Journal Club

Presenter: Dr. Shahma

Chair: Dr. Aishwariya
British Journal of Psychiatry

● A leading international peer-reviewed journal

● Impact factor - 10.671
● 5 year impact factor - 11.171
● Editor-in-chief - Prof Kamaldeep Bhui CBE, Oxford University, UK.
 Association between polypharmacy and depression
relapse in individuals with comorbid depression and
type 2 diabetes: a UK electronic health record study

A. Jeffrey, C. Bhanu, K. Walters, I. C. K. Wong, J. Osborne, D. F. Hayes

Background

● Bidirectional relationship
● Polypharmacy and physical comorbidities associated with increased depression symptoms
● Higher risk of depression relapse
● Discontinuing antidepressant treatment at higher risk of relapse
Cohort study
● Type of analytical (observational) study
● Association between suspected cause and disease.
● Cohort - group of people who share a common characteristic or experience within a defined time
period.

Cohort Disease Total

Yes No

Exposed to putative A B A+B

aetiological factor

Not exposed to aetiological C D C+D

putative factor
● Incidence of disease in exposed group = a/(a+b)
● In non-exposed group = c/ (c+ d)
● The elements of a cohort study are :
a. Selection of study subjects
b. Obtaining data on exposure
c. Selection of comparison groups
d. Follow-up, and
e. Analysis.
Aims
To describe:

● Proportion of individuals who restarted antidepressant treatment within the first year following
discontinuation of treatment.
● The association between the number of concurrent medications prescribed concurrently before
discontinuation of treatment and subsequently restarting antidepressant treatment
● The association between the previous duration of antidepressant treatment and subsequently
restarting antidepressant treatment.
● The interactions between the number of concurrent medications prescribed and the duration of the
previous antidepressant treatment, with regards to restarting antidepressant treatment.

Restarting antidepressant - indicator of relapse

Study design and setting

● Cohort study
● Database: UK Clinical Practice Research Datalink (CPRD) - a longitudinal data-set containing EHRs of 60
million people across 2000 primary care practices in the UK.
○ Demographic details, diagnoses, symptoms, lab tests
○ Representative of the UK population with respect to age, gender and ethnicity.
● Study period: 1 January 2000 to December 2018
Participants
INCLUSION CRITERIA
● Individuals with a clinical code for depression
symptom, diagnosis or process of clinical
care.
● Individuals with at least two blood/serum
glucose/HbA1c tests recorded above the
threshold for T2DM, and either a clinical
code for T2DM or at least one antidiabetic
medication prescription code.
EXCLUSION CRITERIA
● Individuals who only had depression codes
related to dementia, maternity,
schizophrenia or bipolar disorder.
● Individuals with clinical codes for type 1
diabetes mellitus, individuals with <6 months
between the date of the first recorded oral
antidiabetic prescription and the first
recorded insulin prescription, or individuals
who only had codes or medication for T2DM
present during periods of pregnancy.
 ● Individuals whose first recorded
antidepressant prescription was
monotherapy with a common first-line
antidepressant (citalopram, escitalopram,
fluoxetine, mirtazapine, paroxetine,
sertraline, venlafaxine).
● Individuals with <6 months of antidepressant-
free data before the date of their first
antidepressant prescription; individuals whose
first recorded antidepressant was an agent
not listed in the inclusion criteria above.
● <60 days follow up after expected duration of
final antidepressant.

Antidepressant discontinuation was defined as the absence of a recorded prescription for any other
antidepressant within the first 60 days after expected duration of the last antidepressant prescription.
Outcomes

● The outcome was restarting antidepressant treatment within 365 days after the expected end date of
the last antidepressant prescription before discontinuation.
● Participants were censored after 365 days, at the date of death, the date that their primary care
practice registration ended or 31 December 2018, whichever was sooner.
Exposures

● Primary exposure: Number of concurrent medications prescribed simultaneously with the last
antidepressant medication prior to discontinuation, or upto 90 days prior.
● Secondary exposure: Duration of the initial course of antidepressant treatment prior to
discontinuation. They were categorized as:
○ Early discontinuation: 0-6 months
○ NICE recommendations: 7-9 months
○ WHO recommendations: 10-13 months
○ Medium-term: 14-24 months
○ NICE + WHO recommended maintenance for high risk patients: >/= 25 months
Confounders

● Calendar year
● Age
● Gender
● Ethnicity (missing ethnicity - White)
● Primary care practice
Sensitivity analyses

3 sensitivity analyses were done.

● To differentiate between repeat and one-off prescriptions - at least two prescriptions within 180 days
prior to the index date, with at least one of these being within 90 days.
● Effect of coding participants with missing ethnicity as ‘White’ - ‘complete cases’ only.
● Role of timing for depression relapse - limited to 182 days.
Statistical analyses

● 2 univariable analyses
● 2 multivariable analysis - adjusted for the demographic confounders.
● Finally, interaction terms between the number of concurrent medications and the previous duration of
antidepressant medication with regards to restarting antidepressants were modelled and examined.
Results

Median treatment
duration of first
antidepressant
prescribed was 2.79
months.
Hazard ratios for the changing rate of restarting antidepressant treatment, by the number of concurrent medications prescribed
at the time of prior antidepressant discontinuation (adjusted for duration of previous antidepressant treatment, age, gender,
ethnicity, calendar year and primary care practices). Reference group, 0 concurrent medications. CI = confidence interval.
Discussion

● Main Finding: Over a third of participants (35%) restarted antidepressant treatment within the first
year of discontinuation.
● As the number of concurrent medications increased, the rate of restarting antidepressants also
increased considerably, up to 115%.
● The longer the previous antidepressant treatment duration, the higher the rate of restarting
antidepressants.
● General population - discontinuation is more associated with relapse
● Duration of treatment could be proxy to severity
● Shorter duration of treatment could be associated with intolerance.
Strengths and limitations of the study

Strengths:

● Large sample size

● CPRD is representative of the UK population in terms of age, gender and ethnicity.
● Use of spline functions to attain minimum and maximum values for association with outcome

Limitations: .

● Unable to account for previous depression severity.

● Only included most commonly prescribed antidepressants in the UK.
● Only included participants with depression.
Strengths

● Addresses a focused issue

● Censoring of data was done
● Three sensitivity analyses were done to minimise bias
● Clear association between primary exposure and outcome was abtained
Limitations

● Other confounding factors not taken into account.

● Degree of diabetic control
● Restarting antidepressant as an outcome variable
● Other comorbid conditions
THANK YOU