Addition of benzodiazepines to selective serotonin reuptake inhibitors to optimize treatment of depression: a hospital based study

S. A. Dar, B. A. Bhat, M. M. Jan


Background: Selective serotonin reuptake inhibitors ameliorate depression and anxiety slowly and in fact increase anxiety or insomnia initially. Addition of clonazepam to escitalopram improves response: thereby improving symptoms associated with depression, reducing side-effects and alleviating core depressive symptoms. The aim of study was to assess the benefits of adding benzodiazepines in management of depression.

Methods: It was an open label prospective study of 8 weeks of escitalopram group versus escitalopram with benzodiazepine group in moderate to severe depression. 51 subjects who gave written informed consent and were fulfilling the inclusion and exclusion criteria were included in the study and grouped into escitalopram alone or escitalopram with benzodiazepines.

Results: In the present study nearly 60% of the patients were prescribed clonazepam. Though combined group with benzodiazepines had faster onset of action in controlling depressive symptoms than escitalopram group alone at 4 weeks of treatment, there was no significant difference in the pattern of reduction of MADRS score in both the groups at 8 weeks of follow up.

Conclusions: Augmenting benzodiazepines to antidepressants are more effective in management of depression associated anxiety and sleep disturbances initially till SSRIs start action.


Clonazepam, Depression, Escitalopram, MADRS score

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National Collaborating Centre for Mental Health. The nice guideline on the treatment and management of depression in adults. the British psychological society and the royal college of psychiatrists. 2010. Available from: URL:

World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Health Organization; 1992. American Psychiatric Association, American Psychiatric Association. DSM-IV-TR: Diagnostic and statistical manual of mental disorders, text revision. Washington, DC: American Psychiatric Association. 2000;75:78-85.

World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Health Organization;1992.

Thapar A, Collishaw S, Pine DS, Thapar AK. Depression in adolescence. Lancet. 2012 Mar 17;379(9820):1056-67.

Sareen J, Cox BJ, Afifi TO, de Graaf R, Asmundson GJ, ten Have M, et al. Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Archives of general psychiatry. 2005 Nov 1;62(11):1249-57.

Bolton JM, Cox BJ, Afifi TO, Enns MW, Bienvenu OJ, Sareen J. Anxiety disorders and risk for suicide attempts: findings from the Baltimore Epidemiologic Catchment area follow‐up study. Depression and Anxiety. 2008 Jun 1;25(6):477-81.

National Institute of Mental Health. Depression. Available at: topics/depression/index.shtml. Retrieved 15 October 2012.

O'Donnel JM. Shelton RC. Hypnotics and sedatives. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman andGilman's: The pharmacological basis of therapeutics. 12th edition. New York. McGraw-Hill;2011:607-629.

American Psychiatric Association. Practice Guidelines for the Treatment of Psychiatric Disorders: Compendium 2004. Arlington, Va: American Psychiatric Association. 2004

Shader RI, Greenblatt DJ. Approaches to the treatment of anxiety states. In: Shader RI, ed. Manual of Psychiatric Therapeutics Third ed. Philadelphia, Pa: Lippincott Williams and Wilkins. 2003:184-209.

Sheeran T, Zimmerman M. Social phobia: still a neglected anxiety disorder? J Nerv Ment Dis. 2002;190:786-8.

Nutt DJ. Overview of diagnosis and drug treatments of anxiety disorders. CNS Spectr. 2005;10:49-56.

Susman J, Klee B. The role of high-potency benzodiazepines in the treatment of panic disorder. Prim Care Companion J Clin Psychiatry. 2005;7:5-11.

Berk M. Selective serotonin reuptake inhibitors in mixed anxiety-depression. Int Clin Psycho Pharmacol. 2000;15(2):S41-S45.

Williams JB, Kobak KA. Development and reliability of a structured interview guide for the Montgomery-Åsberg Depression Rating Scale (SIGMA). Brit J Psychiatry. 2008 Jan;192(1):52-8.

Stein DJ. Comorbidity in generalized anxiety disorder: impact and implications. J Clin Psychiatry. 2001;62(Suppl 11):29-34.

Attending to anxiety disorders in primary care. Stein MB J Clin Psychiatry. 2003;64 Suppl 15:35-9.

Gorwood P. Generalized anxiety disorder and major depressive disorder comorbidity: an example of genetic pleiotropy?. European Psychiatry. 2004 Jan 1;19(1):27-33.

Weisberg RB, Dyck I, Culpepper L, Keller MB. Psychiatric treatment in primary care patients with anxiety disorders: a comparison of care received from primary care providers and psychiatrists. American J Psychiatry. 2007 Feb;164(2):276-82.

Smith WT, Londborg PD, Glaudin V, Painter JR. Short-term augmentation of fluoxetine with clonazepam in the treatment of depression: a double-blind study. Am J Psy. 1998;155(10):1339-45.

Goddard AW, Brouette T, Almai A, Jetty P, Woods SW, Charney D. Early coadministration of clonazepam with sertraline for panic disorder. Archives General Psychiatry. 2001;58(7):681-6.

Pollack MH, Simon NM, Worthington JJ, Doyle AL, Peters P, Toshkov F, et al. Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder. J Psychopharmacol. 2003 Sep;17(3):276-82.

Seedat S, Stein MB. Double-blind, placebo-controlled assessment of combined clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder. J Clin Psychiatry. 2004;65:244-8.

Birkenhager TK, Moleman P, Nolen WA. Benzodiazepines for depression? a review of the literature. Int Clin Psycho Pharmacol. 1995;10:181-95.

Mirowsky J. Age and the gender gap in depression. J Health and Social Behavior. 1996 Dec 1:362-80.

C Pollack MH, Simon NM, Worthington JJ, Doyle AL, Peters P, Toshkov F, et al. Combined paroxetine and clonazepam treatment strategies compared to paroxetine monotherapy for panic disorder. J Psychopharmacol. 2003;17(3):276-82.

Londborg PD, Smith WT, Glaudin V, Painter JR. Short-term cotherapy with clonazepam and fluoxetine: anxiety, sleep disturbance and core symptoms of depression. J Affect Disord. 2000;61:73-9.

Furukawa TA, Streiner DL, Young LT. Antidepressant and benzodiazepine for major depression. Cochrane Database Syst Rev. 2002;1:CD00026.

Murphy JM. Diagnosic comorbidity and symptom cooccurence: the Stirling County Study. In: Maser JD, Cloninger CR editor(s). Comorbidity of Mood and Anxiety Disorders. Washington DC: American Psychiatric Press;1990:153-76.

Bouhassira M, Allicar MP, Blachier C, Nouveau A, Rouillon F. Which patients receive antidepressants? A ’real world’ telephone study. J Affective Disorders. 1998;49(1):19-26.

Rickels K, Schweizer E, Case WG, Greenblatt DJ. Long term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation. Archives of General Psychiatry. 1990;47(10):899-907.

Spiegel DA. Psychological strategies for discontinuing benzodiazepine treatment. J Clin Psycho pharrnacol. 1999;19(6suppl2):17S-22S.

Schweizer E, Rickels K, Case WG, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper. Arch Gen Psychiatry. 1990;47:908-16.