Undergraduate Honors Theses

Thesis Defended

Spring 2011

Document Type

Thesis

Department

Integrative Physiology

First Advisor

Kenneth P. Wright Jr., PhD

Abstract

Introduction: Melatonin and melatonin agonists like ramelteon have been shown to be successful at treating insomnia without the significant side effects and withdrawal effects of the sedatives and hypnotics that are traditionally prescribed for this condition. Furthermore, traditional pharmacological treatments for insomnia do not address the underlying physiological, psychological, and behavioral causes of insomnia. When combined with behavioral therapy, treatments for insomnia are more effective and longer lasting. In addition, some types of insomnia are connected with circadian misalignment with the external environment. Melatonin and melatonin agonists may treat these types of insomnia by adjusting circadian phase. The aim of this thesis was to compare the change in circadian phase, as determined by salivary melatonin levels, from pre- and post-treatment with 8mg of ramelteon combined with multi-component behavioral therapy (MCBT) or with ramelteon alone compared to placebo in chronic insomniacs. The hypothesis of this thesis is that there will be a greater change in circadian phase with ramelteon and MCBT than in the placebo group. We expect that a change in circadian phase will be correlated with improvement in subjective sleep quality. Methods: Thirty one adults aged 18-64 that met the criteria for chronic insomnia (sleep onset latency of more than 30 minutes on at least 3 nights a week and average total sleep time less than 6.5 hours) were studied at the University of Arizona under the supervision of Dr. Richard Bootzin. Subjects received either 8mg ramelteon or placebo daily in combination with MCBT. Subjects in the MCBT/ramelteon condition received weekly therapy sessions in addition to the drug. Sleep diaries and subjective sleep measures were recorded throughout the treatment period. Saliva samples were taken under dim light conditions (<25 lux) every hour during pre and posttreatment visits to assess circadian phase. Frozen saliva samples were shipped to the University of Colorado where they were assayed using a high sensitivity ALPCO ELISA kit. DLMO was determined using a 3pg/mL threshold and the change in circadian phase was calculated by comparing the difference between pre- and post- treatment bedtimes and DLMO. Results: A significant (p<.05) change in phase angle was found between the ramelteon-only group and placebo. Significant improvements in subjective measures were seen in all groups. There was no association between change in phase angle and treatment efficacy. Conclusion: Our findings further support existing evidence that a standard 8mg dose of ramelteon can effectively shift the circadian clock so that individuals sleep at a more appropriate biological time. Although we did not find that a change in phase angle was associated with treatment efficacy, ramelteon alone or in combination with MCBT continues to show promise in the treatment of insomnia. However, further research needs to be done to verify and test the scope of these results.

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