title: Agomelatine: new drug. Adverse effects and no proven efficacy.
abstract: (1) When an antidepressant is considered a necessary addition to psychological support in treating patients with depression, the first-line drug is a tricyclic such as clomipramine or a selective serotonin reuptake inhibitor (SSRI) such as paroxetine; (2) Agomelatine, a melatonin receptor agonist, is approved in the European Union for the treatment of depression; (3) Available evaluation does not include any clinical trials designed to compare the efficacy of agomelatine with that of a tricyclic or a selective serotonin reuptake inhibitor. Most data come from 7 placebo-controlled trials; (4) Agomelatine (25 mg/day) was statistically more effective (on a rating scale) than placebo in only 3 of these 7 trials. The clinical relevance of the score improvements is questionable. No data are available on the cure rate or on suicide prevention; (5) In one trial, increasing the daily dose from 25 mg to 50 mg provided no supplementary benefit; (6) A trial in 367 patients failed to show that agomelatine was any more effective than placebo in preventing new depressive episodes (29% after one year). In another trial including 339 patients, the relapse rate was statistically lower after 6 months on agomelatine (20.6%) than on placebo (41.4%); (7) Very high doeses of agomelatine are oncogenic in animals. The risk in humans is not known. Dizziness, gastrointestinal and cutaneous disorders have been observed. Agomelatine is probably hepatotoxic; (8) In summary, agomelatine has unproven efficacy and poorly documented adverse effects. It is better to continue to use older antidepressants such as tricyclics or serotonin reuptake inhibitors.
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015982:Bias; D002273:Carcinogens; D002986:Clinical Trials as Topic; D003511:Cyclohexanols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D017277:Drug Approval; D005060:Europe; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008550:Melatonin / Q000819:agonists* / Q000494:pharmacology / Q000627:therapeutic use; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D044094:Receptors, Melatonin / Q000187:drug effects*; D012008:Recurrence; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013405:Suicide; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D002273:Carcinogens; D003511:Cyclohexanols; D005473:Fluoxetine; D006993:Hypnotics and Sedatives; D008550:Melatonin; D017374:Paroxetine; D044094:Receptors, Melatonin; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; C084711:agomelatine; D009281:Naphthalenes