Tricyclic antidepressants (TCA) are also called cyclic antidepressants and are one of the first antidepressants developed. This class of drugs has been proven quite effective but its medical use has been limited as there are newer antidepressants with less side effects. However, this drug is still prescribed to patients who fail to respond to other treatments.
Tricyclic depressant alleviate depression by making changes in the way neurotransmitters communicate with each other. TCAs increase the level of serotonin, norepinephrine, and two neurotransmitters. They also block the action of another neurotransmitter called acetylcholine. By restoring the neurotransmitters’ balance, tricyclic antidepressants will relieve depression.
There are different kinds of TCAs and some of these are desipramine, nortriptyline, doxepin, amitriptyline, amoxapine and trimipramine. 1
Screening Cut-off and Detection Time
Analysis for drugs of abuse do not necessarily or routinely include test for tricyclic antidepressants. However, rapid screening for tricyclic antidepressants in the urine is quite important in cases of toxicity, overdose, and other emergency situations. 4
There are various drugs classified under TCA and not all share the same cut-off level. In general, detection time is up to 10 days. 5
- Nortriptyline 1000 ng/ml
- Amitriptyline 1000 ng/ml
- Chlorpromazine3500 ng/ml
- Clomipramine10000 ng/ml
- Cyclobenzaprine 1500 ng/ml
- Desipramine500 ng/ml
- Diphenyldramine 20000 ng/ml
- Doxepine 1000 ng/ml
- Imipramine800 ng/ml
- Nordoxepine 1000 ng/ml
- Opipramol4000 ng/ml
- Protriptyline 3000 ng/ml
- Perphenazine 25000 ng/ml
- Promazine 200 ng.ml
DEA Drug Class
The DEA is the US federal agency in-charge of all drug-related production, trade, smuggling, use and abuse. It is the implementing arm of the Controlled Substance Act (CSA). Under the CSA are five schedules of substances, drugs and chemicals rated based on their potential for abuse, safety and medical use.3
Under the CSA, all types of tricyclic antidepressants not in combination with any drug are not-controlled drugs.
Tricyclic antidepressants are actually chemical compounds that treat depression. It is a group of drugs so named because of their chemical structure that have three rings. Tetracyclic antidepressants(TeCAs), which are closely related to TCA, have four rings of atoms.
Forms and Routes of Administration
Tricyclic antidepressants are mostly available in tablets, capsules and liquid form (oral concentrate), and cream. Doses vary from one type of TCA to another.
Amoxapine (Asanin) comes in oral tablets and in strengths of 25mg, 50mg, 100mg and 150 mg. The usual dose for an adult is:6
- initial dose: 50mg orally 2-3 times a day
- maintenance dose: 100mg orally 2-3 times a day
- maximum does: 600mg orally daily
Amitriptyline (Vanatrip, Elavil, Endep) comes in tablet form in strengths of 10mg, 25mg, 50mg, 75mg, 100mg and 150mg. It is also available in oral concentrate of 10mg/ml. Dosing for this drug varies for outpatient and inpatient, with an initial dose of 75 mg and maximum dose of 150mg for outpatients per day; 100mg initial dose and 300mg maximum dose for inpatients per day.
Protriptyline (Vivactil) comes in doses of 5mg and 10 mg.
Doxepin (Silenor) is available in tablets of 3mg, 6mg, 10mg, 25mg, 50mg, 75mg, 100mg and 150mg. Oral concentrate of this TCA comes in 10mg/ml strength. Cream for topical application comes in 30g and 40g jars. This is for addressing itching.
Doctor’s Prescription is based on the patient’s:
- Age of patient
- Possible side-effects
- Other medical problems
- Previous use of antidepressants
- History of medicines that the patient has taken
Interaction with other Drugs
TCAs have interaction with numerous drugs. Amitriptyline alone has more than major interactions with 250 drugs including cold remedies and cough syrup.
Doxepin cannot be taken with warfarin (blood thinner).
Generally, TCAs cannot be taken together with:7
- MAO inhibitors within 14 days of taking them
- Atropine-like drugs, antihistamine, sedatives, phenytoin
- Clonidine, guanadrel, ephedrine, cimetidine
- Estrogens, Fluoxetine, fluvoxamine
- Ritonavir and all protease inhibitors
- Meperidine, methylphenidate
- Oral contraceptive
- Thyroid medications
- Stimulants refer to amphetamine, methamphetamine and cocaine.
Some of the most common TCA prescribed today are:
- amoxapine (Asendin)
- desipramine (Norpramin)
- clomipramine (Anafranil)
- trimipramine (Surmontil)
- nortriptyline (Pamelor)
- protriptyline (Vivactil)
- doxepin (Sinequan)
Tricyclic antidepressants were first used to treat depression. However, they are now often prescribed off-label for the treatment of nerve pain due to shingles or diabetes, to manage a patient’s mood in panic disorder, and to help prevent depression. When prescribed for the management of chronic pain, TCA is often given in lower doses. In higher dosed, TCA works as an antidepressant.8
Approved by the Food and Drugs Administration (FDA), TCA is used for:
- Treating several types of depression
- Obsessive compulsive disorder
For off-label uses (not FDA approved), TCA has been used for the management of:
- Panic disorder
- Chronic pain such as tension headache, migraine, diabetic neuropathy, neuralgia due to herpes
- Phantom limb pain
- Premenstrual symptoms
- Chronic itching
Effects and Symptoms
All medications have side effects. However, not everyone feels the side effect or others can tolerate the side effects. In prescribing medications with major side effects, the doctor weighs the pros and cons of such medication before prescribing it.
Common Side Effects
Tricyclic antidepressants may cause a number of side effects, including:
- Blurred vision
- Dry mouth
- Dizziness or lightheadedness
- Racing heartbeat
- Urinary retention
- Increased appetite
- Low sex drive
- Difficulty achieving an erection, and other sexual difficulties
- Low blood pressure when rising to a stand
- Confusion in the elderly
- Increased sweating
- Weight gain
When to call 911
- Swelling of face, throat, lips, tongue occur
- Trouble breathing
When to call your doctor
- When the person has suicidal thoughts
- Develops hives
- Restless and agitated
- Nausea and vomiting
- Fast hear rate
Health Conditions that Make Propoxyphene Dangerous
The FDA requires drug companies that all their tricyclic antidepressants products carry a black-box warning on the label that says that these drugs make some people commit suicide or have suicidal thoughts.
People with the following condition must not take tricyclic antidepressant.9
- Recently suffered a heart attack
- Allergic to TCA
- Under 25 years old and over 65 years old
- Have thyroid, diabetes, heart disease problems
- Have enlarged prostate
- Condition affecting the urinary tract
- Have glaucoma
- History of dizziness, epilepsy
- Have liver disease
- Taking mood-management medications
- Pregnant, breast-feeding, and women planning on getting pregnant should seek medical help before taking TCA.
Tolerance, Dependence and Withdrawal
Dosing for this group of drugs starts at the lowest dose possible to manage the medical condition, then builds up to the maximum allowable dose. Some people build tolerance to the drugs, while some do not.
Some TCA have sedative effect but they are not generally classified as tranquilizers. Most people who take this drug can stop taking it without any problem. However, it is recommended to taper off TCA over a course of four weeks before completely stopping the medication. This is because some people are more sensitive to TCA and develop withdrawal symptoms when the medication is abruptly stopped. The medical community prefers to call this withdrawal period “discontinuation syndrome” in order to separate it from the illicit drug-related withdrawal period.
Discontinuation Syndrome Symptoms are:
- Anxiety and agitation
- Flu-like symptoms
- Sleep disturbance
- Mood swings
- Abdominal cramps
- Pins and needles sensations
- Low mood
These symptoms are unlikely to manifest if the TCA dosing is reduced gradually. Symptoms usually last for less than two weeks.
TCAs are basically harmless in terms of tolerance and addiction. The danger with this group of drugs comes when it used in combination with drugs such as depressants, opioids, alcohol and other illicit drugs.
The 1950s was marked by discoveries and innovation in psychopharmacology. Paul Charpentier, chief chemist of Rhône-Poulenc, synthesized chlorpromazine from synthetic antihistamines in December 1950. It was in 1952 that the psychiatric impact of this drug became evident and prompted other chemists to study derivatives of the drug.
The first TCA synthesized for the treatment of depression was imipramine. Clinical trial of this drug was in 1955. By 1957 the antidepressant effects of this TCA was reported by Roland Kuhn. Amitriptyline was introduced by Merck as the second drug in the TCA family. Other derivatives of tricyclic antidepressants were developed.2
TCAs were the drug of choice for the treatment of clinical depression. They are highly effective but have been less prescribed because of new antidepressants such as SSRIs and MAOI, which have fewer side effects. However, tricyclic antidepressants have been proven to be more effective than newer drugs in treating melancholic depression, and treatment-resistant depression.