tricyclic antidepressant
(TCA)
A medication used primarily as an antidepressant, for the management of depression.
It contains 3 rings of atoms in its structure.
It is a second-line antidepressant.
(Mechanism of action)
They can act through NMDA (N-Methyl-D-aspartate) receptor antagonists, opioidergic effects, sodium, potassium and calcium channel blocking, through interfering with the reuptake of serotonin and acting as antagonists to SHAM (serotonin, histamine, alpha, muscarinic) receptors.
(Indications)
• mood disorders (e.g. major depressive disorder, dysthymia, and treatment-resistant variants) (primarily)
• cyclic vomiting syndrome
• anxiety disorders (e.g. generalized anxiety disorder, social phobia (social anxiety disorder), obsessive-compulsive disorder, panic disorder)
• post-traumatic stress disorder (PTSD)
• body dysmorphic disorder
• eating disorders (e.g. anorexia nervosa, bulimia nervosa)
• personality disorders (e.g. borderline personality disorder)
• neurological disorders (e.g. attention-deficit hyperactivity disorder, Parkinson's disease, chronic pain, neuralgia, fibromyalgia)
• headache, migraine
• smoking cessation
• tourette syndrome
• trichotillomania
• irritable bowel syndrome (IBS)
• interstitial cystitis
• nocturnal enuresis
• narcolepsy
• insomnia
• pathological crying and/or laughing
• chronic hiccups
• ciguatera poisoning
• adjunct in schizophrenia.
(Side effects)
Antimuscarinic properties:
• dry mouth, dry nose
• blurry vision
• constipation
• urinary retention
• dementia
• hyperthermia
Other properties:
• drowsiness
• anxiety
• emotional blunting (apathy/anhedonia)
• confusion
• restlessness
• dizziness
• akathisia
• hypersensitivity
• changes in appetite and weight
• sweating
• muscle twitches
• weakness
• nausea, vomiting
• hypotension
• tachycardia, arrhythmia (rarely)
Caused by overdose:
• twitching
• hallucinations
• delirium
• coma
• cardiotoxic (e.g. prolonging heart rhythms, increasing myocardial irritability): They behave like class 1A antiarrhythmics, such as terminating ventricular fibrillation, decreasing cardiac contractility, and increasing collateral blood circulation to ischemic heart muscle.
(Comparisons)
By structure:
• tricyclic antidepressant: Contain 3 rings of atoms.
• tetracyclic antidepressant: Contain 4 rings of atoms. An antidepressant similar to tricyclic antidepressant.
By efficacy:
• selective serotonin reuptake inhibitor: A first-line drug.
• tricyclic antidepressant: A second-line drug.
(Types)
Based on the tricyclic ring system:
• dibenzazepines: E.g. imipramine, desipramine, clomipramine, trimipramine, lofepramine.
• dibenzocycloheptadienes: E.g. amitriptyline, nortriptyline, protriptyline, butriptyline.
Based on the ring system:
• dibenzoxepins: E.g. doxepin.
• dibenzothiepines: E.g. dosulepin.
• dibenzoxazepines: E.g. amoxapine.
Based on the number of substitutions of the side chain amine:
• tertiary amines: E.g. imipramine, clomipramine, trimipramine, amitriptyline, butriptyline, doxepin, dosulepin.
• secondary amines: E.g. desipramine, nortriptyline, protriptyline.
(Examples)
• clomipramine
• imipramine
• trimipramine
• desipramine
• maprotiline
• nortriptyline
• protriptyline
• amitriptyline
• amitriptylinoxide
• amoxapine
• doxepin
Cf. serotonin–norepinephrine reuptake inhibitor, norepinephrine reuptake inhibitor