Presentation is loading. Please wait.

Presentation is loading. Please wait.

Efficacy of the Novel Antidepressant Agomelatine on the Circadian Rest-Activity Cycle and Depressive and Anxiety Symptoms in Patients With Major Depressive.

Similar presentations


Presentation on theme: "Efficacy of the Novel Antidepressant Agomelatine on the Circadian Rest-Activity Cycle and Depressive and Anxiety Symptoms in Patients With Major Depressive."— Presentation transcript:

1 Efficacy of the Novel Antidepressant Agomelatine on the Circadian Rest-Activity Cycle and Depressive and Anxiety Symptoms in Patients With Major Depressive Disorder: A Randomized, Double-Blind Comparison With Sertaline Mohammed Almoslem Pharm.D. Candidate King Saud University & King Khalid University Hospital Psychiatric Rotation Supervised by: Dr. Solafa Fatani Ms.c. Journal Club Presentation

2 Outline Introduction Relevance Validity – Method – Statistical analysis Results Strengths Limitations Conclusion Final Message

3 Title: – Efficacy of the Novel Antidepressant Agomelatine on the Circadian Rest-Activity Cycle and Depressive and Anxiety Symptoms in Patients With Major Depressive Disorder: A Randomized, Double-Blind Comparison With Sertaline Journal: – The journal of clinical psychiatry Authors: – Kasper S, Hajak G, et al Study Design: – International, Randomized, double-blind, parallel-group Funding: – This study was sponsored by Servier (Courbevoie,France) Introduction Paper Information

4 16.2% of the population had a history of Major Depressive Disorder More than 6.6% had episodes in one year. MDD medication are classified as following: – Monoamine Oxidase Inhibitors (MAOIs) Hypertensive crisis, food interaction – Tricyclic Antidepressants (TCAs) Anticholenergic, orthostatic hypotension – Selective Serotonin Reuptake inhibitors (SSRIs) Wait gain, sexual dysfunction – Serotonin-Norepinephrine Reuptake inhibitors (SNRIs) Hypertension, liver toxicity – Atypical antidepressants Liver toxicity, psychosis Dipiro, et al, pharmacotherapy a pathophysiological approach 7 th edition Introduction Major Depressive Disorder (MDD)

5 Introduction Agomelatine The first melatonergic antidepressant Potent MT 1 / MT 2 receptor agonist 5-HT 2C receptor antagonist Resynchronize altered circadian rhythm in depressive or healthy individuals

6 Endogenous physiological processes that regulates the cycle of 24 hour in living beings Circa: around or approximately Diem or dies: day Introduction Circadian Rhythm

7

8 A useful proved method that measures the circadian rest and activity patterns Indirectly measurement of sleep and characterize 24-hour sleep-wake cycle Introduction Actigraphy

9 Introduction Objective Primary: Demonstrate that agomelatine (25–50 mg/d) improved the circadian rest-activity cycle faster than sertraline in MDD outpatients Secondary: Assess the efficacy and tolerability of agomelatine on depressive and anxiety symptoms compared with sertraline through its effect on sleep efficacy and latency

10 Sleep disruption is a major symptom in depression, with over 90% of patients suffering from sleep complaints There is a close link between the regulation of sleep and circadian rhythms and the regulation of mood Thase ME. Antidepressant treatment of the depressed patient with insomnia. J Clin Psychiatry. 1999;60(suppl 17):28–31, discussion 46–48. PubMed Birchler-Pedross A, Schroder CM, Munch M, et al. Subjective well-being is modulated by circadian phase, sleep pressure, age and gender. J Biol Rhythms. 2009;24(3):232–242. PubMed doi:10.17/ Boivin DB, Czeisler CA, Dijk DJ, et al. Complex interaction of the sleepwake cycle and circadian phase modulates mood in healthy subjects. Arch Gen Psychiatry. 997;54(2):145–152 Relevance

11 Validity Method Hypothesis: The nocturnal disturbances of sleep onset, continuity, and/or awakening, together with daytime retardation and napping, lead to a reduced Relative Amplitude, and that improvement of the former leads to increase of the latter.

12 Randomization: – International, double-blind, parallel-group – Conducted from in 37 centers in 6 European countries (France, Germany, Austria, Spain, Italy, and Poland) Validity cont. Method

13 Allocation: – Inclusion criteria MDD diagnosed male and female outpatients aged 18 to 60 years Confirmed by the Mini-International Neuropsychiatric Interview Match the items standard of Hamilton Depression Rating Scale (HDRS) Single or recurrent episodes that match the criteria of DSM-IV-TR The current episode had already lasted at least 4 weeks Should not have seasonal pattern, psychotic features, or catatonic symptoms and were not postpartum Validity cont. Method

14 Allocation: – Exclusion criteria High risk of suicide or a previous suicide attempt within 6 months Bipolar disorder Anxiety symptoms Drug abuse or dependency within the past 12 months Previous antidepressants resistance ECT therapy or formal psychotherapy within 3 months Light-therapy started within 2 weeks Positive screened for sleep disorders Neurologic disorders Obesity with functional impairment Serious or not stabilized organic Other antidepressants were prohibited for washout Validity cont. Method ECT: electroconvulsive therapy

15 Validity cont. Method Allocation: – Disposition of included patients:

16 Validity cont. Method Attrition – 6 patients were not included in the Full Analysis Set 4 in agomelatine group 2 in sertaline group Due to absence of treatment intake or no postbaseline efficacy assessment – The Actigraphy Analysis Set comprised only (73%) 233 pts. 117 (76%) of the agomelatine 116 (73%) of sertaline

17 Validity cont. Method Demographic characteristics:

18 Blindness and concealment – Blindness: All patients took orally 2 tablets once a day in the evening Daily dosage irrespective to the treatment Same appearance and the taste of the study treatment during the study period for all patients The packaging and the labeling were identical Statistical analysis group ?????? – Concealment: Three hundred seventy-two patients were screened, and 313 patients were randomly assigned to receive – Agomelatine (154 patients) – Sertaline (159 patients). The concealment was NOT mentioned in the study. Validity cont. Method

19 Intention to treat: – The actigraphy analysis set (AAS), defined, for objective sleep criteria analyses, as all randomized patients who took at least 1 dose of study treatment and had 1 reliable baseline value and at least 1 reliable postbaseline value for the RA – The full analysis set (FAS), defined, for other efficacy criteria analyses, as all randomized patients who took at least 1 dose of study treatment and had at least 1 postbaseline efficacy assessment (other than actigraphic) over the 6-week treatment period. Validity cont. Method

20 Actigraphy Analysis Set (AAS) – For sleep data analysis Mixed-effects model with repeated measures (MMRM) Full Analysis Set (FAS) – For depression data analysis Hamilton Depression Rating Scale (HDRS) – 2-way analysis of covariance – 2-sided Student t test – X2 test – Post hoc analysis Clinical Global Impressions scale (CGI) Leeds Sleep Evaluation Questionnaire (LSEQ) – For anxiety data analysis Hamilton Anxiety Rating Scale (HARS) – 1-way analysis of covariance – Post hoc analysis Validity cont. Statistical Analysis

21 Results cont. Efficacy on the Circadian Rest-Activity Cycle Mean ± SDP-value Mean RA 1 st week.010 AAS evolution of the mean RA over time.023 Mean RA 2 nd week.148 Mean RA 3 rd week.521 Mean M10 Agomelatine (386.6 ± ).006 Sertraline ( ± ) Mean L5 Agomelatine ( ± ).121 Sertraline ( ± ) RA: relative amplitude. M10: activity of maximum 10 hours. L5: activity of minimum 5 hours.

22 Baseline and Difference in Sleep Efficiency (A) and Sleep Latency (B) Between Treatment Groups Over Each Postbaseline 7-Day Period in the Actigraphy Analysis Set Results cont. Efficacy on Actigraphy-Derived Sleep Parameters

23 Change in LSEQ Getting to Sleep (A) and Quality of Sleep (B) Scores (mm) From Baseline to Last Postbaseline Value Over the Week 0–Week 6 Period in the Full Analysis Set a: P value, treatment effect: 2-sided Student t test for independent samples. Abbreviation: LSEQ = Leeds Sleep Evaluation Questionnaire Results cont. Efficacy on Subjective Sleep

24 Change in HDRS Total Score From Baseline to Last Postbaseline Assessment Over the 6-Week Period (week 0–week 6) in the Full Analysis Set a: Two-way analysis of covariance with treatment and center (as random effect) as factors and week 0 HDRS total score as covariate. b: Estimate (standard error) of the difference between adjusted treatment group means: sertraline minus agomelatine. c: 95% CI of the difference. d: P value of treatment effect. Abbreviation: HDRS = Hamilton Depression Rating Scale. Results cont. Efficacy on Depressive symptoms

25 Results cont. Clinical Global Impressions scale The data will be provided later on

26 Results cont. Efficacy on Anxiety Symptoms The data will be provided later on

27 Most Frequently Reported Emergent Adverse Events ( 5.0% of patients in any treatment group), Expressed as Percentage of Affected Patients Among Exposed Patients During the Double-Blind Treatment Period in the Safety Set Results cont. The safety data were not statistically analyzed and only emergent adverse events (EAEs) that reported by less than 5% of the patients were NOT provided

28 . Study Strengths

29 . Study Limitations

30 . Study Conclusion

31 . Final Message

32 Thank You …


Download ppt "Efficacy of the Novel Antidepressant Agomelatine on the Circadian Rest-Activity Cycle and Depressive and Anxiety Symptoms in Patients With Major Depressive."

Similar presentations


Ads by Google