After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone. In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at usual therapeutic concentrations and are not expected to affect the disposition of concomitantly administered medications. Although drug interactions with newer antidepressants are potentially, but rarely, clinically significant, the use of antidepressants with a more favourable drug interaction profile is advisable. Knowledge of the interaction potential of individual antidepressants is essential for safe prescribing and may help clinicians to predict and eventually avoid certain drug combinations

This paper reports combined antidepressant treatment with isocarboxazid /mianserin in 60 patients with endogenous depression/melancholia. The combination was used as the first drug treatment choice in 33 cases. Thirty-two patients obtained complete remission and one responded only incompletely. The depression improved after a few days´ treatment, and full recovery was obtained after approximately 2 weeks. There were no serious side-effects or interactions, but weight gain was a common problem

The use of monoamine oxidase inhibitors (MAOIs) in the treatment of depression has been bedeviled by reports of potentially dangerous or even fatal interactions with dietary amines and other drugs together with reports of more conventional toxicity to organs such as the liver. As a result, these otherwise very important and useful drugs have not been employed clinically as much as their effectiveness as antidepressants would indicate. Many of these unwanted actions were due partially or entirely to the fact that the older MAOIs all inhibited MAO irreversibly. The introduction of reversible inhibitors of monoamine oxidase-A (RIMAs) has greatly reduced both the number and severity of these interactions and, in particular, the risk of hypertensive crises following the ingestion of tyramine (the ´cheese effect´). Potential interactions may remain with inhibitors of the uptake of 5-hydroxytryptamine, including pethidine and rapid release formulations of nasal decongestant amines. Potential interactions between RIMAs and other drugs that compete for the same metabolic pathways may still occur but should only result in changes in duration of action

http://www.ema.europa.eu/docs/da_DK/document_library/EPAR_-_Product_Information/human/002717/WC500159449.pdf

Toxic interaction of venlafaxine and isocarboxazide