Plain English Summary
Background and study aims
Depression is a common condition that affects between 2% and 3% of the population at any one time. Depression is commonly treated with antidepressant medication. In England and Wales there were 47 million prescriptions for antidepressants in 2011. Selective serotonin reuptake inhibitors (SSRIs) are the first-line antidepressant recommended by the NICE guidelines. Some people with depression will recover spontaneously and it is not clear at present which people will benefit from a course of antidepressants. Depression is also difficult to assess accurately during a short primary care consultation. As a result, general practitioners often have to make a difficult decision about whether an individual will benefit from an SSRI. This study is designed to refine the indications for the use of antidepressants in people with depression. The aim of this study is to investigate the response to sertraline in people with depression by assessing the severity and duration of their depressive symptoms using a self-administered computerised assessment that could be used in primary care.
Who can participate?
Patients aged 18-74 with depressive symptoms
What does the study involve?
Participants are randomly allocated to take either sertraline or placebo (dummy) capsules for 12 weeks, with assessments at 2, 6 and 12 weeks.
What are the possible benefits and risks of participating?
Some people find it rewarding to take part in medical research, and appreciate the additional monitoring and contact with the researchers. Taking the study medication may improve symptoms of depression, but this cannot be guaranteed, and half of the participants take a dummy pill or placebo. The long-term benefits of the study are improved guidance/treatment recommendations for primary care clinicians, thereby increasing the likelihood that a prescription will lead to clinical benefit, while reducing prescriptions that are not needed.
Where is the study run from?
UCL Division of Psychiatry (UK)
When is the study starting and how long is it expected to run for?
May 2014 to May 2018
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Larisa Duffy
Larisa.duffy@ucl.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Ms Larisa Duffy
ORCID ID
Contact details
UCL Division of Psychiatry
Maple House
149 Tottenham Court Road
London
W1T 7NF
United Kingdom
-
larisa.duffy@ucl.ac.uk
Additional identifiers
EudraCT number
2013-003440-22
ClinicalTrials.gov number
Protocol/serial number
16264
Study information
Scientific title
A phase IV, double-blind randomised placebo-controlled, parallel group multi-site trial of sertraline compared to placebo in patients presenting with depressive symptoms in primary care where treatment with SSRIs is uncertain. What are the indications for Prescribing ANtiDepressants that will leAd to a clinical benefit? (PANDA RCT)
Acronym
PANDA
Study hypothesis
Depression is a common condition that affects between 2% and 3% of the population at any one time. Depression is commonly treated with antidepressant medication. In England and Wales there were 47m prescriptions for antidepressants in 2011. Selective serotonin reuptake inhibitors (SSRIs) are the first line antidepressant recommended by NICE guidelines. Some people with depression will recover spontaneously and it is not clear at present which people will benefit from a course of antidepressants. Furthermore it is not known whether the current diagnostic criteria for depression as described in ICD10 or DSM5 indicate benefit from antidepressants. Depression is also difficult to assess accurately during a short primary care consultation. As a result, general practitioners often have to make a difficult decision about whether an individual will benefit from an SSRI. This study is designed to refine the indications for the use of antidepressants in people with depression. The aim of this study is to carry out a randomised controlled trial in order to investigate the severity and duration of depressive symptoms that are associated with a clinically important response to sertraline in people with depression. The trialists plan to assess severity and duration using a standardised assessment that can then be used to guide prescription in primary care. The trialists will include patients presenting in primary care aged 18-74 with depressive symptoms and both the GP and patient are unsure whether there will be significant clinical benefit from taking SSRI antidepressants. Sertraline will be provided in 50mg capsules. The usual dose in primary care is 100mg and the trialists will recommend that all participants take 2 capsules (100mg) unless they cannot tolerate that dose. The participants can increase to 3 capsules if they have not responded and with the agreement of the PI.
Ethics approval
13/EE/0418
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Topic: Mental Health Research Network, Primary Care Research Network for England; Subtopic: Depression, Not Assigned; Disease: Depression, All Diseases
Intervention
Sertraline vs Placebo: The sertraline will be encapsulated and matching placebo capsules produced in order to maintain the blind during the study. Trial treatment will be for 12 weeks with assessments at 2, 6 and 12 weeks. The main treatment response compared to placebo occurs within about 6 weeks. The trialists also want to obtain an early account of adverse events and clinical response at 2 weeks as the first signs of improvement can occur at that point. The 12-week assessment will provide evidence for any sustained benefit.
Follow Up Length: 3 month(s)
Study Entry: Single Randomisation only
Intervention type
Drug
Phase
Phase IV
Drug names
Sertraline
Primary outcome measure
Depressive symptoms, measured with the PHQ9 questionnaire; Timepoint(s): 6 weeks follow up
Secondary outcome measures
Added 11/07/2017:
1. Depressive symptoms, measured with the PHQ-9 at 2 and 12 weeks as a continuous outcome and at 2, 6 and 12 weeks as a binary outcome
2. Depressive symptoms, measured with the BDI-II at 2, 6 and 12 weeks
3. Anxiety symptoms, measured by the GAD-7 at 2, 6 and 12 weeks
4. Quality of life, measured with the EQ-5D-5L and SF-12 at 2, 6 and 12 weeks
5. Emotional processing task scores, measured at baseline, 2 and 6 weeks
6. Costs associated with health care use, time off work and personal costs over the 6 months period and measured at 12 weeks
Overall trial start date
05/05/2014
Overall trial end date
30/11/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Participants presenting in primary care aged 18-74 with depressive symptoms and both the GP and patient are unsure whether there will be significant clinical benefit from taking SSRI antidepressants and not currently on antidepressants (or in previous 8 weeks).
The trialists want to keep the inclusion criteria pragmatic and broad to reflect the current dilemma in clinical practice. They therefore think that the uncertainty of GP and patient about the possible benefits of antidepressants is the key entry criterion for the trial. They have included participants up to 74 years as additional clinical issues concerned with cognitive decline and social care become more common after that age.
There may be situations where people with severe depressions would be included in the study and might receive placebo. The patient will always be free to consult their general practitioner during the study about any of their health concerns. The patient and GP can contact the PI at any time and seek advice about continuing with the study medication to stop the randomised treatment if there was deterioration or any other clinical need to start antidepressants. The trialists would allow hypnotic medication and other non-pharmacological treatment options including low intensity psychosocial treatments as provided by IAPT or counselling. The trialists will record this information and can investigate any impact on the findings in secondary analyses (and also use for the economic analysis).
There is marked comorbidity between depression and anxiety disorders. The trialists are relying upon the GP referring subjects into the study to exclude all anxiety disorders that they have identified and wish to treat with SSRIs. The trialists will assess anxiety disorders at baseline and any influence of comorbid anxiety (that they expect will be quite common) on outcome can be examined in exploratory analyses.
Target Gender: Male & Female; Upper Age Limit 74 years ; Lower Age Limit 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 547; UK Sample Size: 547
Total final enrolment
655
Participant exclusion criteria
1. Anyone who is incapable of completing the questionnaires or who has other psychiatric disorders including psychosis, bipolar disorder, dementia, eating disorder, substance dependence, schizophrenia, mania, hypomania
2. Known allergies to the IMP, placebo or excipients
3. Poorly controlled epilepsy
4. Hepatic impairment
5. Currently on contraindicated medication: monoamine oxidase Inhibitors within 14 days or pimozide
6. Pregnant women
Added 07/07/2017:
7. People with bleeding disorders such as haemophilia, Christmas disease and von Willebrands disease, as well as those with past medical history of bleeding gastric or duodenal ulcers or other significant bleeding disorders
8. An episode of Torsade’s de Pointes
Recruitment start date
26/01/2015
Recruitment end date
31/08/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Centre for Academic Mental Health
Oakfield House
Oakfield Grove
Bristol
BS8 2BN
United Kingdom
Trial participating centre
UCL Division of Psychiatry
Maple House
149 Tottenham Court Road
London
W1T 7NF
United Kingdom
Trial participating centre
Mental Health and Addiction Research Group
Department of Health Sciences
University of York
Heslington
York
YO10 5DD
United Kingdom
Trial participating centre
University of Liverpool
B121 Waterhouse Buildings
Liverpool
L69 3GL
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research (UK) - Programme Grants for Applied Research; Grant Codes: RP-PG-0610-10048
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
1. Trial protocol paper - submitted as of 11/07/2017
2. Main results paper from RCT - expected January 2018
3. Main NIHR Report - to be submitted March 2018
4. Emotion processing tasks in RCT - manuscript expected January 2018
5. General predictors outcome - a paper exploring participants' predictions whether they were in the active or placebo arm: how accurate they were, what reasons they gave, and maybe whether their predictions were linked to outcome
IPD sharing statement
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
01/01/2018
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
2019 results in https://www.ncbi.nlm.nih.gov/pubmed/31543474 (added 25/09/2019)
2019 cost-effectiveness results in https://www.ncbi.nlm.nih.gov/pubmed/31777008 (added 02/12/2019)