Tricyclics and Tetracyclics

TCAs

• Adapin/Sinequan (generic name: doxepin), starting dose 75 mg/day, maximum dosage 150 mg/day
• Anafranil (generic name: clomipramine), starting dose 25 mg/day, maximum dosage 200 mg/day for outpatients
• Asendin (generic name: amoxapine), starting dose 150 mg/day, maximum dosage 400 mg/day
• Aventyl/Pamelor (generic name: nortyptyline), usual adult dosage 25 mg three or four times daily
• Elavil/Endep (generic name: amitryptyline), minimum dosage 10 mg/day, maximum dosage 150 mg/day
• Ludiomil (generic name: malprotiline), minimum dosage 25 mg/day, maximum dosage 75 mg
• Norpramin (generic name: desipramine), usual adult dosage 200 mg/day
• Tofranil/Janimine (generic name: imipramine), starting dosage 100 mg/day
• Vivactil (generic name: protryptyline), starting dosage 15 mg, maximum dosage 60 mg

Tricyclic and tetracyclic anti-depressants, known as TCAs, are so named because of their three-ring and four-ring atomic structures. TCAs work by blocking serotonin and norepinephrine levels in the nervous system, essentially allowing the flow of over-firing nerve impulses, which increase anxiety, to return to normal levels.

The problem with TCAs is that they also interfere with other neurotransmitters, affecting nerve cell communication all over the brain. The more neurotransmitters affected, the more side effects are created.

TCAs act on the body’s natural histamine receptors, turning on the “fight or flight” response by increasing adrenaline and increasing heart rate. Histamine reactions deflect the body’s resources away from normal bodily functions, such as the processing of waste in the renal system, and can seriously affect major organs like the liver, gall bladder, and kidneys.

As a class of antidepressant medications, the different TCAs share many features, including side effects, but they do vary in side effect intensity and likelihood.

TCAs have a poor history in emergency rooms, and are widely understood to cause a disproportionate number of deaths by suicide because of its rapid toxicity when taken in overdose.

The Louisiana Poison Control Center estimates that 70% of suicidal patients who take a TCA overdose die before they can be assisted in the ER (see Poison Pearls, Louisiana Poison Control Center).

TCAs can also affect blood sugar levels, are highly sedating, and can cause harmful skin reactions such as severe sunburn due to causing an increased sensitivity to sunlight. Other typical side effects include:

* increased heart rate * decreased blood pressure * drowsiness * dizziness when moving from a sitting or lying-down position to a standing one * constipation * weight gain * urinary retention * impotence * blurred vision * confusion

Amitriptyline, clomipramine, doxepin, trimipramine, and imipramine are the TCAs with the highest probability for these side effects.

Alcohol is toxic in combination with TCAs and should be avoided at all costs by patients taking them. Higher doses of TCAs are also proven to increase the likelihood of sudden cardiac death; in a recent study by Vanderbilt University, patients taking a 100mg dose or higher had a 41% better chance of sudden cardiac death.

TCAs have a long list of potentially serious side effects. If you are experiencing any of these symptoms while taking a tricyclic or tetracyclic medication, you should contact your medical doctor immediately:

* Shakiness * Dizziness * Vomiting * Abnormal dreams * Eye pain * Diminished sex drive * Slow pulse * Inflamed tongue * Jaundice * Hair loss * Joint pain * Abdominal pain * Palpitations * Fever * Rash * Chills * Palpitations * Visual changes * Hiccups * Muscle aches * Back pain * Nasal congestion * Irregular heartbeat * Fainting * Difficult and/or frequent urination

Tricyclic and tetracyclic antidepressants are commonly prescribed for the off-label treatment of chronic pain. The shutting down of nerve impulses may help to relieve pain by easing pain signals to the brain. TCAs for these uses are typically prescribed in lower doses and take affect quickly.

Source: Dr. Ray, Sarah Meredith, M.B.B.S., M.Sc., Purushottam B. Thapa, M.B.B.S., and others, “Cyclic antidepressants and the risk of sudden cardiac death,” Clinical Pharmacology & Therapeutics 75 (March 2004) 234-241.