How Do Tricyclic Antidepressants Work?

Tricyclic antidepressants(TCAs) are some of the earliest medications developed to treatdepression和otherpsychiatricconditions. TCAs derive their name from the three rings of atomsintheir molecular structure. TCAs alleviate depression by altering the levels of neurotransmitters in the大脑和modulating their activity.

Neurotransmitters are chemicals released bynervecells (neurons) into the space (synapse) between them to communicate nerve signals. Neurotransmitters bind toproteinmolecules known as receptors on the adjoiningcellsurfaces to activate them.

Neurotransmitters enable the regulation of physiological functions such asbreathing,heart rate和digestion, and are also responsible for learning,memory,sleep, emotions and behavior. Imbalance in certain neurotransmitters can disrupt normal neurotransmission of signals, resulting in depression,anxiety和other disorders.

TCAs increase the levels ofserotonin和去甲肾上腺素by preventing theirreabsorption(reuptake), a naturalprocessin the brain. The functions of serotonin include regulation of sleep, digestion,cognition, mood and behavior, and increasing their levels helps in relieving depression and anxiety.

TCAs also blockhistaminereceptors and some of them are used to treatchronicitching. Additionally, TCAs block the activity ofacetylcholine,一个neurotransmitterthat makes muscles contract, which is useful formusclerelaxation and sedation.

TCAs have a lower threshold for overdose compared to more advancedantidepressants,一个nd also a higher risk forsuicideideation. With thedevelopmentof newer classes of antidepressants with better side effect profiles, currently, TCAs are used as second-line treatment for depression.

Tricyclic antidepressants areoraltablets, capsules or solutions approved by theFDAfor the treatment of the following conditions:

• Depression
• Depression with anxiety
• Obsessive-compulsive disorder
• Insomnia
• Enuresis(incontinence)

标示外使用包括:

• Postherpetic neuralgia
• Migraineprophylaxis
• Analgesiaforchronic pain
• Eating disorder
• Premature ejaculation
• Vulvodynia (chronicpainin thevulva)
• Chronicurticaria(hives)
• Nocturnalpruritus(itching)
• Angioedema(swelling in the tissues under theskin和mucousmembranes)
• Nocturnal enuresis(bedwettingin children)
• Smoking cessation
• Attention deficit hyperactivity disorder(ADHD)

Side effects of tricyclic antidepressants may include the following:

• Sedation
• Somnolence(drowsiness)
• Fatigue
• Weakness
• Lethargy
• Dizziness
• Headache
• Ataxia(impaired coordination andbalance)
• Extrapyramidal symptoms (drug-induced movement disorders)
• Xerostomia(dry mouth)
• Constipation
• Nausea
• Anorexia(loss of appetite)
• Diarrhea
• Flatulence
• Bloating
• Vomiting
• Dyspepsia(消化不良)
• Blurred vision
• Increasedocularpressure
• Mydriasis(dilationof pupils)
• Agitation
• Anxiety
• Confusion
• Nervousness
• Restlessness
• Insomnia
• Hallucination
• Vividdreams
• Mania
• Worsening depression
• Suicidalthoughts
• Tremor
• Seizure
• Coma
• Stroke
• EEGabnormalities
• Arrhythmia
• ECGchanges
• Tachycardia(rapid heartbeat)
• Brugada syndrome(irregular, rapid heartbeat in theventricles)
• 沪元pertension(high blood pressure)
• Myocardial infarction(heart attack)
• Palpitations
• Orthostatic hypotension(blood pressuredrop when standing up from sitting or lying down)
• Syncope(fainting)
• Tinnitus(ringing in the ears)
• Paresthesia(pricklingsensation)
• Paralytic ileus(blockage of intestines due toparalysisof intestinal muscles), rare
• Edema
• Sweating
• 沪元persensitivity reactions such as:
  • Rash
  • Urticaria (hives)
  • Alopecia(hair loss)
  • Photosensitivity
  • Drug rash witheosinophilia和systemicsymptoms (DRESS)
• Stomatitis (inflammationin themouth)
• Nasalcongestion
• Fever
• Blooddyscrasias (disorders) such as:
• Agranulocytosis(lowgranulocytes,immunecells with granules)
• Leukopenia(low levels ofleukocytes,一个type of immune cell)
• Thrombocytopenia(decrease inplatelet count)
• Pancytopenia(decrease in all types of blood cells)
• Hepatotoxicity (toxicityto theliver)
• Elevated liverenzymes
• Hepaticdysfunction
• Jaundice
• 沪元perglycemia(increasedblood glucoselevels)
• 沪元ponatremia(lowsodiumin the blood)
• Urinaryretention
• Weight change
• 沪元perprolactinemia (increasedprolactinlevels in the blood)
• Galactorrhea(abnormalmilk production and leakage)
• Sexual dysfunction
• Ejaculationfailure
• Impotence
• Anorgasmia(inability to reachorgasm)
• Libidochange
• Menstrual irregularity
• Syndrome of inappropriate antidiuretic hormonesecretion (SIADH, a disorder which causeswater retention)
• Neurolepticmalignantsyndrome(a rare life-threatening drug reaction)

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

Generic和brand names of tricyclicantidepressantdrugs include:

• amitriptyline
• amoxapine
• Anafranil
• chlordiazepoxide/amitriptyline
• clomipramine
• desipramine
• doxepin
• imipramine
• Norpramin
• nortriptyline
• Pamelor
• protriptyline
• Silenor
• Tofranil
• trimipramine