Antidepressants, Venlafaxine and Mirtazapine

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Indications for venlafaxine & mirtazapine. • Major depression - where 1st line SSRI's are ineffective/ not tolerated • Generalised anxiety disorder (venlafaxine)
MOA of venlafaxine & mirtazapine. Venlafaxine is a serotonin & noradrenaline reuptake inhibitor (SNRI), interfering with uptake of these neurotransmitters from the synaptic cleft. Mirtazapine is an antagonist of inhibitory pre-synaptic α2-adrenoceptors. Both drugs increase availability of monoamines for neurotransmission, which appears to be the mechanism whereby they improve mood & physical symptoms in moderate-to-severe (but not mild) depression. Venlafaxine is a weaker antagonist of muscarinic & histamine (H1) receptors than tricyclic antidepressants, whereas mirtazapine is a potent antagonist of histamine (H1) but not muscarinic receptors. They therefore have fewer antimuscarinic side effects than tricyclic antidepressants, although mirtazapine commonly causes sedation.
SE's of venlafaxine & mirtazapine. • GI upset • CNS effects (headache, abnormal dreams, insomnia, confusion, convulsions) • Hyponatraemia • Serotonin syndrome - see SSRI's • Suicidal thoughts & behaviour • Prolongs QT interval • ^Risk of ventricular arrhythmias • Sudden drug withdrawal - GI upset, neurological & flu like symptoms, sleep disturbance
CI's, cautions, & important interactions of venlafaxine & mirtazapine. CI's: • None Cautions: • Elderly • Renal impairment (reduce dose) • Hepatic impairment (reduce dose) • CVD associated with inc risk of arrhythmias Important interactions: The combination of these drugs with drugs from other antidepressant classes can ^risk of adverse effects (including serotonin syndrome, see Antidepressants, selective serotonin reuptake inhibitors) & should, in general, be avoided.
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