[Clinically relevant drug interactions with new generation antidepressants and antipsychotics].
ABSTRACT Because antidepressants and antipsychotics are commonly described in combination with drugs used to treat comorbid psychiatric or somatic disorders (e.g. anxiolytics, mood stabilizers, cardiovascular drugs, antimicrobial agents), they may be involved in drug interactions. Furthermore, agents such as lithium and atypical antipsychotics may be used to augment the antidepressant response in cases of refractory depression. Based on their mechanisms, drug-drug interactions can be classified either as pharmacokinetic or pharmacodynamic in nature. The well-documented risk of potentially harmful pharmacodynamic drug interactions with first-generation anti-depressants, e.g. monoamine oxidase inhibitors (MAOIs), with regard to the induction of the serotonin syndrome, has contributed to a gradual decline in their use in clinical practise. Second- and third-generation antidepressants have gradually replaced tricyclic antidepressants (TCAs) and MAOIs, mainly because of their improved tolerability and safety profile. The second- and third-generation antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and other compounds with different mechanisms of action. These drugs and also the majority of antipsychotics are metabolized in the liver by the cytochrome P450 (CYP) enzyme system. Therefore, the use of these compounds may be associated with clinically relevant pharmacokinetic interactions with other medications. The knowledge about the CYP metabolism of drugs may be used to guide the selection of an antidepressant or an anti-psychotic with a low drug-drug interaction potential for an individual patient. The aim of the present article is to review drug-interaction potentials with specific focus on second-generation antidepressants (SSRIs), newer antidepressants (SNRIs: venlafaxine and duloxetine; bupropion, mirtazapine, trazodone), novel atypical antidepressants (agomelatine), as well as new generation atypical antipsychotics (aripiprazole, paliperidone).
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ABSTRACT: Paliperidone, or 9-hydroxyrisperidone (Invega(®), Janssen, Antwerp, Belgium) is the major active metabolite of the atypical antipsychotic risperidone (Risperdal(®), Janssen). It possesses a similar, though not identical, receptor pharmacology to the parent molecule. There are additional differences in terms of its predominant renal metabolism, lower protein binding and decreased inhibition of P-glycoprotein leading to decreased potential for drug-drug interactions. Paliperidone is approved as an extended release (ER) tablet based on an osmotic-controlled release oral Push-Pull™ delivery system (Oral Osmotic System, OROS(®), Alza Corporation) for the treatment of schizophrenia. The ER formulation results in decreased fluctuations in plasma drug levels and allows for once-daily administration with initial tolerability that permits treatment initiation at a clinically effective dose without the need for titration. This achieves therapeutic levels rapidly and simplifies dosing regimens, leading to potentially better adherence and improved outcome. The present review focuses on the clinical implications of the pharmacology and formulation of paliperidone ER.Expert Review of Neurotherapeutics 12/2012; 12(12):1399-410. DOI:10.1586/ern.12.138 · 2.83 Impact Factor
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ABSTRACT: In the last decade, it has been increasingly recognized that antidepressant drugs may exert a range of effects, in addition to their well-documented ability to modulate neurotransmission. Although as a group they act on monoaminergic systems and receptors in different ways, a number of studies have demonstrated that at least some antidepressants might have other properties in common, including immunomodulatory, cyto/neuroprotective, analgesic and anti-inflammatory activities. These properties are partly related to the influence of antidepressants on glial cell function. Recently, emerging information about the possible anticancer properties of antidepressants has sparked increased interest within scientific community, and there is now evidence that these drugs affect the key cellular mechanisms of carcinogenesis. This review examines the putative cellular targets for the anticancer action of antidepressant drugs, and presents examples of the interaction between antidepressants and anticancer drugs. By reviewing the current state of research in this area, we hope to focus the attention of oncologists and researchers engaged in the study of cancer on the role that antidepressant drugs could play in the complementary therapy of cancer.Experimental Biology and Medicine 08/2013; 238(8):849-58. DOI:10.1177/1535370213493721 · 2.23 Impact Factor