Pharmacodynamics of milnacipran in young and elderly volunteers

Aims To investigate the pharmacodynamics of milnacipran in healthy young an d elderly volunteers. Methods Randomized double-blind crossover designs were employed and a stand ardized psychometric battery was administered pre and post dose for both st udies. In the first study 10 healthy young volunteers received milnacipran 12.5 mg, 25 mg, 50 mg, 100 mg as a single dose or matched placebo. The test battery was administered at baseline and at 1, 2, 4 and 6 h post dose. The second study compared the effects of milnacipran 75 mg (50 mg+25 mg) per d ay, amitriptyline 50 mg (25 mg+25 mg) per day and placebo for 3 days' dosin g in healthy volunteers aged over 65 years. The test battery was administer ed at baseline and at 2, 10 and 24 h post dose. The psychometric battery in cluded critical flicker fusion (CFF), choice reaction time (CRT), compensat ory tracking (CTT) and tests of short-term memory (STM), subjective sedatio n (LARS) and subjective sleep (LSEQ). Results Milnacipran produced no significant dose related effects in the you ng volunteers. For the elderly milnacipran significantly (P<0.05) raised CF F scores compared with placebo but had no significant effects on ally of th e other measures used. Amitriptyline, in contrast, significantly (P<0.05) l owered CFF threshold, lengthened CRT and increased error on the CTT. On the subjective variables, LARS and LSEQ, amitriptyline increased ratings both of sedation and of difficulty in waking from sleep. Conclusions The results showed that milnacipran at single doses of up to 10 0 mg in healthy young volunteers is free from disruptive effects on cogniti ve function and psychomotor performance. In addition, milnacipran 75 mg (50 +25 mg) appears to be free of negative effects on cognitive function in eld erly volunteers, where it seemingly improves performance on CFF. In contras t, the tricyclic antidepressant amitriptyline, used here as a positive inte rnal control, significantly impaired performance in the elderly on the majo rity of psychometric measures used in this study. This finding not only val idated the sensitivity of this current test battery but also indicates the potential behavioural toxicity of amitriptyline in clinical use in the elde rly.