Abstract
The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P=0.01) including five individual items, Hamilton depression scale (P=0.002) including ten individual items, CGI of severity (P=0.01) and therapeutical index (P=0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P=0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P=0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn (revised). Washington, DC
Ansseau M (1992) The Atlantic gap: clinical trials in Europe and the United States. Biol Psychiatry 31:109–111
Ansseau M, Diricq St, Bataille M, Breulet M, Cerfontaine JL, Collard J, Coûteaux F, Dufrasne M, Fraipont J, Gernay P, Troisfontaines B, Bobon D (1985) Une physionomie comparée originale de l'activité clinique des antidépresseurs. Acta Psychiatr Belg 85:644–661
Ansseau M, Bataille M, Bobon D, Cerfontaine JL, Charles G, Coûteaux F, Diricq St, Fraipont J, Gernay P, Troisfontaines B (1988) Evaluation de l'activité clinique de la fluoxétine (Prozac) selon “les étoiles de Liège”. Acta Psychiatr Belg 88:127–137
Ansseau M, von Frenckell R, Mertens C, De Wilde J, Botte L, Devoitille JM, Evrard JL, De Nayer A, Darimont P, Dejaiffe G, Mirel J, Meurice E, Parent M, Couzinier JP, Demarez JP, Serre C (1989a) Controlled comparison of two doses of milnacipran (F 2207) and amitriptyline in major depressive inpatients. Psychopharmacology 98:163–168
Ansseau M, von Frenckell R, Papart P, Mertens C, De Wilde J, Botte L, Devoitille JM, Evrard JL, De Nayer A, Koch-Bourdouxhe S, Darimont P, Lecoq A, Mirel J, Couzinier JP, Demarez JP, Serre C (1989b) Controlled comparison of milnacipran (F 2207) 200 mg and amitriptyline in endogenous depressive inpatients. Hum Psychopharmacol 4:221–227
Ansseau M, von Frenckell R, Gérard MA, Mertens C, De Wilde J, Botte L, Devoitille JM, Evrard JL, De Nayer A, Darimont P, Mirel J, Troisfontaines B, Toussaint C, Couzinier JP, Demarez JP, Serre C (1991) Interest of a loading dose of milnacipran in endogenous depressive inpatients: comparison with the standard regimen and with fluvoxamine. Eur Neuropsychopharmacol 1:113–121
Benfield P, Ward A (1986) Fluvoxamine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic eficacy in depressive illness. Drugs 32:313–334
Benfield P, Heel RC, Lewis SP (1986) Fluoxetine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 32:481–508
Clerc G, Pagot R, Bouchard JM, Oules J, Guibert M, Amicot M, Guillard A, Cottin M, Dachary JM. Bezoury JP, Parmentier G, Gresle P, von Frenckell R, Serre C (1990) Intérêt thérapeutique du milnacipran et de la clomipramine au cours d'un traitement de 3 mois: résultats d'un essai comparatif. Psychiatr Psychobiol 5:137–146
Covi L, Lipman R, McNair DM, Czerlinski T (1979) Symptomatic volunteers in multicenter drug trials. Prog Neuropsychopharmacol 3:521–533
Guy W (ed) (1976) ECDEU Assessment manual for psychopharmacology (revised). National Institute of Mental Health, Psychopharmacology Research Branch, Rockville, MD
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 12:56–62
Macher JP, Sichel JP, Serre C, von Frenckell R, Huck JC, Demarez JP (1989) Double-blind placebo-controlled study of milnacipran in hospitalized patients with major depressive disorders. Neuropsychobiology 22:77–82
Mathieu M (1990) New drug development: a regulatory overview. Parexel, Cambridge, MA
Ministère des Affaires Sociales et de l'Emploi, Ministère chargé de la Santé et de la Famille, Direction de la Pharmacie et du Médicament (1987) Bonnes pratiques cliniques. Avis aux promoteurs et aux investigateurs pour les essais cliniques des médicaments. Texte officiel en langue française. Paris, France
Montgomery A, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134:382–389
Moret C, Charveron M, Finberg JPM, Couzinier JP, Briley M (1985) Biochemical profile of midlacipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology 24:1211–1219
Puozzo C, Filaquier C, Briley M (1985) Plasma levels of F 2207, midalcipran, a novel antidepressant, after single oral administration in volunteers. Br J Clin Pharmacol 20:291P-292P
Raskin A, Schulterbrandt J, Reatig N, Rice CE (1967) Factors of psychopathology in interview, ward behavior and self-report ratings of hospitalized depressions. J Consult Psychol 31:270–278
Schwartz D (1970) L'essai thérapeutique chez l'homme. Flammarion, Paris
Solles A, Serre C, Sutet P, Briley M (1991) Milnacipran: a potent antidepressant with combined NA and 5-HT mechanism of action. In: Ansseau M, von Frenckell R, Franck G (eds) Biological markers of depression: state of the art. Excerpta Medica, Amsterdam, pp 197–202
Van Praag HM (1980a) Central monoamine metabolism in depressions. I. Serotonin and related compounds. Compr Psychiatry 21:30–43
Van Praag HM (1980b) Central monoamine metabolism in depressions. ll. Catecholamines and related compounds. Compr Psychiatry 21:44–54
Van Praag HM (1984) Studies in the mechanism of action of serotonin precursors in depression. Psychopharmacol Bull 20:599–602
von Frenckell R, Ansseau, M, Serre C, Sutet P (1990) Pooling two controlled comparisons of milnacipran (F 2207) and amitriptyline in endogenous inpatients. Int Clin Psychopharmacol 5:49–56
von Frenckell R, Cheuvart B, Gratton R, Copp J, Gammans R, Vanbrabant E (1992) Clinical trials of antidepressants in the US and in Europe. The Atlantic gap. Clin Neuropharmacol 15 [suppl 1]: 516B
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ansseau, M., Papart, P., Troisfontaines, B. et al. Controlled comparison of milnacipran and fluoxetine in major depression. Psychopharmacology 114, 131–137 (1994). https://doi.org/10.1007/BF02245454
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245454