Clinical trial NCT02347033: Trial of Sertraline Versus Cognitive Behaviour Therapy for Generalised Anxiety
Official title: RCT of Sertraline Versus Cognitive Behavioural Therapy for Anxiety Symptoms in People With Generalised Anxiety Disorder Who Have Failed to Respond to Low Intensity Psychological Interventions as Defined by the NICE GAD Guidelines
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Generalised Anxiety Disorder
Keywords: Sertraline
Selective Serotonin Reuptake Inhibitor (SSRI)
Cognitive Behavioural Therapy (CBT)
Increasing Access to Psychological Therapies (IAPT)
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: NHS Health Technology Assessment Programme
name: National Institute for Health Research, United Kingdom
First posted: 2015-01-27
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Generalised Anxiety Disorder (GAD) is common, causes unpleasant symptoms and impairs people's functioning. It is often chronic and may be accompanied by depression and other anxiety disorders. It is not currently clear whether medication or psychological therapy provides better long term outcomes for those not responding to simpler low intensity treatments so we propose to compare the clinical effectiveness of a pharmacological treatment (the drug Sertraline) with a Cognitive Behavioural Therapy (CBT) intervention.

Our hypothesis is that in people with GAD who have not responded to low intensity psychological interventions, CBT will lead to a greater improvement in their GAD symptoms as measured using the GAD-7 scale at 12 month follow-up than Sertraline.

Detailed description: The investigators propose to undertake a randomised controlled trial (RCT) to compare the clinical effectiveness in terms of symptoms and function of a pharmacological treatment (the SSRI Sertraline) prescribed at therapeutic doses, with a manualised psychological intervention (Cognitive Behavioural Therapy, CBT) delivered by trained psychological therapists to patients with persistent generalised anxiety disorder (GAD) which has not improved with low intensity psychological interventions as defined by NICE (the National Institute for Clinical Effectiveness).

The investigators will recruit people via the Increasing Access to Psychological Therapies (IAPT) service from up to 15 sites in England. People still scoring highly on an anxiety measure (GAD-7) despite having received a low intensity psychological intervention will be given a brief flyer about the trial. Names of those interested in taking part who have given written consent to having their details released will be passed to the research team and the IAPT staff will also let the research team know the name of the participant's general practice, with their permission.

The research team will then contact potential participants offering them an appointment for an interview/assessment to discuss the study, sending them a patient information sheet to reach them at least 48 hours beforehand. The study information will explain that the medication being evaluated, Sertraline, although not currently licensed for GAD was recommended by NICE on the basis of its effectiveness in clinical trials and that the study team will be available to clarify any issues arising from this.

At the baseline assessment patients will be asked to give informed consent by a member of the research team and both medical suitability (as confirmed by fax/secure email from the GP) and the meeting of other inclusion/exclusion criteria will be checked. Upon confirmation of eligibility, baseline assessments will be carried out by a member of the research team and consenting patients randomised to receive either the medication or CBT. The Chief Investigator or other medically qualified persons within the research team will review all eligibility information and confirm that the patient is eligible.

Eligible participants will be randomised via an independent web-based computerised system to one of two interventions. The research team will provide the relevant contact details/instructions to patients in order to initiate treatment. The trial interventions consist of: (a) The medication sertraline prescribed by their GP according to a trial protocol matching current clinical recommendations and within a dosage between 25 and 150mg daily. We will ask GPs to review patients regularly (at least 6 times in 12 months) and patients to take the medication for a year unless they have significant adverse effects. Side-effects will be regularly monitored. (b) The other intervention is CBT delivered by high intensity therapists from local IAPT services. They will provide 14 to 16 sessions of a manualised treatment developed for use in GAD and will be trained in its delivery. The primary outcome will be the GAD-7 score measured at 12 months. Participants will also be asked to complete this outcome measure by postal questionnaire at 3, 6 and 9 months, as well as a range of secondary outcomes.

Eligibility criteria: Inclusion Criteria:

* Aged 18 or above
* Positive score of 10+ on GAD-7
* Primary diagnosis of GAD as diagnosed on MINI
* Failure to respond to NICE defined low intensity psychological interventions

Exclusion Criteria:

* Inability to complete questionnaires due to insufficient English or cognitive impairment;
* Current major depression
* Other comorbid anxiety disorder(s) of more severity or distress to the participant than their GAD;
* Significant dependence on alcohol or illicit drugs;
* Comorbid psychotic disorder, bipolar disorder;
* Treatment with antidepressants in past 8 weeks or any high intensity psychological therapy within past 6 months;
* Currently on contraindicated medication: monoamine oxidase Inhibitors within the past 14 days or pimozide;
* Patients with poorly controlled epilepsy;
* Known allergies to the Investigational Medicinal Product (IMP) or excipients;
* Concurrent enrolment in another Investigational Medicinal Product trial;
* Severe hepatic impairment;
* Women who are currently pregnant or planning pregnancy or lactating
* Patient on anti-coagulants
* History of bleeding disorders

Primary outcomes:
measure: GAD-7
timeFrame: GAD-7 score at 12 months
Secondary outcomes:
measure: GAD-7
timeFrame: GAD-7 score at 3 months
measure: GAD-7
timeFrame: GAD-7 score at 6 months
measure: GAD-7
timeFrame: GAD-7 score at 9 months
measure: HAM-A
timeFrame: HAM-A score at 12 months
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: PHQ-9 score at 3 months
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: PHQ-9 score at 6 months
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: PHQ-9 score at 9 months
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: PHQ-9 score at 12 months
measure: Work and Social Activity Scale (WASAS)
timeFrame: WASAS score at 12 months
measure: Euroquol-5 item-3 level (EQ-5D-3L)
timeFrame: Utility score at 3 months
measure: Euroquol-5 item-3 level (EQ-5D-3L)
timeFrame: Utility score at 6 months
measure: Euroquol-5 item-3 level (EQ-5D-3L)
timeFrame: Utility score at 9 months
measure: Euroquol-5 item-3 level (EQ-5D-3L)
timeFrame: Utility score at 12 months
measure: Employment and Social Care Questionnaire (ESC)
timeFrame: ESC score at 6 months
measure: Employment and Social Care Questionnaire (ESC)
timeFrame: ESC score at 12 months
measure: (CSQ) Client Satisfaction Questionnaire
timeFrame: CSQ score at 3 months
measure: (CSQ) Client Satisfaction Questionnaire
timeFrame: CSQ score at 12 months
measure: Patient preference rating scale
timeFrame: Patient preference rating scale score at 12 months
Other outcomes:
measure: Health service outcome - General practitioner (GP) contacts
timeFrame: GP contacts at 12 months
measure: Health service outcome - Practice nurse contacts
timeFrame: Practice nurse contacts at 12 months
measure: Health service outcome - referrals to secondary care medical services
timeFrame: Referrals to secondary care medical services at 12 months
measure: Health service outcome - referrals to psychological therapy services
timeFrame: Referrals to psychological therapy services at 12 months
measure: Health service outcome - referrals to psychiatric services
timeFrame: Referrals to psychiatric services at 12 months
measure: Health service outcome - prescriptions for psychotropic medication
timeFrame: Prescriptions for psychotropic medication at 12 months
Locations:
city: London
country: United Kingdom
facility: Camden & Islington (with Kingston)
Study officials:
affiliation: University College, London
name: Marta Buszewicz
role: PRINCIPAL_INVESTIGATOR
References: