Serotonin and noradrenaline reuptake inhibitors

• venlafaxine is a serotonin and noradrenaline reuptake inhibitor - it inhibits the presynaptic reuptake of noradrenaline, serotonin and, to a significantly lesser extent, dopamine. Serotonin reuptake is inhibited at both high and low doses of venlafaxine. Noradrenaline reuptake with venlafaxine occurs more prominently with higher doses
• indications include for the treatment of depression
• there is evidence that, in patients with depressive disorders, venlafaxine is more effective than selective serotonin reuptake inhibitors. Dropout rates do not differ between venlafaxine and other types of antidepressants (1)

Following the announcement from the Medicines and Healthcare products Regulatory Agency (MHRA) in December 2004 several important changes were made to the UK Summary of Product Characteristics for venlafaxine (Efexor®) and venlafaxine XL (Efexor® XL) (2)

These are summarised as follows:

• both are now indicated only for "Moderate to severe major depressive disorder"
• venlafaxine XL (Efexor® XL) may also be used for "Moderate to severe Generalised Anxiety Disorder"
• venlafaxine should not be used in patients with: heart disease, electrolyte imbalance or those who have untreated or uncontrolled hypertension

The MHRA advises that for existing patients treated with venlafaxine (2):

• those that are doing well on treatment should continue to take their medication as normal until the course in complete
• those with known heart disease or at significant risk factors for heart disease should be reviewed at their next routine appointment.

NICE have modified their guidance regarding use of venlafaxine (3,4):

• in depression (3)
  • if an initial antidepressant has been ineffective or poorly tolerated then venlafaxine may be considered, especially for more severe depression
    • "..reasonable choices for a second antidepressant include a different SSRI or mirtazapine, but consideration may also be given to other alternatives, including moclobemide, reboxetine and lofepramine. Other tricyclic antidepressants (except dosulepin) and venlafaxine may be considered, especially for more severe depression.."
  • NICE also suggest that, before prescribing venlafaxine, practitioners should take into account the increased likelihood of patients stopping treatment because of side effects, and its higher cost, compared with equally effective SSRIs
  • practitioners should ensure pre-existing hypertension is controlled in line with the current NICE guideline on hypertension. Venlafaxine should not be prescribed for patients with uncontrolled hypertension
  • for patients prescribed venlafaxine, NICE suggest blood pressure should be checked on initiation and regularly during treatment, particularly during dosage titration. For patients who experience a sustained increase in blood pressure, the dose should be reduced or discontinuation considered
  • practitioners should monitor patients prescribed venlafaxine for the signs and symptoms of cardiac dysfunction, particularly in those with known cardiovascular disease, and take appropriate action as necessary
  • when prescribing antidepressants (particularly fluoxetine, fluvoxamine, paroxetine, tricyclic antidepressants, or venlafaxine), NICE state that practitioners should be aware of clinically significant interactions with concomitant drugs. They should consider consulting appendix 1 of the 'British National Formulary'
  • venlafaxine and tricyclic antidepressants (with the exception of lofepramine) should not be prescribed for patients with a:
    • high risk of serious cardiac arrhythmias
    • recent myocardial infarction
  • venlafaxine should only be prescribed at high dose (300 mg/day or more) under the supervision or advice of a specialist mental health medical practitioner
• in generalised anxiety disorder (4)
  • venlafaxine has marketing authorisation for the treatment of generalised anxiety disorder
  • dose of venlafaxine should be no higher than 75 mg per day
  • the cautions with respect to issues such as hypertension, cardiac disease and drug interactions are repeated in this guideline as in the depression guideline

See NICE guidance (3,4) for detailed advice.

The summary of product characteristics should be consulted before prescribing this drug.

Reference:

1. Br J Psychiatry 2002 May;180:396-404
2. Medicines and Healthcare products Regulatory Agency (December 2004). Venlafaxine and Venlafaxine MR - changes to indications.
3. NICE (April 2007). Management of depression in primary and secondary care.
4. NICE (April 2007).Management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care.
5. Prescribers' Journal (1999); 39 (4):243-247.