Gloucestershire
Sent by email to:

26 February 2025

Dear Ms Skerrett

Regulation 28 Report to Prevent Future Deaths - touching on the death of Thomas Henry
Robin Kingston

Thank you for sharing a copy of your report touching on the tragic death of Thomas Henry Robin
Kingston. | am responding on behalf of the Royal College of General Practitioners as Honorary
Secretary to Council. Firstly, can | convey our sincere condolences to the family and friends of
Thomas.

You asked me to specifically comment on two matters of concern:

1. Whether there is adequate communication of the risks of suicide associated with the
selective serotonin reuptake inhibitor (SSRI) medications, and

2. Whether the current guidance to persist with SSRI medication or switch to an alternative
SSRI medication is appropriate when no benefit has been achieved and/ or especially
when any adverse side effects are being experienced.

General comments

The GP Curriculum includes within its Clinical topic guides a section on Mental Health mentioning
a role of the GP to specifically communicate effectively, professionally, and sensitively with
patients, relatives and carers, recognising potential difficulties in communicating with people with
mental health conditions and the importance of generating and maintaining rapport. There is a
recognition to assess risk to make the patients safety a priority and offer patients relatives and
carers advice and support regarding prevention, prescribing monitoring, and self-management of
both mental and physical multimorbidity. The curriculum recognises the emerging issue of suicide
prevention in mental health care.

Royal College of General Practitioners
30 Euston Square, London, NW1 2FB

Tel: 020 3188 7400 | info@rcgp.org.uk | rcgp.org.uk
Patron: HRH The Duke of Edinburgh (1972-2021) | Registered Charity Number 223106

Shared Decision making

10 years ago, the RCGP recognised that GPs were leading the way in shared decision making
and called for more guidance on shared decision making. The College has pioneered the
development of a Person-Centred Care toolkit which includes support for shared decision making
and in 2023 RCGP Scotland's joint chair Chris Williams Commenting on the prescription of
antidepressants by GPs, RCGP Scotland Joint Chair Dr Chris Williams said:

“Depressive illness affects many adults and causes a huge burden of disease worldwide.

“When prescribed appropriately, evidence shows that antidepressants can be an effective
treatment for many patients suffering from mental health conditions such as depression and
anxiety. As with any medication, GPs carefully consider the benefits and risks when prescribing
antidepressants, the various factors relevant to the individual patient, alongside new Clinical
guidance as it is published.

“Shared decision-making is an evidence-based health communication framework that is
commonly used in general practice. A person with mild to moderate depression may have more
than one treatment option, including where medication might be used on its own or in combination.

“GPs are highly trained to have frank and sensitive conversations with our patients, and this
includes any potential side effects which may occur from taking antidepressants. Once a
prescription has been made, follow-up appointments and ongoing medication reviews can assist
GPs to assess whether a patient’s symptoms have improved, any side effects they may have
experienced as well as if additional support is needed.

“Improved access to alternatives to anti-depressant medication, such as talking therapies and
CBT, may be beneficial, but resourcing and access issues persist for these treatments. Improved
access to these treatment pathways through further resourcing may be beneficial for patients.”

The Royal College of Psychiatrists published a Position statement in 2019 on antidepressants
and depression. They mentioned the importance of shared decision making.

‘To ensure informed consent and shared decision-making, the use of antidepressants should
always be underpinned by a discussion with the patient, and family/carer (as appropriate), about
the potential level of benefits and harms, including withdrawal, and concordance about initiation
and continuation. Greater emphasis is also required on regularly reviewing antidepressant use
(supported by adequate resourcing and better use of technology) to monitor how well the
treatment is working and any side effects, as well as to ensure that long-term use remains
clinically indicated’.

They also raised the issue of risk of suicide when using antidepressants looking at the current
evidence at that time.

The Royal College of Psychiatrists have also published comprehensive information for patients
on how to stop antidepressants which is as important as starting them.

Specific comments

In answer to the two specific questions:

Is there adequate communication of the risks of suicide with SSRI medication?

There can always be more effective communication of risk and in General Practice we use a
personalised care approach with an emphasis on the domain of shared decision making. Shared
decision making is a process where effective communication between the GP and the patient
reaches a decision based on a shared understanding of the risks and benefits of different
treatment options. Shared decision aids have been produced to help patients_in_ managing
depression . This shared decision aid (SDA) is not specific to particular medication such as SSRIs
and does not highlight suicide risk. An SDA for SSRIs which balances the benefits and risks for
patients would be an effective basis for a discussion between the GP and their patient before
starting treatment.

Is current guidance to persist with SSRI medication or switch to an alternative SSRI
medication appropriate when no benefit has been achieved and/ or especially when any
adverse side effects are being experienced?

There are specific guidelines for Depression produced by NICE and most GPs shall follow NICE
CKS (Clinical Knowledge Summaries). The guidance specifically covers the consideration of
antidepressant drug treatment (using shared decision making to agree an appropriate treatment
plan). The guidance includes advising ‘that symptoms of anxiety, agitation, hopelessness, or
suicidal ideas may increase when starting treatment, and advise when to seek urgent review’.
Advice is also given regarding review and switching antidepressant medication. This does
mention considering a switch to a drug that the person has previously found helpful or prefers. In
this case it is not clear whether there was a previous preference for a particular SSRI. It is however
usual to switch to a different class if there has not been a benefit or side effects and there are
recommendations in the guidance on how to switch drugs safely between classes due to
interactions and different bioavailability. It is also important to be clear on the indication for an
SSRI and use of diagnostic criteria for both anxiety as well as depression, as the conditions can
be separate or mixed and this can guide various treatment options. The RCGP also has a Mental
Health toolkit which provides evidence-based guidelines for medical and psychological treatments
for both depression and anxiety.

I trust that this reply is helpful and if you have any questions, please do not hesitate to contact
me. Our sincere condolences are with Thomas’ family.

Yours sincerely

RCGP Honorary Secretary