H1-histamine receptor affinity predicts weight gain with antidepressants.

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Salvi V, Mencacci C, Barone-Adesi F

H1-histamine receptor affinity predicts weight gain with antidepressants.

Eur Neuropsychopharmacol. 2016 Oct;26(10):1673-7. doi: 10.1016/j.euroneuro.2016.08.012. Epub 2016 Sep 1.

PubMed ID

27593622 [ View in PubMed

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Abstract

Weight gain and metabolic abnormalities are extensively found in patients taking psychotropic medications. Although mainly antipsychotics have been implicated, also antidepressants carry the potential to induce weight gain, with tricyclics and mirtazapine being associated with the greatest weight gain. It has been suggested that this could be due to the different ability of antidepressants to block adrenergic, cholinergic, and histaminergic postsynaptic receptors. To date, however, the link between antidepressant-induced weight gain and their receptor affinity profile has not been established. We reanalysed data from a previous meta-analysis to evaluate whether weight change is associated with specific receptor affinity of antidepressants. We retrieved data from the only meta-analysis that assessed weight change with antidepressants. We searched in the Psychoactive Drug Screening Program (PDSP) Ki database data on the affinities of antidepressants to receptors hypothetically linked with weight change: H1-histamine, 5HT2c, M3-muscarinic, and alpha1A-adrenergic receptors. The association between weight change and receptor affinities was estimated using meta-regression. We found a significant association between the affinity of antidepressants to H1-receptor and weight gain (p value: <0.001). An association between weight gain and receptor affinity was also observed in the models for 5HT2c, M3, and alpha1A receptors. However, the association disappeared when H1-receptor was included in the models. This reanalysis of data demonstrates that anti-histaminergic activity is the strongest predictor of weight gain with antidepressants. These results further stress a reclassification of antidepressants according to their pharmacodynamic properties, and suggest avoiding prescribing antidepressants with an anti-histaminergic profile to patients at risk for cardio-metabolic disturbances.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mirtazapine	Histamine H1 receptor	Protein	Humans	No	Antagonist	Details