Toxicology of Antidepressant Drugs

As many pharmacodynamic effects carry over from animals to man, many toxic effects may also be predicted from observations made in animals. However, some important toxic effects are not predictable from animal studies (WHO, 1966) and this limitation may apply particularly to drugs acting on the central nervous system, such as the antidepressants. Nevertheless, the recognition of species differences and similarities in responses is considered as an important means of predicting toxic effects in man. In the following, some degree of correlation is attempted by the comparison, whenever feasible, between toxicity in laboratory animals and adverse effects described in man, particularly in cases of acute intoxication. However, due to the differing amount of data that was available on various drugs and the widely varying experimental conditions employed, such a comparison may not always prove to be reliable. The following review has been restricted to antidepressants in clinical use and, as far as evidence was available from the literature, concentrated on two main categories of antidepressants, the monoamine oxidase (MAO) inhibitors and the tricyclics. The lithium salts are considered in a separate chapter of this volume. Read more […]

Types of Drug Dependence

The WHO expert committee has recognized that different groups of drugs produce different types of dependence and that the type should be specified. The currently accepted types, the main classes of drugs involved and the clinical characteristics of the dependence are shown in Table Dependence types currently recognized and their clinical features. Apart from noting the great variety of types that are now recognized, the majority of classes can be ignored for the purpose of the present paper and attention can be concentrated on the groups of ethanol and barbiturate/sedative. There are still divergent opinions on whether they should be grouped together, for both show psychological and physical dependence with virtually identical withdrawal reactions, or whether they should be separated. In favour of their being put into a single group is the extensive cross tolerance that can occur among drugs with similar actions, regardless of chemical structure, and the partial effectiveness of one group in ameliorating the withdrawal effects of the other. Thus, for example, severe ethanol withdrawal reactions can be prevented by barbiturates, phenothiazines, benzodiazepines, chloral hydrate and paraldehyde. Conversely ethanol Read more […]