Antidepressant induced weight gainBMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k2151 (Published 23 May 2018) Cite this as: BMJ 2018;361:k2151
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In their editorial Drs. Serretti and Porcelli rightly put the issue of antidepressant-induced weight gain in the spotlight. Antidepressants, previously deemed as weight-neutral, yet convey substantial weight gain that must be taken into account.
Given their widespread use, it is important to assess whether specific antidepressants are associated with a higher risk of causing weight gain. In a recent reanalysis of data from the large meta-analysis of Serretti and Mandelli , we observed that the ability of antidepressants to induce weight gain was associated with their affinity for H1-histamine receptor , whose blockade is responsible for appetite increase and metabolic changes . This mechanism outperforms the blockade of other receptors (muscarinic-M3, serotonergic 2C, alpha2-adrenergic) putatively called upon to explain weight gain with antidepressants . Therefore, antidepressant medications with a strong anti-histaminergic activity such as amitriptyline, mirtazapine, nortriptyline have the potential for causing the highest weight gain and should be administered with great caution, especially in at-risk patients.
Interestingly, these results match similar findings showing that the weight gain potential of different antipsychotics is associated with their H1 receptor affinity , which claims to be the common mechanism responsible of weight gain with psychotropic medications.
Beyond weight gain, H1 receptor antagonism has also been linked with other metabolic abnormalities. In a previous clinical study we showed that the use of antidepressants with high H1-receptor affinity, and not use of antidepressants as a whole, was associated with decreased HDL cholesterol levels and increased prevalence of metabolic syndrome in patients with bipolar disorder .
In conclusion, we think that the use of antidepressant medications in itself should not be demonized. On the other hand, caution must be taken when employing anti-histaminergic antidepressants.
As a final remark, in agreement with a panel of renowned psychopharmacologists  we think that a pharmacodynamic-based classification of psychotropic medications based on current knowledge on neurotransmitter function and receptor affinities can be more informative than classic nomenclature and should therefore be implemented.
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Competing interests: No competing interests
I read the editorial by Alessandro Serretti and Stefano Porcelli with some interest. They have pointed out the some of the risks of not using antidepressants but I would like to add an important fact from the UK.
According to the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness, only 27% of individuals who go on to commit suicide have accessed mental health services in the year before their death. This indicates that the quite a significant proportion of those unfortunate individuals, would have contacted their primary care physicians, before the untimely demise.
Given the type of headlines this article has generated, I would hope a balance to the study could have been suggested as above before a discussion regarding shared decision making (http://research.bmh.manchester.ac.uk/cmhs/research/centreforsuicidepreve...).
My biggest concern is driving people away from appropriate help and while I am the first to acknowledge that antidepressants is not the be all and end all, we cannot have our primary care physicians caught up in a bind as to when the most appropriate intervention could be an antidepressant, along with psychological and social intervention.
This might be the last thing we need with mental health services struggling to cope with demand.
Competing interests: No competing interests