Evidence-Based Pharmacotherapy of Anxiety Symptoms in Patients with Major Depressive Disorder: Focus on Agomelatine

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Patients with depression require thorough clinical assessment, which should include symptom profile, severity and staging, personality factors, antecedent and concurrent psychiatric comorbidity, physical comorbidity, neurocognitive function, exposure to stressors in early life (e.g. trauma) or recently (e.g. bereavement), and protective factors. The presence of anxiety symptoms in a depressed patient is associated with more severe depression, increased suicidality and worse outcomes compared with non-anxious depression. A network meta-analysis of antidepressant treatments found that agomelatine, citalopram, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were all significantly more effective than other antidepressants for the treatment of depression, and that agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine were better tolerated than other antidepressants. Agomelatine has been shown to have two major effects—relieving depressive symptoms, and supporting symptomatic and functional recovery—and these benefits have been demonstrated in patients with depression as well as in patients with generalised anxiety disorder, including those with more severe symptoms. Agomelatine has also been shown to be efficacious and well tolerated in patients with depression plus concomitant anxiety symptoms. A pooled analysis of data from six agomelatine studies of depression (three placebo-controlled and three with active comparators—fluoxetine, sertraline and venlafaxine) found that agomelatine was significantly more effective than placebo at relieving the anxiety subscore on the Hamilton Depression Rating Scale, and that the difference between agomelatine and placebo was even more marked in the subgroup of patients with severe anxiety symptoms at baseline. Irrespective of the pharmacotherapy used in patients with depression, the likelihoods of response and remission are increased when pharmacotherapy is combined with psychotherapy, with this approach being more effective than either pharmacotherapy or psychotherapy alone. Persistence with treatment is important, and clinicians should therefore encourage patients to keep trying to obtain relief.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalNeurology and Therapy
StatePublished - Apr 2023
Externally publishedYes


  • Agomelatine
  • Anxiety
  • Anxious depression
  • Depression


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