Melatonin Versus Placebo for Benzodiazepine Discontinuation in Patients With Schizophrenia

NCT ID: NCT01431092

Last Updated: 2014-06-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2014-06-30

Brief Summary

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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.

Detailed Description

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Treatment of schizophrenia frequently includes prolonged administration of benzodiazepines despite lack of evidence of its use. It is often difficult to discontinue use of benzodiazepines because of development of dependence.

After being randomized to prolonged-release melatonin (Circadin®) 2 mg daily versus matching placebo, participants are required to slowly taper off their benzodiazepine dose towards no intake. Data are collected at baseline and at 6 months follow-up regarding medical treatment, cognition, psychophysiology, sleep, laboratory tests, adverse events, psychopathology, social function, and quality of life. Data on medical treatment, cognition, adverse events, social function, and quality of life are also collected at 2 and 4 months follow-up.

The results from this trial will assess if melatonin has a role in withdrawing long-term benzodiazepine administration in schizophrenia patients. This group of patients is difficult to treat and therefore often subject to polypharmacy which may play a role in the reduced life expectancy compared to the background population. In addition, the data of the trial are also analyzed as an observational cohort design to investigate the association of benzodiazepine dose reduction/discontinuation with psychophysiology, cognition, sleep, quality of life, and other selected variables (not further described below, see trial protocol). Knowledge of these important clinical aspects is lacking in this group of patients.

Conditions

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Schizophrenia Schizoaffective Disorder Bipolar Affective Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Melatonin

Group Type EXPERIMENTAL

Melatonin

Intervention Type DRUG

Prolonged-release melatonin (Circadin®) 2 mg, once daily, 1-2 hours before bedtime.

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Both Circadin and placebo are encapsulated in lactose containing gelatin capsules to optimize the blinding.

Interventions

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Placebo

Both Circadin and placebo are encapsulated in lactose containing gelatin capsules to optimize the blinding.

Intervention Type DRUG

Melatonin

Prolonged-release melatonin (Circadin®) 2 mg, once daily, 1-2 hours before bedtime.

Intervention Type DRUG

Other Intervention Names

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Prolonged-release melatonin Circadin®

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Glostrup University Hospital, Copenhagen

OTHER

Sponsor Role collaborator

Copenhagen Trial Unit, Center for Clinical Intervention Research

OTHER

Sponsor Role collaborator

Lone Baandrup

OTHER

Sponsor Role lead

Responsible Party

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Lone Baandrup

MD, Ph.D.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Lone Baandrup, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CNSR/CINS

Birte Glenthøj, MD, MSc

Role: STUDY_CHAIR

CNSR/CINS

Locations

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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 Municipality, , Denmark

Site Status

Countries

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Denmark

References

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Volz A, Khorsand V, Gillies D, Leucht S. Benzodiazepines for schizophrenia. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD006391. doi: 10.1002/14651858.CD006391.

Reference Type BACKGROUND
PMID: 17253592 (View on PubMed)

Monti JM, Monti D. Sleep disturbance in schizophrenia. Int Rev Psychiatry. 2005 Aug;17(4):247-53. doi: 10.1080/09540260500104516.

Reference Type BACKGROUND
PMID: 16194796 (View on PubMed)

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. doi: 10.1136/bmj.38731.532766.F6. Epub 2006 Feb 10.

Reference Type BACKGROUND
PMID: 16473858 (View on PubMed)

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. doi: 10.4088/jcp.v61n0509.

Reference Type BACKGROUND
PMID: 10847313 (View on PubMed)

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. doi: 10.4088/jcp.v68n0208.

Reference Type BACKGROUND
PMID: 17335321 (View on PubMed)

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. doi: 10.1001/archinte.159.20.2456.

Reference Type BACKGROUND
PMID: 10665894 (View on PubMed)

Baandrup L, Fasmer OB, Glenthoj BY, Jennum PJ. Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial. BMC Psychiatry. 2016 Oct 13;16(1):348. doi: 10.1186/s12888-016-1062-8.

Reference Type DERIVED
PMID: 27737649 (View on PubMed)

Baandrup L, Fagerlund B, Jennum P, Lublin H, Hansen JL, Winkel P, Gluud C, Oranje B, Glenthoj BY. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol. BMC Psychiatry. 2011 Oct 5;11:160. doi: 10.1186/1471-244X-11-160.

Reference Type DERIVED
PMID: 21975110 (View on PubMed)

Other Identifiers

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2010-024065-46

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2010-024065-46

Identifier Type: -

Identifier Source: org_study_id

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