Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans

Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans: an Open (e.g. Unblinded) Randomized Stay-Switch Pilot Trial

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01662297

Enrollment

Registered

2012-08-10

Start date

2012-07-31

Completion date

2015-10-31

Last updated

2018-10-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Insomnia, Mental Health Disorder, Substance Use Disorder

Keywords

Quetiapine, Trazodone, Insomnia, Dual Diagnosis

Brief summary

This is a pilot comparative effectiveness study designed to determine whether trazodone is as effective as quetiapine for treatment of insomnia in veterans with a history of addiction and mental health issues. The study will have two concurrent phases (parts); first an acceptability determination phase, to determine whether and why (or why not) veterans already taking quetiapine are willing to try an alternative to quetiapine for sleep; and second, a randomized trial phase which will test whether staying on quetiapine has any advantage over switching to trazodone. The purpose of the first phase will be a) to document the proportions of patients and physicians who are willing to agree to such a switch, b) to characterize sociodemographic and clinical characteristics of potentially eligible subjects associated with a willingness to switch from quetiapine to trazodone and c) to record the reasons given why patients and their prescribers are (or are not) willing to accept a switch from quetiapine to trazodone. It will also function to provide some educational background to patients and a reminder to providers about the potential severe side-effects of quetiapine, and will thus facilitate clinical informed consent for the clinical trial phase of the study. Completion of the first part of the study will also serve as the screening component for part II. Part II includes, first, obtaining written informed consent from eligible subjects, and then randomly assigning them to continue quetiapine or to be switched to trazodone in open-label real world fashion for the duration of 4 weeks, followed by another four weeks of open, non-randomized follow- up. The purpose of the second part of the study is to determine if trazodone is an adequate substitute for quetiapine, primarily in terms of treating insomnia. The investigators hypothesize that trazodone will not be inferior to quetiapine in maintaining good quality of sleep measured by sleep scales (i.e., scores will not significantly worsen once switched). This study is open to Veterans in the VA system only. Eligible subjects must have a history of dual diagnosis (i.e., a history of addiction and mental illness).

Detailed description

Part I of the study involves identification through VA records of subjects eligible for the study based on their prescription of quetiapine. Potentially eligible subjects will be contacted by the research team. Subjects will answer a brief questionnaire about their experience with the medication quetiapine as used for insomnia. If subjects are interested in participated in part II, the clinical trial portion of the study, they will be further screened for eligibility. Part II consists of a 4 week clinical trial in which subjects are randomized to stay on quetiapine or switch to trazodone, all of which will be open-label. Subjects will be evaluated for symptoms of sleep quality and excessive daytime sleepiness. subjects will also be assessed for changes in mood, and alcohol/drug use. After the initial 4 week treatment period, subjects on trazodone can choose to switch back to quetiapine or continue on trazodone. Subjects will also be evaluated after an additional 4 weeks (8weeks from start of the study) on outcome measures.

Interventions

DRUGQuetiapine

Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.

DRUGTrazodone

Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Inclusion/

Exclusion criteria

(PHASE 1): * Identified by their VA prescribing provider as taking quetiapine primarily as a sedative/hypnotic agent for some form of insomnia for at least 1 month * Identified by their VA prescribing provider as having dual diagnosis; a lifetime history of substance use disorder and a mental disorder * Willing to meet with a research assistant to answer several questions regarding their use of and experience with quetiapine. * Appear not to be regularly on any medication which would be an exclusion for Part II (see Part II

Design outcomes

Primary

Measure	Time frame	Description
Change in Average Pittsburgh Sleep Quality Inventory (PSQI)Score	From baseline (week 0) to end of 4 week and end of week 8	Data analyzed for change from score at baseline, to week 4, to week 8. The range of scores is 0-21 on this scale, with higher scores indicating worse sleep quality. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL PSQI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The first four weeks of treatment is the active acute experiment phase, and this will be the main comparison time period for the endpoint, but the investigators will also analyze change in PSQI until the follow-up point at the end of week 8.

Secondary

Measure	Time frame	Description
Change in Epworth Sleepiness Scale (ESS) Over Time	From baseline (week 0) to end of week 8	Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on ESS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).The minimum score on ESS is 0-24 units, with higher score representing greater sleepiness.
Change in RAND Short Form 36 Item Health Survey (RAND-SF36) General Health Subscale Over Time	from week 0 (baseline) to end of week 8	Scores range from 0-100 representing percentage, with a higher score representing better functioning. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. The change from week 4 to week 8 (post-intervention) will also be measured and analyzed, reported. This is a comparison between groups (trazodone versus quetiapine)of the change on RAND-SF36 scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
Change in Brief Symptom Inventory (BSI) Over Time	from week 0 (baseline) to end of week 8	The Brief Symptom Inventory scale measures a broad range of psychiatric symptoms (psychological distress) and is meant to provide an overall measure of mental health symptomatology. The BSI has 53 items that use a 5-item Likert scale response. In general, higher scores correspond to greater symptomatology and distress. Usually, the range of scores goes from 0 - 4, since it is averaged over the number of responses, however, we report the raw total score which is the sum of all responses, thus the range is 0-212. Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups of the change on BSI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments.
Change in Insomnia Severity Index (ISI) Scores	from baseline (week 0) to the end of week 4 and at week 8	THE RANGE OF SCORES IS FROM 0-28, WITH 28 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL ISI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
Percentage of Heavy Drinking Days	from week 0 (baseline) to end of week 8	This is a comparison between groups of the mean percent heavy drinking days during the first 4 weeks, and then through to the follow up point (end of week 8). The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
Percentage of Negative Urine Drug Screens	from week 0 (baseline) to end of week 8	This is a comparison between groups of the mean percent of negative urine drug screens. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8). THIS IS A CUMULATIVE PERCENTAGE. MAXIMUM SCORE IS 100%, MINIMUM 0%.
Medical Outcomes Study Sleep Scale- Sleep Index (Short)	from baseline (week 0) to the end of week 8 sample	THE RANGE OF SCORES IS FROM 0-100, WITH 100 REPRESENTING SEVERE INSOMNIA SYMPTOMS. Measurements made and reported at baseline, week 2, week 4. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. . This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL MOS-SS scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).
Change in Alcohol Urge Questionnaire (AUQ)Scores Over Time	from week 0 (baseline) to end of week 8	The lowest possible score for the AUQ is 8 (representing less urge to drink) and the highest score would be a 56 (more urge to drink). Measurements made at baseline, week 2, week 4, week 8. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on AUQ scores over time. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The investigators will first report the comparison during the active treatment phase (baseline to end of week 4) as the main comparison, but will also examine and report changes on the outcome at the follow up point (end of week 8).

Countries

United States

Participant flow

Participants by arm

Arm	Count
Quetiapine Veterans remaining on quetiapine for insomnia. Quetiapine: Quetiapine will be administered at a dosage prescribed by veterans' current providers for the treatment of insomnia.	0
Trazodone Veterans switching from quetiapine to trazodone for the treatment of insomnia. Trazodone: Veterans willing to switch from quetiapine to trazodone for the treatment of insomnia will receive up to 400mg of trazodone daily.	1
Total	1

Baseline characteristics

Characteristic	Total	Trazodone
Age, Categorical <=18 years	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	1 Participants	1 Participants
Age, Continuous	60 years	60 years
Region of Enrollment United States	1 participants	1 participants
Sex: Female, Male Female	0 Participants	0 Participants
Sex: Female, Male Male	1 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 0	1 / 1
serious Total, serious adverse events	0 / 0	1 / 1

Outcome results

Primary

Change in Average Pittsburgh Sleep Quality Inventory (PSQI)Score

Data analyzed for change from score at baseline, to week 4, to week 8. The range of scores is 0-21 on this scale, with higher scores indicating worse sleep quality. Data will be presented and analyzed for those time points with the main outcome measured as the change from baseline to week 4. This is a comparison between groups (trazodone versus quetiapine)of the change on TOTAL PSQI scores over time using repeated measures analysis. This is a non-superiority analysis, so the hypothesis is that there is no significant difference between treatments. The first four weeks of treatment is the active acute experiment phase, and this will be the main comparison time period for the endpoint, but the investigators will also analyze change in PSQI until the follow-up point at the end of week 8.

Time frame: From baseline (week 0) to end of 4 week and end of week 8