Toxicology of Antidepressant Drugs: Tricyclic Antidepressants

Animal Toxicity General Toxicology The LD 50 values for a number of tricyclic antidepressants, when administered to mice and rats in single oral or parenteral doses, are listed in Table Acute LD50 valuesa of some tricyclic antidepressants. Acute poisoning by tricyclic antidepressants usually leads to symptoms of central excitation followed at the higher and lethal dose levels by central inhibition. The symptomatology includes muscular weakness, twitching, stupor, respiratory disorders, ataxia, and tonic-clonic convulsions. Table Acute LD50 valuesa of some tricyclic antidepressants Imipramine Doxepine Nortriptyline Viloxazine Maprotiline Mouse i.v. p.o. 35 666 15- 20 148-178 26 327 60 1000 31 660- 900 Rat i.v. p.o. 22 625 13- 19 346-460 22 502 60-77 2000 38- 52 760-1050 a The values given are for LD50, single administration, in mg/kg body weight It is evident from Table Acute LD50 valuesa of some tricyclic antidepressants or from the reports of Pluviage () and of Ueki et al. () that no major differences in the acute toxicity of tricyclic antidepressants are apparent. Information on animal studies relating to the tolerance of tricyclic antidepressants Read more […]

Tricyclic Antidepressants: Teratology

Antidepressants comprise only a small portion in the vast assortment of drugs that may be taken by pregnant women. In a sample of 3,072 subjects, the number of gravid women receiving antidepressant drugs was estimated to be in the order of 0.1 % (). Similar to other drugs that are used much more frequently during pregnancy (), particularly during the first trimester (the most sensitive period of embryonal development), some antidepressants have been suspected to carry a teratogenic risk. In a short note published 1972, McBride reported on one child with amelia and mentioned two others with a similar limb deformity he felt were caused by imipramine taken by the mothers in early pregnancy. Two further cases were subsequently reported (). Doubt was, however, cast upon the validity of the McBride’s notion of a causal relation between imipramine or other tricyclic antidepressants such as amitriptyline and congenital abnormalities. The Australian Drug Evaluation Committee (1973) and the results of further clinical and epidemiologic studies failed to associate the ingestion of these drugs in early pregnancy with malformations (). Likewise, neither on account of the review presented by one manufacturer () nor on the basis Read more […]

Benzodiazepines in Masked Depressions

Depressive illness is gradually becoming the pathology-symbol of our era of crisis, showing ever-growing epidemic proportions in its several forms and clinical manifestations: endogenous (MDP and involutional melancholia), reactive (depressive reactive psychosis), neurotic (neurotic depressions), symptomatic (in other psychiatric disturbances) and many organic diseases. In 1977, in Sao Paulo, Brazil, the prevalence of depressive illness was considered by all the physicians (more than 7000, mostly non-psychiatrists) interviewed by our group, to have increased by 83 %. In the past decades, besides an increase in the prevalence of depressive illness, a kind of ‘mutation’ has been noted in depressive symptomatology translated as a more frequent phenomenon of ‘depressive somatization’. This brings patients to seek repeated somatic examination, searching in vain for physical changes that lead to expensive and varied clinical and surgical treatments. Although thymopathic masking can appear in different forms (obsessions, aggressiveness, alcoholism, toxicomania, etc.), the term ‘masked depression’ usually refers to a depressive illness in which classic psychopathological symptoms of depression do exist, but are masked Read more […]

Benzodiazepines and Depression

The use of anxiety-reducing drugs in the treatment of anxiety syndromes accompanied by depression or of depressive illness with an anxiety component has been extensively debated in recent times. Many workers in this field have written about the efficacy of treatment of patients with symptoms of neurosis characterized by anxiety and depression. According to some of these authors, neither the anxiety-reducing drugs nor the hypnosedatives have been very successful in the treatment of depression-anxiety syndromes. On the other hand, it has been shown that these drugs can lead to the development of acquired tolerance and habit formation, a problem involving the barbiturates especially and, to a lesser degree, the minor tranquillizers. Emphasis has been placed on the fact that anxiety and depression tend to occur simultaneously in an anxiety-depression syndrome. Taking this frequent coincidence of anxiety and depression as our base, we will discuss the advantages and drawbacks of using tranquillizers when depression is seen in an anxious patient. Before proceeding with this, however, we would like to establish some basic concepts to provide a better understanding of this complex matter. Concept of depression According Read more […]