Posted by SLS on December 15, 2009, at 11:45:16
In reply to Re: Combining Nortriptyline and Parnate » inanimate peanut, posted by SLS on December 15, 2009, at 11:39:33
REVIEW
Tricyclic antidepressant pharmacology
and therapeutic drug interactions updatedPK Gillman
PsychoTropical Research, Bucasia, Queensland, Australia
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.
British Journal of Pharmacology (2007) 151, 737748; doi:10.1038/sj.bjp.0707253; published online 30 April 2007
poster:SLS
thread:929389
URL: http://www.dr-bob.org/babble/20091206/msgs/929397.html