Amalan Karthigeyan

Dr Amalan Karthigeyan Euro Global Summit and Medicare Expo on Weight Loss Euro Weight Loss 2015 Frankfurt

 Consumption of large amounts of food without control and the use of purging behaviours.  DSM-V – autonomous eating disorder. Previously categorised as Eating Disorder not Otherwise Specified.

ANTIDEPRESSANTS

 Shown to be effective in bulimia nervosa.  Overlap with anxiety and depression/depressive disorder.  Dysfunction of serotonergic, noradrenergic and dopaminergic systems in binge eating disorder.

 Tricyclic antidepressants (desipramine, imipramine)  Selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, sertraline, citalopram)  Selective noradrenergic reuptake inhibitors (atomoxetine, venlafaxine, sibutramine)

Desipramine 12-week placebo control trial with 23 women with non-purging bulimia nervosa – 63% decrease in weekly binge eating frequency and mean weight loss of 3.5kg compared to 16% frequency decrease and 1.2kg weight loss on placebo. (McCann and Agras, 1990) Imipramine 8-week placebo control trial - decreased binge eating demonstrated in 23 subjects but placebo response also high. (Alger et al 1991) Demonstrated significant reduction in binge frequency and weight loss when used in combination with adjunctive therapy compared to placebo which demonstrated weight gain. (Laederach-Hofmann et al 1999)

Four placebo-control trials using SSRIs - ≥ 50% decrease in binge frequency Fluoxetine Suppression of short-term food consumption and mean energy intake. However GI symptoms are a side effect – may have contributed. 6 week placebo controlled trail of 60 patients – decreased binge eating frequency and BMI (Arnold et al 2002) Fluvoxamine Reduced binge eating frequency and subsequent weight loss demonstrated by trials (Hudson et al). Sertraline 6-week double blind placebo controlled trial of 34 patients – reduced binge eating frequency and BMI (McElroy et al 2000) 8-week randomised control trial on 34 patients with night eating syndrome – improvement in night eating symptoms (O’Reardon et al 2006) Citalopram 6-week placebo controlled trial of 38 patients – significant reduction in binge eating frequency and weight (McElroy et al 2003).

Atomoxetine 10-week randomised placebo-controlled double blind trial of 40 patients – decreased frequency of binge eating episodes (4 patients dropped out) (McElroy et al 2007b). Venlafaxine Study of 35 patients treated over 120 days – decreased weekly frequency in binge eating. (Malhort et al 2002). Sibutramine Open trial on 10 obese patients over 12 weeks – 7/10 demonstrated decreases in binge frequency and body weight (Appolinario et al 2002). 12-week randomised double-blind placebo controlled trial on 60 subjects - decreased binge frequency and weight (Appolinario et al 2003). Withdrawn in 2010 due to risks outweighing the benefits.

ANTICONVULSANTS

 Bipolar disorder reported to co-occur with binge eating disorder. Anticonvulsants shown to be effective in either the manic phase or depressive phase.  Proven effective for psychiatric conditions characterised with impulsive behaviours or traits that co-occur with binge eating disorder.  Some anticonvulsants associated with weight loss and anorexia in epileptics.  Animal studies show that glutamate agonists e.g. kinate/AMPA agonists stimulating the lateral hypothalamus induces increased food intake.

 Zonisamide - Decreased binge eating episode frequency, binge day frequency, degree of hunger and BMI demonstrated by 12-week trial of originally 15 patients decreased to 8 due to side effects of medication (McElroy et al 2006).  Topiramate – trial of 13 patients: 9 demonstrated reduction in binge eating and weight (Shapira et al 2000). Trial on 8 obese patients: 4 out of 6 who completed the trial showed reduction in binge frequency and weight (Appolinario et al 2002). Same findings in a placebo-controlled trial of 61 patients which showed 64% of patients on topiramate stopped binge eating compared to 30% on placebo and there was an average weight loss of 5.9kg compared to 1.2kg on placebo. However there was a high dropout rate due to side effects (McElroy et al 2003).  Lamotrigine – Only one randomised placebo-controlled trial (51 patients over 16 weeks) which demonstrated no difference in binge frequency compared to placebo but greater difference in weight loss (Guerdjikova et al 2009).

ANTI-OBESITY AGENTS

 Binge eating consists of an increased appetite and reduced satiety.  Binge eating disorder consists of obesity.  Some anti-obesity agents have been shown to reduce appetite and increase satiety.

 D-Fenfluramine – Investigated because of its serotonergic action. Found to suppress binge eating but no evidence of reduction in body weight (Stunkard et al 1996). However has been withdrawn in 1997 due to associations with cardiac valve lesions and pulmonary hypertension.  Orlistat – gastrointestinal lipase inhibitor. 7.4% weight reduction vs 2.3% for placebo (Golay et al 2005).  Phentermine – sympathomimetic amine. Believed to supress appetite by promoting release of norepinephrine. No studies of phentermine as monotherapy. Phentermine and fenfluramine shown to improve binge eating and weight loss (Alger et al 1999). Phentermine and fluoxetine in a 20 week study – 95% decrease in weekly binge frequency and decreased body weight.

 Atomoxetine identified as a new agent.  Acamprosate – glutamate receptor modulator. Used to maintain abstinence in alcohol dependence. Suggested that decreased glutamate function decreases binge eating by preclinical and clinical trials. 10-week placebo controlled trial of 40 patients – secondary endpoint analysis demonstrated improvement in binge day frequency, slight decrease in weight with acamprosate and increase with placebo (McElory et al 2011).  Baclofen – Also shown to be effective in alcohol dependence. 10-week trial on 7 women – 5/7 showed reduced binge frequency by 50% and 3/7 free from binge eating (Broft et al 2007). Double-blind placebo-controlled trial on 12 patients – binge eating significantly decreased in both baclofen and placebo.

 Antidepressants have been effective in bulimia nervosa. They are used because of overlaps of anxiety and depression with BED and has effect on serotonergic, noradrenergic and dopaminergic systems which demonstrate dysfunction in BED.  Anticonvulsants have been effective in manic or depressive phase in bipolar disorder and other behaviours or traits which co-occurs with BED. They have been associated with weight loss and anorexia.  There are anti-obesity agents being used.  Numerous trials have been conducted demonstrating the effectiveness of these medications.  New treatments for BED are being found.

 Pharmacological Approaches in the Treatment of Binge Eating Disorder, Appolinario and McElroy, Current Drug Targets, 2004, 5,  Latest advancements in the pharmacological treatment of binge eating disorder, Marazziti et al, European Review for Medical and Pharmacological Sciences, 2012; 16:  The Pharmacological Options in the Treatment of Eating Disorders, Milano et al, ISRN Pharmacology, Volume 2013, Article ID  World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Eating Disorders, Aigner et al, The World Journal of Biological Psychiatry, 2011; 12:  Pharmacotherapy of Binge Eating Disorder: A Review, Goracci et al, J Addict Med 2015; 9: 1-19  Binge Eating Disorder diagnosis and treatment: a recap in front of DSM-5, Amianto et al, BMC Psychiatry (2015) 15: 70  Pharmacological management of binge eating disorder: current and emerging treatment options, McElroy et al, Therapeutics and Clinical Risk Management 2012; 8,

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