Tricyclic Antidepressants; Uses, Side Effects, Interactions

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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

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

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

• Major depressive disorder  
• Dysthymia, and treatment-resistant? variants. They are also used in the treatment of a number of other medical disorders, including
• Anxiety disorders 
• Generalized anxiety disorder 
• Social phobia
• Social anxiety disorder
• Obsessive-compulsive disorder
• Panic disorder 
• Post-traumatic stress disorder 
• Body dysmorphic disorder
• Anorexia nervosa and bulimia nervosa, certain
• Personality disorders such as
• Borderline personality disorder   
• Attention-deficit hyperactivity disorder 
• Parkinson’s disease as well as 
• Chronic pain,
• Neuralgia 
• Neuropathic pain
• Fibromyalgia, 
• A headache, 
• A migraine,
• Smoking cessation, 
• Irritable bowel syndrome 
• Interstitial cystitis 
• Nocturnal enuresis
• Narcolepsy,
• Insomnia, 
• Pathological crying
• Chronic hiccups,
• Schizophrenia.

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

• Decreased sexual desire or ability
• Failure to discharge semen (in men)
• chest pain
• a headache
• joint painPain
• dizziness
• nausea and vomiting
• Severe? stomach ache
• epigastric pain,
• diarrhea,
• anorexia,
• flatulence?,
• a headache,
• dizziness,
•  fainting?, fast or pounding heartbeats.

More common

• Fast or irregular heartbeat
• fever
• Back pain
• dizziness
• a headache
• increased cough
• Acid or sour stomach
• decreased appetite
• Agitation
• chest congestion
• chest pain
• cold sweats
• confusion
• decreased sexual ability or desire
• diarrhea or loose stools
• heartburn
• sleepiness or unusual drowsiness
• stomach or abdominal cramps, gas, or pain
• trouble sleeping

Less common

• Abnormal dreams
• change in sense of taste
• congestion
• discouragement, feeling sad, or empty
• Suicide attempts
• Acting on dangerous impulses
• Aggressive or violent behavior
• Thoughts about suicide or dying
• New or worse depression
• New or worse anxiety or panic attacks
• Agitation, restlessness, anger, or irritability
• Trouble sleeping
• An increase in activity or talking more than normal

Drug Interactions of Tricyclic Antidepressants

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

• anticholinergic medications (e.g., atropine, diphenhydramine, hydroxyzine)
• barbiturates (e.g., phenobarbital)
• benzodiazepines (e.g., diazepam, lorazepam)
• butyrophenones (e.g., haloperidol)
• carbamazepine
• clarithromycin
• cimetidine
• domperidone
• erythromycin
• epinephrine or
• guanethidine
• MAO inhibitors (e.g., phenelzine, moclobemide)
• methadone
• methylphenidate
• metoclopramide
• phenothiazines (e.g., chlorpromazine, thioridazine)
• phenylephrine
• sibutramine
• sotalol
• SSRI antidepressants (e.g., fluoxetine, fluvoxamine, paroxetine)
• terbinafine
• tramadol
• ziprasidone

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