- Email: [email protected]
Naltrexone treatment C anorexia nervosa and bulimia: Preliminary results of controlled clinical trials
BIOL PSYCHIATRY 1992;31:61A-252A
90A
Eating Disorders
Vietnam, Korea, or WWlI received structured serial assessments. PTSD was the most prevalent condition followed by major depression, panic, generalized anxiety, and phobic disorder or symptoms. Histories of endogenomorphic features overlapping other clinical populations (e.g., melancholia, sleep panic attacks) were common. Patterns of phobic and compulsive symptoms suggested traumatic influence. Unlike generalized anxiety ,a.nd past substance disorders, the mean onsets of phobias, major depression, and panic, respectively, occurred later than ,.-':'T,~D. We also found the prevalence of hypertension to be elevated (particularly in the older subgroup) relative to a comparitive psychiatric group. We conclude that PTSDrelated syndromes may progress toward phenomena that occur with increasing autonomy (e.g., anxiety elicited by trauma-related stimuli, phobic anxiety, spontaneous panic, autonomic reactivity, hypertension). Theoretical treatment implications and preliminary data on biological measures in PTSD with comorbidity will be explored.
EATING DISORDERS T h u r s d a y , A p r i l 30, 4 : 3 0 - 6 : 0 0 aM
66
Ballroom
NALTREXONE TREATMENT C ANOREXIA NERVOSA AND BULIMIA: PRELIMINARY RESULTS OF CONTROLLED CLINICAL TRIALS
Mary Ann Marrazzi, Joseph Kinzie, Elliot D. Luby Wayne State University School of Medicine and Harper-Grace Hospitals, Detroit, Mi 48201. Our auto-addiction opioid model of anorexia nervosa and hulimia purposes that endogenous opioids are released during an initial period of dieting and literally get the patient "high" on dieting and thus addicted to it (lnt J Eating Dis 5:191-208, 1986; and The Brain as an Endocrine Organ, eds. M. Cohen, P. Foa, 1990, pp 46-55). Atypical features of the endogenous opioid system biologically predispose some individuals, so that t'or them dieting triggers an addiction. Both anorexia nervosa and bulimia are viewed as opioidmedicated addictions. Accordingly, narcottc antagonists, such as naltrexone, may be therapeutically useful in interru,ting tl~c addieti,,~ cycle, so that psychotherapy is more effective. Promising case studies have been published (above ref. and J Clin Psychopharmacol 7:52-53, 1987). We are currently conducting controlled clinical trials tbr both anorexia nervosa and bulimia using outpatient and a double-blind randomized crossover design. Preliminary results indicate that when comparing active drug and placebo in the same patient, 13 of 16 responded to the drug on some parameters. The data were analyzed blindly and assessments were made of which one was the drug period. In every case when the code was broken, these experimenter's assessments and the patients' subjective assessments were confirmed.
67
CSF CCK-8 IN BULIMIA NERVOSA Timothy D. Brewerton, R. Bruce Lydiard, Margery C. Beinfeld, Michelle Laraia, Gail Stuart, James C. Ballenger Institute of Psychiatry, Medical University of South Carolina, Charleston, SC 29425-0742. Cholecystokinin-8 (CCK-8) is an octapeptide found in gut and brain, which appears to play an important role in the mediatioa of both satiety and anxiety. Although plasma CCK responses to a liquid testmeal have been reported to be signilicantly lower in nonnal weight patients with bulimia nervosa (BN) than controls, CSF CCK-8 concentrations have not been studied in BN patients. We therefore measured CSF concentrations of CCK-8 in drug-free, normal-weight females with DSM-III-R defined BN and healthy controls. After 4 days of a low monoamine diet and overnight bedrest, CSF was obtained (I 2-26 cc) from I I female bulimic patit:n~s and 16 controls (8 females, 8 males). Bulimics had lower CSF concentrations of CCK-8 (13.5 _+ 6.5 pg/ml) than controls (20.5 _ 7.5 pmol/L, p -< 0.03, unpaired t-test). In addition, CCK-8 concentrations were inversely correlated to several subscale scores of the Eating Disorders Inventory, including AngerHostility (rho = -0.51, p < 0.0003), Anxiety (rho = -0.60, p -< O.0013), and Intelpersonal Sensitivity
90A
Eating Disorders
Vietnam, Korea, or WWlI received structured serial assessments. PTSD was the most prevalent condition followed by major depression, panic, generalized anxiety, and phobic disorder or symptoms. Histories of endogenomorphic features overlapping other clinical populations (e.g., melancholia, sleep panic attacks) were common. Patterns of phobic and compulsive symptoms suggested traumatic influence. Unlike generalized anxiety ,a.nd past substance disorders, the mean onsets of phobias, major depression, and panic, respectively, occurred later than ,.-':'T,~D. We also found the prevalence of hypertension to be elevated (particularly in the older subgroup) relative to a comparitive psychiatric group. We conclude that PTSDrelated syndromes may progress toward phenomena that occur with increasing autonomy (e.g., anxiety elicited by trauma-related stimuli, phobic anxiety, spontaneous panic, autonomic reactivity, hypertension). Theoretical treatment implications and preliminary data on biological measures in PTSD with comorbidity will be explored.
EATING DISORDERS T h u r s d a y , A p r i l 30, 4 : 3 0 - 6 : 0 0 aM
66
Ballroom
NALTREXONE TREATMENT C ANOREXIA NERVOSA AND BULIMIA: PRELIMINARY RESULTS OF CONTROLLED CLINICAL TRIALS
Mary Ann Marrazzi, Joseph Kinzie, Elliot D. Luby Wayne State University School of Medicine and Harper-Grace Hospitals, Detroit, Mi 48201. Our auto-addiction opioid model of anorexia nervosa and hulimia purposes that endogenous opioids are released during an initial period of dieting and literally get the patient "high" on dieting and thus addicted to it (lnt J Eating Dis 5:191-208, 1986; and The Brain as an Endocrine Organ, eds. M. Cohen, P. Foa, 1990, pp 46-55). Atypical features of the endogenous opioid system biologically predispose some individuals, so that t'or them dieting triggers an addiction. Both anorexia nervosa and bulimia are viewed as opioidmedicated addictions. Accordingly, narcottc antagonists, such as naltrexone, may be therapeutically useful in interru,ting tl~c addieti,,~ cycle, so that psychotherapy is more effective. Promising case studies have been published (above ref. and J Clin Psychopharmacol 7:52-53, 1987). We are currently conducting controlled clinical trials tbr both anorexia nervosa and bulimia using outpatient and a double-blind randomized crossover design. Preliminary results indicate that when comparing active drug and placebo in the same patient, 13 of 16 responded to the drug on some parameters. The data were analyzed blindly and assessments were made of which one was the drug period. In every case when the code was broken, these experimenter's assessments and the patients' subjective assessments were confirmed.
67
CSF CCK-8 IN BULIMIA NERVOSA Timothy D. Brewerton, R. Bruce Lydiard, Margery C. Beinfeld, Michelle Laraia, Gail Stuart, James C. Ballenger Institute of Psychiatry, Medical University of South Carolina, Charleston, SC 29425-0742. Cholecystokinin-8 (CCK-8) is an octapeptide found in gut and brain, which appears to play an important role in the mediatioa of both satiety and anxiety. Although plasma CCK responses to a liquid testmeal have been reported to be signilicantly lower in nonnal weight patients with bulimia nervosa (BN) than controls, CSF CCK-8 concentrations have not been studied in BN patients. We therefore measured CSF concentrations of CCK-8 in drug-free, normal-weight females with DSM-III-R defined BN and healthy controls. After 4 days of a low monoamine diet and overnight bedrest, CSF was obtained (I 2-26 cc) from I I female bulimic patit:n~s and 16 controls (8 females, 8 males). Bulimics had lower CSF concentrations of CCK-8 (13.5 _+ 6.5 pg/ml) than controls (20.5 _ 7.5 pmol/L, p -< 0.03, unpaired t-test). In addition, CCK-8 concentrations were inversely correlated to several subscale scores of the Eating Disorders Inventory, including AngerHostility (rho = -0.51, p < 0.0003), Anxiety (rho = -0.60, p -< O.0013), and Intelpersonal Sensitivity