Tricyclic Antidepressants; Uses, Side Effects, Interactions

Tricyclic Antidepressants; Uses, Side Effects, Interactions

Tricyclic antidepressants with anticholinergic and sedative properties. Amitriptyline appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines.


Tricyclic antidepressants are a class of medications that are used primarily as antidepressants. Tricyclic antidepressants (often abbreviated to TCAs) are a class of drugs that are traditionally used to treat depression; however, they may also be used in the treatment of other mood disorders, to relieve chronic nerve-related pain, to reduce bed-wetting, to manage obsessive-compulsive behaviors, and to prevent.T hey are named after their chemical structure, which contains three rings of atoms. Although TCAs are sometimes prescribed for depressive disorders, they have been largely replaced in clinical use in most parts of the world by newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs).

Types of Tricyclic Antidepressants

Those that preferentially inhibit the reuptake of serotonin (by at least 10-fold over norepinephrine) include

  • Butriptyline (relatively weak serotonin reuptake inhibitor)
  • Clomipramine
  • Imipramine
  • Trimipramine  (relatively weak serotonin reuptake inhibitor)

Those that preferentially inhibit the reuptake of norepinephrine (by at least 10-fold over serotonin) include

  • Desipramine
  • Dibenzepin
  • Lofepramine
  • Maprotiline – can be classed with the TCAs though more frequently classed with the TeCAs
  • Nortriptyline
  • Protriptyline

Whereas either fairly balanced reuptake inhibitors of serotonin and norepinephrine or unspecified inhibitors include

  • Amitriptyline
  • Amitriptylinoxide
  • Amoxapine  – can be classed with the TeCAs but more frequently classed with the TCAs
  • Demexiptiline
  • Dimetacrine
  • Dosulepin
  • Doxepin
  • Fluacizine
  • Imipraminoxide
  • Melitracen
  • Metapramine
  • Nitroxazepine
  • Noxiptiline
  • Pipofezine
  • Propizepine
  • Quinupramine

And the following are TCAs that act via main mechanisms other than serotonin or norepinephrine reuptake inhibition

  • Amineptine – norepinephrine-dopamine reuptake inhibitor
  • Iprindole – 5-HT2 receptor antagonist
  • Opipramol  – σ receptor agonist
  • Tianeptine atypical μ-opioid receptor agonist
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Overall Classifications of Tricyclic Antidepressants

Mechanism of Actions of Tricyclic Antidepressants

Tricyclic antidepressants work by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, which is thought to contribute to relieving symptoms of depression. In addition to acutely inhibiting neurotransmitter re-uptake, imipramine causes down-regulation of cerebral cortical beta-adrenergic receptors and sensitization of post-synaptic serotonergic receptors with chronic use. This leads to enhanced serotonergic transmission.

Indications/Uses of Tricyclic Antidepressants

The TCAs are used primarily in the clinical treatment of mood disorders such as

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Contra-Indications of Tricyclic Antidepressants

  • Overactive thyroid gland
  • Decreased blood Platelets
  • Decreased neutrophils a type of white blood cell
  • Schizophrenia
  • Behaving with excessive cheerfulness and activity
  • The mild degree of mania
  • Manic-depression
  • Having thoughts of suicide
  • Alcoholism
  • Serotonin syndrome – adverse drug interaction
  • Closed-angle glaucoma
  • Heart attack within the last 30 days
  • Coronary artery disease
  • Prolonged QT interval on EKG
  • Abnormal heart rhythm
  • Disease of the heart and blood vessels
  • Abnormal EKG with QT changes from birth
  • Stroke
  • Liver problems
  • Kidney disease with a reduction in kidney function
  • Enlarged prostate

Side Effects of Tricyclic Antidepressants

The most common

More common

Less common

Drug Interactions of Tricyclic Antidepressants

Tricyclic antidepressants  may interact with the following drugs, supplements & may decrease the efficacy of the drug

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Tricyclic antidepressants


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