GUIDELINES FOR THE PHARMACOLOGICAL TREATMENT

OF EATING DISORDERS By Heba Essawy

Prof Of Psychiatry

EATING DISORDERS Eating disorders including: •Anorexia nervosa.(AN) •Bulimia nervosa. (BN) •Eating disorder not otherwise specified Binge eating disorder.(BED) Night eating syndrome.(NED) * Obesity.

COMORBIDITY IN EATING DISORDERS Affective and anxiety disorders . Obsessive compulsive disorders,

impulse control disorders . Psychosis . Substance use disorders. Pain Disorder.

EATING DISORDER: TREATMENT

Complex process -Psychotropic drugs -Psychotherapy -Nutritional counseling, -Treatment of medical complications.

MANAGEMENT OF ED

A .Coordinating Care and Collaborating with Other Clinicians.B .Assessing and Monitoring Eating Disorder Symptoms and Behaviors.c. Assessing and Monitoring the Patient's General Medical Condition.d. Assessing and Monitoring the Patient's Safety and Psychiatric Status.E-Providing Family Assessment and Treatment

SELECTION OF TREATMENT SITE

1.Outpatient 2.Partial hospitalization (full-day outpatient care) 3.Residential treatment center 4.Inpatient hospitalization

HOSPITALIZATION IN ANBefore the onset of medical instability. Abnormalities in vital signs -Marked orthostatic hypotension -Increase in pulse of 20 bpm. -Drop in standing bl pr. 20mmHg.

-Bradycardia <40 bpm. -Tachycardia >110 bpm. - Hypothermia.

HOSPITALIZATION IN BN Serious concurrent medical problems -Metabolic abnormalities. - Hematemesis. - Uncontrolled vomiting Serious psychiatric disturbances - Suicidality. - Other psychiatric diagnosis. - Severe alcohol or drug dependence .

AIM OF TREATMENTS FOR AN 1) Restore patients to a healthy weight: * with the return of menses *normal ovulation in female patients. * normal sexual drive and hormone levels in male . * normal physical and sexual growth in children. 2) Treat physical complications. 3) Enhance motivation to enhance healthy Eating patterns . 4) Education for healthy Nutrition and Eating patterns.

AIM OF TREATMENTS FOR AN 5) Change core dysfunctional cognitions, attitudes, motives, conflicts. 6) Treat associated psychiatric conditions, mood and impulse and self-esteem and behavioral problems 7) Provide family counseling. 8) Prevent Relapse.

TREATMENT WITH ANTIDEPRESSANTS

The rationale for treating AN (1) Dysfunction in the serotonergic and noradrenergic system in the pathophysiology (2) Comorbidity with * Anxiety disorders. *Obsessive compulsive *Depression.

TRICYCLICS - Clomipramine: increased hunger,

appetite and energy intake, but no weight gain.

(Lacey and Crisp (1980) ) - Amitriptyline : No significant weight gain. (Biederman et al. (1985))

No clear evidence for the general use of tricyclic in AN except for depression.

SSRIS : CITALOPRAM

Open randomized study of Fassino(2002) No differences in BMI or weight gain . Improvement in : - Depression. - Obsessive-compulsive symptoms. - Impulsiveness -Trait-anger in AN-R type.

FLUOXETINE Gwirtsman et al.(1990) : diminished

depressive symptoms was associated with weight gain.

Kaye et al. (2001): patients on fluoxetine(1 year): reducion in relapse rate

increase weight and reduction of symptoms. Walsh et al.(2006a) : No benefit from

fluoxetine in reducing relapse rate AN but ttt obsessive symptoms.

SERTRALINE. Effectiveness for sertraline

regarding - Depressive symptoms - Not concerning weight gain

(Santonastaso et al., 2001)

MIRTAZAPINE Efficacious with long-standing AN . After 9-month follow-up :

- weight gain. - improve mood.

Mirtazapine: for older, chronically ill patients comorbid depression.

( Safer et al. (2010) )

DISCUSSION: ANTIDEPRESSANTS

Antidepressants : may be used in AN -with depressive symptomatology - with comorbid obsessive disorder - Not in general.

ANTIPSYCHOTICS:HALOPERIDOL

Cassano et al. (2003) report an opentrial with haloperidol AN-R over 6 month.

Haloperidol - might be effective as adjunct treatment for AN-R ( severe cases) .

ANTIPSYCHOTICS SULPIRIDE : - No statistical sig. over placebo .

PIMOZIDE: - Induce weight gain ?.

Vandereycken (1984)

ATYPICAL ANTIPSYCHOTICS:OLANZAPINE Promising weight gain &

psychopathological improvement in AN (Barbarich et al., 2004)

Reduced anorexic ruminations but no difference in BMI (Mondraty et al. (2005).

Superior for rate of weight gain, Early achievement of target BMI Early in reduction of obsessive (Bissada

et al. (2008). Olanzapine** seems to be a promising inAN–BP type.

ATYPICAL ANTIPSYCHOTICS RISPERIDONE* may be useful in AN .

(Newman-Toker, 2000)

QUETIAPINE* :Low-dose (100-400mg) resulted in both psychological and physical improvements, with minimal side-effects.

( Court et al. (2010))

ATYPICAL ANTIPSYCHOTICS AMISULPRIDE : promising results with

combination with fluoxetine.

(Ruggiero et al. (2001)

ARIPIPRAZOLE : need longer period time

(Trunke et al. (2010)

ANTIHISTAMINICS Cyproheptadine: Effective in severely ill AN patient in

weight gain.

Increased weight gain in non-bulimic group and impaired treatment in bulimic group.

(Bartra et al., 2006).

TREATMENT WITH OTHER PHARMACOLOGICAL COMPOUNDS Zinc** : in Adolescent with AN at risk

for zinc deficiency , good respond after zinc supplementation (50 mg elemental zinc/day).

( Safai-Kutti (1990)

Oral administration of 14 mg of elemental

zinc daily for 2 months in AN is routine.

(Birmingham (2006))

TREATMENT WITH OTHER PHARMACOLOGICAL COMPOUNDS Lithium : -One RCT found no efficacy for Lithium over placebo. -One RCT found efficacy over placebo concerning binges or purges. (Gross et al. (1981)

-Cisapride: concerning gastric emptying are conflicting. Whereas one study found no

efficacy over placebo, 1 study found a difference for gastric emptying. (Category

grade E evidence).

TREATMENT : NALTREXONE Naltrexone : - Auto-addiction model for AN and BN - 100 mg naltrexone twice a day with for 6 weeks . - Decrease Binge and Purging behaviour AN and BN. -No weight restoration in AN in week 6.

(Marrazzi et al. (1995))

GROWTH HORMONE recombinant human growth hormone (rhGH) :

No weight gain between pharmacological group and placebo group

( Hill et al. (2000)

NASOGASTRIC TUBE FEEDING

Weight gain was 39% higher in the tubegroup than in the control group.

After discharge the relapse free period was longer in the tube group.

( Rigaud et al. (2007) .

COMBINING PHARMACOTHERAPY WITH PSYCHOTHERAPY No clear evidence to recommend the

addition of pharmacotherapy to psychotherapy in AN with comorbidities

- depression. -obsessions. - compulsions. - anxiety.

BULIMIA NERVOSA : TRICYCLIC AD

Imipramine: reduce bulimic behaviour .

Amitryptiline :with no clear evidence of superiority only in the depressive subgroup.

Desipramine: reduce bulimic

behaviour.

SSRIS Citalopram : no clear efficacy in

bulimia nervosa over placebo Fluoxetine***: showing an efficacy

over placebo concerning bulimic behaviour.

Fluvoxamine** 3 RCTs with 2 showingefficacy over placebo concerning bulimic behaviour Sertraline **: one RCT that showsefficacy over placebo concerning bulimic behaviour

MAOI Moclobemide shows no efficacy in BN in 1 RCT .

Phenelzine shows an efficacy concerning bulimic behaviour ( Cheese reaction ) ( Not recommended )

ANTIDEPRANSANT – MOOD STABILIZERS No RCT, no evidence for -Duloxetine. -Bupropion - Lithium - Trazodone - Mianserin -Carbamazepine - Oxcarbamazepine

ANTIEPILEPTIC, LIGHT THERAPY Topiramate*** with efficacy in reducing

BN associated psychopathology behaviour. for topiramate in BN, with a moderate risk-benefit ratio.

Naltrexone Inconsistent results

Methylphenidate Inconsistent results

Light therapy in reducing psychopathology in BN.

PHARMACOTHERAPY IN BN Available literature on pharmacological

treatment of BN is based on trials of relatively short duration( less 6 months)

No enough information on the long-term efficacy of these treatments.

BINGE EATING DISORDER (BED) Antidepressants ; 3 RCTs 2 with

imipramine*** 1 with Desipramine showing a reduction in binge frequency.

Citalopram/escitalopram***: 2 RCTs showing

efficacy in BED over placebo .

Fluvoxamine: 3 studies with no favourable results .

BINGE EATING DISORDER (BED): TREATMENT Fluoxetine: there are conflicting resultsconcerning efficacy in BED.

Sertraline*** Effective in 2 RCTs over placebo concerning psychopathology and BE.

Atomoxitine** : one RCT that shows efficacy in BED .

Venlafaxine : One RCT suggests that there might be efficacy in BED.

BINGE EATING DISORDER (BED): TREATMENT

Venlafaxine**:effective over placebo. Sibutramine ***: over placebo in BED

but low risk-benefit ratio. Reboxetine *:in BED . Topiramate ***: 3 RCTs that suggest

efficacy over placebo in BED with moderate risk-benefit ratio.

BINGE EATING DISORDER (BED): TREATMENT Zonisamide ** efficacy in

psychopathology, weight and BED behaviour.

Baclofen* : may be helpful in reducing frequency of binge eating.

Orlistat *** : effective in 3 RCTs over placebo in reducing weight in BED with low to moderate risk -benefit ratio.

d-fenfluramin **: efficacy over placebo for in reducing binges per week in BED

Naltroxone **: efficacy over placebo inreducing binge duration in BED .

BINGE EATING DISORDER (BED): CONCLUSION The available literature on

pharmacological treatment of BED is based on trials

of relatively short duration ( less than 6 months ) No enough information on the long-term

efficacy of these treatments.

NUTRITIONAL REHABILITATION

1.Establishment of healthy target weights 2.Nutritional rehabilitation and refeeding programs 3.Establishment of expected rates of controlled weight

gain 4.Setting advancing intake levels 5.Vitamin and mineral supplementation (e.g.,

phosphorous) 6.Monitoring of serum potassium and rehydration 7.Setting physical activity 8.Other treatments, when indicated, including liquid

food supplements; nasogastric feedings; parenteral feedings

9.Monitoring and treatment of symptoms and conditions associated with gaining weight (e.g., anxiety, abdominal pain, constipation)

PSYCHOSOCIAL INTERVENTIONS IN AN

1.Family psychotherapy for children and adolescents

2.Family group psychoeducation for adolescents 3.Cognitive-behavioral therapy (CBT) for adults 4.Interpersonal therapy (IPT) and/or

psychodynamically oriented individual or group psychotherapy for adults

5.Psychosocial interventions based on addiction models

6.Support groups led by professionals . 7.Internet-based support . 8.Non-verbal therapeutic methods (e.g., creative

arts, movement therapy, occupational therapy)

PSYCHOSOCIAL INTERVENTIONS 1) Understand and cooperate with their

nutritional and physical rehabilitation. 2) understand and change the

behaviors and dysfunctional attitudes related to their eating disorder.

3) improve their interpersonal and social functioning.

4) address comorbid psychopathology and psychological conflicts that reinforce or maintain eating disorder behaviors.

Anorexia Bulimia

Ch.byDisturbed body image Binge eating

Weight loss 85% of expected.

Wt loss 15%

Specify typeRestricting Purging

Binge/Purging Non purging

Life time prevailing in female

0.5-3.7% 1-4%

Age of onset 10-30ys 16-18ys

M:F 1: 10 1:5

Biological etiology

MHPG in urine a CST NE

endorphins 5-HT

endorphins

Course

40% recovery relapse in 50% in system

30% improve

30% chance

Anorexia Bulimia

Treatment Hospitalization Hospitalization

Weight Metabolic alkalosis

Metabolic balance

Pharmacotherapy FluoxetineMirtazapine

Fluxetine Fluvoxamine-sertraline

Olanazapine, resperidone -quetiepine

Topiramate

cyproheptadine -

Elemental zinc -

Psychological Group therapy Individual therapy

Cognitive Cognitive

Family therapy Group therapy.

TREATMENT IN BED Antideprasant Imipramine. Citalopram- ecitalopram. Sertraline. Mood stabilizer Topiramate Atomoxitine. Sibutramine.

Thank s a lot

DRUG

Antideprasants: Fluxetine

Mirtazapine

Antipsychotics olanzapine

Resperidone

Quetiapen

Antihistaminic Cyproheptadine

supplements Zinc