Taffy Makaya, Rebecca Poole and Kavitha Rozario
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to be given (so minimising side effects), whilst enabling two different anti-
obesity pathways to be targeted. Phen/TPM, however, was rejected for use in
the European Union. The European Medicines Agency cited concerns over the
long-term effects of the combined medication on the cardiovascular and
central nervous systems, and also the known teratogenic potential of
Topiramate [89]. Other concerning side effects of this combined treatment are
cognitive and psychiatric effects, and the risk of metabolic acidosis.
Naltrexone/Bupropion
Naltrexone/Bupropion is another combination drug that was approved by
the FDA in September 2014 for use in the treatment of obesity. Bupropion is
more commonly used in the treatment of depression and smoking cessation,
and is a dopamine and norepinephrine reuptake inhibitor. Naltrexone is an
opioid receptor antagonist used to treat addiction to alcohol and opioids.
Whilst both drugs have been investigated as monotherapies in the treatment of
obesity, their individual use resulted in only minimal weight loss. Combined
together, however, they are understood to have a synergistic effect, with
naltrexone reducing the activation of the hypothalamus in response to food
stimuli and Bupropion improving self-control [93]. A recent review of trial
data investigating Naltrexone/Bupropion concluded its use led to a moderate
weight loss of at least 5%, with minimal side effects, mostly nausea. However,
its cardiovascular effects are still not yet completely clear [93].
Naltrexone/Bupropion has been shown to result in an elevated blood pressure
and heart rate, and as such further trials to assess cardiovascular risk have been
required by the FDA.
Conclusion
In summary, obesity is a highly complex disease, whose presence in any
given child can be due to a combination of different factors. Therefore,
development of one effective drug, that will only target one such pathway, is
inevitably a huge challenge. Whilst Orlistat remains the only obesity
medication approved for use in children (used off-licence in the UK), it is only
modestly effective and its use is limited by its side effects. Not surprisingly, in
the hunt for a better alternative, we have seen different drugs being combined
to enable a multi-faceted approach to this complex disease. Of course, for
effective treatment of obesity, medical management alone will not suffice.
Successful treatment requires specialist multidisciplinary support, with a