How Do SSRI Antidepressants Work?

Selective serotonin reuptake inhibitor (SSRI) antidepressants are the most common medications prescribed to treat depression and many other psychiatric conditions. SSRIs selectively increase the levels of serotonin and regulate its activity.

Serotonin is an important natural chemical (neurotransmitter) released by nerve cells (neurons) in the brain to transmit nerve signals. Serotonin plays a vital role in neurotransmission in the central and peripheral nervous systems and regulates virtually all the systems in the body.

Some of the functions of serotonin include regulation of sleep, digestion, cognition, mood, and behavior. An increase in serotonin levels helps relieve anxiety and reduce depression symptoms.

SSRIs increase serotonin concentration in the space (synapse) between neurons by preventing its reabsorption (reuptake). Reuptake of neurotransmitters is a natural recycling process after the completion of neurotransmission. SSRIs prevent serotonin reuptake by inhibiting serotonin transporter (SERT), a protein in the transmitting neuron.

SSRI antidepressants are oral tablets, capsules or solutions approved by the FDA for the treatment of the following conditions:

• Major depressive disorder
• Generalized anxiety disorder
• Obsessive-compulsive disorder
• Bulimia nervosa
• Panic disorder
• Premenstrual dysphoric disorder
• Social phobia/Social anxiety disorder
• Posttraumatic stress disorder (PTSD)
• Menopausal vasomotor symptoms/hot flashes

Off-label uses include:

• Alcoholism
• Binge-eating disorder
• Impulsive aggressive behavior
• Insomnia
• Fibromyalgia
• Migraine
• Hot flashes due to hormonal chemotherapy
• Raynaud phenomenon
• Stuttering
• Vasovagal syncope (a sudden drop in heart rate and blood pressure that leads to fainting)
• Diabetic neuropathy
• Pruritus (itching)
• Orphan designations:
• Body dysmorphic disorder
• Autism

Side effects of SSRI antidepressants may include the following:

• Xerostomia (dry mouth)
• Nausea
• Somnolence (drowsiness)
• Insomnia
• Hyperhidrosis (excessive sweating)
• Headache
• Ejaculation disorder
• Impotence
• Decreased libido
• Anorgasmia (inability to reach orgasm)
• Dysmenorrhea (menstrual cramps and pain)
• Amenorrhea (absence of menstruation)
• Diarrhea
• Anorexia (loss of appetite)
• Increased or reduced appetite
• Constipation
• Dyspepsia (indigestion)
• Vomiting
• Abdominal pain
• Flatulence
• Asthenia (weakness)
• Fatigue
• Dizziness
• Lethargy
• Anxiety
• Nervousness
• Agitation
• Akathisia (restlessness)
• Confusion
• Abnormal dreams
• Abnormal thinking
• Emotional lability (mood swings)
• Amnesia (loss of memory)
• Mania or hypomania
• Exacerbation of depression
• Acute psychosis
• Anger and aggression
• Depersonalization
• Hallucinations
• Nightmares
• Paranoia and panic reaction
• Suicidal thought and attempt (rare)
• Tremor
• Myoclonus (involuntary muscle jerk or twitch)
• Ataxia (impaired coordination)
• Abnormal gait
• Falls
• Bone fracture
• Trismus (lockjaw)
• Seizures
• Rhinitis (inflammation of the nasal passage)
• Sinusitis (inflammation of the sinuses)
• Flu-like syndrome
• Fever
• Malaise
• Upper respiratory infection
• Cough
• Yawning
• Increased saliva
• Sweating
• Abnormal taste
• Dysphagia (swallowing difficulties)
• Gastrointestinal (GI) hemorrhage
• Gastroesophageal reflux
• Pancreatitis (inflammation of the pancreas)
• Rectal hemorrhage
• Toothache
• Neck/shoulder pain
• Arthralgia (joint pain)
• Myalgia (muscle pain)
• Back pain
• Migraine
• Mydriasis (dilation of pupils)
• Abnormal vision
• Diplopia (double vision)
• Angle-closure glaucoma (a condition with high intraocular pressure that damages the optic nerve)
• Nystagmus (involuntary eye movement)
• Orthostatic hypotension (blood pressure drop when standing up from sitting or lying down)
• Vertigo
• Tinnitus (ringing in the ears)
• Dysarthria (speech disorder)
• Paresthesia (prickling sensation)
• Hypoesthesia (loss of sensation)
• Polyuria (excessive urination)
• Frequent urination
• Urinary retention
• Dysuria (painful urination)
• Acute renal failure
• Hypersensitive reactions such as:
  • Rash
  • Pruritus (itching)
  • Urticaria (hives)
  • Ecchymosis (skin discoloration from bleeding underneath)
  • Erythema multiforme (round lesions like a bullseye)
  • Alopecia (hair loss)
  • Photosensitivity
  • Angioedema (swelling in the tissue under the skin or mucous membranes)
  • 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)
  • Anaphylaxis (severe allergic reaction)
• Bruising
• Edema
• Abnormal bleeding (rare)
• Longer blood clotting time
• Reduced blood count conditions such as:
  • Agranulocytosis (low granulocytes, immune cells with granules)
  • Anemia (low red blood cell count)
  • Aplastic anemia (anemia due to reduced red cell production)
  • Hemolytic anemia (anemia from rapid destruction of red cells)
  • Leukopenia (low levels of leukocytes, a type of immune cell)
  • Thrombocytopenia (decrease in platelet count)
  • Thrombocytopenic purpura (easy bruising and bleeding due to thrombocytopenia)
• Tachycardia (rapid heartbeat)
• Palpitations
• Hypertension (high blood pressure)
• Chest pain
• Atrial fibrillation
• Bradycardia (slow heartbeat)
• Torsades de Pointes (irregular heart rhythm in which the ventricles beat faster and out of synchronization with the atria)
• Cardiac failure
• Myocardial infarction
• Vasodilation
• Flushing
• Cerebrovascular accident
• Hypotension (low blood pressure)
• Deep vein thrombosis (blood clot in the vein)
• Phlebitis (inflammation of the vein)
• Weight change
• Elevated liver enzyme levels
• Acute hepatitis (rare)
• Liver necrosis and failure
• Dyspnea (shortness of breath)
• Epistaxis (nasal bleeding)
• Pulmonary embolism
• Pulmonary hypertension of the newborn
• Hyponatremia (low blood sodium)
• Hypokalemia (low blood potassium)
• Hypercholesterolemia (high cholesterol in the blood)
• Dysglycemia (unstable blood sugar levels) in diabetic people
• Diabetes mellitus
• Risk of seizure with concomitant electroconvulsive therapy (rare)
• Hyperprolactinemia (increase in prolactin levels)
• Galactorrhea (abnormal milk production and leakage)
• Menorrhagia (prolonged heavy menstrual bleeding)
• Spontaneous abortion
• Priapism (persistent, painful erection)
• Serotonin syndrome
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH, a disorder which causes water retention)
• Muscle cramp, stiffness, and weakness
• Extrapyramidal disorders (drug-induced movement disorders)
• Parkinsonism
• Restless legs
• 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 SSRI antidepressant drugs include:

• Brisdelle
• Celexa
• citalopram
• escitalopram
• fluoxetine
• fluvoxamine
• Lexapro
• Luvox
• paroxetine
• Paxil
• Paxil CR
• Pexeva
• Prozac
• Sarafem
• sertraline
• Zoloft