Augmentation of antipsychotic medication with anticonvulsant in the management of treatment resistant schizophrenia
- Conditions
- SchizophreniaMental and Behavioural Disorders
- Registration Number
- ISRCTN77257074
- Lead Sponsor
- King's College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped
- Sex
- All
- Target Recruitment
- 371
Current inclusion criteria as of 04/05/2021:
1. Aged 18 and above at the time of consent
2. Adequate command of English to understand the information leaflet
3. Capacity to consent to participation in the study
4. Confirmation of DSM-5 diagnosis of schizophrenia or schizoaffective disorder using SCID-5
5. PANSS total symptom severity score > 70
6. At least one PANSS psychotic item rating of at least moderate severity (> 3 on one or more psychotic item rating in PANSS)
7. Received treatment with at least one non-clozapine antipsychotic drug at adequate dose (as defined by Maudsley guidelines)for a duration of at least 6 weeks and in case of a depot be stable for at least 2 treatment cycles or at least 30 days
8. On a stable dose of antipsychotic treatment for at least 2 weeks in case of oral dosage forms
9. Good adherence to antipsychotic treatments as determined by a score > 4 on the Medication Adherence rating scale
10. Female subject of child bearing potential must agree to the MHRA pregnancy prevention programme which includes a negative serum pregnancy test, use of a highly effective form of birth control and signing an annual risk acknowledgement form
_____
Previous inclusion criteria:
1. Aged 18 and above at the time of consent
2. Adequate command of English to understand the information leaflet
3. Capacity to consent to participation in the study
4. Confirmation of DSM-5 diagnosis of schizophrenia or schizoaffective disorder using SCID-5
5. PANSS total symptom severity score > 70
6. At least one PANSS psychotic item rating of at least moderate severity (> 3 on one or more psychotic item rating in PANSS)
7. Received treatment with at least one non-clozapine antipsychotic drug at adequate dose (as defined by Maudsley guidelines)for a duration of at least 6 weeks and in case of a depot be stable for at least 2 treatment cycles or at least 30 days
8. On a stable dose of antipsychotic treatment for at least 2 weeks in case of oral dosage forms
9. Good adherence to antipsychotic treatments as determined by a score > 4 (ideally > 6) on the Medication Adherence rating scale
10. Female subject of child bearing potential must agree to the MHRA pregnancy prevention programme which includes a negative serum pregnancy test, use of a highly effective form of birth control and signing an annual risk acknowledgement form
1. Subject having a rating of 4 or above on the clinical frailty scale
2. Female subject who is pregnant or breast-feeding
3. Subject with a known history of urea cyclic disorder
4. Subject with a known history of porphyria
5. Subject with a known history of severe renal insufficiency
6. Subject with a known history of a mitochondrial disorder and in the opinion of the recruiting researcher will impair the safety of the subject and/or the scientific integrity of the study
7. Subject with carnitine palmitoyltransferase (CPT) type II deficiency
8. Subject currently taking clozapine
9. Subject currently taking valproate
10. Subject who had stopped taking valproate in the past six weeks prior to screening due to adverse effects
11. Any recent change (<2 weeks) change in antipsychotic regimen
12. Subject answers yes” to Suicide Ideation” Items 4 (active suicide ideation) with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) on the C-SSR during the screening visit
13. Subject has attempted suicide within 3 months prior to screening
14. Subject having known hypersensitivity to valproate or other ingredients in the tablet or placebo
15. Significant sustained abnormality when vital signs are measured at screening
16. Patients with a personal or family history of significant liver disease (e.g. severe hepatic dysfunction, cirrhosis)
17. Any other medical condition in the opinion of the recruiting researcher that will impair the safety of the subject and/or the scientific integrity of the study
18. Participation in a clinical trial within 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
19. Participation in a research study that in the opinion of the investigator will affect the safety of the volunteer or scientific integrity of either study
20. Taking a drug that may have a clinically significant effect on the metabolism of valproate or where valproate may have a clinically significant effect on its metabolism including oxcarbazepine, lamotrigine, phenobarbital, primidone, phenytoin, ethosuximide, rufinamide, phenytoin, carbapenem antibiotics, topiramate, acetazolamide, warfarin and other coumarin anticoagulants and in the opinion of the recruiting researcher will impair the safety of the subject and/or the scientific integrity of the study
(added 04/05/2021)
21. Women of childbearing potential unwilling to follow the study contraception requirements
22. Subject with a known history of active liver disease
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Psychotic (positive), negative and general symptom severity in schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS) positive subscale at the 12-month visit
- Secondary Outcome Measures
Name Time Method