Plain English Summary
Background and study aims
Acute mania or a milder form called hypomania are ways in which bipolar disorder (manic depression) presents. Patients often require hospitalisation and usually require drug treatment with anti-psychotic drugs and mood stabilisers as well as valium-like tranquilisers. The main symptoms include over-activity, racing thoughts, grandiose beliefs and sleep loss. Melatonin is a naturally occurring hormone in the human body which is produced in darkness and suppressed by light. In animal studies it has been shown to inform body tissues about seasonal and light/dark information. In previous studies it caused an improvement in manic symptoms. A further small study of five people showed no effect but was too small a study to answer whether melatonin helps for mania/hypomania. In view of the above it is proposed that melatonin could help as a treatment for acute episodes of mania.
Who can participate?
Manic or hypomanic individuals aged from 18 to 65.
What does the study involve?
Participants will be randomly allocated to take either a melatonin (circadin) tablet or a placebo (dummy) tablet every night 1 hour 30 minutes before sleep for 21 days. Mood and sleep rating scales would be used to assess the progress of the patients on the treatments as well as a special watch which picks up levels of activity and sleep, called an Actiwatch. We will also test if melatonin can improve sleep in this group and reduce overactivity.
What are the possible benefits and risks of participating?
We would expect to see early sleep improvements as well as improvement in other symptoms on a more gradual basis in the group taking melatonin. If successful, it is hoped that early use of melatonin might enable some people to stay out of hospital for their period of relapse and get well sooner.
Where is the study run from?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
July 2008 to December 2009
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Digby Quested
Dr Digby Quested
+44 (0)1865 223703
Melatonin In Acute Mania Investigation (MIAMI-uk): a randomised controlled phase 2 trial
Melatonin as a possible treatment for mania.
Ethics Committee Oxford REC A, 04/09/2009, ref: 09/H0604/63
Double-blind randomised controlled phase 2 trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Melatonin (circadin) 2 mg tablet orally at night 1 hour 30 min before sleep, or placebo for 21 days.
Primary outcome measure
Young Mania Rating Scale at baseline, days 4, 7, 14 and 21.
Secondary outcome measures
1. Activity on the Actiwatch to continue for 21 days
2. Quick Inventory of depressive symptoms C16 (Clinician) at baseline, days 4, 7, 14 and 21
3. Quick Inventory of depressive symptoms SR16 (self report) at baseline, days 4, 7, 14 and 21
4. Altman mania rating scale at baseline, days 4, 7, 14 and 21
5. Adverse events. Duration of follow-up: 21 days
6. Leeds Sleep Evaluation Questionnaire (LSEQ), carried out at baseline, day 4, day 7, day 14 and day 21
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
1. Age limit from 18 to 65, both genders
2. Young Mania Rating Scale >=20
3. In or out-patients meeting the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM4) criteria for bipolar disorder
4. Currently experiencing manic symptoms
5. Capacity to give informed consent
Target number of participants
Total final enrolment
Participant exclusion criteria
1. Clinically significant substance abuse
2. Comorbid Axis 1 disorders (DSM4)
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
University of Oxford (UK)
John Radcliffe Hospital
National Institute for Health Research, Research for Innovation, Speculation and Creativity (RISC) programme (UK)
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
30/04/2018: Results presented at British Association of Psychopharmacology Conference 2013 https://www.bap.org.uk/pdfs/BAP2013_abstractbook.pdf (page 26)
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)