Seasonal Affective Disorder
Conditions
Keywords
Seasonal Affective Disorder, Ramelteon, Psychiatry, Randomized Controlled Trial, Hamilton Depression Rating Scale- SAD Version, Circadian Rhythm
Brief summary
The purpose of this study is to determine whether treating sleep difficulties in patients with seasonal affective disorder also improves their depressive symptoms.
Detailed description
Seasonal affective disorder(SAD) is a type of depression in which a patient's depressive symptoms worsen in the winter. These patients' depressive symptoms often lessen in the spring and summer months. Much of the focus of the treatment of SAD (light therapy and melatonin) has involved the brain's suprachiasmatic nucleus(SCN), as it is hypothesized that one potential reason for SAD is a desynchronized SCN. Ramelteon offers a new and more pharmacologically exact mechanism to re-synchronize the SCN. The administration of ramelteon for this patient population may improve sleep, and in addition, do so in a manner that may also reduce their seasonal affective depressive symptoms. Patients eligible for enrollment will be administered either ramelteon or placebo and return to the study office for 4 monthly visits over the winter months, to evaluate the effects of ramelteon versus placebo on sleep and mood.
Interventions
DRUGRamelteon
one 8 mg tablet at bed for up to 4 months
DRUGPlacebo
one tablet at bedtime for up to 4 months
Sponsors
Takeda Pharmaceuticals North America, Inc.
Lehigh Valley Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female age 18-65 yrs. * A diagnosis of seasonal affective disorder * A Pittsburgh Sleep Quality Index \>5 * English speaking * Be able to sign informed consent
Exclusion criteria
* Active substance abuse * Current psychotic symptoms * Severe personality disorders * Primary sleep disorders * Severe chronic obstructive pulmonary disease (COPD) * Prescription fluvoxamine(Luvox) use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Monthly for duration of treatment (up to 4 months) | Self-rated scale to measure quality of sleep via questions regarding sleep latency, duration, efficiency, disturbances, use of sleep medication, and daytime dysfunction. Score ranges from 0-21, higher scores represent more significant sleep disturbance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Monthly for duration of treatment (up to 4 months) | Self-rated scale to measure severity of depressive symptoms. Score ranges from 25-100, higher scores reflect more depression. |
| Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Monthly for duration of treatment (up to 4 months) | Clinician-rated measure of mood; evaluates classical 21 Hamilton Depression items, and 8-item subscale measuring atypical depression symptoms which commonly occur during SAD episodes. Score ranges from 0-89, higher scores indicate higher levels of depression. |
Countries
United States
Participant flow
Recruitment details
Recruitment began in August 2006 and was completed by October 2007. Participants, who at the time were receiving outpatient psychiatric services through Lehigh Valley Hospital, were recruited via referral through the department of psychiatry, and also through print advertisement. Participants received no compensation for participating in the study.
Pre-assignment details
50 individuals signed the informed consent document, one was a screen failure, so 49 participants started study medication. During the study, both treatment groups were maintained on their usual medications for depression and allowed treatment as usual, including medication adjustments.
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon 8 mg pill taken by mouth nightly | 25 |
| Placebo inactive sugar pill taken by mouth nightly | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | No longer met criteria | 1 | 0 |
| Overall Study | Screen Failure | 0 | 1 |
| Overall Study | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Ramelteon | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 25 Participants | 25 Participants |
| Age Continuous | 46.08 years STANDARD_DEVIATION 11.04 | 45.49 years STANDARD_DEVIATION 11.81 | 47.76 years STANDARD_DEVIATION 10.23 |
| Region of Enrollment United States | 50 participants | 25 participants | 25 participants |
| Sex: Female, Male Female | 37 Participants | 19 Participants | 18 Participants |
| Sex: Female, Male Male | 13 Participants | 6 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / — | 5 / — |
| serious Total, serious adverse events | 1 / — | 0 / — |
Outcome results
Primary
Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI)
Self-rated scale to measure quality of sleep via questions regarding sleep latency, duration, efficiency, disturbances, use of sleep medication, and daytime dysfunction. Score ranges from 0-21, higher scores represent more significant sleep disturbance.
Time frame: Monthly for duration of treatment (up to 4 months)
Population: Intention to Treat analysis; excludes one screen failure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ramelteon | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Month 1 | 9.52 scores on a scale | Standard Error 0.84 |
| Ramelteon | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Month 3 | 8.07 scores on a scale | Standard Error 0.83 |
| Ramelteon | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Month 2 | 7.57 scores on a scale | Standard Error 0.84 |
| Ramelteon | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Month 4 | 7.05 scores on a scale | Standard Error 0.85 |
| Ramelteon | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Baseline | 11.56 scores on a scale | Standard Error 0.75 |
| Placebo | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Month 4 | 9.61 scores on a scale | Standard Error 0.87 |
| Placebo | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Baseline | 11.45 scores on a scale | Standard Error 0.77 |
| Placebo | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Month 1 | 8.67 scores on a scale | Standard Error 0.9 |
| Placebo | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Month 2 | 8.62 scores on a scale | Standard Error 0.89 |
| Placebo | Sleep Satisfaction at Baseline and Measured Monthly, as Measured by the Pittsburgh Sleep Quality Index (PSQI) | Month 3 | 9.88 scores on a scale | Standard Error 0.85 |
Secondary
Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD)
Clinician-rated measure of mood; evaluates classical 21 Hamilton Depression items, and 8-item subscale measuring atypical depression symptoms which commonly occur during SAD episodes. Score ranges from 0-89, higher scores indicate higher levels of depression.
Time frame: Monthly for duration of treatment (up to 4 months)
Population: Intention to Treat analysis; excludes one screen failure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Month 1 | 16.16 scores on a scale | Standard Error 1.88 |
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Month 3 | 11.69 scores on a scale | Standard Error 1.66 |
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Month 2 | 14.81 scores on a scale | Standard Error 1.9 |
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Month 4 | 9.15 scores on a scale | Standard Error 1.67 |
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Baseline | 22.68 scores on a scale | Standard Error 1.6 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Month 4 | 23.68 scores on a scale | Standard Error 1.71 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Baseline | 19.99 scores on a scale | Standard Error 1.63 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Month 1 | 15.97 scores on a scale | Standard Error 2.04 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Month 2 | 19.47 scores on a scale | Standard Error 1.96 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Structured Interview Guide for the Hamilton Depression Rating - Seasonal Affective Disorder (SIGH-SAD) | Month 3 | 20.65 scores on a scale | Standard Error 1.67 |
Secondary
Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS)
Self-rated scale to measure severity of depressive symptoms. Score ranges from 25-100, higher scores reflect more depression.
Time frame: Monthly for duration of treatment (up to 4 months)
Population: Intention to Treat analysis; excludes one screen failure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Month 1 | 54.35 scores on a scale | Standard Error 2.7 |
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Month 3 | 49.26 scores on a scale | Standard Error 2.81 |
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Month 2 | 53.51 scores on a scale | Standard Error 2.71 |
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Month 4 | 46.14 scores on a scale | Standard Error 2.65 |
| Ramelteon | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Baseline | 63.06 scores on a scale | Standard Error 1.92 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Month 4 | 61.65 scores on a scale | Standard Error 2.74 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Baseline | 58.63 scores on a scale | Standard Error 1.96 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Month 1 | 56.40 scores on a scale | Standard Error 2.86 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Month 2 | 58.59 scores on a scale | Standard Error 2.8 |
| Placebo | Depressive Symptoms at Baseline and Measured Monthly, as Measured by the Zung Depression Scale (ZDS) | Month 3 | 58.62 scores on a scale | Standard Error 2.89 |