Wake Therapy in the Treatment of Depression

Study Overview
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Brief Summary
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This pilot study seeks to replicate previous findings that sleep deprivation results in marked improvement in depression symptoms, as well as to test whether concurrent treatment with Light Therapy and Lithium are successful in locking in and maintaining therapeutic effects in both bipolar and unipolar depressed subjects.

Detailed Description
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Both refractory depression and bipolar depression are difficult to treat. A night of complete sleep deprivation has been shown to result in marked improvement in 60% of depressed patients, although maintenance of therapeutic effects have not been sustained with wake therapy alone. This pilot study will assess the effectiveness of wake therapy in treating both bipolar depression (5 participants)and major depression (5 participants), as well as the effectiveness of concomitant light therapy and lithium in maintaining the therapeutic effects. Participants will undergo direct observation in the hospital for one week during initial treatment with alternating nights of sleep deprivation, light therapy and lithium treatment, and then will be seen weekly as outpatients for 6 weeks.

Official Title
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Combined Wake Therapy, Light Therapy, and Lithium for Bipolar and Refractory Depression

Conditions
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Major Depressive Disorder, Bipolar Disorder

Intervention / Treatment
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* Behavioral: Wake Therapy
* Device: light box
* Drug: Lithium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: current major depressive episode (MDD, BP-I or BP-II) if not BP-I or BP-II, treatment refractory to ≥ 2 adequately used antidepressants having different mechanisms If BP-I or BP-II, treatment refractory to ≥ 1 standard treatment, such as lithium or valproate physically healthy age 18-75 not taking current antidepressants(antidepressants deemed effective will not be discontinued Exclusion Criteria: medically unstable condition past intolerance of lithium (bipolar only) history of (or current) psychosis or epilepsy current (past six months) drug or alcohol abuse/dependence pregnancy contraindication to lithium (bipolar only) significant retinal pathology (e.g., retinitis pigmentosa, macular degeneration) currently taking effective antidepressant cognitive dysfunction Parkinson's Disease Thyroid Stimulating Hormone > 5 milli International Units/Liter left ventricular hypertrophy symptomatic mitral valve prolapse abnormal creatinine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Wake Therapy + light box +/- lithium<br>Bipolar patients must take lithium; others do not take lithium all patients are hospitalized for a week during which they do not sleep on alternating nights for six weeks, including the week in the hospital all patients sit in front of bright lights at specified times and for specified durations | Behavioral: Wake Therapy<br>* Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day.<br>Device: light box<br>* use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire<br>* Other names: Day Light;Drug: Lithium<br>* For patients not already taking lithium, dose will start at 600 mg daily (all in the evening) and be adjusted in 300 mg/d increments according to weekly blood levels (i.e., lithium dose may be changed once a week if most recent blood level is too low; if too high, it will be decreased or temporarily discontinued as clinically indicated; 150 mg increments will be utilized if multiples of 300 mg result in intolerance or blood levels outside the target range (0.6 - 1.0 mEq/L)<br>* Other names: Lithobid, lithium carbonate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Structured Interview for the Hamilton Depression Scale With Atypical Depression Supplement(SIGH-ADS) | This is a structured interview to obtain 17 Hamilton Depression Rating Scale ratings, with 8 additional items added to measure reverse vegetative features common in bipolar depression and depression with atypical features. There are total 25 items, score ranges from 0 to 90. Higher score means worse depression. | up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morningness-Eveningness Questionnaire (MEQ), | This is a standard self-report instrument for measuring the extent to which an individual is an early bird vs. a night owl, asking a variety of questions concerning the time of day individuals prefer engagement in various activities. Scores correlate highly with biologic measures of circadian rhythm phase and will be used to custom program the timing of each patient's light therapy and habitual sleep Numerical scales: Multiple choice, 4-5 point scale. The sum gives a score ranging from 16 to 86; scores of 41 and below indicate evening types, scores of 59 and above indicate morning types, scores between 42-58 indicate intermediate types; 49.8% of the total population was classified as morning type compared to 5.6% having an evening-type preference | up to 6 weeks | 
| Symptom Check List (SCL-90) | This a standard listing covering most major categories of psychiatric symptoms. It allows measurement not only of depressive symptoms over time, but also other common symptoms, such as those of panic attacks or other anxiety disorders. It consists of 90 items that yields nine scores along primary symptom dimensions and three scores among global distress indices. Each item scores 0-4, higher scores indicate greater distress. Mean of the respective item scores are used. Range from 0-4, higher value indicate greater distress. | up to 6 weeks | 
| Quick Inventory of Depressive Symptoms, Self Rated (QIDS-SR 16) | The responses to this question set, adapted from John Rush's Inventory of Depressive Symptoms: Total QIDS scores range from 0 to 27, with scores of 5 or lower indicative of no depression, scores from 6 to 10 indicating mild depression, 11 to 15 indicating moderate depression, 16 to 20 reflecting severe depression, and total scores greater than 21 indicating very severe depression | up to 6 weeks | 
| Hypomania Interview Guide, Current Assessment Version (HIGH-C) | The HIGH-C is structured like the SIGH-ADS, and provides assessments of manic and hypomanic symptoms , in order to help identify and quantify switches and mixed states. All items are scored from 0 to 4, range from 0-60. An item score of 0 indicates absence of the symptom; 1 and 2 indicate incremental levels of mild presentations short of hypomania (but typical of hyperthymia); 3 indicates moderate severity, persistent and uncharacteristic for the patient, and in most cases, observable by others(as is typical of hypomania); and 4 indicates a marked or severe symptom (typical of mania). The sum of points on all items constitutes the total HIGH-R score. | up to 6 weeks | 
| Clinical Global Improvement (CGI) | This is a standard measure of the clinician's overall impression of how the patient is doing. It includes two measurements, one for the patient's severity of overall symptomatology, and the other for improvement since starting treatment. is rated on a seven-point scale: Compared to the patient's condition at admission to the project [prior to medication initiation], this patient's condition is: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment. | up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression