Schizophrenia Clinical Trial
— SMARTOfficial title:
Prolonged-release Melatonin Versus Placebo for Benzodiazepine Discontinuation in Patients With Schizophrenia: a Randomized Clinical Trial
In this trial, researchers aim to investigate if prolonged-release melatonin can facilitate the withdrawal of chronic benzodiazepine administration in patients with schizophrenia. Furthermore, researchers will investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life.
Status | Completed |
Enrollment | 86 |
Est. completion date | June 2014 |
Est. primary completion date | June 2014 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Patients diagnosed with schizophrenia, schizoaffective disorder, or bipolar affective disorder (ICD-10 criteria for schizophrenia (F20), schizoaffective disorder (F25) or bipolar affective disorder (F31) must be fulfilled at inclusion or previously as documented by chart review; fulfillment of relevant DSM-IV-TR criteria will also be registered). - Treated with the same antipsychotic drug for at least 3 months before inclusion (change of dose, antipsychotic polypharmacy and prescription/discontinuation of add-on drugs allowed but the basic antipsychotic treatment should be the same). - Continuously treated with at least one benzodiazepine (chlordiazepoxide, diazepam, clobazam, clonazepam, flunitrazepam, nitrazepam, bromazepam, alprazolam, lorazepam, lormetazepam, oxazepam, triazolam) or benzodiazepine related drug (zolpidem, zopiclone, zaleplon) for at least 3 months before inclusion. - Age 18+. - Fertile women: negative pregnancy test at baseline and use of safe contraceptives (intrauterine devices or hormonal contraception) throughout the trial period and 1 day after withdrawal of trial medication. This does not apply to sterile or infertile participants, i.e. surgically sterilized or post menopausal (missing period for at least 12 months before inclusion) women. - Written informed consent. Exclusion Criteria: - Known aggressive or violent behavior. - Mental retardation, pervasive developmental disorder, or dementia. - Epilepsy, terminal illness, severe comorbidity or unable to understand Danish. - Allergic to compounds in the trial medication (melatonin, lactose, starch, gelatin, talc). - Hepatic impairment (known diagnosis). - Pregnancy and nursing. - Missing informed consent. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Denmark | Center for Neuropsychiatric Schizophrenia Research (CNSR)/Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), University of Copenhagen, Mental Health Centre Glostrup, Mental Health Services - Capital Region of Denmark | Glostrup |
Lead Sponsor | Collaborator |
---|---|
Lone Baandrup | Copenhagen Trial Unit, Center for Clinical Intervention Research, Glostrup University Hospital, Copenhagen |
Denmark,
Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Vohra S, Klassen TP, Baker G. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ. 2006 Feb 18;332(7538):385-93. Epub 2006 Feb 10. Review. — View Citation
Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999 Nov 8;159(20):2456-60. — View Citation
Monti JM, Monti D. Sleep disturbance in schizophrenia. Int Rev Psychiatry. 2005 Aug;17(4):247-53. Review. — View Citation
Shamir E, Laudon M, Barak Y, Anis Y, Rotenberg V, Elizur A, Zisapel N. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry. 2000 May;61(5):373-7. — View Citation
Suresh Kumar PN, Andrade C, Bhakta SG, Singh NM. Melatonin in schizophrenic outpatients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry. 2007 Feb;68(2):237-41. — View Citation
Volz A, Khorsand V, Gillies D, Leucht S. Benzodiazepines for schizophrenia. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD006391. Review. Update in: Cochrane Database Syst Rev. 2012;11:CD006391. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Benzodiazepine (including benzodiazepine related drugs) dose at 6 months follow-up. | The general linear model is used with the outcome measure (dose after 6 months) as the dependent variable and the indicator of intervention and the baseline value as the independent variables. If the assumptions of the model cannot be fulfilled either directly or after transformation a non-parametric method will be used. | 6 months follow-up. | No |
Secondary | Pattern of benzodiazepine dose over time. | The mixed model with repeated measures will be used to analyze the time course. The model is outcome measure = int + baseline + a*t + b*t*t + c*baseline*t + d*baseline*t*t + e*I + f*I*t + g*I*t*t where t is time, I the intervention indicator, int the intercept, and a through g the coefficients. Using Akaike's criterium the best co-variance matrix is first chosen among an unstructured, a compound symmetric, or a first order autoregressive. | 2, 4, and 6 months. | No |
Secondary | The fraction of participants who has completely discontinued benzodiazepines 6 months after initiating trial medication. | The analysis will be done using a logistic regression model where logit(p) is the dependent variable, p is the probability of completing the withdrawal, and a binary intervention indicator is the independent variable. | 6 months follow-up. | No |
Secondary | Pattern of P300 amplitude (psychophysiology) over time. | The mixed model with repeated measures will be used to analyze the time course. The model is outcome measure = int + baseline + a*t + b*t*t + c*baseline*t + d*baseline*t*t + e*I + f*I*t + g*I*t*t where t is time, I the intervention indicator, int the intercept, and a through g the coefficients. Using Akaike's criterium the best co-variance matrix is first chosen among an unstructured, a compound symmetric, or a first order autoregressive. | 2, 4, and 6 months. | No |
Secondary | Pattern of Brief Assessment of Cognition in Schizophrenia (BACS) composite score over time. | The mixed model with repeated measures will be used to analyze the time course. The model is outcome measure = int + baseline + a*t + b*t*t + c*baseline*t + d*baseline*t*t + e*I + f*I*t + g*I*t*t where t is time, I the intervention indicator, int the intercept, and a through g the coefficients. Using Akaike's criterium the best co-variance matrix is first chosen among an unstructured, a compound symmetric, or a first order autoregressive. | 2, 4, and 6 months. | No |
Secondary | Sleep efficiency (polysomnography) at 6 months follow-up. | The general linear model is used with the outcome measure (sleep efficiency) as the dependent variable and the indicator of intervention and the baseline value as the independent variables. If the assumptions of the model cannot be fulfilled either directly or after transformation a non-parametric method will be used. | 6 months. | No |
Secondary | Pittsburgh Sleep Quality Index (PSQI) global score at 6 months follow-up. | The general linear model is used with the outcome measure (PSQI) as the dependent variable and the indicator of intervention and the baseline value as the independent variables. If the assumptions of the model cannot be fulfilled either directly or after transformation a non-parametric method will be used. | 6 months. | No |
Secondary | Pattern of Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ-2) score over time. | The mixed model with repeated measures will be used to analyze the time course. The model is outcome measure = int + baseline + a*t + b*t*t + c*baseline*t + d*baseline*t*t + e*I + f*I*t + g*I*t*t where t is time, I the intervention indicator, int the intercept, and a through g the coefficients. Using Akaike's criterium the best co-variance matrix is first chosen among an unstructured, a compound symmetric or a first order autoregressive. | 2, 4, and 6 months. | No |
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