The clinical profile of mianserin

Abstract

Drug licensing authorities throughout the world share a common concern to ensure that the drugs which are licensed are both effective and safe. However, the relatively small number of patients exposed to a drug in clinical trials make it extremely unlikely that serious but rare adverse drug reactions (ADRs) will be detected early in a clinical testing programme. Estimates of incidence of rarely occurring ADRs can only be made during post-marketing surveillance. Deaths from serious ADRs are less common than deaths from toxicity in overdosage with the older tricyclic antidepressants. Nomifensine, for example, was withdrawn when it was shown to be associated with 7 deaths per million prescriptions and no deaths from overdosage whereas amitriptyline continues to be used despite being shown to be associated with 48 deaths from overdosage per million prescriptions. In the risk benefit calculation the advantage of mianserin in terms of increased safety in overdose needs to be weighed against the risks of dysirasias. The newer antidepressants appear to be much safer that the older tricyclic antidepressants. Coroner's reports in England and Wales provide a basis for calculations of the relative toxicity of different antidepressants associated with deaths in overdosage and can be used as a form of independent marketing surveillance. The older tricyclic antidepressants with an average of 30 deaths per million prescriptions appear to be much more dangerous in overdose than the newer antidepressants. Amitriptyline and dothiepin appear to be far the most dangerous with 46-48 deaths per million prescriptions. Claims for relative safety in overdose with the newer antidepressants mianserin (6 per million), lofepra-mine (0), and trazadone (11 per million) are supported by these calculations. Mianserin has been shown to selectively reduce suicidal thoughts compared with maprotiline. This was originally thought to be a serotonergic effect of mianserin perhaps mediated with its 5-HT_1C,1D, 5HT₂ or 5HT₃ receptor antagonism. Recent data suggests however that maprotiline is associated with an increase of suicidal attempts compared with placebo in long term treatment which raises the question that some other antidepressants may actually induce suicide attempts.

Key Words:

• Antidepressants
• Benefits
• Risks
• Safety