Antidepressants, venlafaxine and mirtazepine

Key examples

• Venlafaxine 
• Mirtazepine 

 

Common indications

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

 

Mechanisms of action

• Venlafaxine is a serotonin and 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 and physical symptoms in moderate-to-severe (but not mild) depression.
• Venlafaxine is a weaker antagonist of muscarinic and 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.

 

Important adverse effects

• Common adverse effects of both drugs include gastrointestinal upset (e.g. dry mouth, nausea, change in weight and diarrhoea or constipation) and central nervous system effects (e.g. headache, abnormal dreams, insomnia, confusion and convulsions). Less common but serious adverse effects include hyponatraemia and serotonin syndrome (see Antidepressants, selective serotonin reuptake inhibitors). Suicidal thoughts and behaviour may increase. Venlafaxine prolongs the QT interval and can increase the risk of ventricular arrhythmias.
• Sudden drug withdrawal can cause gastrointestinal upset, neurological and influenza-like symptoms and sleep disturbance. Venlafaxine is associated with a greater risk of withdrawal effects than other antidepressants.

 

Warnings

• As with many centrally acting medications, the elderly are at particular risk of adverse effects. A dose reduction should be considered in people with hepatic or renal impairment. Venlafaxine should be used with caution (if at all) in patients with cardiovascular disease associated with an increased risk of arrhythmias.

 

Important interactions

• The combination of these drugs with drugs from other antidepressant classes can increase the risk of adverse effects (including serotonin syndrome, see Antidepressants, selective serotonin reuptake inhibitors) and should, in general, be avoided.