Serotonin Reuptake Inhibitors and the Treatment of Bulimia Nervosa -- A Comprehensive Review

John P. Galla, Clifford T. Stewart, Lawrence A. Fehr, Joseph Paola, Michele Hyman-Dollar,

Widener University

Joyce L. Donnini,

Temple University

Abstract

The serotonin hypothesis of bulimia nervosa suggests that bulimia is the behavioral manifestation of functional underactivity of serotonin in the central nervous system. Fluoxetine (Prozac), fluvoxamine (Luvox), and fenfluramine (Pandomin) are selective serotonin reuptake inhibitors (SSRIs) which presumably increase the availability of serotonin. All have been employed in the treatment of bulimia nervosa. This paper is a critical review of bulimia treatments which employ these drugs, either exclusively, or as an adjunct to psychotherapy. Information is presented that includes a description of objectives, designs, settings, patients, interventions, outcome measures, results, and conclusions of analytical hypotheses regarding SSRIs, and their contributions to the successful treatment and understanding of individuals with bulimia.

Copyright © 1995 John P. Galla

National Social Science Perspectives Journal, 7 (2), 40-51.

Bulimia (Bulimia Nervosa) is an eating disorder which is most often manifested by recurrent episodes of binge eating followed by inappropriate compensatory behaviors such as self-induced vomiting; misuse of laxatives, diuretics, or other medications; fasting; or excessive exercise. According to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., to be clinically diagnosed as bulimic these behaviors must occur, on average, at least twice a week for 3 months and there must be a persistent over-concern with body shape (American Psychiatric Association, 1994, p. 539, p. 549).

In 1987, Pope and Hudson estimated that at least one million American women and tens of thousands of American men suffer from bulimia. The incidence of bulimia as described in the DSM-IV is estimated to be between 1% and 3% in adolescent and young adult women (DSM-IV, 1994; Fahy, Eisler, & Russell, 1993), whereas the incidence of bulimic behaviors that do not meet the DSM-IV criteria may be between 10% and 20% of adolescent and young adult women (Cesari, 1986; Connors, & Johnson, 1987; Wells & Logan, 1987).

The rate of occurrence of bulimia in males is approximately one-tenth that of females, but a disproportionate number of male bulimics are athletes or homosexual (American Psychiatric Association, 1993; Andersen, 1986; Carlat & Carmargo, 1991; DSM-IV, 1994; Pope & Hudson, 1986a; Robinson & Holden, 1986; Schneider & Agras, 1987; Yager, Kurtzman, Landsverk, & Wiesmeier, 1988). Unless otherwise specified, the articles reviewed in this paper deal with individuals (female and male) who are clinically diagnosed as bulimic.

At least 90% of all bulimics are female (DSM-IV, 1994). The typical bulimic is a white woman in her early to mid twenties. Mean onset of bingeing is 18 years of age with purging beginning approximately one year later (usually by vomiting). Weight may range from underweight to overweight although many bulimics exhibit normal weight for their age. Familial history of obesity or alcoholism is common (Osvold & Sodowsky, 1993; Strober & Humphrey, 1987). Even within the "typical" demographic profile, frequency of bingeing and purging demonstrates great variance and cannot be predicted (American Psychiatric Association, 1993; Fairburn, 1991; Mitchell, Soll, Eckert, & Pyle, 1989; Rand & Kuldau, 1992; Schlesier-Stroop, 1984).

Obsessive thoughts concerning food, eating and purging themselves of food, and preoccupation with weight (i.e., fear of becoming overweight and misperceiving themselves as overweight when they are not) are major characteristics of the bulimic psychopathology. There is also evidence that depression, anxiety, obsessive-compulsive behaviors, personality disorders and substance abuse exhibit positive relationships with bulimia (Jacobs, 1995; Katz, 1990; Kennedy, & Garfinkel, 1992; Mitchell, Specker, & de Zwaan, 1991; Rothenberg, 1990; Schlesier-Stroop, 1984).

The Role of Serotonin The serotonin hypothesis of bulimia nervosa suggests that bulimia is the behavioral manifestation of functional underactivity of serotonin in the central nervous system (CNS) (Goldbloom & Garfinkel, 1990). Animal studies suggest that serotonin plays an inhibiting role in feeding behavior (Fava, Copeland, Schweiger, & Herzog, 1989; Morley, 1989; Weiss, Papadakos, Knudson, & Leibowitz, 1986). When applied to the paraventricular nucleus (PVN) of the hypothalamus, it specifically inhibits the ingestion of carbohydrates (Kalat, 1995). Serotonin also acts on the ventromedial hypothalamus (VMH) which is considered to be a satiety system.

In addition to satiety, serotonin has been implicated in macronutrient selection. Apparently, low serotonin levels in various nuclei of the hypothalamus lead to increased carbohydrate intake and satiety impairment (Goldbloom & Garfinkel, 1990).

Another way in which serotonergic functioning bears on a discussion of bulimia is that bulimics often present with depression, anxiety, obsessive-compulsive behaviors, and impulsivity, all of which have independently been associated with serotonin dysfunction (Fava et al., 1989; Goldbloom & Garfinkel, 1990). Indeed, understanding the implications of serotonergic dysfunction may even help explain why bulimia is more prevalent among women than men. That is, evidence suggests that dietary restriction can lead to the dysregulation of serotonin functioning, especially in women (Goldbloom, Garfinkel, & Shaw, 1991). In one experimental three-week diet among healthy male and female individuals, significant changes occurred in women but not men, suggesting the capacity of dieting to alter CNS serotonergic mediated responses in a gender-specific manner (Goldbloom et al., 1991). The relationship of this finding to bulimia would seem obvious. There is already a known gender predominance of women displaying bulimia (DSM-IV, 1994). Moreover, for a variety of reasons women are known to "diet" more than men (Chaiken & Pliner, 1987; Hsu, 1991; Lundholm & Anderson, 1986). If there is a gender specific sensitivity of serotonergic functioning in women to the effects of dieting, then dieting may serve as an initiating behavior, a perpetuating behavior, or both, for the differential development of bulimia in women.

Norepinephrine and dopamine dysfunction have also been implicated in eating disorders (Fava et al., 1989; Goldbloom & Garfinkel, 1990; Morley, 1989). However, unlike serotonin, with regard to feeding behavior, norepinephrine and dopamine act differently in different parts of the brain. Norepinephrine stimulation of animal PVN elicits a feeding response. It acts to increase meal size (not frequency) and causes preferential ingestion of carbohydrate-rich foods (Morley, 1989). Dopamine exhibits dose-related effects on feeding behavior. Low doses of dopamine and its agonists stimulate feeding. High doses inhibit feeding (Goldbloom et al., 1991; Morley & Blundell, 1988). Norepinephrine and dopamine, as well as adrenergic agonists such as amphetamine, apparently inhibit feeding when applied to the perifornical region of the hypothalamus (Goldbloom & Garfinkel, 1990; Stanley & Gillard, 1994).

Additional evidence that these monoamines play some role in bulimia comes from studies assessing their presence in bulimics. For example, Jimerson, Lesem, Kaye and Brewerton (1992) found low serotonin and dopamine metabolite concentrations in the cerebrospinal fluid (CSF) of bulimic patients with frequent binge eating episodes. Kaye et al. (1990) measured CSF monoamine concentrations in normal weight bulimics and normal weight non-bulimic volunteers. They found significantly lower mean CSF norepinephrine in the bulimics, but found normal levels of both CSF 5-hydroxyindoleacetic acid (5-HIAA), the major serotonin metabolite, and CSF homovanillic acid (HVA), the major dopamine metabolite. Fava et al. (1989) report that bulimia nervosa is accompanied by marked alterations in serotonin and norepinephrine activity which might contribute to the perpetuation of the eating disorder and accompanying psychopathologic symptoms, including anxiety and depression.

One of the few things we think we know about bulimia is that bulimics suffer specifically from carbohydrate craving (Chiodo & Latimer, 1986; Goldbloom & Garfinkel, 1990; Marrazziti, Macchi, Rotondo, Placidi & Cassano, 1988; Turner et al., 1991). Given the putative role of serotonin in eating behavior, and evidence that increased consumption of carbohydrates increases production of serotonin, this assumption has led directly to the use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of bulimia (Walsh & Devlin, 1992; Wilcox, 1990; Bazire, 1988; Walsh, 1988; Kaye, Gwirtsman, Brewerton, George, & Wurtman, 1988; Agras & McCann, 1987).

Not all of the evidence supports the notion of carbohydrate craving (Walsh, Kissileff, Cassidy, & Dantzic, 1989). Moreover, the DSM-IV (1994) points out that, in terms of a macronutrient connection the "...fractions of calories derived from protein, fat, and carbohydrate.." among bulimics are similar to those of persons without bulimia (p. 545).

The issue of carbohydrate craving notwithstanding, as mentioned earlier, a large proportion of bulimics present as clinically depressed, behaviorally impulsive, or both (Jimerson, Lesem, Kaye, Hegg, & Brewerton, 1990b; López-Ibor, Jr., 1988; Newton, Freeman, & Munro, 1993; Pryor, McGilley, & Roach, 1990; Rossiter, Agras, McCann, Schneider, & Götestam, 1991; Van Kammen, 1987), behavioral syndromes which have been linked to serotonin dysfunction. Thus the use of SSRI antidepressants, such as fluoxetine (Prozac) or fluvoxamine (Luvox), as adjuncts to the treatment of bulimia is often justified on these bases.

Antidepressant Drug Treatment Prior to the advent of SSRIs, other antidepressant drugs which serve as serotonin agonists were used in the treatment of bulimia, including monoamine oxidase inhibitors and the tricyclics. Monoamine oxidase inhibitors (MAOIs) block the catabolism of serotonin into 5-HIAA, and thereby increase the availability of serotonin at the synapse. MAOIs are not specific to serotonin, however. They also block the catabolism of the monoamines norepinephrine and dopamine. Tricyclic antidepressants block the reuptake of serotonin by the presynaptic releasing cell. Like the MAOIs, the tricyclics have similar effects on norepinephrine and dopamine (Jacobs, 1995). SSRIs act at the synapse to prevent the reuptake of serotonin by the presynaptic neuron, thus prolonging the effect of serotonin on the serotonergic receptor cites of the postsynaptic cell. Unlike the MAOIs or the tricyclics, however, SSRIs, as their name suggests, are selective for serotonin only.

The MAOIs, tricyclics, and most SSRIs were developed as antidepressants based on the theory that the biochemical etiology of depression is a deficiency in the levels of monoamines at the synapse (Van Kammen, 1987). Prior to 1988, when the first SSRIs were introduced into the U. S. (Egli, 1993), and given the presumed depression / bulimia connection, MAOIs and tricyclic antidepressants were the drugs of choice in the treatment of bulimia (Fahy, Eisler, & Russel, 1993; Mitchell, 1988; Pope & Hudson, 1986b, 1987,1989; Rockwell, 1986; Walsh, 1991; Wells & Logan, 1987).

Throughout the 1980s and early 1990s, several placebo-controlled, double-blind studies looked at the effectiveness of various tricyclic and MAOI antidepressants in the treatment of bulimia (Agras, Dorian, Kirkley, Arnow, & Bachman ,1987; Agras, Rossiter, Arnow, Pope, Hudson, Jonas, & Yurgelun-Todd, D.,1983; Barlow, Blouin, Blouin, & Perez, 1988; Blouin, Blouin, Perez, & Barlow, 1989; Hughes, Wells, Cunningham, & Ilstrup, 1986; Kennedy et al., 1988; McCann & Agras, 1990; Mitchell & Groat, 1984; Sabine, Yonace, Farrington, Barrat, & Wakeling, 1983; Schneider, Telch, Raeburn, Perl, & Koran, 1992; Walsh, Stewart, Roose, Gladis, & Glassman, 1984). The essential findings of these studies are presented in Table 1.

With regard to the tricyclic antidepressants, Imipramine (Tofranil) was found to significantly decrease both binge eating and purging (Agras et al., 1987; Pope et al., 1983). Imipramine, metabolized in the body becomes desipramine (Norpramin). Desipramine resulted in a significant decrease in vomiting among bulimics who purge (Agras et al., 1992; Barlow et al., 1988; Blouin et al., 1989; Hughes et al., 1986) and a significant decrease in binge eating among non-purging bulimics (McCann & Agras, 1990). It should be noted that imipramine and desipramine act primarily to block the reuptake of norepinephrine (Brovar, 1980).

Although mianserin did not significantly decrease either binge eating or purging, it is possible that the dose employed was too low (Sabine et al., 1983). Amitriptyline (Elavil) treatment significantly reduced vomiting but was not significantly different from the placebo in this regard. Behavioral therapy provided to both treatment and placebo groups may account for this finding (Mitchell & Groat, 1984). Interestingly, prior to the introduction of SSRIs, amitriptyline was the preferred drug treatment for depression involving serotonin dysfunction. Although it is not an SSRI it apparently acts primarily to block serotonin reuptake (Brovar, 1980).

With regard to the MAOIs, Walsh et al. (1984) found significant declines in vomiting with the use of phenelzine (Nardil), and Kennedy et al. (1988) indicated similar findings with isocarboxazid (Marplan).

In reviewing many of these antidepressant drug studies several researchers have suggested that, at least in the short term, bulimic symptoms can be treated effectively with specific tricyclic and MAOI antidepressants, (Agras & McCann, 1987; Walsh, 1988). Further, Walsh (1988) indicated that both depressed and non-depressed bulimic patients respond equally well to antidepressant drugs and Agras and McCann (1987) pointed out that the effectiveness of these antidepressants is comparable to treating bulimia with cognitive-behavioral psychotherapy but that the drop out rate is higher for drug treatment (possibly due to drug side effects and dietary constraints).

With regard to concomitant use of cognitive-behavioral therapy and pharmacological treatment, Rossiter, Agras, Losch and Telch, (1988) found superior therapeutic maintenance following cognitive-behavioral compared with imipramine therapy, and both Agras and McCann (1987) and Wells and Logan (1987) have suggested that the combination of cognitive-behavioral therapy and drug treatment might hold the most promise for the prevention of relapse (a suggestion which we will revisit later in this paper).

Selective Serotonin Reuptake Inhibitors Since 1988 the SSRIs have, to a large degree, replaced these less specific monoamine blockers and inhibitors for two reasons. First, SSRIs have fewer serious negative side effects (Fuller & Wong, 1990; Leonard, 1993; Trygstad, 1990). Tricyclics and MAOIs are said to have "anti-cholinergic" side effects because they interfere with activities mediated by acetlycholine. These side effects include constipation, headache and dry mouth. In addition, MAOIs require dietary restrictions on foods that have a high tyramine content such as cheese and most foods that are aged, fermented (including alcoholic beverages), or smoked. There are also restrictions on such things as tea, coffee and chocolate. Eating such foods could increase blood pressure and even lead to stroke. Normally, these foods would have little or no effect on blood pressure because tyramine is metabolized in the liver by MAO. Since MAOIs block MAO, people on these drugs have difficulty metabolizing tyramine and are susceptible to surges in blood pressure (Pinel, 1993). Food restrictions such as these make MAOIs impractical in treating a food related disorder. SSRIs, on the other hand, have been shown to be highly effective in treating depression, without the anticholinergic, antihistaminergic, or anti-adrenergic side effects (Fuller & Wong, 1990).

Second, as mentioned earlier, the serotonergic system is directly implicated in the physiology of eating (Fuller & Wong, 1990; Jimerson et al., 1990b; McBride, Anderson, Khait, Sunday, & Halmi, 1991; Morley, 1989), particularly in the suppression of carbohydrate intake (Jimerson, Lesem, Hegg, & Brewerton, 1990a; Marrazziti, et al., 1988), which is thought by many to be a predisposing factor, a perpetuating factor, or both, in the course of the disorder, in the regulation of satiety, and in macronutrient selection (Goldbloom, Garfinkel, Shaw, 1991; Goldbloom, Hicks, & Garfinkel, 1990; Walsh, 1991). In animals, SSRIs cause a decrease in serotonin turnover and a concomitant behavioral decrease in food intake (Fuller & Wong, 1990).

Early open trial studies with specific serotonergic agonists suggested that fluoxetine (Prozac), fluvoxamine (Luvox), and fenfluramine (Pondimin) could be effective in reducing symptoms of bingeing and purging (Fava et al., 1990; Freeman & Munro, 1988; Kaye, Waltzing, Hsu, & Bulik, 1991; Lewis & Brisman, 1992; Mitchell et al., 1989; Morley, 1988; Solyom, Solyom, & Ledwidge 1989; Spigset & Pleym, 1991; Trygstad, 1990; Walsh, 1991; Wilcox, 1990). Fluoxetine and fluvoxamine are SSRI central anorectics as well as antidepressants. Fenfluramine is considered to be an SSRI central anorectic, but not an antidepressant (Morley, 1988).

Only one completely independent, placebo controlled, double-blind study has been reported for fluoxetine (Fichter et al., 1991). Two other double-blind studies are associated with Eli Lilly & Company, the manufacturer of Prozac, and appear to be part of the clinical trials used to gain FDA approval of Prozac as a treatment for bulimia (Fluoxetine Bulimia Nervosa Collaborative Study Group, 1992; Goldbloom & Olmsted, 1993). Two independent, placebo controlled, double-blind studies have been reported for fenfluramine (Blouin, Blouin, Perez, Bushnik, Zuro, & Mulder, 1988; Fahy et al., 1993), and none, to date, have been reported for fluvoxamine. Other well known SSRI antidepressants for which no research literature exists are sertraline (Zoloft) and paroxetine (Paxil). The essential findings of the double-blind, placebo controlled studies are presented in Table 2.

Fluoxetine hydrochloride is better know by its commercial name, Prozac. Prozac is the world's largest selling antidepressant. It is approved in the U. S. for the treatment of clinical depression and obsessive compulsive disorder. Its also approved in 16 countries other than the U. S. for the treatment of bulimia. In November, 1994, Eli Lilly & Company, the manufacturers of Prozac, received an FDA letter of approval for the use of Prozac in the U. S. for the treatment of bulimia (Business Wire, 1994). To date, fluoxetine is the only drug approved by the FDA for the treatment of bulimia.

FDA action was based largely on Lilly's three clinical trials involving a total of 785 patients. The results of these trials showed that patients who took 60 mg of fluoxetine a day significantly reduced their number of binges and purges per week compared to patients who took a placebo (Rodgers, 1994). In these trials no psychotherapy was used. Although the single independent, placebo controlled, double-blind study of fluoxetine is not inconsistent with this finding, the effectiveness of fluoxetine when used in conjunction with psychotherapy is less than overwhelming (Fichter et al., 1991).

Fichter et al. (1991) looked at the efficacy of fluoxetine (60 mg/day) as compared to a placebo in patients receiving intensive behavior therapy. There were no statistically significant differences between treatment and placebo groups on "urges to binge" or "binge attacks." Both groups showed significant improvement over time on the Eating Disorder Inventory but there was no difference between groups. In fact, the only difference between fluoxetine and placebo groups was a significant weight loss in the fluoxetine group. It was concluded that fluoxetine, in combination with behavior therapy, did not demonstrate a greater statistically significant effect on eating attitudes or eating behavior, compared to the placebo, that went beyond the effects of the behavior therapy.

The Fluoxetine Bulimia Nervosa Collaborative Study Group (1992) compared the efficacy of fluoxetine (20 mg/day), fluoxetine (60 mg/day) and a placebo over an 8 week period. No psychotherapy was used (See next paragraph: Goldbloom & Olmsted, 1993). Fluoxetine (60 mg/day) was found be significantly better than fluoxetine (20/mg day) and the placebo in reducing binge eating and vomiting. Other aspects of bulimia, such as depression, carbohydrate craving, and abnormal attitudes concerning eating improved with fluoxetine (60 mg/day), as well.

Goldbloom and Olmsted (1993) compared the efficacy of fluoxetine (20 mg/day), fluoxetine (60 mg/day) and a placebo over an 8 week period. No psychotherapy was used. They used an individual change model to examine the clinically significant effect of fluoxetine on the attitudes and belief characteristics of 382 adult female patients with bulimia nervosa. Behavioral change was assessed with self-monitored measures of binge eating and purging; psychological change was measured with the self-rated Eating Disorder Inventory (EDI) and the Hamilton Rating Scale for Depression (HRSD). On the majority of psychological measures, more women taking fluoxetine than the placebo showed clinically significant change. Behavioral improvement was significantly associated with the likelihood of demonstrating clinically significant psychological change. The effect of fluoxetine on attitudinal change was not related to the presence of depression.

Prior to FDA approval and the publication of Goldbloom and Olmsted (1993), Walsh (1991) reviewed the literature on fluoxetine in the treatment of bulimia. He found that, in general, in both open trial and double-blind studies, fluoxetine was associated with a significant reduction in abnormal eating behaviors and attitudes, with patient improvement generally lasting at least as long as the drug treatment. He concluded that fluoxetine is about as effective as earlier antidepressants, but without the serious side effects. He suggested, as Agras and McCann (1987) had suggested with earlier antidepressants, that the role of antidepressants in relationship to psychotherapy in the treatment of bulimia needs to be clarified. Fichter's et al. (1991) results support this suggestion.

Fahy et al. (1993) conducted a placebo-controlled, double-blind study of d-fenfluramine in 43 patients with bulimia. They compared the d-fenfluramine (45 mg/day) group with a placebo over an 8 week period. All participants in both groups also received cognitive-behavioral therapy. The treatment effect was assessed using food diaries of eating behavior as well as results of the Bulimic Investigatory Test (BITE) and Eating Attitudes Test (EAT), both of which are self-rating questionnaires. Thirty-nine participants finished the study. Abnormal eating behavior and attitudes improved significantly in both groups, with a significant reduction in vomiting and binge eating, as well as a significant reduction in abnormal attitudes about eating. Although the authors concluded that d-fenfluramine is not effective in treating bulimia, in light of the suggestions of Agras and McCann (1987), Fichter et al. (1991), Rossiter et al. (1988), Wells and Logan, 1987), and Walsh (1991), it is possible that use of psychotherapy obscured the role of d-fenfluramine in the results.

Blouin, Blouin, Perez, Bushnik, Zuro, and Mulder (1988) carried out a placebo-controlled, double blind, crossover study comparing the effects of fenfluramine and desipramine with a placebo. Of 22 participants, 12 were randomly assigned to the fenfluramine group and 10 to the desipramine group. Half of the participants in each group received the active drug for 6 weeks and half the placebo. After a 3 week washout period, participants were crossed over for the remaining 6 weeks. No psychotherapy was employed.

A greater proportion of participants who had received fenfluramine than desipramine showed a decrease in binge eating and vomiting, but both drugs were superior to placebo. It was suggested that fenfluramine could be an effective antibulimic agent. Although fenfluramine is not considered to be an antidepressant, it was reported that in this study fenfluramine had antidepressant qualities and evidence was cited from other researchers consistent with this notion. According to Blouin et al. (1988), although not marketed as such, fenfluramine may lead "...first to fairly effective control over the primary symptoms of bulimia, accompanied by secondary alleviation of depressive symptoms..." (p. 267).

Conclusions The evidence suggests that serotonin dysfunction plays some role in bulimia and that SSRIs can increase the availability of serotonin, presumably in the ventromedial hypothalamus (VMH) (the so called satiety center), and thus should, and by most accounts probably do, help alleviate the frequency of binge-purge episodes associated with the disorder. Serotonergic dysfunction, as we have seen, may even help explain why bulimia is more prevalent among women than men. However, we also know that from a biological / biochemical perspective, serotonin is not the only transmitter, and the VMN not the only central structure, implicated in pathophysiology of eating disorders.

For example, neuropeptide Y (NPY) is a powerful transmitter which produces prolonged overeating in sated animals when applied centrally to the PVN, a region in which norepinephrine also stimulates feeding behavior (Gray & Morley, 1986). However, the primary locus of NPY's effects on eating is the perifornical region, which has been found to be the locus in which norepinephrine and dopamine are most effective in suppressing eating (Stanley & Gillard, 1994). Kaye, Berrettini, Gwirtsman, and George (1990) found that a structurally related amino acid peptide called peptide YY (PYY) may contribute to the drive to overeat in a binge fashion in normal-weight bulimics. To the extent that monoamines and neuropeptide transmitters may be important in the regulation of food intake, the study of their influences in hypothalamic and extra-hypothalamic brain regions needs to be addressed in the context of eating disorders such as bulimia. Other substances, such as cholecystokinin (CCK), and vasopressin, have also been implicated in the regulation of eating (Kaye & Weltzin, 1991).

Most clinicians and researchers now view bulimia as having a multidetermined, heterogeneous etiology, including biochemical and psychosocial factors which could predispose an individual to develop bulimia, perpetuate the disorder, or both (Fairburn, 1991; Goldbloom et al., 1991). In this context the evidence suggests that treating bulimia with SSRIs alone and without the use of psychotherapeutic intervention is not effective in the long run (Donnini et. al., 1995; Lewis & Brisman, 1992).

To be able to delineate those factors that initiate bulimia and distinguish them from those that perpetuate or exacerbate the disorder, we need to bring together the study of neuronal systems that have evolved to regulate eating behavior and the psychosocial factors that are both influenced by and also influence these systems. That is to say, if feelings and behavior are determined by what we think (this being the basic premise of cognitive-behavioral therapy), we know that SSRIs alone are not the answer to treating bulimia. Even though they help alleviate bulimic symptoms, without some structured psychotherapeutic intervention, effective drug treatment is likely to be abandoned by the patient (Lewis & Brisman, 1992). How individuals with bulimia defines themselves vis-ŕ-vis the disorder and the external world is critical to making appropriate choices of what, when, why, and how much they eat (Donnini et al., 1995; Stanley & Gillard, 1994).

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Table 1

Placebo-controlled, double-blind studies of tricyclic and monoamine oxidase inhibitor antidepressants^*

^*Note: Although most studies excluded individuals who also met criteria for anorexia nervosa, some included such individuals. Moreover, many women included in these studies could be classified with borderline personality disorder, obsessive-compulsive disorder, mixed personality disorder and/or current or life time diagnosis of major depression.

Table 2

Placebo-controlled, double-blind studies of specific serotonin reuptake inhibitors