Success with the SSRIs lends support to the theory of altered serotonin activity in BN. Nonetheless, neurotransmitter dysregulation in the disorder is more complex, and it has been known for some time that the noradrenergic system is implicated as well.15,16 In a study by Kruger and Kennedy,17 some tricyclic antidepressants with prominent noradrenergic effects, including desipramine and imipramine, were shown to reduce binge eating and purging.
This class of drugs may be associated with greater adverse effects in BN and thus these drugs are rarely used.3 However, it is surprising that no controlled trials have been conducted with the newer generation noradrenergic antidepressants. Small open trials in Austria and Italy used reboxetine, a selective noradrenaline reuptake inhibitor not available in the United States. Results showed a decrease in bingeing and purging symptoms as well as other psychological variables.18,19
There are no reports of venlafaxine as a treatment for BN; however, a retrospective review found some efficacy for this serotonin-norepinephrine reuptake inhibitor (SNRI) in patients with the related condition of binge-eating disorder.20 The other currently prescribed SNRI, duloxetine, has appeared in a single case report of treatment-refractory BN, in which the patient achieved remission of bingeing and purging symptoms on a high dosage of 120 mg/d.21 Clearly, controlled trials are needed to assess the efficacy of SNRIs for treating BN.
Bupropion is another antidepressant worth mentioning. In 1988, the immediate-release formulation was found to be effective in reducing BN symptoms in a controlled study; however, 4 of 69 patients who received the drug had generalized seizures, resulting in its contraindication by the FDA for use in eating disorders.22 Subsequently, the investigators of the study reported doing an intensive examination of the patients who had experienced seizures. They found no common features in these patients' medical histories, laboratory results, concomitant medication use, or other variables that might explain predisposition to seizure, and concluded that the increased incidence of seizures could not be explained.22,23 Although no study has attempted to replicate these findings using the lower doses and longer-acting forms of the drug more commonly prescribed today, clinicians in the eating disorders field generally avoid using bupropion when treating patients with BN.
Antidepressants were initially proposed for treatment of BN because of the frequent accompanying mood symptoms of these patients. However, such medications also have proved helpful in patients with BN without comorbid anxiety and depressive disorders; they appear to independently target symptoms of binge eating, purging, and preoccupation with shape and weight.24 This result, along with a generally more rapid onset of action and, for fluoxetine, a higher dosage requirement than is seen with treatment of depression, suggests that drug action for BN symptoms may occur by a different mechanism, perhaps relating in part to underlying variance in the serotonergic abnormalities found in BN patients versus those with major depression.25 Such a possibility has led to case reports and small trials of novel medica-tions, most notably topiramate and ondansetron.
The anticonvulsant topiramate has been linked to appetite suppression and weight loss, and interest in its use in BN followed suggestions of efficacy in patients with binge eating disorder.26 Results from the first randomized, double-blind, placebo-controlled trial of topiramate in BN were reported in 2003. The 10-week trial of 69 patients began with a dosage of 25 mg/d titrated to a maximum of 400 mg/d (median 100 mg/d). Topiramate was found to be more efficacious than placebo in decreasing frequency of bingeing and purging behaviors (to a similar degree as that seen in antidepressant trials) and in improving other psychological measures, including anxiety, self-esteem, eating attitudes, and body image. Adverse events were generally mild to moderate, resolved with time or dose reduction, and did not usually lead to withdrawal from the study.27,28 A 10-week controlled trial in 2004 found similar results with regard to reductions in bingeing and purging behaviors, and a decrease in weight was reported in the topiramate group.
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