How Do Alpha-2 Antagonist Antidepressants Work?

Alpha-2 antagonist antidepressants are medications prescribed to treat depression. Alpha-2 agonist antidepressants work on the central nervous system to increase the levels and modulate the activity of norepinephrine and serotonin, chemical messengers (neurotransmitters) released by nerve cells (neurons).

Mood regulation is one of the many functions of norepinephrine and serotonin and increased levels and modulation of their activity improves mood. It is not clear how exactly alpha-2 antagonist antidepressants are effective for depression, but studies suggest they may work in the following ways to reduce depression:

• Block alpha-2 receptors, protein molecules on the membranes of neurons that play an inhibitory role, enhancing the availability and activity of norepinephrine and serotonin. Norepinephrine stimulates the sympathetic nervous system, which results in an increase in metabolism and activity.
• Block serotonin receptors 5HT2 and 5HT3 which increase anxiety when stimulated by serotonin. The increased level of serotonin stimulates 5HT1, which improves mood.
• Block H1 histamine receptors which produce a calming and sedating effect.

Alpha-2 antagonist antidepressants are oral tablets approved by the FDA for the treatment of major depressive disorder in adults. In addition, alpha-2 antagonist antidepressants are used off-label in the treatment of the following conditions:

• Posttraumatic stress disorder (PTSD)
• Hot flashes
• Insomnia

Side effects of alpha-2 antagonist antidepressants may include the following:

• Somnolence (drowsiness)
• Weight gain
• Xerostomia (dry mouth)
• Increased appetite
• Constipation
• Asthenia (weakness)
• Dizziness
• Increased thyroglobulin levels in the blood
• Dream disorder
• Disturbance in thinking
• Increased level of liver enzyme ALT (alanine aminotransferase)
• Peripheral edema
• Myalgia (muscle pain)
• Confusion
• Urinary frequency
• Tremor
• Back pain
• Dyspnea (shortness of breath)
• Mania
• Grand mal seizure
• Exacerbation of depression
• Status epilepticus (a medical emergency, when a seizure lasts longer than five minutes)
• Suicidal thoughts, suicide (rare)
• Agranulocytosis (low granulocytes, immune cells with granules)
• Neutropenia (low blood count of neutrophils, a type of immune cells)
• Hypersensitive reactions such as:
• Bullous dermatosis (skin disease with blisters)
• Erythema multiforme (round lesions like a bullseye)
• Stevens-Johnson syndrome (a rare medical emergency with flu-like symptoms and a painful rash)
• Toxic epidermal necrolysis (a severe skin condition with widespread redness, skin cell death, and exfoliation which can lead to sepsis)
• Arrhythmia Torsades de Pointes (irregular heart rhythm in which the ventricles beat faster and out of synchronization with the atria)
• Hyperprolactinemia (high prolactin levels in the blood, which can induce abnormal breast milk production and other hormonal disorders)
  • Galactorrhea (abnormal milk production and leakage)
  • Gynecomastia (breast tissue development in males)
  • Increased creatine kinase levels in the blood
  • Rhabdomyolysis (breakdown of skeletal muscle cells)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of alpha-2 antagonist antidepressant drugs include:

• mirtazapine
• Remeron
• Remeron SolTab