Insomnia is nearly twice as common among older adults as it is in the general population. This is of significant clinical concern as insomnia is a risk factor for new onset and recurrent psychiatric and medical illness. Taken together, the prevalence and consequences of insomnia in older adults suggests that insomnia should not go untreated. This potential clinical imperative is further underscored by 1) the reconceptualization of Insomnia within the DSM-5 and ICSD-3 as a disorder (vs. a symptom of other disorders) and 2) the findings that targeted treatment of sleep continuity disturbance may produce clinical gains for medical and psychiatric disorders that occur comorbidly with insomnia. Thus, at present, the question is not whether to treat but how to best treat the disorder in general, and specifically in the context of older adults. Of the available medical treatments, the best studied strategies are benzodiazepines and benzodiazepine receptor agonists (BZRAs). In both cases, treatment is typically accomplished with either nightly or intermittent dosing. In the case of nightly dosing (QHS), BZRAs have been found to be safe and efficacious for periods of up to a year. Less clear is whether such efficacy can be maintained over the course of years or decades. In the case of intermittent dosing (IDS), the reduced usage strategy is thought to extend the efficacy and safety half-life of pharmacotherapy, but at a cost: little or no clinical effects on non-medication nights. In order to address this issue, we propose to evaluate an alternative approach that is based on the behavioral principles of conditioning and reinforcement. Specifically, we propose to garner treatment responses with full dose treatment (1 month) and then conduct maintenance therapy using intermittent dosing with placebos on non-medication nights. This approach, by expectancy alone, should provide for better clinical outcomes than standard intermittent dosing. What makes the study theoretically interesting is the underlying concept: that the initial treatment response allows for the medication vehicle (the capsule) to become a conditioned stimulus for the therapeutic response (sleepiness and sleep) and that this can be maintained over time (if not indefinitely) with partial reinforcement. Building upon the findings from our prior investigation with partial reinforcement, we propose to assess two low frequency approaches to maintenance therapy in a three phase study. In Phase 1, all subjects receive zolpidem nightly for one month and are assessed for treatment response. In Phase 2, responders are randomized to one of four maintenance conditions for three months: Nightly medication use (QHS); one of two low frequency partial reinforcement conditions (1 or 3 active doses per week with placebos on non-medication nights); and a low frequency IDS condition (1 to 3 active doses per week, without placebos). Phase 3 will be an extension period to assess, over 9 months, the long-term durability of the approaches. The outcomes for the study will be: rate of relapse, latency to relapse, average sleep continuity, and number and severity of medical symptoms during treatment. The primary hypothesis for the study is that the partial reinforcement conditions will produce similar outcomes to nightly dosing and superior outcomes to the IDS condition.
If the behavioral therapeutic approach proves successful for the management of chronic insomnia, it will provide for a form of maintenance therapy that will increase the efficacy half-life of hypnotics, reduce the incidence of adverse events, and may serve to reduce overall morbidity in older adults owing to long term improved sleep and the medical and psychiatric prophylaxes this may provide. If it is found, over the course of multiple investigations, that behavioral pharmacotherapeutic strategies are broadly applicable (e.g., not only for insomnia but for other disease states), this will almost certainly change how maintenance therapy is conducted. While 'prn' use of medication will always be an ideal strategy for managing chronic disease that is episodic, the management of unremitting chronic illness requires a different strategy - one that minimizes habituation effects, obviates the need for dose escalation, reduces the risk of dependence, diminishes the incidence of side effects and adverse events, and (if possible) provides a means towards curtailing treatment costs. The application of behavioral principles to pharmacotherapy holds precisely this promise.
