Abstract
This randomized double-blind study in 342 mildly to moderately depressive outpatients investigated the antidepressant effectiveness and speed of action of lorazepam, alprazolam and amitriptyline versus placebo. Six weeks of drug treatment were followed by a drug taper period, a control period with placebo and a control period without placebo, of 2 weeks duration each. Clinical improvement was assessed by rating scales (Clinical Global Impressions, Hamilton Rating Scales for Depression and Anxiety) and patient's self-ratings (Patient's Global Impressions, Self-rating Depression Scale and Visual Analogue Scale). At the end of week 6 all active drugs showed similar efficacy which was significantly superior to placebo. Compared to placebo, onset of efficacy was earlier on benzodiazepines than on amitriptyline. While tapering by decreasing the dosage, replacing drug with placebo and finally discontinuing placebo, clear withdrawal phenomena were not seen, but 20% of patients, equally distributed to all treatment groups, did not want to stop taking tablets after replacing drug with placebo. Drop-out rate during the treatment period was very low (9%). Significantly interfering adverse effects were seen in 27 patients, without predominance in one of the active drug groups.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amsterdam JD, Kaplan M, Potter L, Bloom L, Rickels K (1986) Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder. Psychopharmacology 88:484–488
Ansseau M, Devoitille JM, Papart P, Vanbrabant E, Mantanus E, Timisit-Berthier E (1991) Comparison of adinazolam, amitriptyline, and diazepam in endogenous depressive inpatients exhibiting dst nonsupression or abnormal contingent negative variation. J Clin Psychopharmacol 11:160–165
Bech P, Allerup P, Gram LF, Reisby N, Rosenberg R, Jacobsen O, Nagy A (1981) The Hamilton depression scale. Evaluation of objectivity using logistic models. Acta Psychiatr Scand 63:290–299
Bellantuono C, Reggi V, Tognoni G, Garattini S (1980) Benzodiazepines: clinical pharmacology and therapeutic use. Drugs 19:195–219
Feighner JP, Aden GC, Fabre LF, Rickels K, Smith WT (1983) Comparison of alprazolam, imipramine, and placebo in the treatment of depression. JAMA 249:3057–3064
Feighner JP, Boyer WF, Hendrickson GG, Pambakian RA, Doroski VS (1990) A controlled trial of adinazolam versus desipramine in geriatric depression. Intern Clin Psychopharmacol 5:227–232
Guy W (1976) ECDEU: Assessment manual for psychopharmacology. Rev Ed Rockville Maryland, pp 179–192
Haberman SJ (1973) The analysis of residuals in cross-classified tables. Biometrics 29:205–220
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62
Hamilton M (1976) 048 HAMA. Hamilton anxiety scale. In: Guy W. (ed) ECDEU Assessment manual for psychopharmacology. Rev Ed. Rockville, Maryland, pp 193–198
Johnson DAW (1983) Benzodiazepines in depression. In; Trimble W (ed) Benzodiazepines divided. Wiley, New York London, pp 247–257
Jonas JM, Cohon MS (1993) a comparison of the safety and efficacy of alprazolam versus other agents in the treatment of anxiety panic, and depression: a review of the literature. J Clin Psychiatry 54:25–45
Laakmann G (1981) Studienmodell zur Prüfung von Psychopharmaka in der ärztlichen Praxis. Zeitschrift für Allgemeinmedizin 57[2]:103–111
Laakmann G, Blaschke D, Hippius H, Messerer D (1986) Alprazolam versus amitriptyline in the treatment of depressed out-patients: a randomized double-blind trial. In: Lader HL, Davies HC (ed) Drug treatment of neurotic disorders. Churchill Livingstone, Edinburgh London Melbourne and New York, pp 129–136
Laakmann G, Baghai T, Bossertz-Zaudig S, Haag C, Kuhn K (1994) Benzodiazepine derivates in the treatment of depressive disorders. In: Abstracts of the XIXth Collegium Internationale Neuro-Psychopharmacologicum, Washington, D.C., June 27 – July 1, 1994, Neuropsychopharmacology 10[3S/part 2]:46S
Lader M (1984) Benzodiazepine dependence. Prog Neuropsychopharmacol Biol Psychiatry 8:85–95
National Institut of Mental Health (1976) 028 CGI. Clinical global impressions. In: Guy W (ed) ECDEU Assessment manual for psychopharmacology. Rev Ed. Rockville, Maryland, pp 217–222
Nolen WA, Haffmans PM, Bouvy PF, Duivenvoorden HJ (1993) Hypnotics as concurrent medication in depression. A placebo-controlled, double-blind comparison of flunitrazepam and lormetazepam in patients with major depression, treated with a (tri)cyclic antidepressant. J Affect Disord 28:179–188
Overall JE, Biggs J, Jacobs M, Holden K (1987) Comparison of alprazolam and imipramine for treatment of outpatient depression. J Clin Psychiatry 48:15–19
Paykel ES, Freeling P, Hollyman JA (1988) Are tricyclic antidepressants useful for mild depression? A placebo controlled trial. Pharmacopsychiatry 21:15–18
Rickels K, Feighner JP, Smith WT (1985) Alprazolam, amitriptyline, doxepin, and placebo in the treatment of depression. Arch Gen Psychiatry 42:134–141
Rickels K, Chung HR, Csanalosi I, Hurowitz AM, London J, Wiseman K, Kaplan M, Amsterdam JD (1987) Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Arch Gen Psychiatry 44:862–866
Rickels K, Schweizer E, Case WG, Greenblatt DJ (1990) Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation [published erratum appears in Arch Gen Psychiatry 1991, 48[1]:51. Arch Gen Psychiatry 47:899–907
Rickels K, London J, Fox I, Hassmann H, Csanalosi I, Weise Ch (1991) Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study. Pharmacopsychiatry 24:127–131
Schatzberg AF, Cole JO (1978) Benzodiazepines in depressive disorder. Arch Gen Psychiatry 35:1359–1365
Schatzberg AF, Cole JO (1981) Benzodiazepines in the treatment of depressive, borderline personality, and schizophrenic disorders. Br J Clin Pharmacol 11:17–22
Shammas E (1977) Controlled comparison of bromazepam, amitriptyline and placebo in anxiety-depressive neurosis. Dis Nerv Syst. 38:201–207
Singh AN, Nair V, Suranyi-Cadotte B, Schwarz G, Lizondo E (1988) A double-blind comparison of alprazolam and amitriptyline hydrochloride in the treatment of nonpsychotic depression. Can J Psychiatry 33:218–222
Weissman MM, Prusoff BA, Kleber HD, Sholomskas AJ, Rounsaville BJ (1985) Alprazolam (Xanax) in the treatment of major depression. In: Burrows GD (ed) Clinical and pharmacological studies in psychiatric disorders. John Libbey, London, pp 52–58
Weissman MM, Prusoff B, Sholomskas AJ, Greenwald S (1992) A double-blind clinical trial of alprazolam, imipramine, or placebo in the depressed elderly. Clin Psychopharmacolpgy 12:175–182
WHO (1978) World Health Organization mental disorders: glossary and guide to their classification in accordance with the ninth revision of the international classification of diseases. WHO, Geneva
Zung WWK (1976) 073 SDS. Self-rating depression scale. In: Guy W (ed) ECDEU Assessment manual for psychopharmacology. Rev Ed. Rockville, Maryland, pp 333–336
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Laakman, G., Faltermaier-Temizel, M., Bossert-Zaudig, S. et al. Treatment of depressive outpatients with lorazepam, alprazolam, amytriptyline and placebo. Psychopharmacology 120, 109–115 (1995). https://doi.org/10.1007/BF02246151
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02246151