Each week we will aim to bring out a concise email that provides 4-5 key pieces of information addressing a specific issue in clinical therapeutics. This week:
SSRI drug interactions (part one)
Worldwide, and in Australia, the Selective Serotonin Reuptake Inhibitors (SSRIs) are amongst the most commonly prescribed antidepressants. The SSRIs are associated with a range of significant drug interactions. Some of these interactions are mediated by inhibition of CYP450 isoenzymes in the liver, and the extent to which these interactions manifest will be influenced by genetic variability in native hepatic enzyme activity, as well as the doses of both SSRI and the interacting drug.
- Citalopram and escitalopram have relative less effect upon CYP450 than other SSRIs – in the absence of risk factors for QTC segment prolongation these agents are probably the safest drugs to use for people with otherwise extensive polypharmacy.
- Paroxetine and fluoxetine, and to a lesser extent, sertraline, are the most potent inhibitors of CYP2D6 – inhibition of this isoenzyme increases the serum concentration of some drugs, which may in turn accentuate the effects of drugs such as perhexiline (creating potential for serious toxicity), metoprolol (causing bradycardia), haloperidol & risperidone (increased akathisia and parkinsonism) and some opioids such as oxycodone (enhanced CNS suppression). On the other hand, codeine relies upon metabolic activation by CYP2D6 and analgesic effects may be diminished or even abolished by concurrent SSRI use.
- Fluvoxamine, fluoxetine and sertraline can inhibit CYP1A2, increasing serum concentrations (& potential toxicity) of several drugs including clozapine, olanzapine, donepezil and theophylline. CYP1A2 inhibition also interferes with caffeine metabolism, meaning that during treatment it is necessary to modulate intake of coffee, tea, cola beverages, and chocolate.
- Fluvoxamine, fluoxetine and sertraline can also inhibit CYP3A4, which may increase serum concentrations (& potential toxicity) of a wide range of drugs. Examples include statins (potential for myopathy), immunomodulators such as cyclosporine and tacrolimus, carbamazepine, colchicine, and many others.
Please consider these issues when preparing RMMR reports or education sessions. Contributions of content or suggested topics are welcome and should be sent directly to firstname.lastname@example.org