Drug interactions newer antidepressants

Antidepressants are commonly used in combination with antipsychotics to treat depressive symptoms in individuals with schizophrenia. Different antidepressants have been reported to inhibit metabolism of different P450 pathways. Table 66-10 summarizes the potential metabolic drug interactions between antidepressants and SGAs. Potential enzyme inhibitor interactions with clozapine are the most clinically significant. Increased clozapine serum concentrations with a CYP 1A2 inhibitor such as fluvoxamine may precipitate seizures. With the newer atypical antipsychotics, enzyme inhibitors are more likely to cause side effects such as increased sedation, orthostatic hypotension, or increased risk of akathisia and other extrapyramidal side effects. 

Selected Drug Interactions of Newer-Generation Antidepressants... 

Psychiatric medicines exert multiple effects for two principal reasons. First, they usually interact with more than one receptor type. There are two ways to look at this. You will often hear a medication with multiple receptor interactions called a dirty drug. This is because the more receptor interactions it has, the more effects, and hence side effects, it produces. As a result, great effort has been made to develop newer medications with fewer receptor interactions and, thus, fewer side effects. This effort has been quite successful with antidepressants, as we have moved from the effective but side effect-laden tricyclic antidepressants to newer antidepressants such as selective serotonin reuptake inhibitors. 

Changing a patient from one MAOI to another, or to a TCA, requires a "wash-out" period of at least 2 weeks to avoid the possibility of a drug interaction. There is evidence to suggest that a combination of an MAOI with clomipramine is more likely to produce serious adverse effects than occurs with other TCAs. Regarding the newer non-tricyclic antidepressants, it is recommended that a "wash-out" period of at least 5 weeks be given before a patient on fluoxetine is given an MAOI this is due to the very long half-life of the main fluoxetine metabolite norfluoxetine. 

Spina, E. and Pemcca, E. (1994) Newer and older antidepressants a comparative review of drug interactions. CNS Drugs, 2, 479-497. 

Greenblatt DJ, von Moltke LL, Harmatz JS, et al Drug interactions with newer antidepressants role of human cytochromes P450. J Clin Psychiatry 59 (suppl 15) 19-27, 1998... 

Greenblatt DJ, von Moltke LL, Harmatz JS, et al Human cytochromes and some newer antidepressants kinetics, metabolism, and drug interactions. J Clin Psychopharmacol 19 23S-35S, 1999 Karliova M, Treichel U, Malago M, et al Interaction of Hypericum perforatum (St. John s wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 33 853-855, 2000 Michalets EL Update clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 18 84-112, 1998... 

Greenblatt, D.J., L.L. von Moltke, J.S. Harmatz, and R.I. Shader (1999). Human cytochromes and some newer antidepressants Kinetics, metabolism, and drug interactions. J. Clin. Psychopharmacol. 19 (SuppI 1), 23S-35S. 

It remains to be studied whether the inhibition of P-gp by the newer antidepressants might lead to drug-drug interactions in patients. Such interactions might, for instance, be relevant when drugs with low oral bioavailability because of substantial transport back into the gut lumen are to be coadministered, as has been shown for loperamide when given in combination with quinidine (38). 

Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI (1999) Human cytochromes and some newer antidepressants kinetics, metabolism, drug interactions. J Clin Psychopharmacol 19(Suppl 1) 23S-35S... 

This antidepressant can interact with other drugs via its two mechanisms of action serotonin and NE uptake inhibition. The former action means that the same pharmacodynamic interactions will occur with venlafaxine as with SSRIs, including the serotonin syndrome. At higher doses, venlafaxine is also prone to the same pharmacodynamic interactions as NSRIs such as secondary amine TCAs like desipramine and with newer NSRIs such reboxetine. Thus, the combination of high-dose venlafaxine plus an MAOl could produce a hypertensive crisis as well as the serotonin syndrome. 

A growing number of drugs are used that affect the many neurotransmitters in the brain benzodiazepines and others act on GABAergic transmission antidepressants, such as monoamine oxidase inhibitors and tricyclic antidepressants, are thought to increase the concentration of transmitter amines in the brain and so elevate mood—these will also act at peripheral nerve terminals, so interactions with them are a combination of peripheral and central actions. Levodopa (L-dopa) increases central as well as peripheral dopamine, and the newer class of psychoactive drugs, the selective serotonin reuptake inhibitors (SSRIs) of which the ubiquitous fluoxetine (Prozac) is best known, act in a similar way on serotonergic pathways. 

Some of the newer and more recently developed drugs with MAO inhibitory activity (see Table 32.1 , (below)) interact to a lesser extent than the older MAOIs. This is because they are largely selective. One group of these selective inhibitors targets MAO-A, and are relatively rapidly reversible inhibition of this enzyme is responsible for the antidepressant effect. These selective MAO-A inhibitors (moclobemide, toloxatone) have been given the acronym RIMAs (Reversible Inhibitors of Monoamine oxidase A). They leave MAO-B largely uninhibited so that there is still a metabolic pathway available for the breakdown of amines, such as... 

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