Anorexia Nervosa – A Review of Neurobiology, Diagnosis and Management

HISTORICAL EVOLUTION OF THE CONCEPT OF ANOREXIA NERVOSA

The first examples of self-starvation in Western countries arose from Gnostic philosophy and Christianity. Self-starvation was considered a medium to reach purification. Saint Jerome professed the ascetic regime benefits to Roman women, to the extent that a Roman girl died of self-starvation. [Dell’Osso et al., 2016] 

During the Middle Age (particularly from the 13th to the 16th century), there is evidence of self-induced fasting leading to premature death by starvation, such as Catherina from Siena.

Some authors named the common fasting habits reported in holy women as “holy anorexia” (also known as anorexia mirabilis).

This condition differs from AN in focusing on spiritual purity instead of drive for thinness and over-evaluation of body shape and body weight.

To date, in the Western world, the sharp contrast between the wide availability of cheap, calorific, and highly palatable foods and the excessive value placed on slimness and dietary restraint, along with the daily bombardment with images of emaciated supermodels and other media images of thin role models, has meant that weight and shape concerns and dieting are the norm among young women. [Dell’Osso et al., 2016] 

In 1770, Morton published the seminal monography “Phthisiologia or a Treatise of Consumptions”, which described “nervous atrophy”, a condition of self-imposed reduction of food intake. The author stated that this kind of fasting was caused by an “ill and morbid state of the spirits”, indicating a psychological aetiology.

Since the mid-18th century, feminine beauty’s ideal slowly switched from a rounded figure to a slim and slender appearance. Lord Byron promoted the new ideal of beauty as a pale, languid body, anguished and surrounded by a melancholic aura.

Empress Elizabeth of Austria, also known as Sissy, followed strict diets and practised strenuous physical activity. She embodied the modern ideal of beauty with her tall and very thin figure, during the second half of the 19th century, which gained popularity until the 20th century.

Over the past 30 years, the ideal body image has become progressively thinner. The ever-growing fitness industry has carried the popular misconception that health equals thinness.

From a sociological perspective, globalisation exposes more people to the societal pressures common to the Western culture emphasising female body image and thinness, acting as a risk factor for developing eating disorders.

EPIDEMIOLOGY OF ANOREXIA NERVOSA

In the general population, the lifetime prevalence of anorexia nervosa is around 1% in women and <0.5% in men.

Accurate point prevalence has not been estimable for anorexia nervosa in Australia, but the 12-month prevalence in the New Zealand survey was <1%.

The peak age of onset of anorexia nervosa is early to mid-adolescence but may occur at any age, including in childhood, where the gender balance is more even.

DIAGNOSTIC CRITERIA FOR ANOREXIA NERVOSA

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) working definition was significantly updated from the DSM-4-TR definition for AN. Of note, the DSM-5 does not include a set amount of weight that is required to be lost and instead outlines the following behavioural and psychological criteria:

1. Restrictive energy intake resulting in significantly low body weight
2. Intense fear of weight gain or becoming fat or persistent behaviours that prevent weight gain
3. Body image disturbance (weight and shape) or persistent lack of recognition of the seriousness of their current low body weight

AN severity is also a specific criterion, which is classified across four levels of BMI:

• Mild (≥17 kg/m²)
• Moderate (16–16.99 kg/m²)
• Severe (15–15.99 kg/m²)
• Extreme (<15 kg/m²).

Furthermore, although there is a lack of predictive validity for subtyping due to diagnostic crossover, subtyping may facilitate assessment and treatment planning for AN [Peat et al. 2009]:

• Restricting type – Weight loss is achieved through dieting, fasting, and/or exercise with no evidence in the past 3 months of binge eating or purging behaviours.
• Binge-eating/purging type – Weight loss is achieved through self-induced vomiting and the misuse of laxatives or diuretics.

Amenorrhea (abnormal menstruation caused by hypothalamic dysfunction and low-fat stores) in postmenarcheal females was considered a diagnostic criterion in the DSM-IV; however, this was removed as there is no meaningful data to support its inclusion. [Attia and Roberto 2009]

RISK FACTORS FOR ANOREXIA NERVOSA

• Female gender
• Being from the developed world where the ‘thin ideal’ prevails.
• Migrants from the developing world.
• Urban areas
• Undertaking life pursuits where body image concerns predominate, for example, competitive gymnastics and fashion modelling.
• Increased genetic heritability and family history.
• Family history of ‘leanness.’
• Early menarche (controlling for bodyweight)
• Epigenetic changes to DNA: These can occur following periods of food deprivation (e.g. the Dutch starvation in World War 2), food repletion, or severe environmental stress.
• Low self-esteem (all eating disorders)
• High levels of clinical perfectionism
• Emotional and sexual child abuse

NEUROBIOLOGY

1.Genetics:

• Genetic heritability contributes to approximately 28%-74% of the risk of developing an eating disorder. Twin studies show heritability of 50-60%. [Yilmaz et al., 2015]
• Recently a genome-wide association study has identified 8 risk loci.

Single nucleotide polymorphisms (SNP) based genetic correlations showed :

Negative correlations with

• Fat mass
• Fat-free mass
• BMI
• Obesity
• Type 2 diabetes
• Fasting insulin
• Insulin resistance
• Leptin

Positive correlation with

• HDL cholesterol.

The above correlations were stronger in AN compared to other psychiatric disorders.

A significant bidirectional causal relationship between BMI and AN risk-increasing alleles indicates that low BMI may not simply be a physical consequence of AN related behaviours. A fundamental metabolic dysregulation may contribute to the difficulty individuals with anorexia nervosa have in maintaining a healthy BMI. [Watson et al., 2019]

2. Temperament:

Following are the traits associated with AN:

• Anxiety
• Negative emotionality
• Perfectionism: High levels of perfectionism are known to precede the onset of AN and is associated with poor recovery and shorter duration of remission
• Inflexibility: Impaired set-shifting is identified with cognitive inflexibility as a trait marker
• Harm avoidance
• Obsessive behaviours (order, exactness and symmetry)

Dietary restraint and reduced caloric intake in AN is associated with an anxiety-reducing effect while food consumption has a dysphoric effect.

3. Abnormalities in dopamine and serotonin systems

5HT is involved in mediating satiety, impulse control and mood.

DA is involved in rewarding effects of food, motivation and executive control.

Female gonadal steroids may exacerbate 5HT and DA system dysregulation

Serotonin system abnormalities in AN:

• Altered satiety, impulse control and mood
• Differences in 5HTT function (linked to impulse control)
• Increase in 5HT1A binding
• Decrease in 5HT2A binding
• Exaggerated 5-HT1A versus diminished 5-HT2A could result in hyperpolarizing effects on prefrontal neurons in AN
• Decrease in 5HIAA

Dopamine System abnormalities:

• Aberrant rewarding effects of food
• Individuals with AN may experience DA release as anxiogenic
• Executive corticostriatal circuitry may reflect a heightened response to adverse consequences and/or increased inhibitory control
• Increased binding of D2/D3 receptors in the ventral striatum
• Reduction in intrasynaptic DA concentration or elevation of D2/D3 receptor density or affinity in this region

4. Appetite Regulation in Anorexia Nervosa and Response to Taste 

Individuals with AN show an imbalance between stimulus consumption and anticipation due to a mismatch between limbic hyperarousal and executive control

• The anterior insula is the primary gustatory taste cortex and responds to tastes of food.
• The anterior insula, the anterior cingulate cortex and orbitofrontal cortex code the sensory-hedonic response to taste
• AN patients have an altered set-point, and/or altered sensitivity for sensory-interoceptive reward processes when consuming palatable foods
• The set point in AN mimics a continuous state of satiety in individuals with AN that limits interoceptive and reward processing.
• The nucleus accumbens (NA) plays an important part in assessing reward.
• Food causes dopamine neurons in the VTA to release dopamine in the NA
• Following stimulus conditioning, DA neurons shift firing from the consumption of food to anticipation of food or cues associated with food consumption
• In the ‘addicted brain’ resulting in overeating, the prefrontal cortex (PFC) and cingulate gyrus (CG) have a reduced ability to regulate the compulsive drives. (decreased activation)
• In AN the dorsal executive network and ventral striatal networks are activated, resulting in an altered response to reward cues underpinned by avoidance. Individuals with AN have an enhanced ability to delay reward.

5. Neuroimaging Studies:

• Acute anorexia nervosa is associated with global reductions in grey and white matter, increased cerebrospinal fluid and regional grey matter decrease in the left hypothalamus, and reward-related regions of the basal ganglia and the somatosensory cortex which can recover with weight gain.
• fMRI studies show an altered balance between Reward and inhibition centres which is a hallmark of AN.
• Brain reward circuits are more responsive in AN with greater activation of the ventral striatum, insula, and orbitofrontal cortex  (compared to patients with obesity) suggesting that people with anorexia nervosa are highly sensitive to uncertainty (unpredictable reward).

6. Abnormalities in top-down and bottom-up processing

There is a suggested aberrant functioning of

Bottom-up processing centres:

• Parietal somatosensory regions
• Anxiety-related mesolimbic circuits
• Reward-related regions (e.g., striatum)

Top-down (evaluative) Executive centres 

• Prefrontal cortex.

The imbalance between the bottom-up and top-down processing centres leads to :

• Impaired ability to identify the emotional significance of stimulus (e.g. hunger signals ) associated with altered interoceptive awareness (body image disturbance or failure to respond to hunger signals).
• Increased traffic in circuits with planning leading to increased anxiety.

Link between metabolic markers and reward abnormalities: [Duriez et al, 2019].

Role of Insulin – Hypoinsulinemia and increased striatal insulin sensitivity. 

• Insulin plays an important role in reward based learning via insulin receptors on DA neurons in the nucleus accumbens (ventral striatum).
• Chronic food restriction promotes hypoinsulinemia and increases the sensitivity of striatal DA release to insulin enhancing reinforcement of learned behaviours in AN.
• Insulin mediates food palatability and reward. In AN increased insulin sensitivity reduces food palatability reducing the motivation to eat.

Role of Leptin:

• Leptin mediates the link between physical activity and reward.
• Patients with AN have reduced leptin levels.
• Reduced leptin level is associated with increase in physical activity which is rewarding.
• Addiction to exercise is associated with reduced plasma leptin levels.
• The hyperactivity seen in AN may be mediated by reduced leptin. [Hebebrand et al, 2007]

Role of Ghrelin: 

ASSESSMENT OF ANOREXIA NERVOSA

General Principles:[Hay P et al., 2014]

Build rapport as patients can be ambivalent, guarded and fearful of treatment

Involve significant others :

• Collateral sources such as family members and other clinicians involved in the person’s care should be utilised.
• The perspective of others is critical given that symptom minimisation, poor insight or genuinely poor understandings of the seriousness of symptoms are common aspects of anorexia nervosa

1.Assessment of symptoms of anorexia nervosa

• Dietary restriction
• Weight loss
• Inability to restore weight
• Body image disturbance
• Fears about weight gain
• Bingeing or Purging
• Excessive exercise
• Early satiety
• Constipation
• Use of laxatives, diuretics, or medications to lose or maintain a low weight
• Disturbed eating behaviours, e.g. eating apart from others and ritualistic patterns of eating such as prolonged meal times and division of food into very small pieces
• Assess nutritional and fluid intake, with specific inquiries made about the adequacy of main meals and snacks consumed.

A validated assessment tool is the SCOFF Questionnaire [Morgan et al., 1999]:

• Do you make yourself sick because you feel uncomfortably full?
• Do you worry you have lost control over how much you eat?
• Have you recently lost more than one stone (14 lb) in a three-month period?
• Do you believe yourself to be fat when others say you are too thin?
• Would you say that food dominates your life?

Feasibility data on this simple questionnaire showed that it has 100% sensitivity when comparing AN to bulimia nervosa and distinguishing the restricting type from the binge-eating/purging type. There was a 12.5% false-positive rate in control cases.

2. Assessing medical complications and the current level of medical risk.

Rule out medical complications and take into account any indications for inpatient admission.

• BMI, HR, BP, Temperature
• Blood profile: FBC, ESR, Vit B 12, Ferritin, Iron
• Biochemical profile: Sodium, potassium, ca, Mg, PO4, Creatinine, Urea, LFT, Blood glucose, Albumin, total protein, if elevated creatinine – creatinine clearance.
• ECG
• If low BMI (< 12 kg/m2) – monitoring of sodium, potassium and PO4 at least weekly
• If seizures: EEG, CT/MRI
• Long term illness: DEXA scan
• If unclear thoracic pain or abdominal pain: CXR; Abdominal US, gastroscopy

3. Assessing psychiatric comorbidity

• Anxiety
• Depression
• Substance misuse
• Suicidality
• Personality disorders
• Anxiety disorders
• Deliberate self-harm

4. Cognitive Assessment:

• Slowed thought processing
• Impaired short-term memory
• Reduced cognitive flexibility
• Concentration and attention difficulties

5. Assessment of Aetiological Factors (Formulation)

• Family history of eating disorders
• Early attachment and developmental difficulties
• Premorbid obesity
• Interpersonal problems
• Dieting or other causes of rapid weight loss.
• Rapid weight loss from any cause, including physical illness, can trigger cognitive changes including obsessive thinking about food, in turn precipitating and perpetuating symptoms of anorexia nervosa

Indications for inpatient admission.

Indications for inpatient admission in children and adolescents:

• Medical status
• Heart rate < 50 bpm
• Cardiac arrhythmia
• Postural tachycardia > 20 bpm
• Blood pressure <80/50 mm/Hg
• Postural hypotension > 20mm/hg
• QTc > 450 msec
• Temperature < 35.5
• Hypokalaemia
• Neutropaenia 20 mm >450 msec < 75% of expected body weight or rapid weight loss.

MEDICAL COMPLICATIONS AND PSYCHIATRIC COMORBIDITIES IN ANOREXIA NERVOSA

AN presents with several comorbidities typically caused by the profound effect of starvation on the brain and body. Therefore, adequate and effective nutrition is important, and ideally, this should be supervised and integrated into any therapeutic strategy. [Woodside and Staab 2006]; [Zipfel et al. 2015]

Medical Complications

• Patients with AN develop multiple complications that are associated with the underlying weight loss and malnutrition.
• AN comorbidity includes brittle hair and nails, hyperkeratosis, hypothermia, lanugo, and osteoporosis.
• Cardiovascular complications such as arrhythmia, bradycardia, oedema, and orthostatic hypotension are common and can lead to fatal cardiac arrhythmia.
• AN patients also have an increased lifetime prevalence of autoimmune diseases such as type 1 diabetes [Raevuori et al. 2014].  Type 1 diabetes management requires meticulous food planning, and this persistent focus on food may explain one of the reasons why type 1 diabetes often precedes the onset of AN.
• In children with the paediatric acute-onset neuropsychiatric syndrome (PANS) or paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), food restriction also occurs and has been deemed to be a variant of childhood-onset anorexia nervosa

Psychiatric Comorbidity

• The lifetime prevalence of comorbidity has been reported from 55% in community adolescent samples to 96% in adult samples.
• Between 25% and 75% of patients with anorexia nervosa report a lifetime history of at least one anxiety disorder, which typically precedes anorexia nervosa and starts in childhood.
• The most common was social phobia (42%), followed by posttraumatic stress disorder (26%) and generalised anxiety disorder (23%)
• Anorexia nervosa is associated with an increased risk of suicide, with the suicide standardized mortality ratio estimated to be as high as 31 in one meta-analysis. [Preti A et al., 2011.]
• Obsessive-compulsive symptoms in up to 79% at some time in their life
• OCD – 15-29%
• Alcohol misuse 9-25%
• Aggregation of Autism spectrum disorder in probands of AN and relatives.
• Positive genetic correlations between schizophrenia and AN and OCD and anorexia. [Bulik-Sullivan et al., 2015] 
• Clinicians should be aware that depression, obsessional thinking, anxiety and other psychiatric symptoms can represent the reversible effects of starvation on the brain. [Keys et al., 1950]

TREATMENT PRINCIPLES IN ANOREXIA NERVOSA

1. Prioritisation of needs: The primary aim for treatment is to achieve a minimum of 90% of the average weight for the patient’s sex, age, and height through a joint behavioural and nutritional intervention [Golden et al. 2008]; [Rosen 2012].
2. Engagement
3. Medical stabilisation
4. Reversal of the cognitive effects of starvation
5. Structured psychological treatment.

Engagement: 

• A non-judgemental, inclusive, empathetic and non-threatening stance.
• Psychoeducation
• Involve the family
• Motivational interviewing around what the individual themselves reports as important, appealing to the ‘healthy’ part of the person.

The Setting of Treatment: 

• Most people with anorexia nervosa can be treated as outpatients, but day-patient and inpatient services are needed for those with more severe illness and those who do not improve with outpatient care.
• Brief inpatient care followed by intensive outpatient care could achieve similar efficacy to longer hospital stays in adolescents. Still, there is a paucity of randomised trials to guide service use.
• A multicentre randomised trial reported that a stepped care approach (day-patient treatment after short inpatient care) was equally effective and less costly than inpatient treatment in patients with non-chronic adolescent anorexia nervosa at the end of treatment and 1-year follow-up. [Herpertz-Dahlmann et al., 2014]
• Dr Mark Berlowitz at the Royal Free Hospital in London, has developed a cost-effective program for AN based on intensive community treatment. The treatment costs are about 1/5th of that of inpatient care. [Read more]
• Ideally, people with anorexia nervosa requiring admission should be admitted to a specialist eating disorders unit.
• Eating disorder outreach services (EDOS):  Effective in managing acute issues is admission to general medical or psychiatric beds, with support provided to generalist clinicians by a specialist eating disorder consultation-liaison service. [Painter et al., 2010] 

Comparison of international guidelines for AN show agreement on the amount of recommended weight gain, while recommended daily energy intakes varied considerably. There was also variation in advice on nutritional supplementation. [Hilbert et al., 2017]

REFEEDING AND REFEEDING SYNDROME IN ANOREXIA NERVOSA [MEDICAL STABILISATION AND REVERSAL OF COGNITIVE EFFECTS OF STARVATION]

Refeeding principles: 

According to the RANZCP guidelines: [Hay P et al., 2014]

• Commence refeeding at 6000 kJ/day.
• Increase by 2000 kJ/day every 2–3 days until an adequate intake to meet the person’s needs for weight restoration is reached.
• Recommended rates of weight gain ranging from 500–1,400 g/wk (c.f US – 0.9-1.4 kg/wk in inpatient and 0.2-0.5 kg/wk in outpatient settings; UK guidelines – not reported.) [Yager et al., 2012]; [NICE guidelines]
• Monitor electrolytes regularly
• Supplement diet with phosphate (500mg twice daily) and thiamine (at least 100mg daily for the first week), and thereafter as clinically indicated for patients at high risk of refeeding syndrome (e.g. BMI <13). (US guidelines: Phosphate, magnesium, potassium, calcium, vitamin D, zinc; UK guidelines: Multivitamin and multimineral supplements, bisphosphonates)
• For patients at high risk of refeeding syndrome: commence with continuous nasogastric feeding with low-carbohydrate preparations (i.e. 40–50% of energy from carbohydrates) to avoid triggering postprandial rebound hypoglycaemia due to insulin secretion in patients with inadequate glycogen stores.
• Involve dietician

US guidelines recommend:

• Start at 30–40 kcal/kg (i.e., 1000–1600 kcal)
• Weight gain phase: up to 70–100 kcal/kg

UK guidelines: 

• Inpatient settings: sometimes lower starting intakes (e.g., 5–10 kcal/kg) for severely underweight patients
• Stepwise increase to 20 kcal/kg within 2 days, about 3500–7000 extra calories/week

Refeeding syndrome: 

• Refeeding syndrome is a potentially serious medical complication resulting from refeeding after a prolonged period of starvation.
• Refeeding syndrome is due to the switch from fasting gluconeogenesis to carbohydrate-induced insulin release triggering rapid intracellular uptake of potassium, phosphate and magnesium into cells to metabolise carbohydrates.
• Due to starvation, patients already have low body stores of electrolytes, which can lead to a rapid onset of hypophosphataemia, hypomagnesia, and hypokalaemia.
• Risk of the refeeding syndrome can be reduced by ‘starting low’ and ‘going slow’ with nutrition, and monitoring serum phosphate, potassium and magnesium daily for the first 1–2 weeks of refeeding. Replacing these electrolytes immediately if they fall below the normal range.
• Nutritional therapy includes supervised meals and, if necessary, additional high-protein oral liquid supplements.
• In severely emaciated patients at high medical risk, nasogastric feeding, including professional and supportive supervision, could be indicated.

KEY PRINCIPLES IN MANAGEMENT OF MEDICAL COMPLICATIONS OF ANOREXIA NERVOSA [MEDICAL STABILISATION]

Important clinical practice points: [Hay et al., 2014]

1. Cardiac arrhythmia is a common cause of death.
2. Hypoglycaemia in the first weeks is generally postprandial and occurs several hours after refeeding, hence some units preferentially use nasogastric feeding.
3. Complications may be caused by purging behaviours as well as starvation.
4. Anaemia may be normocytic and normochromic, as characteristic of nutritional deficiency, but microcytic anaemia due to iron deficiency is increasing as more people choose vegetarianism. Copper deficiency may also play a role.
5. For patients at risk of refeeding syndrome (e.g. first 7–10 days of inpatient refeeding) prophylactic phosphate is recommended.
6. Iron injections should not be given to the medically compromised patient as it is potentially hepatotoxic. Oral replacement is preferred.
7. Oral contraceptives are not effective in restoring bone health.
8. Phosphate required to prevent or treat refeeding syndrome should take precedence over calcium. Calcium should not be given at the same time as phosphate.
9. Mild acute pancreatitis is almost universal and not an indication for the proposed intervention.

INDIVIDUAL PSYCHOLOGICAL THERAPIES - EVIDENCE BASED IN ANOREXIA NERVOSA

1.CBT- Enhanced for Anorexia Nervosa [Fairburn, 2008]

As an outpatient therapy treatment, CBT-E has four stages and is available in a short (20 sessions) and a longer version (40 sessions).

Stage 1:

• The focus is on gaining a mutual understanding of the person’s eating problem and helping the patient modify and stabilise their eating pattern.

Stage 2:

• Progress is systematically reviewed, and plans are made for the main body of treatment.

Stage 3:

• Focuses on the processes that are maintaining the eating disorder (e.g., addressing concerns about shape and eating).

Stage 4:

• The emphasis shifts onto the future. There is a focus on dealing with setbacks and maintaining the changes that have been obtained.

In a much larger study (n = 242), researchers compared focal psychodynamic therapy (FPT), enhanced CBT (transdiagnostic personalised psychological treatment for eating disorders), and treatment as usual on weight and eating disorder psychopathology. [Zipfel et al. 2014]

Both FPT and enhanced CBT were advantageous although enhanced CBT regained weight more rapidly and had greater improvements in psychopathology.

2.Specialist supportive clinical management (SSCM) [McIntosh et al., 2006]

The primary focus is on the resumption of normal eating and the restoration of weight, plus a  flexible approach to addressing life issues impacting the eating disorder.

This treatment is delivered by therapists specialised in treating eating disorders and should provide a standardised form of usual outpatient treatment.

• Patients with anorexia nervosa and a BMI of 15 kg/m2 or lower: up to 30 once-weekly individual therapy sessions and four monthly follow-up sessions.
• Patients with a BMI >15kg/m2 the number of sessions could be reduced to 20.

Therapy content includes

• assessment
• identification
• regular review of target symptoms
• psychoeducation
• monitoring of physical status
• establishment of a goal weight range
• nutritional education and advice.

The aim is to help patients link their clinical symptoms and their abnormal eating behaviour and weight and support patients in a gradual return to normal eating behaviour and weight.

The patient determines additional therapy content.

In a small RCT (n = 56), researchers compared specialist supportive clinical management (SSCM) against either CBT or interpersonal therapy (IPT). [McIntosh et al. 2005]

The delivery of SSCM by eating disorder specialists was superior to CBT or IPT over 20 sessions over 20 weeks.

3.The Maudsley model of anorexia nervosa treatment for adults (MANTRA)

This treatment is an empirically based cognitive-interpersonal treatment, which proposes that four broad factors, linked to underlying obsessional and anxious (or avoidant) personality traits, are central to the maintenance of anorexia nervosa.

1. A thinking style characterised by inflexibility, excessive attention to detail, and fear of making mistakes
2. Impairments in the socio-emotional domain (e.g., avoidance of emotional experience, regulation, and expression)
3. Positive beliefs about how anorexia nervosa helps the person in their life
4. Unhelpful responses of close others (e.g., overinvolvement, criticism, accommodation to symptoms).

Key strategies used are:

• Motivational interviewing
• Cognitive remediation
• Flexible involvement of carers.

However, in a randomised controlled trial (RCT), it was shown to be no more effective than SSCM, with recovery rates low in both arms of the trial. [Schmidt et al., 2012]

The MANTRA study (n = 214) compared a Maudsley model of adult AN therapy (empirically based cognitive-interpersonal treatment that includes motivational interviewing, cognitive remediation and flexible involvement of carers) against SSCM. Although there were no significant differences, patients showed a preference for the MANTRA study. [Schmidt et al. 2015]

Differences from other treatments include that the model was developed specifically for anorexia nervosa, it is based on biological and psychological research, and is tailored to characteristic temperamental traits in this disorder. It is unique in its use of a patient workbook, developed in co-production with patients and therapists. It is also unique in its involvement of carers in both the model or formulation and the treatment. [Zipfel et al 2014]

4.Family-based treatment (FBT) [Lock & le-Grange, 2005]

FBT remains the most well-studied treatment for young people with anorexia nervosa and has been associated with persistent positive outcomes on physical and psychological parameters. [Lock et al., 2010]

A three-phase treatment for adolescent patients with anorexia nervosa and their families over 16 1 hour sessions and a 9-month period (initially 10 hours during 6 months).

Phase 1:

• Characterised by attempts to absolve the parents from the responsibility of causing the disorder and complimenting them on their parenting’s positive aspects. Families are encouraged to work out for themselves how best to help restore their child’s weight with anorexia nervosa.

Phase 2:

• Parents are helped to transition eating and weight control back to the adolescent in an age-appropriate manner.

Phase 3:

• Establishing a healthy relationship between the adolescent and the parents. 24 1hour sessions are provided over the 1-year period.

5. Focal Psychodynamic Therapy (FPT) [Friederich, 2019] 

The initial manualised treatment was designed as a 40-hour outpatient psychodynamic-oriented psychotherapy for moderately ill patients with anorexia nervosa (BMI >15 kg/m2).

At the start, the therapist identifies psychodynamic relevant foci using a standardised operationalised, psychodynamic diagnostic interview (OPD-II).

The psychodynamic treatment manual is divided into three treatment phases.

Phase 1:

• Focuses mainly on the therapeutic alliance, pro-anorectic behaviour and ego-syntonic beliefs (attitudes and behaviour viewed as acceptable), and self-esteem.

Phase 2:

• Focuses on relevant relationships and the association between interpersonal relationships and eating (anorectic) behaviour.

Phase 3:

• The transfer to everyday life, the anticipation of treatment termination, and parting.

Before every treatment session, the patient’s weight is assessed and documented.

Other therapies: 

Interpersonal psychotherapy, cognitive analytic therapy, focal psychoanalytic and other psychodynamic therapies.

PHARMACOTHERAPY IN ANOREXIA NERVOSA

Pharmacotherapy

• Low doses of antipsychotics such as olanzapine may be helpful when patients are severely anxious and demonstrate obsessive eating-related ruminations.
• Zinc deficiency is common in anorexia nervosa and may be associated with dermatological change.  In a single small double-blind trial, zinc supplementation was associated with a more rapid rate of body mass increase.
• Recently, stereotactic surgery and deep brain stimulation have been considered for the management of refractory anorexia nervosa.

Osteoporosis Prevention and Treatment

• The most efficient strategy to improve bone density is to restore weight and, in women, menstrual function.
• Oestrogen-replacement therapy, primarily via a transdermal application, only partially increases bone density in adolescents.
• Oral oestrogen-progesterone combinations are ineffective in increasing bone mineral density in adolescent and adult anorexia nervosa patients.

Summary of psychological and pharmacological treatment in AN.

Treatment principles in Adolescents: 

SEVERE AND LONG STANDING ANOREXIA NERVOSA

Severe and long-standing AN is associated with the highest mortality of all mental illnesses. Life skill scores in patients are similar to patients with schizophrenia.

Hence, the treatment approach proposed is a psychiatric rehabilitation model.

Evidence for the efficacy of treatments is limited in this group.

RELAPSE PREVENTION IN ANOREXIA NERVOSA

AN has a relapse rate of 41%, with the highest risk for relapse within 4–9 months after treatment.

[Steinhausen, 2002] reported that 70% of a multicentre European cohort with anorexia nervosa had fully recovered at follow-up at a mean of 6.4 years, and around 75% had no other evidence of psychiatric illness.

The strong associations between AN and its comorbidities have shifted interventions towards effective secondary prevention and early treatment strategies due to the serious illness trajectory, neurocognitive features, and the high risk of relapse. [Harrington et al. 2015]; [Zipfel et al. 2015]

Once the adolescent is an appropriate age, however, food control should transition to the patient, and a healthy relationship between parents and patient is encouraged. [Lock et al. 2005] In adults, nutritional rehabilitation and a focus on weight gain can be facilitated through several psychotherapeutic approaches [Zipfel et al. 2015]:

One small randomised control trial found a manualised cognitive behavioural therapy for anorexia nervosa (CBT-AN) was superior to nutritional counselling and usual care (all treatment, including nutritional counselling delivered by psychologists) in preventing relapse. [Pike et al., 2003]

A multidisciplinary approach is more supported.

LONG-TERM OUTCOMES

In one large longitudinal study, 70% of AN patients had fully recovered after a mean 6.4 years [Steinhausen 2002]. In contrast, in another study it was shown that 87% of patients had a partial recovery after a mean of 59 months and 76% had a full recovery after a mean of 79 months. [Strober et al. 1997]

Up to 40% of adults (and a higher per cent of adolescents) will make a good five-year recovery, further 40% a partial recovery and those with persistent illness may yet benefit from supportive therapies. [Hay et al., 2014]

Relapse is a major influencer of the long-term outcome of therapy, and there is insufficient evidence in the literature on how to successfully prevent relapse. However, the binge/purge subtype has substantially higher rates of relapse, and therefore a more intense follow-up should be provided to reduce the risk of relapse.

CONCLUSION

AN is a severe mental illness with a high degree of morbidity and the highest mortality of all mental illnesses.

Clinicians should recognise the high comorbidity with other psychiatric disorders and evaluate eating disordered behaviour in clinical practice to aid in early detection.

Furthermore, clinicians should be mindful of the significant physical consequences of AN and seek appropriate and early medical advice and intervention.

Although patients with AN can recover with early intervention, there are significant challenges in managing AN.

There continues to be uncertainty about the optimal evidence-based intervention in treatment, and newer interventions based on an enhanced understanding of the disease construct are needed to improve outcomes.

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