english.prescrire.org > Spotlight > Archives : 2015 > Naltrexone + bupropion (Mysimba°): too risky for only modest weight loss

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Naltrexone + bupropion (Mysimba°): too risky for only modest weight loss

FEATURED REVIEW On average, obese or overweight patients taking naltrexone + bupropion lose only a few kilograms. In contrast, its neuropsychiatric adverse effects are numerous and potentially severe. There is also a risk of hypertension, cardiac arrhythmia and gastrointestinal adverse effects.
Full review (4 pages) available for download by subscribers.

Abstract

  • Weight loss and its long-term maintenance are mainly based on dietary measures and regular physical activity. There are currently no weight-loss medications with a favourable harm-benefit balance.
     
  • Bupropion is chemically related to certain amphetamines, while naltrexone is an opioid receptor antagonist. A fixed-dose combination of these two drugs has received marketing authorisation in the European Union for obese patients and for overweight patients with other cardiovascular risk factors.
     
  • In five placebo-controlled, randomised, double-blind trials, the patients, weighing on average between 100 kg and 105 kg (average body mass index 36 kg/m2), the naltrexone + bupropion combination was associated with an average weight loss of a few additional kilograms compared with placebo, after 6 months or one year of treatment. There are no post-trial follow-up data to show whether or not the patients regained their lost weight after treatment discontinuation.
     
  • One trial including more than 8900 patients examined the effect of the naltrexone + bupropion combination on the frequency of major cardiovascular events, but poor handling of an interim analysis undermined the validity of the final results.
     
  • The known adverse effects of bupropion consist of potentially severe neuropsychiatric disorders such as aggressiveness, depression and suicidal ideation, and also allergic reactions, including Stevens-Johnson syndrome. Misuse and excessive consumption have been reported.
     
  • In trials in obese or overweight patients, the naltrexone + bupropion combination caused sometimes severe neuropsychiatric disorders, including seizures, cognitive impairment, dizziness, anxiety, sleep disorders and psychotic symptoms.
     
  • In clinical trials, the combination led to an increase in blood pressure compared with placebo, and also an excess of cardiac arrhythmias. 
     
  • About half of patients who took naltrexone + bupropion experienced gastrointestinal disorders such as nausea, vomiting and constipation.
     
  • The naltrexone + bupropion combination is subject to many pharmacokinetic interactions, as well as pharmacodynamic interactions leading to additive convulsive or hypertensive effects, or undermining the action of antihypertensive drugs.
     
  • A teratogenic effect of bupropion cannot be ruled out.
     
  • In practice, given the limited effect of the naltrexone + bupropion combination on weight loss (a few kilograms), along with the lack of evidence supporting a persistent benefit or a decrease in the clinical complications of obesity, there is no reason to expose patients to its many potentially severe adverse effects. 

©Prescrire 1 October 2015

"Naltrexone + bupropion (Mysimba°). Too risky for only modest weight loss" Prescrire Int 2015; 24 (164): 229-233. (Pdf, subscribers only)
Download the full review.
Pdf, subscribers only

See also:

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EMA recommendation that
must be overturned
(December 2014)
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do no harm (follow-up)
(December 2014)
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Lorcaserin. In obesity:
Unacceptable risks
Prescrire Int 2014;
23 (149): 117-120
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Rimonabant: marketing
authorisation suspended…
at last!  Half-measures.
Prescrire Int 2008;
18 (100): 61.
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Sibutramine:
cardiovascular events
Prescrire Int 2010;
19 (107): 125.
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Obesity: weight loss
without drugs
Prescrire Int 2007;
16 (90): 162-167.
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