The benefits and risks of antidepressant drugs

Abstract

Antidepressant drugs have unequivocally altered the short‐term outcome of depressive illness and reduced considerably the risk of morbidity. Their influence upon the chronic course of depression or upon the excess mortality associated with depressive illness is less easy to quantify. Nevertheless, the benefits of effectively treating depression far outweigh the considerable risks of leaving depressed patients inadequately, inappropriately or untreated. Most antidepressants currently available have broadly equal efficacy, although some drugs may be more appropriate in certain types of patient, when particular symptoms are prominent or when a particular side‐effect is undesirable. Antidepressants vary in their side‐effect profiles, and the newer non‐tricyclic drugs appear to offer a reduced risk of anticholinergic and cardiovascular effects. All of the newer drugs carry additional adverse effects, however, leading in the cases of zimeldine and nomifensin to withdrawal from the market and with mianserin to controls on prescription. Analysis of overdosage data indicates that the greatest risk of any antidepressant is fatality upon overdosage, the numbers of which far exceed fatalities from adverse effects. It is suggested that any assessment of the overall benefitsand risks of antidepressant drugs should include not only risks at therapeutic dosage but also the dangers of overdosage.

Suicide in the course of the treatment of depression

“…While mianserin might be associated with lowered white cell counts, its defenders argued that it was safer in overdose than other antidepressants and that therefore its use would be associated with a lower death rate overall (Pinder, 1988). This debate led to the construction of a fatal toxicity index based on the number of deaths following use of each antidepressant as a proportion of the number of scripts written (Cassidy and Henry, 1987;Pinder, 1988;Henry, 1992). When these calculations were made, desipramine, amitriptyline and dothiepin, which are more toxic in overdose than other antidepressants, appeared to be associated with more deaths.…”

Prospects for Improved Antidepressants

“…Effective drug treatments for depression have been available for more than 3 decades.1 However, the first generation of tricyclic antidepressants (TCAs) such as the monoamine reuptake inhibitors imipramine (1) and amitriptyline (2) were associated with anticholinergic and cardiovascular side effects, while the early monoamine oxidase inhibitors (MAOIs) like iproniazid (3) and phenelzine (4) were plagued by serious and sometimes life-threatening hypertensive crises precipitated by interaction with tyramine-containing foodstuffs.1 Second-H3C 1 i generation antidepressants have tended to be more selective in their pharmacology and atypical in structure and have generally lacked the characteristic side effects of first-generation agents (Table 1). They have increased the likelihood of a clinical response with a reduction in unwanted toxicity.1 Nevertheless, both the early examples of the genre, such as mianserin (5) and trazodone (6), and the later contenders, the selective serotonin reuptake inhibitors (SSRIs) and the reversible 0022-2623/95/1838-4615$09.00/0 inhibitors of MAO-A (RIMAs), have brought their own particular pattern of adverse reactions.…”

“…The major advantage of second-generation antidepressants is their relative safety in overdose. 3 Epidemiological surveys of poisonings associated with antidepressant overdose on both sides of the Atlantic Ocean have suggested that first-generation TCAs have a higher incidence of fatalities than second-generation non-TCAs when prescription volumes are compared, whatever the age of the patient, while MAOIs fall in between.3-6 The TCAs amitriptyline and dothiepin (7) ©…”

Social phobia following maprotiline: the first case report

“…Maprotiline is a tetra cyclic antidepressant drug with actions and uses similar to those of tricyclic antidepressants. It is a selective inhibitor of the neither reuptake of nor epinephrine [ 3 ].…”