AGOMELATINE

brands

Class

• Agonist at melatonergic 1 and melatonergic 2 receptors
• Antagonist at 5HT2C receptors

AGOMELATINE commonly prescribed for

(Bold for FDA approved)

How AGOMELATINE works

• Actions at both melatonergic and 5HT2C receptors may be synergistic and increase norepinephrine and dopamine neurotransmission in the prefrontal cortex; may resynchronize circadian rhythms that are disturbed in depression

• No influence on extracellular levels of serotonin

How long until AGOMELATINE works

• Daytime functioning, anhedonia, and sleep can improve from the first week of treatment

• Onset of full therapeutic actions in depression is usually not immediate, but often delayed 2–4 weeks

• May continue to work for many years to prevent relapse of symptoms

Notable Side Effects

• Nausea and dizziness are most common

• Other adverse reactions are somnolence, fatigue, insomnia, headache, anxiety, diarrhea, constipation, upper abdominal pain, vomiting, hyperhidrosis

• Increase of transaminase levels

Life Threatening Side Effects

✽ Rare hepatitis, hepatic failure

• Theoretically rare induction of mania (class warning)

• Rare activation of suicidal ideation and behavior (suicidality) (short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo beyond age 24) (class warning)

weight gain

unusual

sedation

not usual

What to do about AGOMELATINE side effects

• Wait

• Wait

• Stop if transaminase levels reach 3 times the upper limit of normal

• Switch to another drug

usual dosage range

• 25–50 mg/day at bedtime

Dosage Forms

• Tablet 25 mg

long term use

• Treatment up to 12 months has been found to decrease rate of relapse

habit forming

•No

Renal Impairment

• Drug should be used with caution

Hepatic Impairment

• Contraindicated

Cardiac Impairment

• Dose adjustment not necessary

Elderly

• Efficacy and safety have been established (< 75 years old)

• Dose adjustment not necessary

• Should not be used in patients age 75 years and older

• Should not be used in elderly patients with dementia

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Safety and efficacy have not been established and it is not recommended

Pregnancy

• No controlled studies in humans

• Not generally recommended for use during pregnancy, especially during first trimester

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child

• For many patients this may mean continuing treatment during pregnancy

Breast Feeding

• Unknown if agomelatine is secreted in human breast milk, but all psychotropics assumed to be secreted in breast milk

• Therefore, breast feeding or drug needs to be discontinued

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period