Healthcare Resource Utilisation, Common Mental Health Problems, and Infections in People With Inflammatory Bowel Disease (IBD)
Conditions: Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn Disease
Sponsor: Momentum Data

Healthcare resource utilisation, common 
mental health problems, and infections in 
people with inflammatory bowel disease 
(IBD) 
 
NCT number: Not available at submission 
Document date: 6th Dec 2018 
Academic contributors 
Dr Kevin Barrett1, Dr Peter Irving2, Professor Simon de Lusignan3, 4 
 
1 New Road Surgery, Croxley Green, Hertfordshire, UK  
2 Department of Gastroenterology, Guy's & St Thomas' Hospital, London, UK.  
3 Department of Clinical and Experimental Medicine, University of Surrey, 
Guildford, United Kingdom 
4 Royal College of General Practitioners, London, UK 
 
 
 
 
The research is supported by Momentum Data Ltd 
 
 
 
 

Abstract 
Background 
Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory 
conditions collectively termed inflammatory bowel disease (IBD). Both conditions 
are chronic and involve a lifetime of treatment. Current treatment strategies for 
IBD focus on the use of immune modulating medications, which have the potential 
to increase the risk of common infections. An understanding of the healthcare 
resource utilisation and overall infection risk in IBD is therefore important. 
Despite increasing treatment options, quality of life is significantly reduced in 
people with IBD and a high prevalence of mental health disorders has been 
reported. However, the magnitude of any potential association between IBD and 
mental illness in adults has not yet been fully explored. 
 
Objective 
We aim to provide an accurate and contemporary measurement of the current 
healthcare resource utilisation in people with IBD. We also aim to provide 
estimates of infection incidence in this population and the prevalence of common 
mental health conditions. We will also 
 
Method 
We will identify UC and CD using algorithms validated for accurately identifying 
these conditions from primary care records in the UK. We will identify a prevalent 
cohort of adults with IBD with the RCGP RSC network over the last decade. We will 
identify a matched cohort of people without IBD; matched on age, gender and 
primary care practice. Across these cohorts we will compare healthcare resource 
utilisation (primary care attendances, number of primary care prescriptions for 
antidepressant and anxiolytic medications, number of primary care prescriptions 
for medications used in IBD, recorded secondary care attendances, and issue of 
statements of fitness for work), incident infections (any common infection, any 
viral infection, or any gastrointestinal infection), and common mental health 
conditions (depression, anxiety, and attention deficit hyperactivity disorder). 
 

Lay Summary 
Ulcerative colitis and Crohn’s disease are the commonest types of inflammatory 
bowel disease (IBD). Both conditions range in severity from no symptoms to being 
potentially fatal. Both conditions are treated with medications which supress the 
immune system. It is not known whether this increases the risk for infections in 
these conditions. It is also recognised by healthcare professionals that these 
conditions cause a considerable amount of psychological distress. However, this 
has never been measured in a large population sample. 
 
These studies will investigate any associations with treatment and new onset 
infections. They will also examine the relationship between IBD and common 
mental health problems (specifically, depression and anxiety) and the impact that 
these have on the healthcare use (including number of GP appointments, hospital 
attendances, and medication prescriptions. Combined, these studies should 
provide a better understanding of the impact of IBD on affected people and 
provide evidence to support the correct allocation of healthcare resources. 
 
 

Introduction 
Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory 
conditions collectively termed inflammatory bowel disease (IBD).1 In both 
conditions there is a spectrum of disease ranging from a quiescent state with few 
or no symptoms to potentially fatal disease. Both conditions commonly require 
extensive medical intervention over many decades of disease and may also 
require substantial surgical treatment.2, 3 With the global burden of IBD rising, 
calls have been made for improved treatment options,4 and these been met with 
the development of a range of biologic therapies.1 
 
Current treatment strategies for UC focus on the use of immune modulating 
medications. Whilst frequently effective for disease control, these treatments have 
the potential to increase the risk of common infections,5, 6 which includes both 
common and atypical pathogens.6 An understanding of the infection risk in a 
community-based population with UC is therefore important. However, the 
existing literature on infection rates in people with UC has focused almost 
exclusively on secondary care populations. It therefore remains unclear what the 
total burden of infectious disease is in a population-based cohort with UC and how 
this compares to those without UC. 
 
Despite increasing treatment options, quality of life is significantly reduced in 
people with IBD7 and the prevalence of mental health disorders has been reported 
to be higher in children with IBD.8 However the magnitude of any potential 
association between IBD and mental illness in adults has not yet been fully 
explored. 
 
Given the prolonged course of medical treatment in IBD, it is important for payers 
to have a good understanding of the total healthcare utilisation of people with IBD. 
Again, in this area, existing studies have focussed on secondary care based 
cohorts. Little is known about healthcare resource utilisation in primary care, in 
people with IBD, in the UK. 
 

Aims 
1. We aim to describe the incidence of common infections in a population of 
individuals with IBD, compared to a matched control population without 
IBD. We will explore all common infections and also focus on viral and 
gastrointestinal infections.  
2. We will explore how incidence of infection varies by age, and other factors 
associated with risk of infection in IBD including medication use.  
3. We aim to describe the prevalence of common mental health conditions 
(anxiety, depressive episodes, and recurrent depressive disorder) in 
people with IBD when compared to an age and gender matched cohort. 
4. We aim to explore healthcare utilisation in individuals with IBD with and 
without common mental health problems.  
Methods 
Study design  
We aim to perform a retrospective matched cohort study. We will match people 
with UC and CD, to people without IBD. A history of common mental health 
conditions was assessed at baseline (matching date) in both cohorts, and 
compared. Both cohorts will be followed-up (retrospectively) from the matching 
date for incident infections, and healthcare resource utilisation. 
 
Data source 
We aim to use the Royal College of General Practitioners (RCGP) Research and 
Surveillance Centre (RSC) database. This database contains the pseudonymised 
primary care records of the registered population all from a network of GP 
practices which provide a representative sample of the UK population.9 The RCGP 
RSC database contains complete data on all events and clinical entities coded in 
UK primary care. These include demographic information, clinical diagnoses, 
laboratory test results, primary care issued prescriptions, process of care codes 
(e,g. specialist referrals), and anthropometric measurements (e.g., body mass 
index; BMI),and are coded using the Read coding system.10 
 

UK general practice records provide several advantages for this study type;11, 12 
UK primary care is a registration-based system (a patient can only register with a 
single GP), records have been computerised since the 1990s, and pay-for-
performance targets (introduced in 2004 through The Quality and Outcomes 
Framework; QOF) have resulted in consistent high-quality clinical data entry 
about chronic disease. Studies using the RCGP RSC data have been published 
across a range of chronic diseases.13-15  RCGP RSC practices get feedback on their 
data quality, including using a dashboard.  A particular emphasis of this feedback 
is “episode typing” – designating cases first, new, or ongoing – which helps 
differentiate incidence from prevalence.16 
 
Study population and outcome measures 
All adults (aged ≥18) registered with a GP practice contributing to the RCGP RCS 
at the time of data extraction will be eligible for inclusion.  
 
Definition of the IBD cohort  
All individuals with one or more diagnostic codes for UC or CD prior to the study 
start date were eligible for inclusion in the IBD cohort. The use of diagnostic codes 
to identify IBD from UK primary care records has been validated and shown to be 
accurate and to correctly differentiate between UC and CD.17, 18 The Read codes 
used to identify UC and CD were based on the codes list used by Abrahami et al.,18 
and mapped to both Read code versions used within the RCGP RSC network 
(Appendix 1). The use of diagnostic codes to identify IBD has also been shown to 
have good validity in US claims databases.19 
 
Definition of the matched cohort 
The matched unexposed cohort will be identified by matching individuals with 
IBD to people without IBD.  Matching will be performed on age and gender as a 
minimum. Follow-up for each matched individual will begin at the same baseline 
date as those with IBD. 
 

Infections outcomes 
Infections outcomes will comprise: 
1. The time to first recorded presentation with a new episode of any common 
infection during the study period; a composite of upper respiratory tract 
infections, pneumonia, bronchitis, influenza-like illness, skin infections, 
genital infections, urinary tract infections and gastrointestinal infections. 
2. The time to first recorded presentation with a new episode of any viral 
infection. 
3. The time to first recorded presentation with a new episode of any episode 
of gastrointestinal infection. 
The Read codes used to identify infections will be adapted from the validated 
indicators used in routine surveillance by the RCGP RSC. The chosen infections in 
the composite infections outcomes were selected principally as they represent the 
majority of the primary care adult infectious disease burden, and include a 
mixture of viral, bacterial and fungal infections. First or new episodes of an 
infection are coded accordingly in the database, enabling differentiation from 
chronic infections or follow-up visits for the same episode. If available, we will also 
explore type and pathogens contributing to the incident infections. 
 
Mental health outcomes 
The presence of common mental health conditions at baseline will be determined 
for the case and control cohorts. We will examine three groups of common mental 
illness as defined by the International Statistical Classification of Diseases and 
Related Health Problems 10th Revision (ICD10) classification;20 depressive 
episodes (F32), recurrent depressive disorder (F33), and non-phobia related 
anxiety disorders (F41). These conditions are chosen as they represent the most 
common mental health conditions presenting to primary care.21 These conditions 
will be identified using algorithms validated in UK primary care.22 We selected the 
algorithms used here (Appendix 2) to optimise the positive predictive value. In 
brief, we will use a concurrent diagnosis and treatment code to identify acute 
episodes (depressive episodes and anxiety episodes) and for recurrent depression 
either a historical code for any depression and current treatment or a recurrent 

depression specific diagnosis code (Appendix 2). As a secondary analysis we will 
also explore the prevalence of attention deficit hyperactivity disorder (ADHD) in 
the case and control cohorts. 
 
Healthcare utilisation outcomes 
The components of healthcare utilisation to be examined comprise; number and 
duration of primary care attendances, number of primary care prescriptions for 
antidepressant and anxiolytic medications, number of primary care prescriptions 
for medications used in IBD, recorded secondary care attendances, and issue of 
statements of fitness for work (also termed fit notes or sick notes). 
 
Antidepressant medication classes to be examined comprise, selective serotonin 
reuptake 
inhibitors 
(SSRIs) 
and 
related 
medications 
(serotonin 
and 
norepinephrine reuptake inhibitors; SNRIs), tricyclic antidepressants (TCAs) and 
related medications (tetracyclic antidepressant TeCAs), and monoamine oxidase 
inhibitors (MOAIs). Anxiolytic medications to be examined comprise all 
benzodiazepines and other related medications indicated for use in anxiety states 
(Appendix 3). Medications used for the treatment of IBD to be examined will 
comprise; 
topical 
5-aminosalicylic 
acid 
(5-ASA) 
medications, 
topical 
glucocorticoids, oral 5-ASA medications, oral glucocorticoids, non-biologic 
immunosuppressant medications (cyclosporine, azathioprine, mercaptopurine, 
methotrexate), and biologic therapies (Appendix 3). 
 
Other baseline measures 

Socioeconomic status will be defined using the official national measure; the index 
of multiple deprivation (IMD).23 This is calculated at the point of data extraction, 
using patient postcode, with the resultant scores stratified by deprivation quintile. 
Ethnicity will be extracted from the primary care record and grouped into major 
ethnic groups; white, black, Asian, mixed, and others.24 BMI will be defined as the 
most recently recorded measurement prior to the study start date. Smoking status 
will be defined using the most recently recorded data prior to the study start date. 
Diagnosis codes will be used to define the presence of comorbidities at baseline; 
diabetes, hypertension, atrial fibrillation, angina, myocardial infarction, 
congestive heart failure, stroke, transient ischaemic attack, chronic kidney disease 
(stages 3–5), dementia, rheumatoid arthritis, chronic liver disease, asthma and 
chronic obstructive pulmonary disease (COPD). 
 
Statistical Analyses 
Comparison of the prevalence of mental health conditions 
We will compare the prevalence of the three common mental health conditions in 
people with IBD and matched controls prior to the baseline date (January 1, 2015). 
We will stratify groups by age, and gender, and for those with IBD by condition 
(UC or CD) and duration of disease, and other important baseline factors. We will 
evaluate differences in baseline characteristics between the cohorts using the χ2 
test for categorical variables and the unpaired t-test for continuous data. Other 
statistical tests may be used if appropriate, depending on the data type and 
distribution. 
 
Comparison of healthcare utilisation 
We will compare the measures of healthcare utilisation between people with IBD 
and matched cohorts over a follow-up period. Follow-up will end at the earliest of; 
the study end-date (data extraction date), the date of patient transfer from an 
included practice, or date of death. All individuals contributing at least 1 day of 
follow-up will be included for analysis. We will stratify and compare healthcare 
utilisation in people with IBD by age and gender, condition (UC or CD), duration 
of disease, the presence of mental health conditions, and other important 

confounders. All utilisation outcomes will be adjusted for the duration of follow-
up and reported as event rates. 
 
Where sample size allows we will examine factors associated with increased 
healthcare utilisation. We will use regression analyses to assess potential 
associations between healthcare utilisation outcome measures and important 
patient and treatment factors. 
 
Comparison of infections  
Infection incidence rates will be calculated as the number of events divided by the 
total person-years of follow-up and expressed as the number per 1000 person-
years. We will estimate the risk of infection in people with and without IBD using 
Cox proportional hazards models, and report estimated hazard ratios for 
associations with 95% confidence intervals. We will evaluate factors associated 
with an increased risk of infection. Factors assessed will include age, gender, 
socioeconomic status, household size (if available), comorbidities, and UC 
medications. 
 
All statistical analyses will be performed in the R statistical package. 
 
Ethical approval 
Study approval will be requested from the Research Committee of the RCGP RSC. 
The study does not meet the requirements for formal ethics board review as 
defined using the NHS Health Research Authority research decision tool 
(http://www.hra-decisiontools.org.uk/research/). 
Contributors 
Research support for this project in several areas including data analysis, 
literature searching, and medication writing will be provided by Momentum Data. 
John Dennis and Andrew McGovern of Momentum Data have contributed to the 
writing of this protocol and to the study design. Funding for these studies has been 
provided by Pfizer UK. 

Scientific rigor and study registration 
The team ethos at Momentum Data is to support the highest quality research, for 
patient benefit, with rigorous scientific standards. Publication bias remains an 
issue in observational studies. Therefore, if approval is granted the protocol will 
be registered as an observational study with ClinicalTrials.gov and made publicly 
available prior to the commencement of data analysis. Any protocol amendments 
will be published alongside this public record of the study and will be noted in any 
final publication with the rationale for the modification. Any changes will be 
assessed for the need for ethics approval and further RCGP RSC study approval; 
these will be sought if required. 
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Appendices 
Appendix 1 
Ulcerative colitis 
Read V2 Code 
Term 
ID 
Description 
J41.. 
All 
Ulcerative colitis and/or proctitis 
J410. 
All 
Ulcerative proctocolitis 
J4100 
All 
Ulcerative ileocolitis 
J4101 
All 
Ulcerative colitis 
J4102 
All 
Ulcerative rectosigmoiditis 
J4103 
All 
Ulcerative proctitis 
J4104 
All 
Exacerbation of ulcerative colitis 
J410z 
All 
Ulcerative proctocolitis NOS 
J411. 
All 
Ulcerative (chronic) enterocolitis 
J412. 
All 
Ulcerative (chronic) ileocolitis 
J413. 
All 
Ulcerative pancolitis 
N0454 
All 
Juvenile arthritis in ulcerative colitis 
N0310 
All 
Arthropathy in ulcerative colitis 
Read CTV3 
Code 
Term 
ID 
Description 
XE0ag 
All 
Ulcerative colitis 
XaZ2j 
All 
Left sided ulcerative colitis 
XaYzX 
All 
Ulcerative pancolitis 
XaK6E 
All 
Exacerbation of ulcerative colitis 
J410. 
All 
Ulcerative proctocolitis 
J4100 
All 
Ulcerative ileocolitis 
J410z 
All 
Ulcerative proctocolitis NOS 
Jyu41 
All 
[X]Other ulcerative colitis 
Crohn's disease 
Read V2 Code 
Term 
ID 
Description 
J40.. 
All 
Regional enteritis- Crohn's disease 
J400. 
All 
Regional enteritis of the small bowel 
J4002 
All 
Crohn's disease of the termnal ileum 
J4003 
All 
Crohn's disease of the ileum unspecified 
J4004 
All 
Crohn's disease of the ileum NOS 
J4005 
All 
Exacerbation of Crohn's disease of small intestine 
J400z 
All 
Crohn's disease of the small bowel NOS 
J40.. 
All 
Crohn's disease 
J4012 
All 
Exacerbation of Crohn's disease of large intestine 
J401z 
All 
Crohn's disease of the largel bowel NOS 
J402. 
All 
Regional ileocolitis 
J40z. 
All 
Crohn's disease NOS 

Read CTV3 
Code 
Term 
ID 
Description 
XE2QL 
All 
Crohn's disease 
Xa0lh 
All 
Regional enteritis 
X302r 
All 
Crohn's jejunitis 
X302t 
All 
Crohn's ileitis 
J4003 
All 
Crohn's disease of the ileum unspecified 
J4004 
All 
Crohn's disease of the ileum NOS 
J4002 
All 
Crohn's disease of terminal ileum 
J400. 
All 
Regional enteritis of small bowel 
XaK6C 
All 
Exacerbation of Crohn's disease of small intestine 
J400z 
All 
Crohn's disease of the small bowel NOS 
J401. 
All 
Regional enteritis of the large bowel 
XE0af 
All 
Crohn's disease of the large bowel NOS 
XaK6D 
All 
Exacerbation of Crohn's disease of large intestine 
J40z. 
All 
Regional enteritis NOS 
J4010 
All 
Crohn's colitis 
J4011 
All 
Crohn's proctitis 
X3050 
All 
Perianal Crohn's disease 
Jyu40 
All 
[X]Other Crohn's disease 
Supplementary table S1. Read codes used to identify inflammatory bowel disease 
 
 

Appendix 2 
Clinical entity 
ICD 10 code 
Definition 
Anxiety 
F41 
Any coded anxiety episode AND concurrent 
treatment for anxiety 
Depressive episode 
F32 
Any 
coded 
depressive 
episode 
AND 
concurrent treatment for depression 
Recurrent 
depressive disorder 
F33 
(Any historical code* for a depressive 
episode 
AND 
current 
treatment 
for 
depression) OR Any code for recurrent 
depressive disorder 
Anxiety treatments 
NA 
SSRIs, anxiolytics, counselling, CBT, and 
psychotherapy 
Depression 
treatments 
NA 
SSRIs, TCAs, MAOIs, counselling, CBT, and 
psychotherapy 
Supplementary table S2. Algorithms used to identify anxiety episodes, depression episodes, and 
recurrent major depression. Expressions in capitals equate to Boolean expressions. *More than 1 
year ago. SSRIs = selective serotonin reuptake inhibitors, TCA = tricyclic antidepressants, MAOI = 
monoamine oxidase inhibitors, CBT = cognitive behavioural therapy. 
 
 

Read V2 Code 
Term ID 
Description 
E200. 
All 
Anxiety states 
E2000 
All 
Anxiety state unspecified 
E2001 
All 
Panic disorder 
E2002 
All 
Generalised anxiety disorder 
E2003 
All 
Anxiety with depression 
E2004 
All 
Chronic anxiety 
E2005 
All 
Recurrent anxiety 
E200z 
All 
Anxiety state NOS 
Eu41. 
All 
[X]Other anxiety disorders 
Eu410 
All 
[X]Panic disorder [episodic paroxysmal anxiety] 
Eu411 
All 
[X]Generalized anxiety disorder 
Eu412 
All 
[X]Mixed anxiety and depressive disorder 
Eu413 
All 
[X]Other mixed anxiety disorders 
Eu41y 
All 
[X]Other specified anxiety disorders 
Eu41z 
All 
[X]Anxiety disorder, unspecified 
Read CTV3 
Code 
Term ID 
Description 
E200. 
All 
Anxiety disorder 
XE1Y7 
All 
Panic disorder 
Eu410 
All 
[X]Panic disorder [episodic paroxysmal anxiety] 
E2002 
All 
Generalised anxiety disorder 
X00Sb 
All 
Mixed anxiety and depressive disorder 
X00RP 
All 
Organic anxiety disorder 
E2004 
All 
Chronic anxiety 
E2005 
All 
Recurrent anxiety 
E200z 
All 
Anxiety state NOS 
X00Sc 
All 
Anxiety hysteria 
Eu41. 
All 
[X]Other anxiety disorders 
Eu413 
All 
[X]Other mixed anxiety disorders 
Eu41z 
All 
[X]Anxiety disorder, unspecified 
XE1Zj 
All 
[X]Other specified anxiety disorders 
Supplementary table S3. Read codes used to identify anxiety episodes. 
 
 

Read V2 
Code 
Term 
ID 
Description 
E0013 
All 
Presenile dementia with depression 
E0021 
All 
Senile dementia with depression 
E112. 
All 
Single major depressive episode 
E1120 
All 
Single major depressive episode, unspecified 
E1121 
All 
Single major depressive episode, mild 
E1122 
All 
Single major depressive episode, moderate 
E1123 
All 
Single major depressive episode, severe, without mention of 
psychosis 
E1124 
All 
Single major depressive episode, severe, with psychosis 
E1125 
All 
Single major depressive episode, in partial or unspecified remission 
E1126 
All 
Single major depressive episode, in full remission 
E112z 
All 
Single major depressive episode NOS 
E113. 
All 
Recurrent major depressive episode 
E1130 
All 
Recurrent major depressive episodes, unspecified 
E1131 
All 
Recurrent major depressive episodes, mild 
E1132 
All 
Recurrent major depressive episodes, moderate 
E1133 
All 
Recurrent major depressive episodes, severe, without mention of 
psychosis 
E1134 
All 
Recurrent major depressive episodes, severe, with psychosis 
E1137 
All 
Recurrent depression 
E113z 
All 
Recurrent major depressive episode NOS 
E118. 
All 
Seasonal affective disorder 
E11y2 
All 
Atypical depressive disorder 
E11z2 
All 
Masked depression 
E130. 
All 
Reactive depressive psychosis 
E135. 
All 
Agitated depression 
E2003 
All 
Anxiety with depression 
E291. 
All 
Prolonged depressive reaction 
E2B.. 
All 
Depressive disorder NEC 
E2B1. 
All 
Chronic depression 
E2B0. 
All 
Postviral depression 
Eu204 
All 
[X]Post-schizophrenic depression 
Eu251 
All 
[X]Schizoaffective disorder, depressive type 
Eu32. 
All 
[X]Depressive episode 
Eu320 
All 
[X]Mild depressive episode 
Eu321 
All 
[X]Moderate depressive episode 
Eu322 
All 
[X]Severe depressive episode without psychotic symptoms 
Eu323 
All 
[X]Severe depressive episode with psychotic symptoms 
Eu324 
All 
[X]Mild depression 
Eu325 
All 
[X]Major depression, mild 
Eu326 
All 
[X]Major depression, moderately severe 
Eu327 
All 
[X]Major depression, severe without psychotic symptoms 
Eu328 
All 
[X]Major depression, severe with psychotic symptoms 

Eu32y 
All 
[X]Other depressive episodes 
Eu32z 
All 
[X]Depressive episode, unspecified 
Eu33. 
All 
[X]Recurrent depressive disorder 
Eu330 
All 
[X]Recurrent depressive disorder, current episode mild 
Eu331 
All 
[X]Recurrent depressive disorder, current episode moderate 
Eu332 
All 
[X]Recurrent depressive disorder, current episode severe without 
psychotic symptoms 
Eu333 
All 
[X]Recurrent depressive disorder, current episode severe with 
psychotic symptoms 
Eu334 
All 
[X]Recurrent depressive disorder, currently in remission 
Eu33y 
All 
[X]Other recurrent depressive disorders 
Eu33z 
All 
[X]Recurrent depressive disorder, unspecified 
Eu412 
All 
[X]Mixed anxiety and depressive disorder 
Read CTV3 
Code 
Term 
ID 
Description 
X00Sb 
All 
Mixed anxiety and depressive disorder 
X00SO 
All 
Depressive disorder 
X761L 
All 
Seasonal affective disorder 
Xa0wV 
All 
Recurrent brief depressive disorder 
X00SQ 
All 
Agitated depression 
XE1YC 
All 
Reactive depression 
X00SR 
All 
Endogenous depression 
X00SS 
All 
Endogenous depression first episode 
XE1Y0 
All 
Single major depressive episode 
E1120 
All 
Single major depressive episode, unspecified 
E1120 
All 
Single major depressive episode, unspecified 
E1121 
All 
Single major depressive episode, mild 
E1122 
All 
Single major depressive episode, moderate 
E1123 
All 
Single major depressive episode, severe, without mention of 
psychosis 
E1124 
All 
Single major depressive episode, severe, with psychosis 
XaX53 
All 
Single major depressive episode, severe, with psychosis, psychosis 
in remission 
E1125 
All 
Single major depressive episode, in partial or unspecified remission 
E1126 
All 
Single major depressive episode, in full remission 
E112z 
All 
Single major depressive episode NOS 
XM1GC 
All 
Endogenous depression - recurrent 
E1130 
All 
Recurrent major depressive episodes, unspecified 
E1131 
All 
Recurrent major depressive episodes, mild 
E1132 
All 
Recurrent major depressive episodes, moderate 
E1133 
All 
Recurrent major depressive episodes, severe, without mention of 
psychosis 
E1134 
All 
Recurrent major depressive episodes, severe, with psychosis 
E1135 
All 
Recurrent major depressive episodes, in partial or unspecified 
remission 
E1136 
All 
Recurrent major depressive episodes, in full remission 
E113z 
All 
Recurrent major depressive episode NOS 

X00SU 
All 
Masked depression 
E11y2 
All 
Atypical depressive disorder 
X00S8 
All 
Post-schizophrenic depression 
XSEGJ 
All 
Major depressive disorder 
XSKr7 
All 
Cotard syndrome 
XSGol 
All 
Moderate major depression 
XSGok 
All 
Mild major depression 
XSGom 
All 
Severe major depression without psychotic features 
XSGon 
All 
Severe major depression with psychotic features 
E1137 
All 
Recurrent depression 
E130. 
All 
Reactive depressive psychosis 
E2B.. 
All 
Depressive disorder NEC 
E2B0. 
All 
Postviral depression 
E2B1. 
All 
Chronic depression 
Eu320 
All 
[X]Mild depressive episode 
Eu321 
All 
[X]Moderate depressive episode 
Eu331 
All 
[X]Recurrent depressive disorder, current episode moderate 
XE1Y1 
All 
Recurrent major depressive episodes 
XE1ZY 
All 
[X]Severe depressive episode without psychotic symptoms 
XE1ZZ 
All 
[X]Severe depressive episode with psychotic symptoms 
XE1Za 
All 
[X]Other depressive episodes 
XE1Zb 
All 
[X]Depressive episode, unspecified 
XE1Zd 
All 
[X]Recurrent depressive disorder, current episode severe without 
psychotic symptoms 
XE1Ze 
All 
[X]Recurrent depressive disorder, current episode severe with 
psychotic symptoms 
XE1Zf 
All 
[X]Recurrent depressive disorder, unspecified 
XaB9J 
All 
Depression NOS 
XaCHr 
All 
[X] Single episode agitated depression without psychotic symptoms 
XaCHs 
All 
[X] Single episode major depression without psychotic symptoms 
XaCIs 
All 
Mild depression 
XaCIt 
All 
Moderate depression 
XaCIu 
All 
Severe depression 
E0013 
All 
Presenile dementia with depression 
E0021 
All 
Senile dementia with depression 
Supplementary table S4. Read codes used to identify, depression episodes. 
 
 

Read V2 
Code 
Term 
ID 
Description 
E113. 
All 
Recurrent major depressive episode 
E1130 
All 
Recurrent major depressive episodes, unspecified 
E1131 
All 
Recurrent major depressive episodes, mild 
E1132 
All 
Recurrent major depressive episodes, moderate 
E1133 
All 
Recurrent major depressive episodes, severe, without mention of 
psychosis 
E1134 
All 
Recurrent major depressive episodes, severe, with psychosis 
E1135 
All 
Recurrent major depressive episodes, in partial or unspecified 
remission 
E1136 
All 
Recurrent major depressive episodes, in full remission 
E1137 
All 
Recurrent depression 
E113z 
All 
Recurrent major depressive episode NOS 
E2B1. 
All 
Chronic depression 
Eu32A 
All 
[X]Recurrent major depressive episodes, severe, with psychosis, 
psychosis in remission 
Eu33. 
All 
[X]Recurrent depressive disorder 
Eu330 
All 
[X]Recurrent depressive disorder, current episode mild 
Eu331 
All 
[X]Recurrent depressive disorder, current episode moderate 
Eu332 
All 
[X]Recurrent depressive disorder, current episode severe without 
psychotic symptoms 
Eu333 
All 
[X]Recurrent depressive disorder, current episode severe with 
psychotic symptoms 
Eu334 
All 
[X]Recurrent depressive disorder, currently in remission 
Eu33y 
All 
[X]Other recurrent depressive disorders 
Eu33z 
All 
[X]Recurrent depressive disorder, unspecified 
Read CTV3 
Code 
Term 
ID 
Description 
Xa0wV 
All 
Recurrent brief depressive disorder 
XM1GC 
All 
Endogenous depression - recurrent 
E1130 
All 
Recurrent major depressive episodes, unspecified 
E1131 
All 
Recurrent major depressive episodes, mild 
E1132 
All 
Recurrent major depressive episodes, moderate 
E1133 
All 
Recurrent major depressive episodes, severe, without mention of 
psychosis 
E1134 
All 
Recurrent major depressive episodes, severe, with psychosis 
XaX54 
All 
Recurrent major depressive episodes, severe, with psychosis, 
psychosis in remission 
E1135 
All 
Recurrent major depressive episodes, in partial or unspecified 
remission 
E1136 
All 
Recurrent major depressive episodes, in full remission 
E113z 
All 
Recurrent major depressive episode NOS 
E1137 
All 
Recurrent depression 
E2B1. 
All 
Chronic depression 
Eu331 
All 
[X]Recurrent depressive disorder, current episode moderate 
XE1Y1 
All 
Recurrent major depressive episodes 

XE1Zd 
All 
[X]Recurrent depressive disorder, current episode severe without 
psychotic symptoms 
XE1Ze 
All 
[X]Recurrent depressive disorder, current episode severe with 
psychotic symptoms 
XE1Zf 
All 
[X]Recurrent depressive disorder, unspecified 
Supplementary table S5. Read codes used to identify a diagnosis of recurrent major depression. 
 
 

Counselling 
Read V2 
Code 
Term 
ID 
Description 
67... 
11 
Counselling/health education 
671.. 
All 
Counselling - general 
6712. 
All 
Counselling offered 
6714. 
All 
Counselling carried out 
6715. 
All 
Counselling by other agency 
6716. 
All 
Counselling of benefit 
6717. 
All 
Counselling of no benefit 
671Z. 
All 
Counselling - general NOS 
672.. 
All 
Person counselled 
6721. 
All 
Patient counselled 
6722. 
All 
Family counselled 
673.. 
All 
Person counselled by 
6731. 
All 
Counselled by a doctor 
6732. 
All 
Counselled by a nurse 
6733. 
All 
Counselled by a health visitor 
6735. 
All 
Counselled by a social worker 
6736. 
All 
Counselled by a counsellor 
6737. 
All 
Counselled by a vol. worker 
673Z. 
All 
Counselled by person NOS 
8M8.. 
All 
Counselling requested 
9NJ1. 
All 
In-house counselling 
9NJR. 
All 
In-house counselling first appointment 
9NJT. 
All 
In-house counselling follow-up appointment 
Read CTV3 
Code 
Term 
ID 
Description 
X71Ec 
All 
Counselling 
X71Ep 
All 
Coping strategy counselling 
XaEC1 
All 
Phobia counselling 
XaD27 
All 
Family counselling 
6779. 
All 
Psychological counselling 
XaECG 
All 
Anxiety counselling 
XaECF 
All 
Self-esteem counselling 
XaI8j 
All 
Stress counselling 
672.. 
All 
Person counselled 
6721. 
All 
Patient counselled 
6722. 
All 
Family counselled 
XE1TI 
All 
Person counselled by 
6715. 
All 
Counselling by other agency 
6731. 
All 
Counselled by a doctor 
6732. 
All 
Counselled by a nurse 
6733. 
All 
Counselled by a health visitor 
6735. 
All 
Counselled by a social worker 

6736. 
All 
Counselled by a counsellor 
6737. 
All 
Counselled by voluntary worker 
673Z. 
All 
Counselled by person NOS 
Xa07L 
All 
Counselled by member of primary health care team 
9N2B. 
All 
Seen by counsellor 
XaAS4 
All 
Seen by mental health counsellor 
XaBT1 
All 
Refer to counsellor 
XaAfJ 
All 
Referral to mental health counsellor 
9NJ1. 
All 
In-house counselling 
XaLnp 
All 
In-house counselling first appointment 
XaLnr 
All 
In-house counselling follow-up appointment 
671.. 
All 
Counselling - general 
6712. 
All 
Counselling offered 
6714. 
All 
Counselling carried out 
6716. 
All 
Counselling of benefit 
6717. 
All 
Counselling of no benefit 
671Z. 
All 
Counselling - general NOS 
XaAOd 
All 
Under care of counsellor 
XaAOh 
All 
Under care of mental health counsellor 
Cognitive Behavioural Therapy 
Read V2 
Code 
Term 
ID 
Description 
8G13. 
All 
Cognitive-behaviour therapy 
8G130 
All 
Cognitive behavioural therapy parenting programme 
8G131 
All 
CBTp - cognitive behavioural therapy for psychosis 
7L1a. 
All 
Cognitive behavioural therapy 
7L1a0 
All 
Cognitive behavioural therapy by unidisciplinary team 
7L1a1 
All 
Cognitive behavioural therapy by multidisciplinary team 
7L1ay 
All 
Other specified cognitive behavioural therapy 
7L1az 
All 
Cognitive behavioural therapy NOS 
8G510 
All 
Group cognitive behavioural therapy 
8G15. 
All 
Computerised cognitive behavioural therapy 
8HlK. 
All 
Referral for cognitive behavioural therapy 
Read CTV3 
Code 
Term 
ID 
Description 
Ub0qp 
All 
Cognitive and behavioural therapy 
XaABO 
All 
Cognitive - behaviour therapy 
Xad6J 
All 
Cognitive behavioural therapy for psychosis 
Xaaa6 
All 
Cognitive behavioural therapy parenting programme 
XaQC0 
All 
Guided self help cognitive behavioural therapy 
XaKzQ 
All 
Computerised cognitive behavioural therapy 
Xa8I9 
All 
Generic cognitive behavioural therapy 
XaM2I 
All 
Cognitive behavioural therapy by unidisciplinary team 
XaM2J 
All 
Cognitive behavioural therapy by multidisciplinary team 
XaM2K 
All 
Other specified cognitive behavioural therapy 

XaM2L 
All 
Cognitive behavioural therapy NOS 
XaR2j 
All 
Referral to cognitive behavioural therapist 
XaR5D 
All 
Referral for cognitive behavioural therapy 
XaYgB 
All 
Referral for high intensity cognitive behavioural therapy 
Psychotherapy 
Read V2 
Code 
Term 
ID 
Description 
8G... 
All 
Psychotherapy 
8G1.. 
All 
General psychotherapy 
8G10. 
All 
Psychotherapy - behavioural 
8G100 
All 
Behavioural activation therapy 
8G101 
All 
Dialectical behaviour therapy 
8G102 
All 
Behavioural parent training 
8G11. 
All 
Psychotherapy - cognitive 
8G12. 
All 
Psychotherapy - psychodynamic 
8G120 
All 
Short-term psychodynamic therapy 
8G121 
All 
Dynamic interpersonal therapy 
8G122 
All 
Focal psychodynamic therapy 
8G14. 
All 
Cognitive analytic therapy 
8G15. 
All 
Computerised cognitive behavioural therapy 
8G16. 
All 
Interpersonal psychotherapy 
8G18. 
All 
Cognitive stimulation therapy 
9NlK. 
All 
Seen by psychotherapist 
9NlK0 
All 
Seen by trainee psychotherapist 
8HHT. 
All 
Referral to psychotherapist 
ZV57D 
All 
[V]Psychotherapy, not elsewhere classified 
ZV673 
All 
[V]Psychotherapy or other treatment for mental disorder follow-up 
8G9Z. 
All 
Other psychotherapy NOS 
8G9.. 
All 
Other psychotherapy 
Read CTV3 
Code 
Term 
ID 
Description 
X71bp 
All 
Psychotherapy 
XaaUO 
All 
Cognitive rehabilitation therapy 
XaItc 
All 
Brief solution focused psychotherapy 
Xa8IG 
All 
Psychoanalytic and psychodynamic therapy 
Xa8IJ 
All 
Long-term exploratory psychotherapy 
3841. 
All 
Psychoanalysis 
XaA8V 
All 
Generic psychoanalysis 
XaA8W 
All 
Independent psychoanalysis 
XaA8T 
All 
Kleinian psychoanalysis 
XaA8U 
All 
Bion-based group psychoanalysis 
XaA8X 
All 
Classical psychoanalysis 
XaA8Y 
All 
Lacanian psychoanalysis 
XaA8g 
All 
Group psychoanalysis 
XaA8U 
All 
Bion-based group psychoanalysis 

384Z. 
All 
Psychological analysis NOS 
Xa8IM 
All 
Jungian-based therapy 
Xa8IN 
All 
Generic Jungian-based therapy 
Xa8IP 
All 
Analytical psychology 
Xa8IR 
All 
Long-term psychodynamic psychotherapy 
XaA8Z 
All 
Developmental psychodynamic psychotherapy 
XaA8c 
All 
Supportive expressive psychodynamic psychotherapy 
XaA8d 
All 
Psychodynamic-interpersonal psychotherapy 
XaEVq 
All 
Psychodynamic psychotherapy 
Xad7C 
All 
Focal psychodynamic therapy 
Xa8IR 
All 
Long-term psychodynamic psychotherapy 
XaA8Z 
All 
Developmental psychodynamic psychotherapy 
XaA8c 
All 
Supportive expressive psychodynamic psychotherapy 
XaA8d 
All 
Psychodynamic-interpersonal psychotherapy 
Xa8II 
All 
Short-term psychodynamic therapy 
XaXuc 
All 
Dynamic interpersonal therapy 
XaA9g 
All 
Specific task orientated psychotherapy 
XE0iL 
All 
Psychotherapy/sociotherapy 
8G9Z. 
All 
Other psychotherapy NOS 
8G9.. 
All 
Other psychotherapy 
Supplementary table S6. Read codes used to identify non-medication based treatments for 
depression or anxiety. 
 
 

Appendix 3 
Medication class 
Medications 
Medications for mental health conditions 
SSRIs and related 
medication 
Venlafaxine, Bupropion, Duloxetine, Naltrexone, 
Citalopram, Dapoxetine, Escitalopram, Fluoxetine, 
Fluvoxamine, Paroxetine, Sertraline 
TCAs 
Amitriptyline, Clomipramine, Dosulepin, Doxepin, 
Mianserin, Trazodone, Trimipramine, Imipramine, 
Lofepramine, Nortriptyline 
MAOIs 
Tranylcypromine, Phenelzine, Isocarboxazid, 
Moclobemide 
Anxiolytic medications 
Alprazolam, Chlordiazepoxide, Clobazam, Clonazepam, 
Diazepam, Lorazepam, Oxazepam, Buspirone, 
Meprobamate, Clomipramine, Clomethiazole 
Medication for IBD  
Topical 5-ASA 
Mesalazine, Sulfasalazine 
Topical glucocorticoids 
Budesonide, Hydrocortisone, Prednisolone 
Oral 5-ASA 
Balsalazide, Mesalazine, Olsalazine, Sulfasalazine 
Oral glucocorticoids 
Prednisolone, Cortisone, Dexamethasone, 
Methylprednisolone, Beclomethasone, Betamethasone, 
Budesonide, Deflazacort 
Antimetabolites 
Azathioprine, Mercaptopurine, Methotrexate 
Biologic therapies 
Adalimumab, Golimumab, Infliximab, Vedolizumab 
Supplementary table S7. Medications analysed by medication class. SSRI = selective serotonin 
reuptake inhibitors, TCA = tricyclic antidepressants, MAOI = monoamine oxidase inhibitors, 5ASA 
= 5-aminosalicylic acid.