A comparison of five commonly prescribed antidepressants with particular reference to their behavioural toxicity

Abstract

Five antidepressant drugs (amitriptyline, dothiepin, lofepramine, fluoxetine and paroxetine) were examined for their effects on psychological function and skilled performance using a meta-analytical technique for the combination of separate studies. Furthermore, the drugs were placed and contrasted upon dimensions of efficacy. side-effects, safety in overdose and price in an attempt to formalize and provide a practical example of the considerations which should underlie the selection and use of such compounds. In both these analyses the profile of lofepramine, fluoxetine and paroxetine were found to be favourable compared to those of amitriptyline and dothiepin, suggesting that the prescription of older tricyclic compounds should be the exception rather than the rule in the pharmacotherapy of depression.KEY woms-Antidepressants, behavioural toxicity, meta-analysis.

Effects of tianeptine and mianserin on car driving skills

“…Tianeptine (7-[(chloro-6,11-dihydro-5,5-dioxo-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid, sodium salt), is a novel compound, which in contrast to other antidepressants, facilitates the reuptake of serotonin (5-HT). The welldocumented adverse effects of the tricyclic antidepressants (TCAs) both in patients (Fairweather et al 1993;Montgomery and Kasper 1995) and asymptomatic volunteers (Sherwood and Hindmarch 1993;Dal Pozzo et al 1997) are not generally found with tianeptine (Delalleau et al 1988) and in particular, it has no anticholinergic (Wilde and Benfield 1995), or antihistaminic effects (Kato and Weitsch 1988), which may account for the observed lack of sedation with the drug (Mocaër et al 1988). Furthermore, unlike the TCAs, it has no affinity for the α-adrenergic receptors, the blockade of which is associated with postural hypertension and clumsiness (Delagrange et al 1990).…”

Do We Need New Antidepressants?

“…The muscarinic and histaminergic receptors are believed to be responsible for the sedation and behavioural impairment described above ; in addition, receptor binding results in a variety of somatic adverse events, including orthostatic hypotension, cardiac arrhythmias and tachycardia, convulsions, dry mouth, tremor and blurred vision (Sherwood and Hindmarch, 1993). The cardiovascular eects of TCAs, mediated by cholinergic receptors, make these agents potentially dangerous when taken in overdose.…”

“…Furthermore, the relative risk of road accidents has been reported Figure 1. Maximum drug eects (Cohen`d ' values) after single doses of ®ve antidepressants (Sherwood and Hindmarch, 1993); placebo treatment gives a d value of zero. CFF: critical¯icker fusion; CRT: critical reaction time; CTT: compensatory tracking task.…”

“…The behavioural toxicity of antidepressant drugs has been extensively investigated in double-blind, placebo-controlled, repeated measure studies using a battery of standard tests (Kerr et al, 1991;Sherwood and Hindmarch, 1993;. The principal tests used are the critical icker fusion (CFF) test, the choice reaction time (CRT) test, and the compensatory tracking task (CTT) test.…”

“…The behavioural toxicities of the TCAs amitriptyline, dothiepin and lofepramine, and the SSRIs uoxetine and paroxetine, were compared in a meta-analysis by Sherwood and Hindmarch (1993). In this analysis, drug eects were expressed as Cohen`d ' values (Cohen, 1976) derived from t-values calculated from a repeated-measures analysis of variance.…”