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Abstract

This article will review the treatment research literature on patients with anorexia nervosa. Perhaps somewhat surprisingly, the controlled treatment literature on this disorder is fairly limited. This is attributable to several factors, including the fact that many patients with anorexia nervosa are difficult to engage in treatment and unwilling to participate in randomized trials, and that many of these patients are so critically ill that they require a multiplicity of interventions and long-term therapy, creating design problems for randomized trials. Nonetheless, the extant literature will be reviewed, including pharmacologic and psychotherapeutic interventions in adolescents and adults. One point that needs to be addressed at the outset is the proper venue for the treatment of anorexia nervosa. Many patients, particularly those very low in weight, require in-patient and/or partial hospital treatment as the initial intervention. Although third-party payers are increasingly reluctant to pay for such interventions, they remain the treatments of choice for many anorectic patients. Another issue concerns acute treatment, focusing on weight gain, versus relapse prevention, focusing on weight maintenance and further work on anorectic psychopathology. Different studies have focused on different areas.

Keywords

anorexia nervosa pharmacotherapy psychotherapy treatment

Psychosocial intervention for adolescents with anorexia nervosa

In contrast to the uncertainty of the research outcome data with adults, there is mounting support for a particular family-therapy intervention for adolescents with anorexia nervosa (AN). In general, family therapy for AN has been practised since the mid-1970s, dating back to Minuchin's work on structural family therapy [1] as well as Haley's strategic approach to family therapy [2]. However, in recent years a specific family therapy approach based on the work of the Maudsely group in London and expanded upon by Lock and colleagues [3], has emerged as the treatment of choice for adolescent AN. In this approach, the adolescent is viewed as regressed and in need of parental control over eating, during which time adolescent development can be appropriately addressed without interference from the eating disorder. Control is then gradually returned to the adolescent. At least initially, the exclusive focus of this therapy is on restoration of a healthy weight with the professional encouraging the parents to remain focused on refeeding their offspring. Deviation from this very important task of weight restoration is actively discouraged.

An initial study by Russell and colleagues randomized 80 consecutive, weight-restricted patients to out-patient family therapy or individual therapy [4]. Of the patients, 36 reported an age of onset prior to 18 years; of these, 21 out of 36 had a duration of illness of under 3 years. This study showed that adolescent patients with a short duration of AN demonstrated greater improvements with family therapy than with individual therapy. These improvements were maintained at 5-year follow-up with 90% of patients achieving good outcome compared with only 36% of those assigned to individual therapy. There were no differences in treatment outcome for adolescent patients with a longer duration of illness [5].

Further evidence for family therapy was provided by Robin and colleagues, who randomized 19 adolescents with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IIIR AN diagnosis to behavioral family systems therapy, very similar to the Maudsley approach, and 18 adolescents to an individual, ego-oriented therapy [6]. At the conclusion of an average of 16 months of treatment, both groups showed improvements in eating attitudes, depressive affects, body-shape concerns and family conflict, while the family therapy group showed greater increases in body mass index and a higher incidence of restoration of menses. These results were maintained at 1-year follow-up [7].

Additionally, a more recent study by le Grange, Binford and Loeb, although not randomized, showed that 90% of 45 adolescent patients with a short duration of anorexia achieved good or intermediate outcome after receiving manualized out-patient family therapy [8].

This type of family therapy can be efficaciously delivered in a variety of ways. For example, conjoint delivery (n = 19) and separated delivery (n = 21) of family therapy over the course of 1 year appear to be equivalent, with both yielding significant improvements in psychologic measures, eating disorder symptoms and family expressed emotion [9]. Yet there is evidence, although not always statistically significant, that separated family therapy, where the child and parents are seen separately, may be more effective in treating eating disorder symptomatolgy, while conjoint family therapy, wherein the parents and child are seen together, may be better at producing psychologic change. Separated family therapy appears to be superior in families with higher levels of maternal criticism.

In addition, there do not appear to be differences when family therapy is delivered over the short or long term. Lock and associates randomized 86 adolescents with DSM-IV AN to family therapy delivered in ten sessions over the course of 6 months, or 20 sessions delivered over 12 months, and found no significant differences on any outcome measures [10]. Both groups showed significant improvements in body mass index and on eating disorder symptomatolgy. However, there was a slight, although not statistically significant, support for long-term therapy for those children with severe obsessive compulsive features or for families that were not intact.

Finally, family group psychoeducation may be as effective as family therapy, in an in-patient setting [11]. A total of 25 adolescent females with AN or subthreshold AN were assigned to one of the two treatment groups for 4 months, with both groups showing significant weight gain. In light of no significant differences between groups on any measure of eating or noneating disorder psychopathology, the results may have been confounded by the other treatments they may have received while hospitalized.

As summarized above, although limited by small-to-moderate sample sizes, early results show that family therapy is the most widely supported intervention for adolescent AN. Appropriate candidates for this type of treatment should be under the age of 18 and should ideally be living in the family home, with those patients reporting a shorter duration of illness faring better with this approach. This manualized intervention is delivered in 20 sessions by a trained professional over the course of 1 year and consists of three separate phases [3]:

Initial evaluation and setting up treatment

Helping the adolescent eat on her own

Adolescent issues

Research on family therapy for adolescent eating disorders is ongoing, including several trials funded by the National Institute of Mental Health. For example, le Grange and colleagues at the University of Chicago are currently in year 5 of a controlled trial comparing family-based therapy and separated parent therapy in the treatment of adolescent bulimia nervosa with early promising results. In addition, researchers at the University of Chicago and Stanford are comparing family-based therapy and ego-oriented individual therapy in the treatment of adolescent anorexia.

Psychotherapeutic interventions for adults with anorexia nervosa

Much of what we know about the psychosocial treatment of adults with AN derives primarily from clinical experience rather than empiric evidence. There have been very few randomized controlled trials of psychologic interventions for adults with AN, and many of these have failed to find significant effects; although what research is available can be succinctly reviewed. Russell and colleagues at the Maudsley Hospital in London compared family therapy with individual supportive therapy in a group of eating disordered patients who had initially been treated as in-patients in a relapse prevention trial [4]. Of the sample of 57 patients, 36 were adults with the onset of AN after the age of 18 years. Among these patients, individual supportive psychotherapy appeared superior to family therapy. These results held at the 5-year follow-up [5]. Channon and coworkers compared cognitive behavioral therapy with a control treatment consisting of medical monitoring and nonspecific support in a series of 24 adult out-patients with AN [12]. There was modest improvement in both groups with no significant differences between them. In a study of 30 adult out-patients, Treasure and colleagues found no significant difference between a brief psychodynamically oriented psychotherapy, termed cognitive analytic therapy, and a behavioral therapy approach using primarily educational techniques [13]. Crisp and colleagues treated 90 adult females with AN who were randomly assigned to one of four conditions: in-patient treatment; a combination of out-patient family therapy and nutritional counseling; participation in out-patient multifamily group with nutritional counseling; or no treatment [14]. There were no significant differences among the conditions, although this study was methodologically limited.

Most recently, Pike and colleagues reported the results of a controlled relapse prevention trial comparing cognitive behavioral therapy to nutritional counseling in 33 out-patient women with AN who had been weight restored as in-patients [15]. This was designed as a relapse prevention trial. Cognitive behavioral therapy was associated with a higher number of subjects achieving good outcome and a lower dropout rate compared with nutritional counseling. Lastly, McIntosh and colleagues treated female out-patient AN subjects (n = 56) aged 17 to 40 years with one of three psychotherapies consisting of 20 1-hour long manual-based sessions [16]. The three treatments included cognitive behavioral therapy, interpersonal therapy and what was termed nonspecific supportive psychotherapy, which included clinical management involving education, care and support and a strong emphasis on fostering a therapeutic relationship to promote adherence to treatment. The intention to treat analysis revealed that nonspecific supportive care was superior to interpersonal therapy, and cognitive behavioral therapy and interpersonal therapy did not differ. In the completer analysis, nonspecific supportive care was superior to both cognitive therapy and interpersonal therapy. This finding suggests that a therapy that is not as demanding of patient adherence as cognitive behavioral therapy but that focuses on establishing a therapeutic relationship that involves the patient in treatment planning, may have particular utility in treating this group of often rather treatment-resistant patients.

Pharmacotherapeutic interventions for individuals with anorexia nervosa

AN is an illness associated with an undefined etiology and a corresponding lack of targeted pharmacotherapy. Several impediments to drug therapy research have resulted in the publication of a small number of controlled trials. As described by Zhu and Walsh, the absence of an AN animal model limits the discovery of innovative drug treatments and complicates the elucidation of causal neurobiologic dysfunction(s) [17].

The primary emphasis of treatment in the acute phase of AN is on the promotion of weight gain in patients who are often emaciated and exhibit severe medical sequelae. As weight is restored and the maintenance phase of AN treatment emerges, the primary goal of pharmacotherapy shifts toward improvement of coexisting or underlying psychopathologies.

While potentially empirically beneficial, evidence-based support is lacking for the use of psychopharmacotherapy in the acute treatment phase of AN. The severity of symptoms in this stage of the illness mandates a multidisciplinary approach to treatment. Concomitant psychotherapy, dietary guidance, refeeding programs and medical management generally beget weight gain. Thus, even in the best of study designs, this methodologic challenge makes it difficult to discern a benefit of drug therapy over these necessary simultaneous interventions. Psychopharmacology may play a more vital role in relapse prevention, and additional clinical trials in this area are needed. Barbarich and colleagues, reported that enduring negative mood, obsessiveness, perfectionism, and core eating-disorder symptoms are commonly observed in recovered AN patients [18].

Historically, antidepressant drugs have been the focus of the majority of AN research. Several nonantidepressant compounds have also been explored. More recently, atypical antipsychotic agents have shown benefit in preliminary study and are increasingly becoming a focus of investigation. This review will attempt to provide brief historic overviews, but will focus primarily on the most recent and clinically relevant developments in AN research.

It is estimated that 50 to 75% of AN patients seeking treatment in tertiary care centers present with major depression or dysthymia, the lifetime prevalence of obsessive-compulsive disorder is estimated at 25%, and other anxiety disorders, including social phobia, occur frequently [101]. Thus, a potential role for antidepressant therapy is suggested. Originally, the tricyclic antidepressant (TCA) compounds were tested in controlled trials, primarily in in-patients with AN [19 –21]. Limited efficacy and significant adverse effects were seen in these studies.

Primarily by virtue of their comparably favorable adverse effect profiles, selective serotonin reuptake inhibitors (SSRIs) have widely replaced the TCAs in many areas of psychiatry, including AN research and clinical practice. Fluoxetine has been studied in two controlled studies in AN, the first in an acute treatment paradigm and the second in maintenance treatment [22,23]. Several other noncontrolled trials have also evaluated the usefulness of the SSRIs in AN (Table 1).

Table 1.

Selective serotonin reuptake inhibitor trials in anorexia nervosa.

Study	Drug, mean dose	Duration/study design	N	Diagnosis, in-/out-patient	Outcome	Ref.
Pallanti et al., 1998	Citalopram 36.6 mg/day (+14.7) range: 20–60 mg/day	6 months Open-label	32	AN-R Out-patient (treatment started during refeeding)	46.9% showed satisfactory response (weight gain, menstruation and SCL 90-R). Improvement on several EDI-2 subscales. No change on HAM-D or Y-BOCS. 6 dropped out. Adverse drug reactions minimal.	[24]
Fassino et al., 2002	Citalopram titrated to 20 mg/day	12 week minimum, Prospective, randomized, waiting-list control	52	AN-R Out-patient	Weight gain similar in both groups. Citalopram group had improvements on depression scales, obsessive-compulsive symptoms, trait-anger and impulsiveness. 13 dropped out.	[25]
Gwirtsman et al., 1990	Fluoxetine range: 20–60 mg/day	2–13 months Case series	6	–	Patients had chronic, refractory AN. Weight gain and improved mood observed with fluoxetine.	[26]
Kaye et al., 1991	Fluoxetine	11 plus 6 months Open-label	31	AN-R and AN-BP Out-patient	AN-R patients responded better than AN-BP. On eating behavior, mood and obsessional symptoms, response was good in 10, partial in 17, and poor in 4. 29 out of 31 patients maintained weight >85% average body weight at 11 + 6 months follow-up.	[27]
Strober et al., 1997	Fluoxetine 33.9 mg/day (+18.3)	24 months Naturalistic, prospective, longitudinal follow-up	66§	AN-R Out-patient (medication started as in-patient)	No significant differences between groups on any outcome measure, including probability of remaining at target weight.	[28]
Attia et al., 1998	Fluoxetine 56 mg/day (+11.2)	7 weeks Randomized, placebo-controlled, double-blind	33	AN-R and AN-BP In-patient	17 subjects had current major depression No significant difference on weight gain or mood symptoms between fluoxetine and placebo. Fluoxetine was well-tolerated. 8 dropped out.	[22]
Strober et al., 1999	Fluoxetine 33.9 mg/day (+18.3)	6 weeks Open-label	66§	AN-R Medication started as in-patient	Fluoxetine not significantly better than the control group on eating behavior and weight phobia	[29]
Kaye et al., 2001	Fluoxetine range: 20 mg/day q.o.d. to 60 mg/day q.d.	52 weeks Randomized, placebo-controlled, double-blind	39	AN-R Out-patient (some subjects started on trial during refeeding)	10 out of 16 fluoxetine subjects still on drug at 1 year, compared with three out of 19 placebo subjects. Fluoxetine subjects had higher weight and decreased core symptoms at 1 year.	[23]
Ruggiero et al., 2001	Fluoxetine 28 mg/day (+10.32) Clomipramine 57.69 mg/day (+25.79) Amisulpride 50 mg/day (+0)	3 months Single-blind	35	AN-R In-patient (beginning of refeeding phase)	Weight increase was not significantly different between groups.	[30]
Ruggiero et al., 2003	Fluoxetine 30 mg/day (+ 9.35)	12 months Single-blind (Fluoxetine + nutritional management versus nutritional management alone)	95	AN-R and AN-BP Out-patient	Subjects were more likely to be given fluoxetine if depressed. BMI increased significantly in both groups Fear of fatness and EDI subscale scores decreased significantly only in the nutritional group.	[31]
Frank et al., 2001	Sertraline range: 75–150 mg/day	Case series	5	Underweight Binge–purge	Sertraline appeared to decrease core eating disorder symptoms, depression and obsessional thoughts. Sertraline appeared to enhance weight restoration.	[32]
Santonastaso, et al., 2001	Sertraline range: 50–100 mg/day	64 weeks Open-label (drug group versus matched controls)	22	AN-R Out-patient	Sertraline group had greater improvement in depressive symptoms, ineffectiveness, lack of interoceptive awareness, and perfectionism at 14 weeks. Both groups significantly improved body weight. At 64 weeks, one sertraline treated subject and five control subjects maintained full eating disorder diagnosis.	[33]

AN-BP: Anorexia nervosa, binge–purge type; AN-R: Anorexia nervosa restricting type; BMI: Body mass index; EDI: Eating disorder inventory; HAM-D: Hamilton rating scale for depression; q.d.: Every day; q.o.d.: Every other day; SCL: Symptom checklist; Y-BOCS: Yale-Brown obsessive compulsive scale.

33 fluoxetine, 33 case-matched controls.

Attia and colleagues randomized 33 AN in-patients to either fluoxetine (maximum dose 60 mg/day) or placebo [22]. Weight gain occurred in both groups and there was not a statistically significant difference between fluoxetine- and placebo-treated patients on this measure. Further, depression improvement did not statistically differ between groups. A potential confound to this, however, is that weight gain tends to improve depressive symptoms independently of pharmacotherapy [102]. Further, starvation may negatively impact responsiveness to antidepressants [34].

In contrast to acute treatment, fluoxetine demonstrated benefit in a controlled maintenance trial. Kaye and coworkers randomized 39 subjects to fluoxetine (maximum dose 60 mg/day) for 52 weeks [23]. Of 16 patients treated with fluoxetine, ten remained on the drug for 1 year, compared with 3 out of 19 patients in the placebo group. Subjects who remained on fluoxetine for 1 year exhibited significantly increased weight and decreased core eating disorder symptoms, as well as decreased obsessive thought and depressed and anxious mood. While promising, this study was not without limitations. Some of the subjects were enrolled prior to achieving complete weight restoration. The fluoxetine dose varied considerably, ranging from 20 mg every other day to 60 mg/day. Furthermore, as is commonly seen in AN trials, out-patient psychotherapy was optional.

Since a large proportion of AN patients are adolescent, the clinician must be cognizant of the recent US Food and Drug Administration (FDA) warning and revised antidepressant labeling concerning increased suicidal thoughts in children and adolescents who take them [35]. The FDA reports that an analysis of 24 short-term, depression trials in 4400 children and adolescents revealed a 4% average risk of suicidal thinking or suicidality in those taking antidepressants, compared with a 2% average risk in those taking placebo. No suicides occurred during these trials. The prescriber is left with the responsibility of performing a careful risk-to-benefit assessment on each individual patient prior to suggesting treatment.

Characteristically, AN patients display distorted perceptions about body shape and weight [36]. Aberrant in nature, these thoughts often mirror a delusional state, similar to that seen in psychotic illness [37]. While this is the primary justification for antipsychotic research in AN, a convergent indication is that elected antipsychotics have a virtually unparalleled propensity to stimulate weight gain. Historically, the typical antipsychotics pimozide and sulpiride failed to improve outcome in controlled AN trials [38,39]. Owing to a markedly improved adverse effect profile and a strong weight-promoting liability, the atypical antipsychotics have become a promising source of several recent pilot studies and case reports in both in- and out-patients (Table 2).

Table 2.

Uncontrolled antipsychotic trials in anorexia nervosa.

Study	Drug, dose	Study design	N	In-/out-patient	Outcome	Ref.
Fisman et al., 1996	Risperidone 1 mg/day	Case report	1	In-patient	Maintenance of 2.3 kg weight gain for 1 year Improved behavior and decreased paranoia.	[40]
Hansen, 1999	Olanzapine 5 mg/day	Case report	1	In-patient	Body image improved. Weight increased from 31.2 (admission) to 53.1 kg (discharge).	[41]
Jensen & Majlhede, 2000	Olanzapine 5 mg/day	Case report	3	Outpatient	Weight gain and decreased body image distortion observed.	[42]
La Via et al., 2000	Olanzapine 10 mg/day	Case report	2	In-patient	One patient showed improvements on agitation and core-eating disorder behaviors. Gained 1.36 kg/week; from 16.9 to 33.6 kg The other patient gained 1.82 kg/week; from 48 to 53.2 kg.	[43]
Newman-Toker et al., 2000	Risperidone 1.5 mg/day	Case report	2	Out-patient	One patient showed decreased anxiety, food obsession, and delusional thinking. Achieved and maintained normal body weight. Weight increased from 36.4 to 49.5 kg. Increase in QTC interval from 400–421 ms. The other patient showed increased insight into illness and improved mood. Weight increased from 37.7 to 46.8 kg.	[44]
Gaskill, 2001	Olanzapine range: 1.25–15 mg/day	Open-label (nonrandomized)	46	In-patient	Weight gain was not different between olanzapine and nontreated group.	[45]
Mehler et al., 2001	Olanzapine range: 5–12.5 mg/day	Case report	5	–	Olanzapine failed to increase weekly average weight gain, but decreased delusional thinking and improved social interaction observed Patients aged 12–17 years.	[46]
Ruggiero et al., 2001	Fluoxetine 28 (+10.32) Clomipramine 57.69 (+25.79) Amisulpride 50 mg/day (+0)	Single blind	35	In-patient (beginning of refeeding phase)	Exclusion of subjects with clear depression, anxiety, obsessive compulsive disorder and delusional body image thinking. Weight increase was not significantly different between groups.	[30]
Carver, 2002	Risperidone range: 0.5–1.5 mg/day	Retrospective Chart review	30	In-patient (Refractory AN patients)	Risperidone-treated patients demonstrated slightly higher weight gain (3.6 vs 3.4 kg) and caloric intake (1017 vs 943 kcal).	[47]
Powers et al., 2002	Olanzapine 10 mg/day	Open-label	18	Out-patient	Significant improvement on psychiatric rating scales by week 10 in those who gained weight 10 out of 14 completers gained average of 3.98 kg	[48]
Boachie et al., 2003	Olanzapine 2.5 mg/day	Case report	3	In-patient	Patients ages 10–12 years. All three patients gained weight. One patient showed improved agitation and sleep and improved family interactions. Another patient was also taking fluvoxamine.	[49]
Barbarich et al., 2004	Olanzapine mean: 4.7 (+1.6 mg) range: 2.5–7.5 mg/day	Open-label	17	In-patient	Depression, anxiety and core eating disorder symptoms improved. Weight increased significantly; entrance weight: 69 (+ 10)% IBW, final weight: 81 (+9)% IBW (p = 0.000) Some subjects were also taking SSRIs.	[50]
Powers et al., 2004	Quetiapine (dose unknown)	Open-label	20	Out-patient	10-week ongoing study. Mean weight gain for completers was 0.86 kg. Eight patients gained weight, five lost weight, and three had no change. Among those who gained weight, a significant decline in PANSS Positive Scale scores (p = 0.047) was observed.	[51]

IBW: Ideal body weight; PANSS: Positive and negative symptom scale; SSRI: selective serotonin reuptake inhibitor.

While detrimental in schizophrenia, weight gain is a desirable outcome in AN treatment. Allison and colleagues found that in 10 weeks of treatment with either clozapine or olanzapine, schizophrenic subjects gained 4–4.5 kg [52]. In this meta-analysis, risperidone produced half the weight gain of olanzapine. Olanzapine, risperidone and quetiapine have improved outcomes in several preliminary investigations in AN, and subsequent controlled trials are anticipated. The future applications of atypical antipsychotics in AN treatment are still uncertain. Currently, the available literature remains sparse, and the acceptability of maintenance therapy with weight-promoting atypical antipsychotics to AN patients remains questionable.

The risk of tardive dyskinesia and the emergence of extrapyramidal side effects such as akathisia, pseudoparkinsonism and dystonia are significant limitations to the use of conventional antipsychotics. In contrast, they are infrequent complications of treatment with atypical agents. Unfortunately, atypical antipsychotics appear to be associated with metabolic consequences, including hyperlipidemia and hyperinsulinemia. It is unclear whether atypical antipsychotics have direct effects on glucose–insulin homeostatis and lipid metabolism or whether these aberrations are consequences of increased adiposity [55]. This is an area of current investigation.

The FDA has requested that the labeling of atypical antipsychotics be revised to include a warning about an increased potential for hyperglycemia, which can be extreme and has been infrequently associated with ketoacidosis and hyperosmolar coma or death. Reportedly, the relative risk of effects on gluocose-insulin homeostasis and lipid levels is highest for clozapine and olanzapine, moderate for quetiapine, rather low for risperidone and lowest for ziprasidone [53].

Executive summary

Psychosocial intervention for adolescents with anorexia nervosa

A family therapy approach developed at the Maudsley Hospital in London, for which a detailed treatment manual has been published, appears to be the treatment of choice for younger patients who present with anorexia nervosa (AN). However, this therapy is not widely disseminated and often not available to patients.

Psychosocial interventions for adults with anorexia nervosa

Individual psychotherapy appears superior to family therapy for adults with AN, both at end of treatment and at long-term follow-up. Cognitive behavior therapy has been shown to be superior to nutritional intervention in adult patients post hospital treatment for AN.

Pharmacotherapeutic intervention for individuals with anorexia nervosa

Atypical neuroleptic drugs may be useful in improving the rate of weight gain and improving psychopathology in low weight patients with anorexia AN. Fluoxetine may be useful in preventing relapse in patients post in-patient treatment with AN who are weight recovered and in other psychotherapies as well.

Other pharmacotherapeutic options have been evaluated in AN. Zinc has shown some benefit, and has been investigated because zinc deficiency resembles symptoms seen in AN [54,55]. The low toxicity of zinc and the indication of efficacy have led some to suggest clinical supplementation in AN [58]. Other drugs have generally offered little efficacy or imposed intolerable adverse effects. Included in this list are lithium, tetrahydrocannabinol, naltrexone, clonidine, recombinant human growth hormone, metoclopramide, domperidone and cisapride [57].

Clinical psychopharmacotherapy of AN currently consists primarily of SSRIs and atypical antipsychotic compounds, despite a relative lack of evidence supporting these treatments. Clearly, there is a critical need for additional controlled pharmacotherapy trials in AN, particularly for relapse prevention. It is anticipated that controlled trials with atypical antipsychotics are on the horizon. Research continues to expand on the genetics and hormonal control of eating, thus offering optimism for the identification of an etiologic explanation and subsequent discovery of targeted pharmacotherapy.

Conclusions

The treatment literature on AN remains unfortunately quite limited, and given the difficulties and complexities in conducting treatment research with individuals with AN, this is not surprising. However, the National Institutes of Health have made the development of new treatment strategies for AN a priority and it is hoped that this will stimulate considerably more research on this treatment-resistant, often chronic condition. Available literature would suggest that pharmacotherapy plays a very limited role in the treatment of these patients, although there is growing consensus that the use of atypical neuroleptics may be useful in terms of targeting cognitive dysfunction and improving the rate of weight gain in low-weight anorectic patients. There is also some evidence that antidepressant medications may be useful in preventing relapse, although the data here are quite limited. Relative to psychotherapeutic interventions, the available literature suggests that the treatment of choice for adolescent patients is a family therapy model developed at the Maudsley Hospital in London. Therapy for adult patients and those with chronic forms of the illness are less well studied and although several treatment approaches have been used, including cognitive behavioral therapy, the available literature does not really allow one to draw firm conclusions.

Future perspective

Much work remains to be done in developing effective treatments for patients with AN. This is a very challenging illness that often remains treatment resistant and has a significant associated morbidity and mortality [58]. Due to the problems inherent to doing treatment-outcome research in AN, investigators are increasingly moving to the use of multicenter trials wherein an adequate number of subjects can be recruited in a reasonable period of time to test new interventions. This trend will continue and much of what we will learn in the next 10 years regarding the treatment of this condition will probably result from these multicenter efforts. The use of atypical neuroleptics is increasing but a well designed randomized trial has yet to be completed and should be a priority in the next 10 years. Further work is needed to evaluate family therapy interventions for adolescents. Much work needs to be done in chronic and older patients, many of whom become quite treatment resistant over time.

References

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

Minuchin

Baker

Rosman

Liebman

Milman

Todd

: A conceptual model of psychosomatic illness in children. Arch. Gen. Psychiatry 32, 1031–1038 (1975).

Haley

: Uncommon Therapy: The Psychiatric Techniques of Milton H Erickson. Norton, New York, NY, USA (1973).

Lock

le Grange

Agras

Dare

: Treatment Manual for Anorexia Nervosa: A Family-Based Approach. Guilford Press, New York, NY, USA (2001).

Detailed manual for the Maudsley method of family therapy.

Russell

GFM

Szmukler

Dare

Eisler

: An evaluation of family therapy in anorexia nervosa and bulimia nervosa. Arch. Gen. Psychiatry 44, 1047–1056 (1987).

Eisler

Dare

Russell

Szmukler

le Grange

Dodge

: Family and individual therapy in anorexia nervosa. A 5-year follow-up. Arch. Gen. Psychiatry 54, 1025–1030 (1997).

Long-term follow-up of the Maudsley approach.

Robin

Siegel

Koepke

Moye

Tice

: Family therapy versus individual therapy for adolescent females with anorexia nervosa. J. Dev. Behav. Pediatr. 15, 111–116 (1994).

10.

Robin

Seigel

Moye

Gilroy

Dennis

Sikand

: A controlled comparison of family versus individual therapy for adolescents with anorexia nervosa. J. Am. Acad. Child Adoles. Psychiatry 38, 1428–1489 (1999).

11.

le Grange

Binford

Loeb

: Manualized family-based treatment for anorexia nervosa: a case series. J. Am. Acad. Child Adolesc. Psychiatry 44, 41–46 (2005).

12.

Eisler

Dare

Hodes

Russell

Dodge

le Grange

: Family therapy for adolescent anorexia nervosa: the results of controlled comparison of two family interventions. J. Clin. Psychol. Psychiatry 41, 727–739 (2000).

13.

Lock

Agras

Bryson

Kraemer

: Comparison of short versus long term family treatment for adolescent anorexia nervosa. The Eating Disorders Research Society Annual Meeting. Amsterdam, The Netherlands, 7–9 October 2004 (Abstract).

14.

Study addressing duration of therapy using a family therapy approach.

15.

Geist

Henmaa

Stephens

Davis

Katzman

: Comparison of family therapy and family group psychoeducation in adolescents with anorexia nervosa. Can. J. Psychiatry – Revue Canadienne de Psychiatrie 45, 173–178 (2000).

16.

Channon

de Silva

Hemsley

Perkins

: A controlled trial of cognitive-behavioral and behavioral treatment of anorexia nervosa. Behav. Res. Ther. 27, 529–535 (1989).

17.

Treasure

Todd

Brolly

Tioller

Nehmed

Denman

: A pilot study of a randomized trial of cognitive analytical therapy vs. educational behavioral therapy for adult anorexia nervosa. Behav. Res. Ther. 33, 363–367 (1995).

18.

Crisp

Norton

Gowers

: A controlled study of the effect of therapies aimed at adolescent and family psychopathology in anorexia nervosa. Br. J. Psychiatry 159, 325–333 (1991).

19.

Study often cited to indicate the lack of effectiveness of in-patient treatment for anorexia nervosa, although the methodology is flawed.

20.

Pike

Walsh

Vitousek

Wilson

Bauer

: Cognitive behavior therapy in the posthospitalization treatment of anorexia nervosa. Am. J. Psychiatry 160, 2046–2049 (2003).

21.

Relapse prevention trial demonstrating the superiority of cognitive behavioral therapy over nutritional counseling.

22.

McIntosh Jordan

Carter

: Three psychotherapies for anorexia nervosa: a randomized trial. Am. J. Psychiatry 162, 741–747 (2005).

23.

Zhu

Walsh

: Pharmacologic treatment of eating disorders. Can. J. Psychiatry 47, 227–234 (2002).

24.

Excellent review of drug trials.

25.

Barbarich

Kaye

Jimerson

: Neurotransmitter and imaging studies in anorexia nervosa: new targets for treatment. Curr. Drug Targets CNS Neurol. Disord. 2, 61–72 (2003).

26.

Lacey

Crisp

: Hunger, food intake and weight: the impact of clomipramine on a refeeding anorexia nervosa population. Postgrad. Med. J. 56, 79–85 (1980).

27.

Biederman

Herzog

Rivinus

: Amitriptyline in the treatment of anorexia nervosa: a double-blind, placebo-controlled study. J. Clin. Psychopharmacol. 5, 10–16 (1985).

28.

Halmi

Eckert

LaDu

Cohen

: Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline. Arch. Gen. Psychiatry 43, 177–181 (1986).

29.

Attia

Haiman

Walsh

Flater

: Does fluoxetine augment the inpatient treatment of anorexia nervosa? Am. J. Psychiatry 155, 548–551 (1998).

30.

Trial demonstrating the ineffectiveness of selective serotonin reuptake inhibitors in low-weight anorectic patients.

31.

Kaye

Nagata

Weltzin

: Double-blind placebo-controlled administration of fluoxetine in restricting and purging-type anorexia nervosa. Biol. Psychiatry 49, 644–652 (2001).

32.

Pallanti

Quercioli

Ramacciotti

: Citalopram in anorexia nervosa. Eat. Weight Disord. 2, 216–221 (1997).

33.

Fassino

Daga

Boggio

Garzaro

Piero

: Use of reboxetine in bulimia nervosa: a pilot study. J. Psychopharmacol. 18, 423–428 (2004).

34.

Gwirtsman

Guze

Yager

Gainsley

: Fluoxetine treatment of anorexia nervosa: an open clinical trial. J. Clin. Psychiatry 51, 378–382 (1990).

35.

Kaye

Weltzin

Hsu

Bulik

: An open trial of fluoxetine in patients with anorexia nervosa. J. Clin. Psychiatry 52, 464–471 (1991).

36.

Strober

Freeman

DeAntonio

Lampert

Diamond

: Does adjunctive fluoxetine influence the post-hospital course of restrictor-type anorexia nervosa? A 24-month prospective, longitudinal follow-up and comparison with historical controls. Psychopharmacol. Bull. 33, 425–431 (1997).

37.

Strober

Pataki

Freeman

DeAntonio

: No effect of adjunctive fluoxetine on eating behavior or weight phobia during the inpatient treatment of anorexia nervosa: an historical case-control study. J. Child Adolesc. Psychopharmacol. 9, 195–201 (1999).

38.

Ruggiero

Laini

Mauri

Ferrari

Clemente

Lugo

: A single blind comparison of amisulpride, fluoxetine and clomipramine in the treatment of restricting anorectics. Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 1049–1059 (2001).

39.

Ruggiero

Mauri

Omboni

Volonteri

Dipasquale

Malvini

: Nutritional management of anorexia patients with and without fluoxetine: 1-year follow-up. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 425–430 (2003).

40.

Frank

Kaye

Marcus

: Sertraline in underweight binge eating/purging-type eating disorders: five case reports. Int. J. Eat. Disord. 29, 495–498 (2001).

41.

Santonastaso

Friederici

Favaro

: Sertraline in the treatment of restricting anorexia nervosa: an open controlled trial. J. Child Adolesc. Psychopharmacol. 11, 143–150 (2001).

42.

Slaiman

: Restricted diets restrict antidepressant efficacy. Practitioner 233, 974–975 (1989).

43.

US Food and Drug Administration: Suicidality in children and adolescents being treated with antidepressant medications. US Food and Drug Association, Rockville, MD, USA (2004).

44.

Vigersky

(Ed.): Eating Disorders. In: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. American Psychiatric Association, Washington, DC, USA (1994).

45.

Powers

Santana

: Available pharmacological treatments for anorexia nervosa. Expert Opin. Pharmacother. 5, 2287–2292 (2004).

46.

Review of available drug trials, focusing on antipsychotic therapy.

47.

Vandereycken

Pierloot

: Pimozide combined with behavior therapy in the short-term treatment of anorexia nervosa. Acta Psychiatr. Scand. 66, 445–450 (1982).

48.

Vandereycken

: Neuroleptics in the short-term treatment of anorexia nervosa: a double-blind placebo-controlled study with sulpiride. Br. J. Psychiatry 144, 288–292 (1984).

49.

Fisman

Steele

Short

Byrne

Lavallee

: Case study: anorexia nervosa and autistic disorder in an adolescent girl. J. Am. Acad. Child Adolesc. Psychiatry 35, 937–940 (1996).

50.

Hansen

: Olanzapine in the treatment of anorexia nervosa. Br. J. Psychiatry 175, 592 (1999).

51.

Jensen

Mehlhede

: Anorexia nervosa: treatment with olanzapine. Br. J. Psychiatry 177, 187 (2000).

52.

La Via

Gray

Kaye

: Case reports of olanzapine treatment of anorexia nervosa. Int. J. Eat. Disord. 27, 363–366 (2000).

53.

Newman-Toker

: Risperidone in anorexia nervosa. J. Am. Acad. Child Adolesc. Psychiatry 39, 941–942 (2000).

54.

Gaskill

Treat

McCabe

Marcus

: Does olanzapine affect the rate of weight gain among inpatients with eating disorders? Eat. Disord. Rev. 12, 1–2 (2001).

55.

Mehler

Wewetzer

Schulze

Warnke

Theisen

Dittmann

: Olanzapine in children and adolescents with chronic anorexia nervosa. A study of five cases. Eur. Child Adolesc. Psychiatry 10, 151–157 (2001).

56.

Carver

Miller

Hagman

Sigel

: The use of risperidone for the treatment of anorexia nervosa. The Academy of Eating Disorders Annual Meeting. Boston, MA, USA, 25–28 April 2002 (Abstract).

57.

Powers

Santana

Bannon

: Olanzapine in the treatment of anorexia nervosa: an open label trial. Int. J. Eat. Disord. 32, 146–154 (2002).

58.

Boachie

Goldfield

Spettique

: Olanzapine use as an adjunctive treatment for hospitalized children with anorexia nervosa: case reports. Int. J. Eat. Disord. 33, 98–103 (2003).

59.

Barbarich

McConaha

Gaskill

: An open trial of olanzapine in anorexia nervosa. J. Clin. Psychiatry 65, 1480–1482 (2004).

60.

Powers

Bannon

Eubanks

McCormick

: Anorexia nervosa and quetiapine: effect on weight and psychopathology. The American Psychiatric Association Meeting. New York, NY, USA, 1–6 May 2004 (Abstract).

61.

Allison

Mentore

Heo

Chandler

Cappelleri

Infante

: Antipsychotic-induced weight gain: a comprehensive research synthesis. Am. J. Psychiatry 156, 1686–1896 (1999).

62.

Melkersson

Dahl

: Adverse metabolic effects associated with atypical antipsychotics. Drugs 64, 701–723 (2004).

63.

Birmingham

Goldner

Bakan

: Controlled trial of zinc supplementation in anorexia nervosa. Int. J. Eat. Disord. 15, 251–255 (1994).

64.

Trial suggesting that zinc therapy improves the rate of weight regain.

65.

Lask

Bryant-Waugh

: Zinc deficiency and childhood-onset anorexia nervosa. J. Clin. Psychiatry 54, 63–66 (1993).

66.

Birmingham

: Zinc supplementation in the treatment of anorexia nervosa. Eat. Weight Disord. 7, 20–22 (2002).

67.

Pederson

Roerig

Mitchell

: Towards the pharmacotherapy of eating disorders. Expert Opin. Pharmacother. 4, 1659–1678 (2003).

68.

Sullivan

: Mortality in anorexia nervosa. Am. J. Psychiatry 152, 1073–1074 (1995).

69.

Excellent review of mortality data.

70.

American Psychiatric Association: Disease definition, epidemiology, and natural history (2005). www.psych.org/psych_pract/treatg/pg/eating_revisebook_4.cfm (Accessed June 2005)

71.

Walsh

Devlin

: Psychopharmacology of anorexia nervosa, bulimia nervosa, and binge eating. (2000). www.acnp.org/g4/GN401000153/ch149.html (Accessed June 2005)

Pharmacologic and Psychotherapeutic Treatment of Anorexia Nervosa

Abstract

Keywords

Psychosocial intervention for adolescents with anorexia nervosa

Psychotherapeutic interventions for adults with anorexia nervosa

Pharmacotherapeutic interventions for individuals with anorexia nervosa

Conclusions

Future perspective

References