Products
Tricyclic antidepressants are commercially available in many countries in the form of dragées, tablets, capsules, and drops. The first representative, imipramine, was developed at Geigy in Basel. Its antidepressant properties were discovered in the 1950s by Roland Kuhn at the psychiatric clinic in Münsterlingen (Thurgau). Imipramine was approved in many countries in 1958.
Structure and properties
The name of the drug group is derived from the three fused rings. This structural element is called dihydrodibenzazepine. It is a derivative of dibenzazepine. The tricyclic antidepressants were developed starting from chlorpromazine, a neuroleptic and phenothiazine.
Effects
Tricyclic antidepressants (ATC N06AA) have antidepressant, mood-elevating, sedative (depressant), sleep-inducing, antianxiety, antihistamine, and anticholinergic properties. Their effects are based on inhibition of neurotransmitter reuptake into presynaptic neurons, particularly norepinephrine and serotonin. The tricyclic antidepressants are relatively nonselective compared with newer antidepressants and interact with various receptors, such as histamine H1 receptors, muscarinic acetylcholine receptors, and alpha-adrenoceptors. This contributes to their effects, but also to their adverse effects. The antidepressant effects are delayed within about two to four weeks.
Indications
Indications for use include:
- Depression
- Anxiety disorders, panic disorders
- Chronic pain such as nerve pain
- Enuresis nocturna (bedwetting)
- Migraine prophylaxis
- Obsessive-compulsive disorder
- Sleep disorders (usually off-label).
Dosage
According to the professional information. The dose is adjusted individually. Treatment is usually started gradually and discontinued gradually. Drugs should not be discontinued abruptly.
Abuse
Tricyclic antidepressants can be abused for suicide. Overdose can be life-threatening, including anticholinergic symptoms, seizures, coma, and severe cardiovascular disturbances such as conduction disorders, prolongation of the QT interval, and cardiac arrhythmias. Therefore, an overdose represents an acute medical emergency that must be treated promptly.
Agents
Active ingredients with regulatory approval in many countries:
- Amitriptyline (Saroten).
- Clomipramine (Anafranil)
- Doxepin (Sinquan)
- Opipramol (Insidon)
- Trimipramine (Surmontil, generic).
No longer commercially available in many countries:
- Amineptin (Survector, out of trade).
- Dibenzepine (Noveril TR, off label).
- Desipramine (Pertofran, off label).
- Imipramine (Tofranil, out of trade)
- Nortriptyline (Nortrilen, out of commerce).
Contraindications
Full precautions can be found in the drug label.
Interactions
Tricyclic antidepressants typically have a high potential for drug-drug interactions, for example with MAO inhibitors, antidepressants, St. John’s wort, anticholinergics, sympathomimetics, serotonergic drugs, antihypertensives, antiarrhythmics, and neuroleptics. They interact with CYP450 isoenzymes, typically CYP2D6. Centrally depressant drugs and alcohol may potentiate their effects.
Adverse effects
Possible adverse effects include:
- Fatigue, drowsiness
- Headache, dizziness, lightheadedness, tremor (shaking).
- Dry mouth
- Sweating
- Visual disturbances
- Weight gain
- Constipation
- Micturition problems
- Cardiovascular disturbances such as palpable heartbeats, a rapid heartbeat, and low blood pressure
The side effects are partly due to the anticholinergic properties of the active ingredients.
