Biomedical subjects
Publications and source records attributed to H G Pope.
Six consecutive patients with rapid-cycling bipolar disorder, refractory or only minimally responsive to treatment with lithium salts and neuroleptics, including five also refractory to carbamazepine, all demonstrated a moderate or marked response to the anticonvulsant valproate. These observations suggest that valproate may represent a promising treatment alternative in this often treatment-resistant form of bipolar disorder.
To evaluate the sleep electroencephalogram (EEG) characteristics of bulimia, all-night sleep EEGs were performed on 11 women meeting DSM-III criteria for bulimia. Comparison groups consisted of young women outpatients with major depression (n = 44) and young normal women (n = 20). The sleep EEGs of the bulimic patients were largely indistinguishable from those of the normal controls, except for a trend toward increased rapid eye movement (REM) density in the first REM period among the bulimic subjects. No differences in any sleep EEG measure were observed between bulimic patients with major depression and those without affective disorder. By contrast, the outpatients with major depression displayed marked sleep continuity disturbances, as well as significantly increased REM intensity and REM density, as compared to normal controls. Implications of these results with respect to the hypothesis that bulimia is related to major affective disorder are discussed.
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.
To compare the prevalence of eating disorders in lower income vs. upper income communities, we administered a previously validated questionnaire to 394 women at nine state-regulated bingo tournaments. Surprisingly, eating disorders were more commonly reported by lower income respondents.
Antidepressant therapy has been shown to be efficacious in the treatment of bulimia nervosa, a serious eating disorder that can be associated with substantial morbidity and mortality. Seven antidepressant drugs have been tested in double-blind, placebo-controlled studies. Five of these studies demonstrated strongly positive findings, one a weakly positive finding, and one a negative finding. However, inadequate doses of medication may have been used in the latter two studies. In all of the positive studies, antidepressant agents appeared effective even in bulimic subjects who did not display concomitant depression, indicating that this treatment modality should not be reserved only for depressed bulimic patients. Although not yet tested in double-blind studies, trazodone also appears effective in the treatment of bulimia nervosa. Results from one large open study suggested that trazodone has comparable efficacy to the tricyclic antidepressant agents. Trazodone would be a particularly attractive treatment for bulimia nervosa because of its low anticholinergic side-effects profile; placebo-controlled studies are required, however, before definitive recommendations can be made.
The authors used structured diagnostic interviews to assess the lifetime prevalence of psychiatric disorders, by DSM-III criteria, among 70 women: 51 outpatients with active bulimia and 19 nonpatient subjects with remitted bulimia. Comparison groups consisted of 24 female outpatients with major depression and 28 nonpsychiatric control subjects. The active and remitted bulimic subjects closely resembled each other, with high lifetime rates of major affective disorder, anxiety disorders, and substance use disorders. Atypical depression was equally common among subjects with major affective disorder in all groups. These results are consistent with previous studies suggesting a phenomenologic relationship between bulimia and major affective disorder.
In an 18-month prospective assessment of 679 hospitalized, neuroleptic-treated patients, the authors, using previously defined operational criteria, diagnosed neuroleptic malignant syndrome in six cases (0.9%). This supports their earlier finding that the syndrome appeared in about 1% of neuroleptic-treated patients.
Of 16 patients with Cushing's disease, 13 (81%) had lifetime diagnoses of major affective disorder according to DSM-III criteria. However, the rate of familial major affective disorder among these patients was significantly lower than that found among patients with major depression.
Sodium valproate has been reported to be effective in the treatment of recurrent major affective and schizoaffective disorders. The records of 36 consecutive patients with various psychiatric diagnoses, who received valproate at our center, were retrospectively reviewed. None of these patients displayed a diagnosable neurologic disorder or paroxysmal EEG activity. Sixteen (44%) of the 36 patients experienced a moderate to marked response to valproate. The diagnoses of bipolar or schizoaffective disorder and the presence of nonparoxysmal EEG abnormalities both predicted a favorable response. The authors conclude that valproate deserves further study as a possible treatment for major affective disorder.
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To test the hypothesis that bulimia may be associated with borderline personality traits or frank borderline personality disorder, the authors administered the Diagnostic Interview for Borderlines (DIB) under blind conditions to 52 bulimic subjects, 22 outpatient controls with a history of major depression but no history of an eating disorder, and 13 nonpsychiatric controls. Only 1.9% of bulimic subjects met revised DIB criteria for borderline personality disorder, and mean DIB scores were almost identical in bulimic subjects and controls with major depression. These results argue against a relationship between bulimia per se and borderline personality disorder or traits.
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Clozapine is an antipsychotic drug reported to be virtually free of extrapyramidal effects. On the basis of this, we hypothesized that it would be unlikely to cause the neuroleptic malignant syndrome (NMS), a rare but severe reaction observed with other antipsychotic drugs. However, when we administered clozapine (in conjunction with lithium) to a patient with a past history of NMS with fluphenazine, the syndrome reappeared after about 3 weeks of treatment. This represents, to our knowledge, the first report of apparent NMS with clozapine.
Neuroleptic malignant syndrome, a dangerous but little-known complication of antipsychotic drugs, is often assumed to be rare. To assess the frequency of the syndrome in a large psychiatric hospital, the authors first reviewed the literature and developed operational diagnostic criteria. Using these criteria to survey nearly 500 neuroleptic-treated patients admitted during a 1-year period, they found that seven (1.4%) had experienced definite or probable neuroleptic malignant syndrome. In several cases, including one fatal case, the diagnosis of neuroleptic malignant syndrome was not immediately considered. The authors conclude that neuroleptic malignant syndrome may be more common than previously thought and may be underdiagnosed.
The authors treated 12 consecutive bulimic patients with nomifensine, a novel antidepressant recently approved for American use. Two patients developed fever, necessitating discontinuation of the drug. Of the other 10 patients, nine showed moderate or better improvement, with strikingly few side effects.
More than 30 reports, including 9 placebo-controlled, double-blind studies, have assessed the efficacy of various medications, mostly antidepressants, for the treatment of bulimia. A critical review of the available data suggests that antidepressants, and possibly other thymoleptic agents, are clearly superior to placebo for the treatment of bulimia; the studies have not identified specific subgroups of bulimic patients who are, or are not, candidates for these agents; and tentatively, these agents may benefit major affective disorder and bulimia via similar mechanisms.