Efficacy and side effects of mianserin, a tetracyclic antidepressant.

Antidepressant drugs have been in extensive use for over 20 years. Initially 2 groups of compounds, the monoamine oxidase inhibitors (MAOI) and tricyclic compounds based on the imipramine configuration were widely used. In the early 1960's after a few years ofwide use, interest in the MAOI group fell following the recognition of a serious adverse effect. Blackwell (1963) described the occurrence of hypertensive crisis with occasional fatalities when these compounds were taken with certain foodstuffs. It is of interest, however, that in recent years there has been some resurgence of interest in these compounds and the suggestion that their dangers may have been exaggerated (Tyrer, 1979) or might be ameliorated by combination with tricyclics (Pare et al., 1982). Interest in the tricyclic group however has continued unabated and over the years at least 20 antidepressants based on the original imipramine configuration have been produced. There is now a widespread and extensive accumulated experience of these compounds and although they remain the most widely prescribed antidepressant, it is now clear that they have a number of serious disadvantages. The most important of these are cardiotoxicity, potential fatality in overdose, marked peripheral anticholinergic activity and reduction in seizure threshold (Blackwell, 1981a). As these disadvantages exist to some extent with all the tricyclics produced so far, there have, not surprisingly, been active attempts to produce different and safer antidepressant compounds. Over the last few years a number of different compounds have come into use as antidepressants and these constitute the 'second generation' antidepressant drugs. Included among these are; viloxazine and zimelidine, both bicyclic compounds; nomifensine, a tetrahydro-isoquinoline derivative; maprotiline, a bridged tricyclic compound and the tetracyclic compound mianserin. All differ somewhat in their actions on central neurotransmitter systems and differing claims are made that their antidepressant actions are relatively free from the adverse or unwanted effects of the tricyclics. These claims should be received with caution as there has been an insufficient experience in the use of many of them. Mianserin, however, is probably the most widely used of these compounds and considerable clinical experience of its use has been accumulated over the last few years.