Psychiatry

Major Depressive Disorder

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Aiming for Complete Functional Recovery: 3 Cases Examined

clinical study insights by Joseph F. Goldberg, MD

Overview

Clinical Study Title:
Full Functional Recovery in the Treatment of Depression: Clinical Cases Wth Vortioxetine Treatment

Clinical Study Abstract:
Although many patients initially show a good response to antidepressant therapy, they tend to suffer from residual symptoms that are cross cutting in their impact, affecting social, cognitive, physical, and psychological domains. Such symptoms may impede the patient’s global functioning and quality of life and increase the risk of recurrence. In recent years, researchers have sought to develop drugs able to mitigate the severity of depressive symptoms and also control persistent cognitive and functional disabilities. Vortioxetine, a novel antidepressant, has a multimodal mechanism of action that combines the classical inhibition of serotonin transporter (SERT) with the modulation of serotonin receptor activity. Its efficacy in the treatment of depression and cognitive symptoms has been established in numerous randomized clinical trials. In the present report, 3 cases of patients with depressive disorders are presented. In each case, vortioxetine treatment improved depressive symptoms, cognitive symptoms, and overall patient functioning. The author finds that these anecdotal experiences are supportive in the assertion that vortioxetine, in addition to controlling all symptoms of depression, including cognitive symptoms, may provide functional benefits in patients with depressive disorders.

Reference:
Russo F. Full functional recovery in depression treatment: clinical cases treated with vortioxetine. Riv Psichiatr. 2017;52(3):129-134. 

Overview
Despite progress in the field of pharmacologic treatment for MDD, the recurrence rate may still be as high as 80%, with about 20% of depressed patients tending to progress to a more chronic depressive illness. Although patients may have a satisfactory initial response to treatment, residual symptoms may have a significant impact on the patient’s level of function and quality of life, as well as on the risk of recurrence. In particular, deficits in the cognitive domain may be principal drivers of psychosocial function.

Vortioxetine is a novel multimodal drug that acts by inhibiting serotonin reuptake and, at the same time, modulating the activity of several serotoninergic receptors. In the clinical cases reported by Dr Russo, the use of vortioxetine led to an improvement in depressive and cognitive symptoms and a recovery of the patient’s overall level of functioning. Dr Russo underscores the importance of full functional recovery as the treatment goal in major depressive disorder (MDD) in the presentation of these 3 clinical cases, a summary of which follows:

  • The patient in case 1 was a 49-year-old woman, a stay-at-home mom with MDD and somatoform disorder, both manifesting initially during adolescence/young adulthood. Treatment was pursued; however, most classes of antidepressants achieved mixed results: selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) initially caused irritability and increased anxiety, while in the long run they gave rise to apathy, weight gain, and reduction of sexual function. Agents in the noradrenergic reuptake inhibitors (NARI) and norepinephrine-dopamine reuptake inhibitor (NDRI) classes induced agitation and insomnia. Her regimen at the time of the case series included bupropion, lamotrigine, and a benzodiazepine. In the spring of 2016, after a period of partial remission, there was a profound re-exacerbation of her depression associated with life events. At that time, bupropion treatment was discontinued. A slow titration of vortioxetine was initiated and continued until reaching the daily dose of 20 mg vortioxetine daily, still taking the mood stabilizer (lamotrigine) and benzodiazepine. At the 10-mg daily dose of vortioxetine, an initial improvement in depressive symptoms was appreciated, with reduced apathy, indecision, anhedonia, and less disruption in her sleep-wake rhythm. Improvements became more marked upon reaching the dosage of 20 mg daily; depressive symptoms including apathy, indecision, and anhedonia improved, with normalization of sleep rhythm and improvement in overall functioning. Therapy was well tolerated and did not cause any sexual side effects.
  • The patient in case 2 was a physical education teacher who had been diagnosed with mixed anxiety and depressive disorder, and the patient in case 3 was an electrical engineer who had been diagnosed with depression associated with anxiety symptoms. Both were men of about 60 years of age. In both cases, the patients had been treated with standard first- and second-line antidepressant medications over the years, with insufficient responses and/or side effects, and subsequently responded well to vortioxetine at the 10-mg daily dose, with minimal side effects, prolonged remission, and increased overall function.

Expert Commentary

Joseph F. Goldberg, MD

Clinical Professor of Psychiatry
Icahn School of Medicine
Mount Sinai
New York, NY

Impaired cognitive functioning may be associated directly with impaired day-to-day functioning. I am pleased that the field is talking more about not just reducing a primary outcome score on depression severity, but also looking at recovery and embracing more of the functional, symptomatic, and syndromal aspects of outcomes.

In the real world, patients may be told, in essence, “Well, your Hamilton Rating Scale for Depression (HAM-D) score has dropped below a certain number ‒ and that’s good, but you are still not quite able to get back to work and not really functioning at home with your responsibilities.” I think this really comes up short. The more real-world outcome definitions that I see being discussed and described in the literature bring us that much closer to the goals of treatment.

References

McIntyre R, Harrison J, Loft H, et al. The effects of vortioxetine on cognitive function in patients with major depressive disorder: a meta-analysis of three randomized controlled trials. Int J Neuropsychopharmacol. 2016;19(10):pyw055.

Montgomery SA. Why do we need new and better antidepressants? Int Clin Psychopharmacol. 2006;21(Suppl 1):S1-S10.

Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917.

Joseph F. Goldberg, MD

Clinical Professor of Psychiatry
Icahn School of Medicine
Mount Sinai
New York, NY

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