?First-dose? response to mianserin: effects of age

Abstract

The effects of single 10 mg oral doses of the antidepressant mianserin on psychomotor performance, subjective sedation and supine and standing blood pressure were compared in ten young and nine elderly healthy volunteers. Immediate and residual sedation following this subtherapeutic dose was readily detected in both groups. In contrast to previous studies with benzodiazepines, the sedation effect was not accentuated in the older subjects. Subjective awareness of sedation was significant in the young but not, however, in the elderly. "First-dose" postural hypotension, presumably due to post-synaptic alpha-blockade also occurred in young subjects only. Caution may be needed on initial dosage of mianserin in young individuals who drive or undertake skilled tasks and in the elderly who may be unaware of psychomotor impairment. The reported alpha 2 receptor selectivity of mianserin might explain the lack of postural effects in the elderly, and might constitute a potentially useful characteristic in the development of new compounds.

Continuous attention: rationale and discriminant validation of a test designed for use in psychopharmacology

“…Sedative drugs such as pentobarbital, chlorpromazine, diazepam, mianserin, and nitrous oxide produce impairments in attention-related tasks, whereas stimulants such as caffeine and amphetamine lead to improvements (Clubley, Bye, Henson, Peck, & Riddington, 1979;Fagan, Paul, Drummond, Scott, & Tiplady, 1989;Fagan, C. G. Swift, & Tiplady, 1988;Hart, Hill, Bye, Wilkinson, & Peck, 1976;Mackworth, 1965;Mirsky & Kornetsky, 1964;C. G. Swift, M. R. Swift, & Tiplady, 1988).…”

Assessment of changes in psychomotor performance of elderly subjects

“…The sensitivity and validity of the tests in the APT battery (e.g. CAT, CRT and CFFT) has been established during acute drug studies in elderly people [18][19][20][21][22][23]. However, the repeatability of these tests in elderly people, which may be important in assessing the psychomotor effects of long-term drug therapy, has not been previously assessed.…”

A commentary on Swift, Swift and Tiplady (1988) ?First dose? response to mianserin: effects of age

“…These results highlight reports that some patmnts experience fainting when treatment with tricyclic antidepressants is initiated. Swift, Swift and Tiplady (1988) have also investigated a single dose of mianserin (10 mg) in ten young volunteers (aged 19-37 years) and nine elderly volunteers (aged 67-76 years). The authors concluded that the sedative properties of mianserin were observed to the same extent in both the young and elderly groups.…”

“…No clinically significant abnormalities were seen on the volunteers" screening ECGs or those taken at peak hypotensive effect. Swift et al (1988) postulated that as they had not observed a first dose hypotensive effect of mianserin in the elderly, this may be due to the loss of responsiveness of the post-synaptic cc-2 receptor which occurs with ageing (Hyland and Docherty 1985). Indeed, this may be responsiOffprint requests to: A.K.…”

“…Indeed, this may be responsiOffprint requests to: A.K. Baksi ble for the slight increase in orthostatic blood pressure observed in elderly depressed patients receiving a full therapeutic dose of mianserin (60 mg/day) (Swift et al 1988). Our experience in non-depressed elderly volunteers indicates that first dose postural hypotension can occur on administration of mianserin 10 mg and emphasises the importance of carefully controlled clinical pharmacological studies in both normal and depressed populations.…”