Clinical trial NCT01662297: Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans
Official title: Comparison of Quetiapine and Trazodone Treatment for Insomnia in Dually Diagnosed Veterans: an Open (e.g. Unblinded) Randomized Stay-Switch Pilot Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Insomnia
Mental Health Disorder
Substance Use Disorder
Keywords: Quetiapine
Trazodone
Insomnia
Dual Diagnosis
Lead sponsor: VA Connecticut Healthcare System
Sponsor class: FED
First posted: 2012-08-10
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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 exclusion criteria).

Inclusion Criteria (PHASE 2):

* Willing to provide written informed consent.
* Provider reports that primary use of quetiapine is for insomnia for at least one month and not primary or augmentation treatment of mood, anxiety disorder, psychosis, or mood stabilization.
* Have a self-identified and provider confirmed lifetime history of mental health and substance use disorder (dual diagnosis).
* Currently taking Quetiapine up to 300mg daily for the primary purpose of treating insomnia, and have been taking it for at least 1 month (30 days).
* Use of an acceptable method of birth control by female patients who have a possibility of becoming pregnant.
* The provider should review the patients from the identified charts, and fill out information about the patient and why they are on the drug, and provider should consent to us approaching the client and potentially switching them; the investigators will not approach and begin enrollment for part II on subjects if their provider feels it is not appropriate for them for any reason.

Exclusion Criteria (PHASE 2):

* Physiologic substance dependence requiring detoxification in the past 30 days (substance abuse is not an exclusion).
* Concomitant administration of: other sedative hypnotics, benzodiazepines, prazosin, other atypical antipsychotics, stimulants, ketoconazole and other inhibitors of cytochrome P450 3A (e.g., itraconazole, fluconazole, erythromycin, and protease inhibitors), phenytoin or other strong inducers of cytochrome P450 enzymes.
* Intolerance or hypersensitivity to trazodone.
* Pregnant or lactating women or women planning to become pregnant.
* Hepatic or renal problems AST or ALT (\>3 times upper limit of normal);
* Elevated bilirubin (\>1.2), BUN (\>24), creatinine (\>1.7).
* Unstable, serious medical condition or one requiring acute medical treatment, or anticipation of hospitalization for extended care.
* Dementia, epilepsy, insulin-dependent diabetes, anticoagulation with coumadin.
* Legal entanglements or pending legal charges with potential of incarceration.
* Recent (i.e., past 3 months) assault or suicide gesture currently needing acute intervention.
* Concurrent participation in another clinical trial with an investigational drug during the last 30 days.

Primary outcomes:
measure: Change in Average Pittsburgh Sleep Quality Inventory (PSQI)Score
timeFrame: From baseline (week 0) to end of 4 week and end of week 8
Secondary outcomes:
measure: Change in Insomnia Severity Index (ISI) Scores
timeFrame: from baseline (week 0) to the end of week 4 and at week 8
measure: Change in Epworth Sleepiness Scale (ESS) Over Time
timeFrame: From baseline (week 0) to end of week 8
measure: Change in RAND Short Form 36 Item Health Survey (RAND-SF36) General Health Subscale Over Time
timeFrame: from week 0 (baseline) to end of week 8
measure: Change in Brief Symptom Inventory (BSI) Over Time
timeFrame: from week 0 (baseline) to end of week 8
measure: Change in Alcohol Urge Questionnaire (AUQ)Scores Over Time
timeFrame: from week 0 (baseline) to end of week 8
measure: Percentage of Heavy Drinking Days
timeFrame: from week 0 (baseline) to end of week 8
measure: Percentage of Negative Urine Drug Screens
timeFrame: from week 0 (baseline) to end of week 8
measure: Medical Outcomes Study Sleep Scale- Sleep Index (Short)
timeFrame: from baseline (week 0) to the end of week 8 sample
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: Yale University/Veterans Affairs CT
name: Albert J Arias, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University/Veterans Affairs CT
name: Elizabeth Ralevski, Ph.D.
role: STUDY_DIRECTOR
References: