Subject: A retrospective cross-sectional, observational survey study to analyse role of fixed dose combination of Desvenlafaxine and Clonazepam in depression.

Major depressive disorder is a common disorder, which often leads to poor quality of life and impaired role functioning. It is known to be a major contributor to the global burden of diseases and according to World Health Organization (WHO), depression is the fourth leading cause of disability worldwide.¹

Depression often presents with a combination of symptoms of depressed mood, loss of interest or pleasure, decreased energy and fatigue, reduced concentration and attention, reduced self-esteem and self-confidence, ideas of guilt and unworthiness, bleak and pessimistic views of the future, ideas or acts of self-harm or suicide, disturbed sleep and diminished appetite. Depending on the severity of depression some of these symptoms may be more marked and develop characteristic features that are widely regarded as having special clinical significance.¹

Treatment options for management of depression can be broadly be divided into antidepressants, electroconvulsive therapy (ECT) and psychosocial interventions.¹

The first-line treatment options for MDD, selective serotonin reuptake inhibitor (SSRIs) (e.g., citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), Serotonin and norepinephrine reuptake inhibitors (SNRIs) (e.g., venlafaxine, duloxetine, Desvenlafaxine, levomilnacipran) and atypical antidepressants (e.g., bupropion, mirtazapine, nefazodone, trazodone) are commonly prescribed for patients diagnosed with depression.^{2, 3, 4}

Desvenlafaxine is an SNRI with selective inhibitory activity of neurotransmitter uptake at the human serotonin and norepinephrine monoamine transporters. It has no significant interactions with muscarinic, cholinergic, H1-histaminergic, or a1-adrenergic receptors in vitro, and it lacks significant affinity for any of the numerous other targets tested, including brain/gut peptides, steroids, prostaglandins, growth factors/hormones, ion channels and second messengers.⁵

Clonazepam is a benzodiazepine, and therefore decreases anxiety, agitation, and sleep disturbance. Furthermore studies reported that Clonazepam had a direct antidepressant effect or synergistic effect with antidepressant medication

Clinical utility of Desvenlafaxine 50 mg/d for treating MDD: a review of two randomized placebo-controlled trials for the practicing physician concludes that the efficacy of Desvenlafaxine 50 mg/d for the treatment of MDD on measures of depression and functional outcomes. On the primary efficacy measure (HAM-D17 total score), significant improvements vs placebo were reported starting at week 4 (P =0.019) and at week 6 (P = 0.002) in the trials; significant differences were sustained until end point in both the trials. In the integrated efficacy analysis, sustained statistical separation from placebo on HAM-D17 total score was reported before week 4 and continued through end point (P < 0.001).^{6, 7, 8}

Studies shows Clonazepam reduced not only scores for symptoms of agitation as determined by agitation, anxiety psychic, and hypochondriasis scores in Hamilton Depression Rating Scale (HAM-D) but also inhibited symptoms according to depressive mood, loss of interest, and retardation scores in HAM-D. These findings are consistent with the conclusion that Clonazepam has a direct or synergistic antidepressant effect.⁹