Wake Therapy in the Treatment of Depression
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Wake Therapy + light box +/- lithium 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
Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day.
Device: light box
use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire
Other Names:
Drug: Lithium
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)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Structured Interview for the Hamilton Depression Scale With Atypical Depression Supplement(SIGH-ADS) [up to 6 weeks]
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.
Secondary Outcome Measures
- Morningness-Eveningness Questionnaire (MEQ), [up to 6 weeks]
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
- Symptom Check List (SCL-90) [up to 6 weeks]
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.
- Quick Inventory of Depressive Symptoms, Self Rated (QIDS-SR 16) [up to 6 weeks]
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
- Hypomania Interview Guide, Current Assessment Version (HIGH-C) [up to 6 weeks]
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.
- Clinical Global Improvement (CGI) [up to 6 weeks]
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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Depression Evaluation Service - New York State Psychiatric Institute | New York | New York | United States | 10032 |
| 2 | New York State Psychiatric Institute | New York | New York | United States | 10032 |
Sponsors and Collaborators
- New York State Psychiatric Institute
Investigators
- Principal Investigator: Jonathan W. Stewart, M.D., New York State Psychiatric Institute
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 5491/7316R
- IRB 5491
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium |
|---|---|
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) |
| Period Title: Overall Study | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium |
|---|---|
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) |
| Overall Participants | 8 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
7
87.5%
|
| >=65 years |
1
12.5%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
42.9
(14.6)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
6
75%
|
| Male |
2
25%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
8
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
1
12.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
7
87.5%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
8
100%
|
Outcome Measures
| Title | Structured Interview for the Hamilton Depression Scale With Atypical Depression Supplement(SIGH-ADS) |
|---|---|
| Description | 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. |
| Time Frame | up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium |
|---|---|
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) |
| Measure Participants | 8 |
| Mean (Standard Deviation) [score on a scale] |
16.6
(5.5)
|
| Title | Morningness-Eveningness Questionnaire (MEQ), |
|---|---|
| Description | 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 |
| Time Frame | up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| One patient did not complete the Week 6 assessments, mean and standard deviation are based on the 7 subjects who completed the week 6 assessments. |
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium |
|---|---|
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) |
| Measure Participants | 7 |
| Mean (Standard Deviation) [score on a scale] |
45.3
(11.3)
|
| Title | Symptom Check List (SCL-90) |
|---|---|
| Description | 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. |
| Time Frame | up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium |
|---|---|
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) |
| Measure Participants | 8 |
| Mean (Standard Deviation) [score on a scale] |
1.03
(0.44)
|
| Title | Quick Inventory of Depressive Symptoms, Self Rated (QIDS-SR 16) |
|---|---|
| Description | 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 |
| Time Frame | up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium |
|---|---|
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) |
| Measure Participants | 8 |
| Mean (Standard Deviation) [score on a scale] |
11.5
(4.8)
|
| Title | Hypomania Interview Guide, Current Assessment Version (HIGH-C) |
|---|---|
| Description | 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. |
| Time Frame | up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium |
|---|---|
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) |
| Measure Participants | 8 |
| Mean (Standard Deviation) [score on a scale] |
2.0
(1.3)
|
| Title | Clinical Global Improvement (CGI) |
|---|---|
| Description | 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. |
| Time Frame | up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium |
|---|---|
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) |
| Measure Participants | 8 |
| Mean (Standard Deviation) [score on a scale] |
3.25
(1.04)
|
Adverse Events
| Time Frame | 7 Days | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Wake Therapy + Light Box +/- Lithium | |
| Arm/Group Description | 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 Wake Therapy: Maintaining wakefulness on alternating nights over 7 days, with continued sleep deprivation the next day. light box: use of a lightbox titrated between 15-60 minutes (typically 30 minutes), timed according to chronotype score on the Morningness-Eveningness Questionnaire Lithium: 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) | |
All Cause Mortality |
||
| Wake Therapy + Light Box +/- Lithium | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | |
Serious Adverse Events |
||
| Wake Therapy + Light Box +/- Lithium | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Wake Therapy + Light Box +/- Lithium | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | David Hellerstein |
|---|---|
| Organization | NYSPI |
| Phone | 646-774-8069 |
| david.hellerstein@nyspi.columbia.edu |
- 5491/7316R
- IRB 5491