The oldest anti-anxiety agent is undoubtedly alcohol and it is certain that this drug is still routinely self-administered for this purpose. Towards the end of the eighteenth century, bromide salts were used to relieve conditions akin to anxiety despite the risk of a characteristic toxic delirium, known as 'bromism'. Alternative treatments, such as paraldehyde and chloral hydrate, were also widely used but these too had adverse effects; the former can cause psychosis but the latter is still used as a sedative and anaesthetic agent.
By the turn of the century, barbiturates (e.g. pentobarbitone, Fig. 19.3) were gradually replacing these treatments. Early reports (one as early as 1903) described a 'toxic' behavioural reaction to barbiturates that was attributed to a form of poisoning. It was not until the 1930s that it was recognised that this adverse behavioural effect of barbiturates in fact represented a drug-withdrawal syndrome (Seevers and Tatum 1931). This, together with the overt sedation caused by barbiturates, their narrow therapeutic index and their lethal toxicity in overdose, motivated the search for nonsedative anti-anxiety agents. One compound to carry such claims was meprobamate ('Miltown'; Fig. 19.3), synthesised in the 1950s. However, the initial enthusiasm over the use of this compound as a treatment for anxiety rapidly abated because it too proved to be a potent sedative and, of even more concern, it induced dependence and was widely abused.
This background set the scene for the arrival of the benzodiazepines. The first of these was chlordiazepoxide ('Librium') launched in 1960, followed by diazepam ('Valium'; Fig. 19.3). Like their predecessors, but with greater justification, these drugs were claimed to relieve anxiety at non-sedative doses (see Sternbach, Randall and Gustafson 1964). However, the benzodiazepines are members of the sedative/hypnotic group of anti-anxiety drugs, which also include alcohol, meprobamate and the barbiturates. This means that the liability of all these compounds to induce sedation, or even hypnosis (sleep), is largely a question of dose (Fig. 19.4) although it is offset by the rapid development of tolerance to their sedative effects. Like their predecessors, the
actions of benzodiazepines are not restricted to relief of anxiety: they also induce ataxia, muscle relaxation (used in relief of muscle spasm), anterograde amnesia (used to relieve dental phobia) and increase seizure threshold (used to treat some forms of epilepsy).
Was this article helpful?