In December 2004 NICE issued clinical guidelines regarding depression. These included restrictions on venlafaxine with baseline ECGs and prescribing by specialists only recommended. This was based on unpublished data regarding the cardiac effects of the drug and concerns of toxicity in overdose.
On 31 May 2006, MHRA released a statement following an appeal against the restrictions by the manufacturer, Wyeth. This conceded that baseline ECGs are unnecessary for most patients. Further, MHRA accepted data showing that venlafaxine is more likely than SSRIs to be prescribed to patients at risk of suicide. This leads to an increase in the ‘fatal toxicity index’ (deaths per million prescriptions) for the drug. The absolute risk of toxicity of venlafaxine is probably still higher than for SSRIs, though is far less than the risk from overdose with amitriptyline or dosulepin (dothiepin). MHRA concluded that venlafaxine was an appropriate second-line antidepressant (after an SSRI), and that it can be prescribed by non-specialists in doses less than 300 mg per day.
The original NICE recommendations have had a profound impact. We have examined antidepressant prescribing in three general practices in the North East of England (combined population: 23 217), both immediately before and 6 months after publication of the NICE guidelines. All patients newly prescribed an antidepressant in 3-month periods were identified (764 and 780) and their case notes screened to identify those with depression and/or anxiety. Prescribing of SSRIs significantly increased from 46.5% to 59.4% of patients (P<0.001). However, the proportion prescribed venlafaxine fell from 7.3% to 1.0% (P<0.05). This does not simply reflect practices who assiduously implement NICE guidance. Prescribing of dosulepin, which NICE also recommended for specialist use only, remained unchanged (3.7 versus 3.2%).
Our data raises concerns regarding the impact of NICE guidelines. Recommendations that are contentious and widely discussed, and followed up by industry as was the case with venlafaxine, lead to major changes in practice. However, recommendations that are not widely publicised, such as those regarding dosulepin, can easily get overlooked (especially when the name of the drug has changed). The major concern is that while the confusion over venlafaxine has been resolved, the most toxic of the commonly prescribed antidepressants, dosulepin, continues to be prescribed unchecked. There needs to be a concerted effort by all trust medicines management bodies towards reducing the small but significant numbers of patients prescribed dosulepin to prevent unnecessary deaths.
- © British Journal of General Practice, 2006.
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