Efficacy and safety of agomelatine 25-50 mg/day versus escitalopram 10-20 mg/day in severe generalized anxiety disorder

Stein, Deborah J.; Khoo, Jon-Paul; Ameringen, D.M. Van; Höschl, Cyril; Ahokas, Antti; Bauer, M; Bitter, István; Jarema, Marek; Mosolov, S.N.; Vavrusova, L.; Picarel-Blanchot, F.; Matharan, Sophie; Olivier, Valérie

doi:10.1016/s0924-977x(17)31762-5

Cited by 3 publications

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“…Agomelatine, a melatonin-1/melatonin-2 agonist and 5-HT 2C receptor antagonist, has been studied more extensively in depression, although it was also found to have anxiolytic properties (112). Based on several RCTs including comparisons with escitalopram (113)(114)(115)(116)(117), a meta-analysis of treatments for GAD determined that agomelatine was welltolerated and potentially efficacious with the caveat of small sample sizes (91).…”

Section: Novel Treatments For Anxiety Disordersmentioning

confidence: 99%

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

Garakani¹,

Murrough²,

Freire³

et al. 2021

FOC

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Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha-and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha-and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebocontrolled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and largerscale studies of promising agents with positive results from smaller trials.

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Section: Novel Treatments For Anxiety Disordersmentioning

confidence: 99%

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

Garakani¹,

Murrough²,

Freire³

et al. 2021

FOC

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“…Since the publication of these two studies, subsequent trials have confirmed the efficacy and safety of agomelatine in the treatment of GAD at lower daily dosages (10–25 mg/day) [ 33 ], and in a head-to-head trial versus escitalopram in severe GAD [ 32 ]. In the latter study, both treatments were associated with clinically significant decreases in HAM-A scores at week 12, and were thus efficacious in treating patients with severe GAD.…”

Section: Newer Drugs: Agomelatinementioning

confidence: 99%

“…There were no significant differences between agomelatine and escitalopram in terms of the size of the reductions in HAM-A score from baseline, in either the overall study group (mean ± standard deviation, − 16.0 ± 9.1 vs − 16.9 ± 8.4, respectively) or in more severely anxious patients (− 16.4 ± 9.5 vs − 17.4 ± 8.6, respectively; Fig. 1 ) [ 32 ]. However, the pre-established criteria for non-inferiority of agomelatine versus escitalopram were not met (HAM-A total score estimate, − 0.91; standard error, 0.69; 95% confidence interval − 2.26, 0.44; P = 0.195).…”

Section: Newer Drugs: Agomelatinementioning

confidence: 99%

“…However, the pre-established criteria for non-inferiority of agomelatine versus escitalopram were not met (HAM-A total score estimate, − 0.91; standard error, 0.69; 95% confidence interval − 2.26, 0.44; P = 0.195). Agomelatine was associated with a numerically lower incidence of AEs compared with escitalopram (46.9% vs 58.8%) [ 32 ].

Fig.…”

Section: Newer Drugs: Agomelatinementioning

confidence: 99%

“…

Fig. 1 Mean change between baseline and 12 weeks in Hamilton Anxiety Rating Scale (HAM-A) in a randomised trial comparing agomelatine (25–50 mg/day) versus escitalopram (10–20 mg/day) in the treatment of generalised anxiety disorder [ 32 ]. Error bars represent standard deviation.…”

Section: Newer Drugs: Agomelatinementioning

confidence: 99%

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Evidence-Based Pharmacotherapy of Generalised Anxiety Disorder: Focus on Agomelatine

Stein

2021

Adv Ther

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Recent network meta-analyses support the use of pharmacotherapy in patients with generalised anxiety disorder (GAD). Compared with placebo, drug treatment can improve symptoms and quality of life, and is more effective in preventing relapse. Selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors are generally considered the first-line agents of choice in GAD, but in some patients, an alternative evidence-based treatment with a different mechanism of action may also be considered (e.g. those with severe GAD, inadequate response, adverse effects and/or contraindications). One example is agomelatine, a melatonin receptor agonist and serotonin 2C (5-HT 2C ) receptor antagonist, which has been shown to have efficacy that is greater than placebo in patients with GAD, and to have a tolerability profile that compares favourably with that of escitalopram. Both agomelatine and escitalopram are efficacious in treating patients with GAD, including those with severe symptoms. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01860-1.

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Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action

Millan

2022

Therapeutic Advances in Psychopharmacology

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Generalized anxiety disorder (GAD), the most frequently diagnosed form of anxiety, is usually treated by cognitive-behavioural approaches or medication; in particular, benzodiazepines (acutely) and serotonin or serotonin/noradrenaline reuptake inhibitors (long term). Efficacy, compliance, and acceptability are, however, far from ideal, reinforcing interest in alternative options. Agomelatine, clinically employed in the treatment of major depression, expresses anxiolytic properties in rodents and was effective in the treatment of GAD (including severely ill patients) in several double-blind, short-term (12 weeks) and relapse-prevention (6 months) studies. At active doses, the incidence of adverse effects was no higher than for placebo. Agomelatine possesses a unique binding profile, behaving as a melatonin (MT1/MT2) receptor agonist and 5-HT2C receptor antagonist, yet recognizing neither monoamine transporters nor GABAA receptors. Extensive evidence supports a role for 5-HT2C receptors in the induction of anxious states, and their blockade likely plays a primary role in mediating the anxiolytic actions of agomelatine, including populations in the amygdala and bed nucleus of stria terminalis, as well as the hippocampus. Recruitment of MT receptors in the suprachiasmatic nucleus, thalamic reticular nucleus, and hippocampus appears to fulfil a complimentary role. Downstream of 5-HT2C and MT receptors, modulation of stress-sensitive glutamatergic circuits and altered release of the anxiogenic neuropeptides, corticotrophin-releasing factor, and vasopressin, may be implicated in the actions of agomelatine. To summarize, agomelatine exerts its anxiolytic actions by mechanisms clearly distinct from those of other agents currently employed for the management of GAD. Plain Language Summary How agomelatine helps in the treatment of anxiety disorders Introduction: • Anxiety disorders have a significant negative impact on quality of life. • The most common type of anxiety disorder, called generalized anxiety disorder (GAD), is associated with nervousness and excessive worry. • These symptoms can lead to additional symptoms like tiredness, sleeplessness, irritability, and poor attention. • GAD is generally treated through either cognitive-behavioural therapy or medication. However, widely used drugs like benzodiazepines and serotonin reuptake inhibitors have adverse effects. • Agomelatine, a well-established antidepressant drug, has shown anxiety-lowering (‘anxiolytic’) properties in rats and has been shown to effectively treat GAD with minimal side effects. • However, exactly how it acts on the brain to manage GAD is not yet clear. • Thus, this review aims to shed light on agomelatine’s mechanism of action in treating GAD. Methods: • The authors reviewed studies on how agomelatine treats anxiety in animals. • They also looked at clinical studies on the effects of agomelatine in people with GAD. Results: • The study showed that agomelatine ‘blocks’ a receptor in nerve cells, which plays a role in causing anxiety, called the 5-HT2C receptor. • Blocking this receptor, especially in specific brain regions such as nerve cells of the amygdala, bed nucleus of stria terminalis, and hippocampus, produced the anxiety reduction seen during agomelatine treatment. • Agomelatine also activates the melatonin (MT) receptor, which is known to keep anxiety in check, promote sleep, and maintain the sleep cycle. • Agomelatine should thus tackle sleep disturbances commonly seen in patients with GAD. • Beyond 5-HT2C and MT receptors, signalling molecules in nerve cells that are known to be involved in anxiety disorders (called ‘neurotransmitters’ and ‘neuropeptides’) are also affected by agomelatine. Conclusion: • Agomelatine’s anxiolytic effects are caused by mechanisms that are distinct from those of other medications currently used to treat GAD. • This explains its therapeutic success and minimal adverse side effects.

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Efficacy and safety of agomelatine 25-50 mg/day versus escitalopram 10-20 mg/day in severe generalized anxiety disorder

Cited by 3 publications

References 0 publications

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

Evidence-Based Pharmacotherapy of Generalised Anxiety Disorder: Focus on Agomelatine

Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action

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