Serotonin and Norepinephrine Re-uptake Inhibitors (SNRIs)

This new class of drug (unrelated to other antidepressants) is used in the management of depression and anxiety.¹ Venlafaxine is the first and only drug available in this class in the UK. Both venlafaxine and its major metabolite, O-desmethylvenlafaxine (ODV), inhibit serotonin and norepinephrine reuptake into nerves (and to a lesser extent dopamine).

Note that 'norepinephrine' is the recommended International Nonproprietary Name (rINN) for 'noradrenaline' which is the British Approved Name (BAN).

Venlafaxine should generally be used under specialist supervision, this is particularly so in severely depressed or hospitalised patients² who need doses of 300 mg daily or more.
It should not be prescribed to children aged under 18,¹ because increased risk of self-harm and suicidal thoughts and little evidence for efficacy in this group.²

Milnacipran and duloxetine are other SNRIs in development.³ They may be better tolerated and not have venlafaxine's cardiovascular toxicity (particularly in overdose).

• Major depression including depression accompanied by anxiety¹
• Generalised anxiety disorder

(see individual drug monographs for full list)

• Uncontrolled hypertension (monitor BP in all patients)²
• Patients at high risk of ventricular arrhythmia - e.g. patients with significant LV dysfunction,¹ heart failure, and patients with ECG rhythm abnormalities
• Severe hepatic or renal impairment, and patients with electrolyte imbalances
• Pregnancy or breast feeding
• Children (aged less than 18)¹
• Not to be used concurrently or within 2 weeks of an MAOIs

• Perform a baseline ECG and check BP to help exclude pre-existing hypertension or heart disease
• Avoid in patients with ECG abnormal - eg showing evidence of IHD or arrhythmia - especially QT abnormal
• Reduce dose in hepatic or renal impairment
• Full therapeutic effect may not be apparent over the first two weeks of treatment
• Watch and monitor mental state carefully as this may deteriorate (agitation)

• Repeat BP check within one month or starting drug or dose change, and check at least 6 monthly thereafter
• Ensure patient is reviewed regularly (particularly if recently starting drug or adjusting dose) e.g. for worsening restlessness, agitation, mania, current suicide risk

It is usual to taper dose slowly over a few weeks to avoid withdrawal symptoms.

• Hypertension - if this develops reduce dose or discontinue and consider starting alternative agent (take advice of specialist)⁴
• Serotonin Syndrome