eMJA: Mitchell, Managing depression Box 3

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Mitchell,
Box 3

New antidepressants -- important interactions

Drug	Other medication	Clinical features of interaction	Comments

SSRIs	1. Irreversible MAOIs; moclobemide	Serotonergic syndrome -- hypomania, confusion, hypertension, tremor, diarrhoea, myoclonus, death	Do not prescribe SSRIs within two weeks of MAOIs. Do not prescribe MAOIs within five weeks of fluoxetine, two weeks of other SSRIs
	2. Medications metabolised by cytochrome P450 enzymes in liver (e.g., TCAs, antipsychotics, some antiarrhythmics)	SSRIs inhibit metabolism, leading to increased levels in blood	Avoid TCA/SSRI combination. May need to prescribe lower doses of other medications with SSRIs
Moclobemide (RIMA)	1. Pethidine	Uncertain -- but life-threatening interaction with irreversible MAOIs	Avoid combination
	2. SSRIs, TCAs	Serotonergic syndrome deaths reported with overdose -- particularly with clomipramine	Avoid combination with TCAs, SSRIs, even at therapeutic doses (particularly clomipramine)
Venlafaxine (SNRI)	Irreversible MAOIs; moclobemide	Serotonergic syndrome (as above)	Do not prescribe venlafaxine within two weeks of MAOIs. Do not prescribe MAOIs within one week of venlafaxine
Nefazodone	1. Irreversible MAOIs; moclobemide	Serotonergic syndrome	Do not prescribe nefazodone within two weeks of MAOIs. Do not prescribe MAOIs within one week of nefazodone
	2. Terfenadine, astemizole and cisapride	Nefazodone inhibits metabolism, leading to potentially toxic levels in blood, producing serious cardiac events, including death	Combinations contraindicated

MAOI = monoamine oxidase inhibitor; RIMA = reversible inhibitor of monoamine oxidase; SNRI = serotonin-noradrenaline reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.

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