Generalised Anxiety Disorder (GAD) Mental and Behavioural Disorders
Conditions
Interventions
Participants will be randomised using Sealed Envelope https://www.sealedenvelope.com/ with a 1:1 ratio to pregabalin 50-300 mg or placebo using a flexible dosing strategy that will mimic usual care. P
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
18 Years to 74 Years
Inclusion criteria
Inclusion criteria: Current key inclusion criteria as of 26/11/2025: 1. Meeting ICD-11 criteria for generalised anxiety disorder using the revised clinical interview schedule (CIS-R) 2. Scoring =12 on the CIS-R total score 3. Age 18-74 years (upper age limit to ensure the validity of our measures) 4. Currently taking an SSRI, SNRI or mirtazapine (at specified doses; the full list is in the trial guidance document that all investigators at sites have to follow) for a minimum of 8 weeks prior to randomisation and with good adherence as agreed with PI 5. Treatment with at least one other antidepressant before their current antidepressant _____ Previous key inclusion criteria: 1. Meeting ICD-11 criteria for generalised anxiety disorder using the revised clinical interview schedule (CIS-R) 2. Scoring =12 on the CIS-R total score 3. Age 18-74 years (upper age limit to ensure the validity of our measures) 4. Currently taking an SSRI, SNRI or mirtazapine in BNF recommended doses for a minimum of 8 weeks prior to randomisation 5. Treatment with at least one other antidepressant before their current antidepressant
Exclusion criteria
Exclusion criteria: Current key exclusion criteria as of 26/11/2025: 1. Currently taking pregabalin or use within the previous 1 month (i.e. wash-out of 1 month required) 2. Taking regular antipsychotics 3. Have bipolar disorder, psychosis, or alcohol misuse 4. Current or recent opiate dependence where there is a risk of pregabalin abuse 5. Current use of opiates with a daily dose of >15 morphine milligram equivalents 6. Creatinine clearance (measured by eGFR is acceptable) 7. Requirement to use home oxygen machines daily for respiratory problems 8. Experience breathlessness and score =3 on the MRC Dyspnoea scale (‘Stops for breath after walking about 100 metres or after a few minutes on the level’ or ‘Too breathless to leave the house or breathless when dressing or undressing’) 9. Regular daily use of z drugs >3.75 mg zopiclone or >10mg zolpidem 10. Regular daily use of benzodiazepines or regular night-time use >10mg diazepam or equivalent 11. Currently receiving psychotherapy and within 6 months of starting therapy 12. Pregnancy, planned pregnancy and women who are breastfeeding 13. Unable to complete self-administered scales in English (some scales are not validated in other languages) 14. Taking part in another CTIMP _____ Previous key exclusion criteria: 1. Currently taking pregabalin or use within the previous 1 month (i.e. wash-out of 1 month required) 2. Taking regular antipsychotics 3. Have bipolar disorder, psychosis, or alcohol misuse 4. Current or recent opiate dependence where there is a risk of pregabalin abuse 5. Current use of opiates with a daily dose of >15 morphine milligram equivalents 6. Creatinine clearance 3.75 mg zopiclone or >10mg zolpidem 10. Regular daily use of benzodiazepines or regular night-time use >10mg diazepam or equivalent. 11. Currently receiving or about to receive psychological treatment 12. Pregnancy, planned pregnancy and women who are breastfeeding 13. Unable to complete self-administered scales in English (some scales are not validated in other languages) 14. Taking part in another CTIMP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Anxiety symptoms measured with GAD7 at 12 weeks as a continuous score | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Anxiety and depression: 1.1. Anxiety scores (GAD7) at week 3, week 6, week 26 and week 30 1.2. Dichotomised anxiety scores (present or absent based on a cut-off of GAD7 =10) at week 3, week 6, week 12, week 26 and week 30 1.3. Depressive scores (PHQ9) at week 3, week 6, week 12, week 26 and week 30 1.4. Panic symptoms at all follow-up visits 3, 6, 12, 26, ~30 weeks 2. Global improvement and quality of life measured using EQ5D5L and SF-12 at week 3, week 6, week 12, week 26 and week 30 3. Adherence to study medication assessed using a single item asking if they are still taking study medication and a five-item scale used in the MIR and Cobalt studies repeated at all follow-up visits 4. Withdrawal and adverse events: 4.1. Adverse effects of pregabalin and antidepressants – based on the Toronto scales for antidepressants (as used in GENPOD study) with additional symptoms of pregabalin side effects and pregabalin withdrawal repeated at all follow-up visits 4.2. Withdrawal symptoms from pregabalin – these are included in the adverse effect scale above repeated at all follow-up visits 4.3. Stopping the study medication repeated at all follow-up visits 5. Use of alternative anxiolytic methods: 5.1. Alcohol consumption (AUDIT PC) measured at every visit 5.2. Benzodiazepine use measured at every visit 6. Resource use and employment: 6.1. Primary care resource use (6 months pre and post randomisation) 6.2. Antidepressant medication collected from primary care medical records (6 months pre and post randomisation) 6.3. Self-reported health resource use (baseline and 26 weeks asking about previous 6 months) including psychological therapies 6.4. Self-reported social care resource use (baseline and 26 weeks asking about previous 6 months) 6.5. Employment and time off work (baseline and 26 weeks asking about previous 6 months) 7. Cognitive assessments. Tests of reinforcement learning, working memory and general cognitive function (administered through a web browser using the | — |
Countries
England, United Kingdom
Outcome results
None listed