Venlafaxine and Mirtazapine

Question 1

When is venlafaxine/mirtazapine

indicated?

Answer 1

As an option for treatment of major depression where first-line selective serotonin reuptake inhibitors (SSRIs) are ineffective or not tolerated.
Generalised anxiety disorder (venlafaxine).

Question 2

What is the mechanism of action of venlafaxine?

Answer 2

Venlafaxine is a serotonin and noradrenaline reuptake inhibitor (SNRI), interfering with uptake of these neurotransmitters from the synaptic cleft

Question 3

What is the mechanism of action of mirtazapine?

Answer 3

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 and physical symptoms in moderate-to-severe (but not mild) depression.

Question 4

What are the common adverse effects of both drugs?

Answer 4

gastrointestinal (GI) upset (e.g. dry mouth, nausea, change in weight and diarrhoea or constipation)

neurological effects (e.g. headache, abnormal dreams, insomnia, confusion and convulsions)

Hyponatraemia

Serotonin Syndrome

Increase in suicidal thoughts and behaviour

Venlafaxine: QT elongation and increased risk of ventricular arrhythmias

Question 5

What are withdrawal effects of venlafaxine?

Answer 5

Sudden drug withdrawal can cause GI upset, neurological and influenza-like symptoms and sleep disturbance. Venlafaxine is associated with a greater risk of withdrawal effects than other antidepressants.

Question 6

Which patients require special prescribing of these drugs

Answer 6

Patients with renal or hepatic impairment should have their dose reduced

Care needed when prescribing for the elderly who are more susceptible to adverse reactions.

Venlafaxine should be used with caution (if at all) in patients at risk of ▴arrhythmias (e.g. due to ischaemic heart disease).

Question 7

What are the prescribed doses of these drugs?

Answer 7

Typical starting doses are venlafaxine 37.5 mg orally 12-hrly (titrated to a maximum of 375 mg daily) and mirtazapine 15 mg orally daily (titrated to a maximum of 45 mg daily).

Question 8

When should the dose or the drug be changed if there is no improvement of symptoms?

Answer 8

4 weeks