Clozapine Resistant Schizophrenia
Conditions
Keywords
Clozapine, Schizophrenia, Vitamin-D, Treatment-resistant
Brief summary
Background: Despite improvements in medications, treatment delivery and rehabilitation, schizophrenia outcomes remain suboptimal. There are a proportion of 30-40% treatment-resistant schizophrenia patients. Multiple lines of evidence suggest that vitamin D is a neuro-active steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. Ecological studies support a potential role for vitamin D in schizophrenia. These data include studies that have explored the association between schizophrenia and winter/spring birth and also the apparent increased incidence and prevalence of schizophrenia at higher latitudes. Objective: To evaluate the effect of vitamin-D supplementation on the mental state of clozapine-treated chronic schizophrenia patients, and the relation of disease severity to serum vitamin D levels. Methods: the investigators will use a prospective, interventional, longitudinal, double blinded, placebo-controlled, randomized design. The investigators will recruit 50 clozapine-treated chronic schizophrenia patients, with low level of serum vitamin-D, that will be randomly assigned (1:1 ratio) to receive either weekly oral drops of vitamin D (Cholecalciferol) or oral drops of placebo for 8 weeks follow-up. Repeated assessments will include: clinical severity scales (PANSS, CGI), side effects (SAS, BARS, clozapine side effects), cognitive (MoCA), metabolic parameters and laboratory data. Patients who were assigned to placebo will be supplemented with vitamin D after the 8 weeks period, and then will be assessed again with the same protocol of vitamin D treated patients. All participants will be assessed again after 24 weeks after vitamin D initiation. Analysis: the investigators will use on-way ANOVA with repeated measures for comparison of vitamin D and control groups. The investigators will apply intention to treat and LOCF.
Interventions
DRUGVitamin D3
once weekly oral drops preparation at a daily dose of 2000 IU X 7 = 14,000 IU per week (about 60 drops each week).
DRUGplacebo
Sponsors
Geha Mental Health Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females 2. Age 18-65 years 3. Diagnosis of schizophrenia according to DSM-IV-TR criteria, as confirmed by two senior psychiatrists 4. Total PANSS score \> 70 5. CGI-S \> 3 6. Clozapine treatment for at least 18 weeks 7. Vitamin D deficiency: plasma 25-OH-Vitamin D \<75 nmol/L (20-30 ng/mL) 8. Able to consume oral drops of vitamin-D 9. Able to sign informed consent
Exclusion criteria
1. Mental retardation 2. Organic brain disease 3. Known parathyroid disorder 4. Inborn/acquired vitamin D metabolism disorders 5. Patients already treated with vitamin D supplementation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Positive and Negative Syndrome Scale total score | Baseline to 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in the MoCA Cognitive composite score | Baseline to 8 weeks |
Other
| Measure | Time frame |
|---|---|
| Change in Positive and Negative Syndrome Scale sub-scores | Baseline to 8 weeks |
Countries
Israel
Outcome results
None listed