Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.
Article Details
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Gillman PK
Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.
Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30.
- PubMed ID
- 17471183 [ View in PubMed]
- Abstract
New data on the pharmacology of tricyclic antidepressants (TCAs), their affinities for human cloned CNS receptors and their cytochrome P450 enzyme inhibition profiles, allow improved deductions concerning their effects and interactions and indicate which of the TCAs are the most useful. The relative toxicity of TCAs continues to be more precisely defined, as do TCA interactions with selective serotonin reuptake inhibitors (SSRIs). TCA interactions with monoamine oxidase inhibitors (MAOIs) have been, historically, an uncertain and difficult question, but are now well understood, although this is not reflected in the literature. The data indicate that nortriptyline and desipramine have the most pharmacologically desirable characteristics as noradrenaline reuptake inhibitors (NRIs), and as drugs with few interactions that are also safe when coadministered with either MAOIs or SSRIs. Clomipramine is the only available antidepressant drug that has good evidence of clinically relevant serotonin and noradrenaline reuptake inhibition (SNRI). These data assist drug selection for monotherapy and combination therapy and predict reliably how and why pharmacodynamic and pharmacokinetic interactions occur. In comparison, two newer drugs proposed to have SNRI properties, duloxetine and venlafaxine, may have insufficient NRI potency to be effective SNRIs. Combinations such as sertraline and nortriptyline may therefore offer advantages over drugs like venlafaxine that have fixed ratios of SRI/NRI effects that are not ideal. However, no TCA/SSRI combination is sufficiently safe to be universally applicable without expert knowledge. Standard texts (e.g. the British National Formulary) and treatment guidelines would benefit by taking account of these new data and understandings.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Clomipramine Sodium-dependent serotonin transporter Protein Humans YesInhibitorDetails Dosulepin Histamine H1 receptor Protein Humans YesAntagonistDetails Dosulepin Muscarinic acetylcholine receptor M1 Protein Humans YesAntagonistDetails Dosulepin Muscarinic acetylcholine receptor M2 Protein Humans YesAntagonistDetails Dosulepin Muscarinic acetylcholine receptor M3 Protein Humans YesAntagonistDetails Dosulepin Muscarinic acetylcholine receptor M4 Protein Humans YesAntagonistDetails Dosulepin Muscarinic acetylcholine receptor M5 Protein Humans YesAntagonistDetails Dosulepin Sodium-dependent noradrenaline transporter Protein Humans YesInhibitorDetails Dosulepin Sodium-dependent serotonin transporter Protein Humans YesInhibitorDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Clomipramine Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails Dosulepin Cytochrome P450 1A2 Protein Humans UnknownInhibitorDetails Dosulepin Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Dosulepin Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Dosulepin Cytochrome P450 2D6 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareMirtazapineTryptophan Tryptophan may increase the serotonergic activities of Mirtazapine. MirtazapineFluvoxamine Fluvoxamine may increase the serotonergic activities of Mirtazapine. MirtazapineAmphetamine Amphetamine may increase the serotonergic activities of Mirtazapine. MirtazapinePhentermine Phentermine may increase the serotonergic activities of Mirtazapine. MirtazapineEletriptan Eletriptan may increase the serotonergic activities of Mirtazapine.