How Do SSRI/Antagonist Antidepressants Work?

Selective serotonin reuptake inhibitor (SSRI)/antagonist antidepressants are medications prescribed to treat depression. SSRI/antagonist antidepressants work by increasing the levels of serotonin and norepinephrine and inhibiting the activity of 5HT-2 serotonin receptors and alpha-1 adrenergic receptors.

Serotonin and norepinephrine are natural chemicals (neurotransmitters) released by nerve cells (neurons) in the brain to transmit nerve signals. Regulation of mood and emotions is one of the many functions of serotonin and norepinephrine, and an increase in their levels and regulation of their activity improve symptoms of depression.

Serotonin receptors are protein molecules on the surface of nerve cells that activate regulatory processes when stimulated by serotonin. Alpha adrenergic receptors are stimulated by norepinephrine. Receptors upregulate or downregulate an activity depending on the type of receptors (excitatory or inhibitory) stimulated. 

SSRI/antagonist antidepressants work in the following ways to increase serotonin and norepinephrine levels and modulate their activity:

Block 5HT-2 receptors, which are excitatory serotonin receptors that enhance fear and anxiety, resulting in increased serotonin availability for inhibitory 5HT receptors that have a calming effect.

Inhibit reabsorption (reuptake) of serotonin and norepinephrine by the neurons, a natural recycling process after the completion of neurotransmission.

Block alpha-1 adrenergic receptors which are excitatory receptors, producing muscle relaxation and sedation.

SSRI/antagonist antidepressants are oral tablets approved by the FDA for the treatment of depression in adults.

Side effects of SSRI/antagonist antidepressants may include the following:

• Headache
• Somnolence (drowsiness)
• Nausea
• Xerostomia (dry mouth)
• Dizziness
• Asthenia (weakness)
• Constipation
• Insomnia
• Infection
• Dyspepsia (indigestion)
• Lightheadedness
• Confusion
• Blurred vision
• Abnormal vision
• Increased appetite
• Memory loss
• Paresthesia (prickling sensation)
• Vasodilation
• Decreased concentration
• Ataxia (impaired coordination and balance)
• Decreased libido
• Breast pain
• Decreased hematocrit
• Agitation with discontinuation of treatment
• Orthostatic hypotension (blood pressure drop when standing up from sitting or lying down)
• Bradycardia (slow heartbeat)
• Mania or hypomania
• Seizure
• Suicidal thoughts and suicide
• Worsening depression
• Liver failure (rare)

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.

All the brands of SSRI/antagonist drugs have been discontinued in the US. Generic name of the currently available SSRI/antagonist antidepressant drug is:

• nefazodone