Jeffrey M. Jonas

Phenomenologic relationship of eating disorders to major affective disorder

We administered the National Institute of Mental Health Diagnostic Interview Schedule to 41 patients with a lifetime history of anorexia nervosa (25 with and 16 without bulimia) and to 49 patients with bulimia alone. Results showed that 77% of the patients with eating disorders had a lifetime diagnosis of DSM-III major affective disorder, a rate significantly higher than that found in comparison groups composed of the first-degree relatives of probands with schizophrenia and bipolar disorder. High lifetime rates of anxiety disorders, substance use disorders, and kleptomania were also observed. By contrast, few cases of personality disorders and no cases of schizophrenia were found. These findings combine with the results of studies of family history, long-term outcome, response to biological tests, and treatment response to suggest that anorexia nervosa and bulimia may be closely related to major affective disorder.

A controlled family history study of bulimia.

Using the family history method, we assessed the morbid risk for psychiatric disorders in the first-degree relatives of 69 probands with bulimia, 24 probands with major depression, and 28 nonpsychiatric control probands. The morbid risk for major affective disorder among the first-degree relatives of the bulimic probands was 32%, significantly greater than that found in the nonpsychiatric control probands. The rate of familial major affective disorder was significantly greater in bulimic probands who had a history of major affective disorder themselves than in bulimic probands without such a history - but the latter group, in turn, displayed significantly higher rates than the nonpsychiatric control probands. Eating disorders were slightly, but not significantly, more prevalent in the families of bulimic probands than nonpsychiatric control probands. We present two alternative hypotheses which might explain these findings.

Hypothalamic-Pituitary-Adrenal-Axis Hyperactivity in Bulimia

Hyperactivity of the hypothalamic-pituitary-adrenal axis, demonstrated by nonsuppression of plasma cortisol in the dexamethasone suppression test (DST), has been found in about 50% of patients with major depression. We administered the DST to 47 patients with bulimia and to 22 age- and sex-matched normal controls. Among the bulimics, 47% were nonsuppressors, significantly higher than the 9% prevalence of nonsuppressors in the controls, but similar to the prevalence reported for patients with major depression in other studies. This finding is consistent with evidence from studies of phenomenology, family history, and treatment response which suggest that bulimia may be related to affective disorder.

Efficacy and Safety of Lisdexamfetamine for Treatment of Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial

IMPORTANCE Binge-eating disorder (BED), a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome, lacks approved pharmacotherapies. OBJECTIVE To examine the efficacy and safety of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to severe BED. DESIGN, SETTING, AND PARTICIPANTS We performed a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to-treat analyses included 259 and 255 adults with BED, respectively. INTERVENTIONS Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2) days after the last dose. MAIN OUTCOMES AND MEASURES We assessed the change in binge-eating (BE) behaviors measured as days per week (baseline to week 11) with a mixed-effects model using transformed log (BE days per week) + 1. Secondary measures included BE cessation for 4 weeks. Safety assessments included treatment-emergent adverse events, vital signs, and change in weight. RESULTS At week 11, log-transformed BE days per week decreased with the 50-mg/d (least squares [LS] mean [SE] change, -1.49 [0.066]; P = .008) and 70-mg/d (LS mean [SE] change, -1.57 [0.067]; P < .001) treatment groups but not the 30-mg/d treatment group (LS mean [SE] change, -1.24 [0.067]; P = .88) compared with the placebo group. Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-, and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively. The percentage of participants achieving 4-week BE cessation was lower with the placebo group (21.3%) compared with the 50-mg/d (42.2% [P = .01]) and 70-mg/d (50.0% [P < .001]) treatment groups. The incidence of any treatment-emergent adverse events was 58.7% for the placebo group and 84.7% for the combined treatment group. In the treatment groups, 1.5% of participants had serious treatment-emergent adverse effects. Events with a frequency of at least 5% and changes in heart rate were generally consistent with the known safety profile. The mean (SD) change in body weight was -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group, the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups, respectively (P < .001 for each dose vs placebo group comparison in post hoc analysis). CONCLUSIONS AND RELEVANCE The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement. The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder. Further investigation of lisdexamfetamine in BED is ongoing. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01291173.

Antidepressant treatment of bulimia: A two-year follow-up study

Follow-ups for periods of up to 2 years on 20 bulimic subjects treated with antidepressants are reported. At the time last seen in follow-up, 19 (95%) of the subjects had experienced at least a partial improvement in their bulimia, and 10 (50%) had experienced a complete remission of bulimic symptoms. In addition, most subjects displayed a marked reduction in depressive symptoms. This suggests that antidepressants do not merely reduce binge eating per se, but produce a more general therapeutic effect for bulimic patients. However, these promising findings must be tempered by the fact that antidepressant treatment is not always simple and may require extensive management over the long term.

The use of opiate antagonists in treating bulimia: a study of low-dose versus high-dose naltrexone.

Sixteen individuals with bulimia consented to a 6-week trial of naltrexone, receiving either standard dosages of 50-100 mg each day or high dosages of 200-300 mg each day. At the end of 6 weeks, individuals in the low-dose group had no significant change in their frequency of binge eating or purging, while individuals in the high-dose group had significant reductions in both behaviors. Four individuals in the low-dose group who were crossed over to high-dose naltrexone at the end of the study went on to experience significant reductions in binge eating and purging. These findings support the potential utility of opiate blockade in treating bulimia, but suggest that dosages of naltrexone greater than those needed to block exogenous opiates may be required for therapeutic efficacy in reducing binge eating and purging.

Bulimia in men: a series of fifteen cases.

Comparing 15 consecutive male bulimic patients to a female bulimic control group, the authors found no differences on demography, associated psychopathology, family history, or treatment response. In contrast to a previous report, the authors found little evidence of increased homosexuality or “sexual conflict” in these men.

Use of clonidine in treating neuroleptic-induced akathisia

Six patients with akathisia were treated with clonidine in an open, on-drug/off-drug trial. All six patients demonstrated substantial improvement of their akathisia, with four of the six obtaining complete remission. The dose of clonidine used to treat the remaining two patients was limited by the development of symptomatic hypotension. Daily doses ranged from 0.2 to 0.8 mg, and maximal response to a particular dose occurred within 24 to 48 hours. Although no effects on lithium tremor, parkinsonism, or tardive dyskinesia were observed, two bipolar patients exhibited considerable improvement in their manic and psychotic symptoms during treatment with clonidine.

Memantine in the treatment of binge eating disorder: An open-label, prospective trial†

OBJECTIVE To assess preliminarily the efficacy of memantine in binge eating disorder. METHOD This was an open-label, 12-week, flexible-dose (5-20 mg/day) trial of memantine in binge eating disorder. The primary outcome was frequency of binge days. Secondary outcomes included frequency of binge episodes, body-mass index (BMI), weight, Clinical Global Impressions Severity (CGI-S), Three Factor Eating Questionnaire (TFEQ), Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Sheehan Disability Scale (SDS). Longitudinal random regression analysis was performed for frequency of binge days and episodes, BMI, weight, and CGI-S; analysis of baseline to endpoint change was performed for all outcomes. RESULTS Sixteen individuals received memantine; 15 completed at least one postbaseline evaluation, 9 completed the study. Mean dose at endpoint was 18.3 mg/day. Memantine was associated with significant reductions in frequency of binge days and episodes, severity of illness (p < .001 for both analyses), disinhibition on the TFEQ (p = .015), and disability on the SDS (p < .05 for three subscales). There was no significant change in BMI, weight, MADRS, HAM-A, and TFEQ cognitive restraint and hunger. CONCLUSION In this open-label trial, memantine was well tolerated and effective in reducing binge eating, severity of illness, and disability, but had little effect on BMI and weight.

Treatment of anorexia nervosa with antidepressants

Nine patients with anorexia nervosa were treated with antidepressant medications from three classes: tricyclics, monoamine oxidase inhibitors, and triazolopyridines. A tenth patient was treated with the combination of lithium carbonate and carbamazepine. With either the initial or a subsequent medication trial, four patients had displayed significant improvement in weight and in other anorexic and bulimic symptoms. Three additional patients had a marked or moderate improvement in bulimic symptoms, one with moderate and two without any weight gain. Two other patients had moderate weight gain. Side effects were a significant problem in many of the patients. These preliminary results suggest that antidepressants may be of benefit in the treatment of some patients with anorexia nervosa.