Official Title: “Antidepressant Response to a Sedating Antidepressant Improves Driving Safety in Patients With Major Depressive Disorder”

This concurrent, two-part study will:

I) Using overnight sleep recordings, evaluate the short- and long-term sleep-promoting effects of the antidepressant mirtazapine (Remeron) in patients who have been prescribed this medication for major depressive disorder and sleep disruption.

II) Investigate the psychomotor performance of depressed patients using driving simulation testing before and during treatment with mitrazapine.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety Study

In the treatment of depression, the role of sleep is important as there are mutual relationships between mood disorder and sleep disorders. Over 80% of major depressive disorder (MDD) patients report sleeping problems. Depression can strongly impair cognitive functioning and daytime alertness. (Mirtazapine (Remeron) is an antidepressant and sleep-promoting agent that has been available in Canada for a few years. However, research investigating the effects of mirtazapine on sleep is limited and it is not known what are the short- and long-term changes in sleep architecture associated with this drug and if daytime performance is affected.

Rationale:

The co-existence of depression and sleep difficulties are very common. Mirtazapine is marketed as a single modality of treatment for both depression and impaired sleep. As a sleep clinic in a psychiatry department, a single modality of treatment for depressive and sleep disorders is preferred by patients and can help improve compliance to treatment.

However, there are only 7 published studies investigating the effects of mirtazapine and sleep and these have significant limitations. None of these studies have objectively examined mirtazapine’s short- and long-term on sleep architecture and daytime function (daytime sleepiness, alertness, driving performance) in depressed patients. This study will address these issues.

Hypothesis:

I) Mirtazapine will produce both immediate and long- improvement effects on sleep in patients with major depressive disorders. There may be impairments in alertness for the first two days after starting treatment but daytime alertness will recover after one week.

II) Patients treated with mitrazapine will show a rapid, initial improvement in driving performance with recovery of sleep and slower, further improvement as treatment of their depression translates into better sleep quality as well as improvements in attention, alertness and concentration.

Study Design:

This pilot proposal is a two-part longitudinal, open-label clinical study with consecutive enrollment of subjects.

This research study will take place in conjunction with normal clinical practice. Patients with depression and sleep disorders are commonly seen in our sleep clinic and mirtazapine is one of several antidepressants that is prescribed by our clinicians. In this study, we will follow a group of patients who have been prescribed mirtazapine by one of our clinic physicians and who meet the inclusion and exclusion listed below. There will be an additional number of sleep studies (10 total versus the usual 2 or 3) performed; the usual daytime testing will be conducted as part of the standard of care (Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test (MWT)); we will administer additional questionnaires to assess subjective sleepiness, alertness and fatigue; and, driving simulator testing will be conducted in accordance with our normal standard of care.

Intervention(s) in this Clinical Trial

• Behavioral: Driving Simulator Testing
• Drug: Mirtazapine Treatment

Primary Measures

• Driving performance on the driving simulator

Secondary Measures

• Ability to maintain wakefulness

Inclusion Criteria:

• Fulfilling DSM-IV criteria for Major Depressive Disorder
• Score of Hamilton Rating Scale for Depression (HDRS-17) > 17
• Patient to be prescribed mirtazapine (Remeron) as determined by physician
• Subject has no known clinically significant abnormal vital signs or other clinical findings at screening.
• Patients should have a driving license for more than 3 years and drive over 15,000 km year.
• Females of childbearing potential must willingly use effective birth control.

Exclusion Criteria:

• Night shift workers.
• A history or present condition of: Bipolar Disorder or Depressive Disorder not
• Otherwise Specified,Schizophrenia or other psychotic disorders (according to DSM-IV), Schizotypal or Borderline personality disorder, Organic mental disorders
• A present condition of: Anxiety Disorders (according to DSM-IV), Eating Disorders, Postpartum Depression
• Epilepsy or a history of seizure disorder or ever received treatment with anticonvulsant medication for epilepsy or seizures
• PSG recording of an extremely abnormal sleep EEG (other than that which would be expected with depression)
• Alcohol or substance abuse (according to DSM-IV) during the last 6months prior to baseline.
• Any physical disease, which may explain the symptoms of depression.
• Any chronic physical disease, which is not stabilized.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 25 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University Health Network, Toronto

Overall Clinical Trial Officials and Contacts

Colin M. Shapiro, MBBCh, PhD Principal Investigator University Health Network, Toronto  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00385437

Study ID Number: REB-03-0255-A

ClinicalTrials.gov Identifier: NCT00385437

Health Authority: Canada: Health Canada