Clinical trial NCT03511209: Discontinuation of Hypnotics in Older Veterans
Official title: The Efficacy of Masked Tapering on Discontinuation of Hypnotics in Older Veterans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insomnia
Keywords: Sleep Initiation and Maintenance Disorders
Hypnotics and Sedatives
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2018-04-27
Enrollment: 132
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Sleeping medications, called hypnotics, are often prescribed for insomnia. About one-quarter of Veterans use hypnotics (or bedtime alcohol). Older patients who use hypnotics fall more often and have worse memory than those who do not use them. Stopping hypnotics often reverses these problems. The Department of Veterans Affairs (VA) is trying to reduce hypnotic use among older adults. Currently, there are two main treatments to help patients stop using hypnotics. The first treatment involves a slow decrease in the daily dose until the hypnotic is ultimately discontinued. For safety, the process of decreasing the daily dose is usually supervised by a physician. The second is a treatment for insomnia called cognitive behavioral therapy for insomnia (CBTI).

This study will compare a novel hypnotic tapering method to the usual tapering method offered to older Veterans. The purpose of the study is to determine if the novel tapering method is more effective than the usual tapering method, both in terms of hypnotic discontinuation and improvement in insomnia severity.

Participants will be recruited from among Veterans 55 years and older who receive care from one VA Healthcare System. Following a baseline assessment, participants will be randomly assigned to one of the two 8-week treatment groups (66 participants per group). Each treatment group will receive CBTI, however, one group will receive the novel tapering program and the other group the usual tapering program. Follow-up assessments will be conducted at post-treatment and at 6-months after completion of the treatment.

If the novel tapering program is effective, it will represent a treatment option that can be offered to older Veterans who want to discontinue hypnotics. This tapering program could help VA healthcare providers adhere to clinical guidelines that recommend benzodiazepine discontinuation among older adults. A reduction in chronic hypnotic use may in turn reduce the risk of falls and hip fractures, which ultimately may improve the health and quality of life of older Veterans who receive healthcare at the VA.

Detailed description: Hypnotics such as benzodiazepines and benzodiazepine receptor agonists are often prescribed for insomnia. Among Veterans attending outpatient clinics, approximately one-quarter use hypnotics (or bedtime alcohol). Hypnotics use is associated with an increased risk of falls and worse cognition in older adults. Discontinuing hypnotics often attenuates or reverses these negative effects, and the Department of Veterans Affairs (VA) has initiatives to reduce hypnotic use among older adults. Current discontinuation strategies focus on tapering off the hypnotic and/or treating insomnia symptoms. Common strategies include supervised gradual taper (SGT), cognitive behavioral therapy targeting hypnotic withdrawal (CBT-HW), cognitive behavioral therapy for insomnia (CBTI), and combination therapy (SGT+CBTI). Yet up to 40% of patients eventually resume use of hypnotics with these strategies, suggesting that other mechanisms need to be targeted to achieve and sustain high rates of non-use.

Objectives: 1) To assess the efficacy of a novel taper plus cognitive behavioral therapy-augmented program on hypnotic discontinuation among older Veterans, 2) to determine the impact of the the novel taper intervention on insomnia severity, 3) to assess the impact of the novel taper intervention on participants' beliefs and expectancies for using hypnotics to improve sleep quality and daytime function, and 4) to assess the efficacy of the novel taper intervention on balance and cognition.

To achieve these objectives, we propose to conduct a randomized clinical trial in older Veterans recruited from a single VA site. Veterans will undergo a 3-step screening process (letter with opt-out card, telephone screen, and in-person screen). Eligible participants (N = 132) will be randomized to 8 weeks of the novel taper intervention (CBTI+taper method A) or CBTI+taper method B. Follow-up assessments will be conducted at post-treatment and 6-months. Key 6-month outcomes will include hypnotic discontinuation and use (measured objectively through lab testing and medical record review/state prescription monitoring database query, and subjectively through sleep diary), insomnia severity, beliefs and expectations about hypnotics, balance, and cognition.

This hypnotic discontinuation program could be an important tool to help older Veterans who want to discontinue hypnotics to achieve this goal.

Eligibility criteria: Inclusion Criteria:

Age \>= 55 years

* Use of lorazepam, alprazolam, temazepam, clonazepam, and/or zolpidem for current or prior insomnia symptoms 2 or more nights per week for at least 3 months
* Current or prior insomnia symptoms
* Available to attend weekly in-person or video sessions over 9 weeks

Exclusion Criteria:

High risk for complications in outpatient hypnotic discontinuation program:

* Seizure disorder
* Supratherapeutic/high baseline hypnotic dose (\> diazepam-equivalent of 8 mg/night). Note that for individuals on \> 1 of the targeted hypnotics, total baseline dose in diazepam-equivalents will be calculated \& if \> 8 mg/night, individual will be excluded.
* High risk of complicated withdrawal; benzodiazepine intoxication or current or past symptoms of complicated benzodiazepine/alcohol withdrawal (e.g., seizure, delirium at baseline)
* Polydrug use (e.g., chronic high dose opioids)
* Unable to keep study medications in secure location
* Evidence of prescription fraud (e.g., multiple prescriptions for same drug filled at VA and non-VA pharmacies, diversion)

Discontinuation of hypnotic not appropriate:

* Study-targeted hypnotic used to treat another clinical condition (e.g., Rapid Eye Movement sleep behavior disorder)
* Not willing to begin hypnotic discontinuation program

Poor candidate for CBTI:

* Presence of bipolar disorder
* Cognitive impairment (e.g., Mini-Mental State Examination \< 24)
* Sleep/wake difficulty is better explained by another sleep disorder such as restless legs syndrome, narcolepsy, insufficient sleep syndrome, or circadian rhythm sleep-wake disorders
* Untreated sleep-disordered breathing defined as:

Apnea-hypopnea index (AHI) \> 30 AHI between 15 and 30 and daytime sleepiness (Epworth Sleepiness Scale \> 10)

* Medically/psychiatrically unstable (e.g., recent major hospitalization or planned major surgery during the study; psychosis, suicidal, active alcohol/substance abuse based on history and medical records)
* Unstable housing situation

Primary outcomes:
measure: Rates of Hypnotic Discontinuation
timeFrame: 6 months after treatment ends (which is an average of 8 months from randomization)
measure: Insomnia Severity Index Score
timeFrame: 6 months after treatment ends (which is an average of 8 months from randomization)
Secondary outcomes:
Other outcomes:
Locations:
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
Study officials:
affiliation: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
name: Constance H Fung, MD MSHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fung CH, Martin JL, Alessi C, Dzierzewski JM, Cook IA, Moore A, Grinberg A, Zeidler M, Kierlin L. Hypnotic Discontinuation Using a Blinded (Masked) Tapering Approach: A Case Series. Front Psychiatry. 2019 Oct 24;10:717. doi: 10.3389/fpsyt.2019.00717. eCollection 2019.
citation: McCarthy M, Mak S, Kaufmann CN, Lum HD, Fung CH. Care coordination needs for deprescribing benzodiazepines and benzodiazepine receptor agonists. Res Social Adm Pharm. 2022 Apr;18(4):2691-2694. doi: 10.1016/j.sapharm.2021.06.025. Epub 2021 Jul 1.
citation: Gutierrez L, Ghadimi S, Krall A, Hampson E, Grinberg AM, Moore AA, Dzierzewski JM, Alessi C, Martin JL, Fung CH. Posttraumatic Stress Disorder Risk and Benzodiazepine Dependence in Older Veterans with Insomnia Symptoms. Clin Gerontol. 2022 Mar-Apr;45(2):414-418. doi: 10.1080/07317115.2021.1954123. Epub 2021 Aug 4.
citation: Ghadimi S, Grinberg A, Mitchell MN, Alessi C, Moore AA, Martin JL, Dzierzewski JM, Kelly M, Badr MS, Guzman A, Smith JP, Zeidler M, Fung CH. Sleep characteristics and use of multiple benzodiazepine receptor agonists in older adults. J Am Geriatr Soc. 2023 Dec;71(12):3924-3927. doi: 10.1111/jgs.18528. Epub 2023 Aug 1. No abstract available.
citation: Fung CH, Alessi C, Martin JL, Josephson K, Kierlin L, Dzierzewski JM, Moore AA, Badr MS, Zeidler M, Kelly M, Smith JP, Cook IA, Der-Mcleod E, Ghadimi S, Naeem S, Partch L, Guzman A, Grinberg A, Mitchell M. Masked Taper With Behavioral Intervention for Discontinuation of Benzodiazepine Receptor Agonists: A Randomized Clinical Trial. JAMA Intern Med. 2024 Dec 1;184(12):1448-1456. doi: 10.1001/jamainternmed.2024.5020.