Combination of Citalopram and Nortriptyline in Treatment of Moderate to Severe Major Depression: A Double-blind, Placebo- controlled Trial
Abstract
Objective: Depression is a major health problem, which is not only underrecognized and undertreated, but is also associated with significant morbidity and mortality. It has been suggested that combination therapy rapidly reduces depressive symptoms in patients with moderate to severe depression and is more effective than monotherapy; but this suggestion remains controversial. Serotonergic and noradrenergic enhancement may be synergistic and more effective than serotonergic enhancement alone in the management of depression. The objective of this double blind, placebo-controlled study was to investigate the efficacy and tolerability of the combination of citalopram and nortriptyline for the treatment of moderate to severe major depression.
Method: 45 patients, who met the DSM-IV criteria for major depressive disorder based on the clinical interview, were included in the study. Patients had a baseline Hamilton Depression Rating Scale score of at least 20. In this trial, patients were randomly assigned to receive nortriptyline 50 mg/day plus citalopram 40 mg/day (group1) or placebo plus citalopram 40 mg/day (group2), for an 8 week, double-blind, placebo-controlled trial.
Results: Both protocols significantly decreased the score of Hamilton Depression Rating Scale over the trial period, but the combination of nortriptyline and citalopram showed a significant superiority over citalopram alone in the treatment of moderate to severe major depressive disorder (t = 3.34, d.f. = 36, P = 0.001). The difference between the two groups in the frequency of side effects was not significant.
Conclusion: The results of this study suggest that combination of nortriptyline and citalopram is more effective than citalopram alone in the treatment of depression. This advantage is probably the result of reuptake inhibition of both serotonin and norepinephrine
Sadock BJ, Sadock VA. Comprehensive Textbook of Psychiatry. Philadelphia: Lippincott Williams& Wilkins; 2000.
Sadock BJ, Sadock VA. Synopsis of Psychiatry. Philadelphia: Lippincott Williams& Wilkins; 2003.
World Health Organization. The introduction of a mental health component into primary health care. World Health Organization, Geneva, 1990.
Correa H, Duval F, Claude MM, Bailey P, Tremeau F, Diep TS, et al. Noradrenergic dysfunction and antidepressant treatment response. Eur Neuropsychopharmaco 2001; 11: 163 – 168.
Andrews JM, Ninan PT, Nemeroff CB. Venlafaxine: a novel antidepressant that has a dual mechanism of action. Depression 1996; 4: 48 – 56.
Eriksson E. Antidepressant drugs: does it matter if they inhibit the reuptake of noradrenaline or serotonin? Acta Psychiatr Scand 2000; Suppl 402: 12 –17.
Scates AC, Doraiswamy PM. Reboxetine: a selective norepinephrine reuptake inhibitor for the treatment of depression. Ann Pharmacother 2000,;34:1302-12.
Schatzberg AF. Clinical efficacy of reboxetine in major depression. J Clin Psychiatry 2000; Suppl 61:31-38.
Shelton RC. The use of antidepressants in novel combination therapies. J Clin Psychiatry 2003; Suppl 64: 14-18.
Marangell LB. Augmentation of standard depression therapy. Clin Ther 2000; Suppl 22: A25-38.
Dording CM. Antidepressant augmentation and combination. Psychiatr Clin North Am 2000; 23: 743-755.
Shelton CI. Long-term management of major depressive disorder: are differences among antidepressant treatments meaningful? J Clin Psychiatry 2004; Suppl 65: 29-33.
Thase ME, Entsuah AR, Rudolph RL. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001; 178: 234-241.
Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry 2001; 62: 869-877.
Stahl SM, Entsuah R, Rudolph RL. Comparative efficacy between venlafaxine and SSRIs: a pooled analysis of patients with depression. Biol Psychiatry 2002; 52: 1166-1174.
Rudolph RL. Achieving remission from depression with venlafaxine and venlafaxine extended release: a literature review of comparative studies with selective serotonin reuptake inhibitors. Acta Psychiatr Scand 2002; Suppl 415: 24-30.
Rodolph RL, Feiger AD. A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. J Affect Disord 1999; 56: 171-181.
Bielski RJ, Ventura D, and Chang CC. A double – blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clinical Psychiatry 2004; 65: 1190 – 1196.
Zajecka JM, Albano D. SNRIs in the Management of Acute Major Depressive Disorder. J Clin Psychiatry 2004; Suppl 65: 11-18.
Nelson JC. Augmentation strategies with seotonergic-noradrenergic combinations. J Clin Psychiatry 1998; Suppl 59: 65-68.
Sonawalla SB, Fava M. Severe depression: is there a best approach?CNS Drugs 2001; 15:765-76.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Forth edition (DSM-IV). Washington DC: American Psychiatric Association; 1994.
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 62-66.
Weilburg JB, Rosenbaum JF, Biederman J, Sachs GS, and Pollack MH, Kelly K. Fluoxetine added to non- MAOI antidepressant converts nonresponders to responders: A preliminary report. J Clin Psychiatry 1989; 50: 447-449.
Zajecka JM, Jeffries H, Fawcett J. The efficacy of fluoxetine combined with a heterocycilc antidepressant in treatment – resistant depression: A retrospective analysis. J Clin Psychiatry 1995; 56: 338-343.
Nelson JC, Mazure CM, Jatlow PI, Bowers MB, Price LH. Combining norepinephrine and serotonin reuptake inhibition for treatment of depression: a double-blind, randomized study. Biol Psychiatry 2004; 55: 296-300.
Seth R, Jennings AL, Bindman J, Phillips J, Bergmann K. Combination treatment with noradrenaline and serotonin reuptake inhibitors in resistant depression. Br J Psychiatry 1992; 161: 562-565.
Nelson JC, Mazure CM, Bowers MB, Jatlow PI. A preliminary open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Arch Gen Psychiatry 1991; 48: 303-307.
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Issue | Vol 1 No 1 (2006) | |
Section | Articles | |
Keywords | ||
Antidepressant Citalopram Combination drug therapy Depression Nortriptyline |
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