Venlafaxine is a serotonin and noradrenaline reuptake inhibitor (SNRI) that is licensed for the treatment of depressive illness and generalised anxiety disorder. Its use both in primary and secondary care has been increasing substantially in recent years, partly as a result of suggestions that it may be more potent in the treatment of depression than SSRIs.
In December 2004, NICE issued guidelines for the management of depression as well as guidelines for the management of anxiety disorders including generalised anxiety.
NICE's view of the possible benefits of Venlafaxine over SSRIs was that this was statistically only apparent in patients with severe depression and when higher doses (150mg+) were used. They questioned whether the advantage of Venlafaxine over SSRIs was of clinical significance. Further they raised a number of concerns regarding the cardiotoxicity of Venlafaxine and its toxicity in overdose. As a result, NICE recommends that for both depression and generalised anxiety, Venlafaxine should only be initiated and managed under the supervision of specialist mental health medical practitioners. This includes general practitioners with a special interest in mental health.
While Venlafaxine is not recommended for either first or second line treatment of depression or generalised anxiety, it is recommended for the management of treatment resistant depression by mental health specialists. It is recommended that its use is avoided in patients with cardiac disease, abnormal electrolytes and hypertension. In addition, prescribers are warned to be aware of the increased risk of patients stopping taking Venlafaxine compared to SSRIs due to an increased risk of side effects, a high propensity for discontinuation/withdrawal symptoms and toxicity of Venlafaxine in overdose. NICE further recommend base-line ECG and BP being undertaken in patients before being prescribed Venlafaxine and that consideration should be given for monitoring cardiac function of patients treated with the drug.
The makers of Venlafaxine, Wyeth, are appealing against the recommendations around Venlafaxine, the outcome of which is likely to be known in April or May 2005.
Implication of NICE Guidelines
First and foremost NICE categorically states that patients who are currently established on Venlafaxine and responding well to it should remain on the drug.
Secondly, in patients where a prescriber would previously have recommended Venlafaxine but now wishes to consider an alternative, care should be exercised.
Note that Dosulepin (Dothiepin) is also only recommended for use by specialist mental health medical practitioners and the only tricyclic that is specifically recommended in primary care is Lofepramine. In addition to Lofepramine, NICE recommend that reasonable alternatives to SSRIs are Mirtazapine, Moclobemide and Reboxetine. The recently introduced SNRI, Duloxetine, was licensed after the NICE guidelines had been finalised and was therefore not considered. It is yet to be reviewed by local Drugs and Therapeutics Committee's as to whether this might be an additional reasonable alternative.
If a decision to use Venlafaxine is taken the following physical health monitoring is recommended:
- At baseline measure U&Es, ECG and blood pressure. Do not prescribe Venlafaxine if abnormalities are found with any of these measures.
- Repeat ECG after 3 months or following any substantial increase in dose. If there has been no change compared to baseline, then just repeat at any time if clinically indicated.
- Measure BP after 3 months and after any substantial increase of dose. BP should continue to be monitored on a 3-6 monthly basis for all patients prescribed doses above 150mg daily.
These recommendations are interim while the results of the Wyeth appeal are awaited as well as any further recommendations from MHRA or NICE.