What are the indications for prescribing antidepressants that will lead to a clinical benefit?

ISRCTN	ISRCTN84544741
DOI	https://doi.org/10.1186/ISRCTN84544741
Clinical Trials Information System (CTIS)	2013-003440-22
Protocol serial number	16264
Sponsor	University College London (UK)
Funder	National Institute for Health Research (UK) - Programme Grants for Applied Research; Grant Codes: RP-PG-0610-10048

Submission date: 20/03/2014
Registration date: 20/03/2014
Last edited: 02/12/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

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

Contact information

Ms Larisa Duffy
Scientific

UCL Division of Psychiatry
Maple House
149 Tottenham Court Road
London
W1T 7NF
United Kingdom

Email	larisa.duffy@ucl.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised; Interventional; Design type: Treatment
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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)
Study acronym	PANDA
Study objectives	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(s)	13/EE/0418
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Sertraline
Primary outcome measure(s)	Depressive symptoms, measured with the PHQ9 questionnaire; Timepoint(s): 6 weeks follow up
Key secondary outcome measure(s)	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
Completion date	30/11/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	74 Years
Sex	All
Target sample size at registration	547
Total final enrolment	655
Key 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
Key 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
Date of first enrolment	26/01/2015
Date of final enrolment	31/08/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Centre for Academic Mental Health

Oakfield House
Oakfield Grove
Bristol
BS8 2BN
United Kingdom

UCL Division of Psychiatry

Maple House
149 Tottenham Court Road
London
W1T 7NF
United Kingdom

Mental Health and Addiction Research Group

Department of Health Sciences
University of York
Heslington
York
YO10 5DD
United Kingdom

University of Liverpool

B121 Waterhouse Buildings
Liverpool
L69 3GL
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The current data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/11/2019	25/09/2019	Yes	No
Results article	cost-effectiveness results	01/09/2020	02/12/2019	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

02/12/2019: Publication reference added.
25/09/2019: The following changes were made:
1. Publication reference added.
2. The final enrolment number was added from the reference.
11/07/2017: Publication and dissemination plan added.
07/07/2017: The following changes were made to the trial record:
1. The overall trial end date was changed from 30/05/2017 to 30/11/2017.
2. The target number of participants was changed from 683 to 547.
3. Trial participating centres added.
4. IPD sharing statement added.
09/06/2016: Plain English summary added.