New‐generation, non‐SSRI antidepressants: Drug‐drug interactions and therapeutic drug monitoring. Part 2: NaSSAs, NRIs, SNDRIs, MASSAs, NDRIs, and others

Abstract

After the development of “classical” tricyclic antidepressants and monoamine oxidase inhibitors, numerous other classes of antidepressant drugs have been introduced onto the market. The selective serotonin reuptake inhibitor class is the best‐known one, but many others exist, usually identified by their mechanism of activity. In this second part of the review, focused on new‐generation antidepressants not included among selective serotonin reuptake inhibitors, the following classes are considered: noradrenergic and selective serotonergic antidepressants; norepinephrine reuptake inhibitors; serotonin, norepinephrine and dopamine reuptake inhibitors; melatonergic agonists and selective serotonergic antagonists; norepinephrine and dopamine reuptake inhibitors; and so forth. These different mechanisms underlie tolerability and safety profiles that can be very different among the classes, with each one providing significant advantages and disadvantages in comparison with others. The main characteristics of the following antidepressants are described: mianserin, mirtazapine, setiptiline, reboxetine, viloxazine, teniloxazine, atomoxetine, nefazodone, agomelatine, bupropion, esketamine, and tianeptine. The paper is focused on their metabolism and interactions, but also includes brief notes on analytical methods useful for their therapeutic drug monitoring.

Blues in the Brain and Beyond: Molecular Bases of Major Depressive Disorder and Relative Pharmacological and Non-Pharmacological Treatments

“…The antidepressant effects of these drugs are mainly due to their action as antagonists of α2 presynaptic adrenergic receptors that leads to an increased release of both noradrenaline and serotonin. Moreover, they also act as antagonists of the serotonin receptors 5-HT2A, 5-HT2C and 5-HT3, and this mechanism is thought to underlie the positive effects produced by NASSAs on sleep, helping to restore the circadian cycles that are perturbed in depressive states [105,134]. In line with other ADs, a few studies showed that prolonged treatment with NASSAs increases the expression of BDNF in the rat hippocampus and frontal cortex [135,136].…”

Cardiovascular and temperature adverse actions of stimulants

“…fluoxetine) and NA re-uptake inhibitors (NRI)(e.g. reboxetine) have been found to be effective in treatment of depression, classes of antidepressant acting on transporters now also include: combined NA and serotonin re-uptake inhibitors; combined serotonin, NA and DA reuptake inhibitors (SNDRI); combined NA and DA reuptake inhibitors (NDR) (Protti et al, 2020).…”

“…The monoamine neurotransmitter transporters for noradrenaline (NET), dopamine (DAT) and 5-HT (SERT) (1. in Figure 1) are closely related. Although selective serotonin reuptake inhibitors (SSRI) (e.g., fluoxetine) and noradrenaline reuptake inhibitors (NRI) (e.g., reboxetine) have been found to be effective in treatment of depression, classes of anti-depressant acting on transporters now also include combined noradrenaline and 5-HT reuptake inhibitors; combined 5-HT, noradrenaline and dopamine reuptake inhibitors (SNDRI); combined noradrenaline and dopamine reuptake inhibitors (NDR) (Protti et al, 2020).…”

Quantitative microsampling for bioanalytical applications related to the SARS-CoV-2 pandemic: Usefulness, benefits and pitfalls

“…TDM includes the repeated determination of drugs and metabolites plasma levels, together with the use of chemical-clinical correlations (i.e., correlations between administered drug dose and plasma levels; between plasma levels and therapeutic efficacy; between plasma levels and side and toxic effects) [ [53] , [54] , [55] ].…”