Hypnotic Activity of Melatonin

LETTER TO THE EDITOR

Combined Bupropion-Levodopa-Trazodone Therapy of Sleep-Related Eating and Sleep Disruption in Two Adults with Chemical Dependency Carlos H. Schenck MD, Mark W. Mahowald MD Minnesota Regional Sleep Disorders Center, and Departments of Psychiatry (CHS) and Neurology (MWM); Hennepin County Medical Center and University of Minnesota Medical School, Minneapolis, MN NOCTURNAL SLEEP-RELATED EATING DISORDERS CAN BE IDIOPATHIC or can be associated with various sleep, medical, and psychiatric disorders and their treatments.1-4 A dopaminergic agent, such as levodopa, can be a cornerstone of therapy, and may need to be combined at bedtime with codeine and/or clonazepam.1 The removal of D-fenfluramine from the market almost three years ago has taken away an effective agent for controlling nocturnal eating.2 Additional therapies need to be identified, particularly in specialized clinical situations. We now present two patients with chemical dependency who achieved control of abnormal nocturnal eating and disrupted sleep with combined bupropion, levodopa and trazodone therapy. A 37-year-old married male physician presented with a nine-year history of nightly binge-eating (with weight gain) that first emerged when he achieved sobriety from longstanding alcohol and cocaine abuse. He typically falls asleep rapidly, but in one to two hours he will awaken abruptly and "feel driven to go to the kitchen," where he will consume high-caloric foods in a rapid and messy manner. He will have at least two episodes nightly, with morning anorexia and vague recall of the nocturnal eating. There is no history of sleepwalking (SW), sleep terrors, restless legs, daytime somnolence, or medical/psychiatric disorder (apart from chemical dependency). During polysomnography (PSG), two eating episodes arose from stage 2 sleep, occurring two and six hours after sleep onset. Sleep-disordered breathing, periodic limb movements (PLMs), and clinical/EEG seizure activity were not detected. Treatment with carbidopa/L-dopa was started, but 75/300 mg qHS was ineffective. When bupropion-SR was added (because of its dopaminergic activity), full control of nocturnal eating ensued, although multiple awakenings persisted that were controlled when bedtime trazodone therapy was initi-

ated one month later. Control of nocturnal eating (with 6 kg weight loss) was maintained at one year follow-up on the following regimen: bupropion-SR, 150 mg q a.m., 100 mg q noon, 100 mg q 4 pm; carbidopa/L-dopa, 50/200 mg qHS; and trazodone 200 mg qHS. A 31-year-old divorced female with childhood SW presented with a 16-year history of nocturnal eating that became a nightly problem (with weight gain) six years previously. PSG revealed frequent bruxism and chewing, and three eating episodes arose from stage 1 sleep, REM sleep, and confused wakefulness. Sleep-disordered breathing, PLMs, and clinical/EEG seizure activity were not detected. Nocturnal eating was controlled for five years with combined HS carbidopa/L-dopa, codeine, and clonazepam therapy. She then entered a residential program for treating alcohol/cocaine abuse and major depression. Relapse of nocturnal eating occurred when codeine and clonazepam were discontinued, despite ongoing carbidopa/L-dopa therapy. Nocturnal eating, excessive awakenings, and major depression were then controlled for >2 years on the following regimen: bupropion 225 mg b.i.d.; carbidopa/Ldopa 75/300 mg qHS & carbidopa/L-dopa CR 50/200 mg qHS; and trazodone 150 mg qHS. (Trazodone therapy was begun one month after the start of bupropion-levodopa therapy, in order to control excessive awakenings that had persisted despite control of nocturnal eating.) Weekly urine toxicology screens have verified ongoing abstinence from illicit substances for the past 12 months. These two cases indicate that bupropion—a dopaminergic/noradrenergic anti-depressant5-7 can help control abnormal nocturnal eating in patients with chemical dependency (with or without depression). Whether bupropion alone was sufficient for full control of nocturnal eating (vs. combined therapy with levodopa, or even with trazodone), is indeterminate. Since both patients were reluctant to discontinue levodopa once the nocturnal eating was controlled with bupropion therapy, it remains possible that levodopa potentiated the therapeutic efficacy of bupropion. However, levodopa alone was ineffective. Trazodone at bedtime helped

Accepted for publication April 2000 Address correspondence to: Carlos H. Schenck MD, Hennepin County Medical Center, (Psychiatry 844), 701 Park Ave. South, Minneapolis, MN 55415. Tel: 612-347-6288, Fax: 612-904-4207 SLEEP, Vol. 23, No. 5, 2000

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Letter to the Editor—Schenck et al

control the excessive awakenings that persisted despite control of nocturnal eating. It is possible that trazodone also helped maintain ongoing remission of nocturnal eating. These two cases encourage the use of bupropion therapy (either alone or combined with levodopa and/or trazodone) in controlling nocturnal eating and sleep disruption in patients with histories of alcohol and/or drug abuse. This regimen may also help control nocturnal eating in patients without chemical dependency. REFERENCES 1 Schenck CH, Hurwitz TD, O'Connor KA, Mahowald MW. Additional categories of sleep-related eating disorders and the current status of treatment. Sleep 1993;16:457-466. 2 Spaggiari MC, Granella F, Parrino L, Marchesi C, Melli I, Terzano MG. Nocturnal eating syndrome in adults. Sleep 1994;17:339-344. 3 Manni R, Ratti MT, Tartara A. Nocturnal eating: prevalence and features in 120 insomniac referrals. Sleep 1997;20:734-738. 4 Winkelman JW. Clinical and polysomnographic features of sleep-related eating disorder. J Clin Psychiatry 1998;59:14-19. 5 Terry P, Katz JL. Dopaminergic mediation of the discriminative stimulus effects of bupropion in rats. Psychopharmacology 1997;134:201212. 6 Tella SR, Ladenheim B, Cadet JL. Differential regulation of dopamine transporter after chronic self-administration of bupropion and nomifensine. J Pharmacol Exp Therapeutics 1997;281:508-513. 7 Horst WD, Preskorn SH. Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupriopion. J Affective Disorders 1998;51:237-254.

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Letter to the Editor—Schenck et al