Tricyclic antidepressant side effects

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Tricyclic Antidepressants

Tricyclic antidepressants are used to treat depression as well as manage a variety of other conditions, ranging from obsessive-compulsive disorder to bedwetting. They were one of the first types of antidepressants developed, and though they are effective, they have been largely replaced with newer antidepressants due to their potential for varied negative side effects. However, they may still be used for depression when a person doesn’t respond well to other forms of treatment, and they can be used to treat other conditions such as anxiety, fibromyalgia, chronic pain, and migraines.

What Are Tricyclic Antidepressants?

Tricyclic antidepressants, or TCAs, were first used to manage major depression. They are believed to block the reuptake of the monoamine neurotransmitters—including serotonin and norepinephrine. The resulting increase in activity of these neurotransmitters in the brain is associated with an improvement in certain symptoms of depression. 1,2

Some of the most commonly prescribed TCAs are:1

Uses of Tricyclic Antidepressants

The primary use of TCAs is for the treatment of major depressive disorder. According to the Diagnostic and Statistical Manual of Mental Disorders, a diagnosis of major depressive disorder is made based on the presence of a range of symptoms, including:3

  • Depressed mood.
  • A loss of interest in once-pleasurable activities.
  • Significant weight gain or loss.
  • Insomnia or sleeping more than usual.
  • Slower movement and functioning that is observed by others.
  • A sense of worthlessness.
  • Inability to concentrate.
  • Loss of energy.
  • Suicidal thoughts or plans.

To meet diagnostic criteria, five or more symptoms must be present over the same 2-week period, and at least one of the symptoms must be depressed mood or loss of pleasure.3

In addition to major depression, TCAs are sometimes used to treat:2,4

  • Anxiety.
  • Obsessive-compulsive disorder (OCD).

Off-label uses include:

  • Panic disorder.
  • Pediatric enuresis.
  • Pruritis.
  • Smoking cessation.
  • Migraine prophylaxis.
  • Chronic pain.
  • Pain in conjunction with: fibromyalgia, diabetes, shingles, phantom limb syndrome.

Since the introduction of other antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), the use of TCAs has declined dramatically. Tricyclics have more negative side effects than these drugs, and they are more dangerous if the person overdoses. In some cases, however, they have proved to be effective in treating depression where other treatments have failed.2

Today, however, TCAs serve as a primary method of treatment for people with neuropathic pain. Used for this purpose, TCAs can be divided into what are called secondary and tertiary amine agents. The secondary amines (nortriptyline, desipramine, and maprotiline) are selective inhibitors of norepinephrine. The tertiary amines (amitriptyline, imipramine, and clomipramine) block the reuptake of both serotonin and norepinephrine, and are relatively more effective for treating neuropathic pain. Studies have shown these drugs to be effective treatments for painful diabetic neuropathy, though it may take several weeks before the patient feels relief from pain.5

Side Effects

As mentioned above, tricyclic antidepressants are used far less often since the introduction of SSRIs and SNRIs, primarily due to their wide range of unpleasant side effects.

Reported side effects include:4

  • Anxiety.
  • Insomnia.
  • Drowsiness.
  • Dizziness.
  • Blurred vision.
  • Dry mouth.
  • Rapid heart rate.
  • Palpitations.
  • Excessive perspiration.
  • Abdominal cramps.
  • Nausea.
  • Constipation.
  • Weight gain or loss.
  • Tremors.
  • Difficulty urinating.
  • Sexual dysfunction.
  • Rash.

The risk of dangerous side effects increases if tricyclics are mixed with alcohol, cimetidine (Tagamet), St. John’s wort, or monoamine oxidase inhibitors (MAOIs).4

Risks and Overdose

Tricyclic antidepressants may increase the risk of cardiovascular issues. A study in England found that tricyclics were associated with a 35% increased risk of heart disease. The study authors did not find an increased risk with newer antidepressants such as SSRIs.4

It is also possible to overdose on tricyclic antidepressants. Symptoms of an overdose include:6

  • Dilated pupils.
  • Vomiting.
  • Low body temperature.
  • Severely low blood pressure.
  • Shock.
  • Cardiac dysrhythmias.
  • Congestive heart failure.
  • Fluid buildup in the lungs.
  • Restlessness.
  • Confusion.
  • Hallucinations.
  • Convulsions.
  • Stupor.
  • Coma.

An overdose requires immediate medical attention. If you observe the signs of overdose in yourself or someone else, call 911 right away.

People who wish to stop taking tricyclics should speak to their doctor first. Quitting the medications suddenly can lead to withdrawal symptoms such as upset stomach, flu-like symptoms, anxiety, dizziness, “electric shock” sensations, and seizures.7

Combining Talk Therapy with TCAs

Generally, treatment that includes both an antidepressant medication and talk therapy tends to produce better results than either approach on its own. Both approaches can provide relief from symptoms of depression, but better results have been seen when both medications and psychotherapy are combined.

According to researchers, the results of a meta-analysis published in World Psychiatry provide “clear evidence that combined treatment with psychotherapy and antidepressant medication is more effective than treatment with antidepressant medication alone.”8

The National Alliance on Mental Illness makes a similar recommendation, saying that for many, psychotherapy and medications give better results than either treatment alone. They suggest several approaches to therapy that are well-suited to treating depression in combination with medication, including the following:9

  • Cognitive behavioral therapy (CBT): CBT is designed to identify and adjust negative patterns of thought associated with depression by teaching coping strategies to deal with these thoughts.
  • Interpersonal therapy (IPT): This approach focuses on life challenges that may lead to or exacerbate depression, such as relationships. Practitioners work with clients to examine their interactions and teach techniques for improving their relationships with others.
  • Psychodynamic therapy: The goal of this therapy is to recognize unwelcome patterns of feeling and behavior arising from past experiences and to learn techniques for resolving them.

The Importance of Treatment

Despite the presence of newer medications—and new approaches to psychotherapy—first-wave medications such as tricyclic antidepressants can be effective in addressing the challenges faced by those with major depressive disorder or other mental health issues.

Although they can have significant side effects, tricyclic antidepressants may be able to relieve depression and other conditions, such as diabetic neuropathy, in cases where other medications have not. A discussion with your team of medical professionals is the best way to determine if tricyclic antidepressants are the best choice for you.

Sources

. American Psychological Association. Tricyclic Antidepressant (TCA).

. National Health Service. (2018). Antidepressants: Overview

. Foley, C. (2018). Tricyclic Antidepressants: Do They Work? University Health News Daily.

. ScienceDirect. Tricyclic Antidepressant.

. Food and Drug Administration. (2007). Pamelor.

. National Health Service. (2018). Antidepressants: Dosage.

. National Alliance on Mental Illness. (2017). Depression.

TCAs are a class of drugs that’s been used for decades to treat depression, anxiety, and certain kinds of pain.

Tricyclic antidepressants, also known as TCAs, were first approved by the Food and Drug Administration (FDA) to treat depression and obsessive-compulsive disorder (OCD).

These drugs work by increasing the concentrations of two mood-altering chemicals — the neurotransmitters norepinephrine and serotonin — in the brain.

While TCAs have been around for decades, scientists still aren’t exactly sure how they cause these changes.

TCAs are thought to increase neurotransmitter levels by preventing nerve endings — called synapses — from drawing these chemicals back into their tissues, which is normally how the body reduces their concentrations.

Tricyclic antidepressants include:

  • Amitriptyline
  • Amoxapine
  • Norpramin (desipramine)
  • Pamelor (nortriptyline)
  • Silenor (doxepin)
  • Surmontil (trimipramine)
  • Tofranil (imipramine)
  • Vivactil (protriptyline)

Although first prescribed to treat depression, tricyclic antidepressants are now often prescribed off-label to treat nerve pain caused by diabetes or shingles, to help prevent migraines, to manage mood in panic disorder, and to relieve pain and other sensations felt in limbs that have been removed from the body (phantom limb pain).

Warnings and Precautions

The FDA requires that all tricyclic antidepressants carry a black-box warning on the label, notifying users that these drugs may make some people have suicidal thoughts or commit suicide.

Don’t take a tricyclic antidepressant if you:

  • Are allergic to TCAs or any of the drug’s inactive ingredients
  • Recently had a heart attack

Ask your doctor before taking TCAs if you:

  • Are under age 25 or over age 65
  • Have diabetes, heart problems, or a thyroid disorder
  • Have any conditions affecting your urinary tract or an enlarged prostate
  • Have glaucoma
  • Have a liver disease
  • Have a history of seizures
  • Take medications to help manage your mood

Common Side Effects

Tricyclic antidepressants may cause a number of side effects, including:

  • Dry mouth
  • Blurred vision
  • Sweating
  • Dizziness or lightheadedness
  • Drowsiness
  • Restlessness
  • Racing heartbeat
  • Increased sweating
  • Urinary retention
  • Constipation
  • Tremor
  • Increased appetite
  • Weight gain
  • Low sex drive
  • Difficulty achieving an erection, and other sexual difficulties
  • Low blood pressure when rising to a stand
  • Confusion in the elderly

Drug Interactions

TCAs interact with many different drugs, so ask your doctor or pharmacist about possible interactions before taking a tricyclic antidepressant.

Don’t take TCAs if you’re also taking:

  • MAOIs such as Marplan (isocarboxazid) or Parnate (tranylcypromine)
  • Zyvox (linezolid)
  • Drugs for bowel preparation that contain phosphate, usch as OsmoPrep or Visicol
  • Tagamet
  • Alcohol
  • St. John’s wort

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Tricyclic antidepressants

Tricyclic antidepressants (often abbreviated to TCAs) are a group of medicines that all have a similar structure and all work in a similar way. They may be used for the treatment of other conditions, not only depression.

Experts believe TCAs work by increasing levels of two neurotransmitters (these are chemicals that relay messages in the brain), norepinephrine and serotonin. Norepinephrine helps with attention and modulates emotional response. Serotonin is often referred to as the “feel good hormone”. It carries messages between brain cells and contributes to well-being, good mood, and appetite, as well as helping to regulate the body’s sleep-wake cycle and internal clock. TCAs may also block the actions of other neurotransmitters, such as acetylcholine and histamine.

Some TCAs affect these neurotransmitters more than others which explains why some TCAs work better for conditions other than depression or are more likely to cause side effects such as constipation, dry mouth, or sedation.

Antidepressants is the name given to all medicines that relieve the symptoms of depression. TCAs are just one of several classes of antidepressant. Other types include norepinephrine and dopamine reuptake inhibitors (NDRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitor (SARIs), tetracyclic antidepressants (TeCAs), and the miscellaneous antidepressants.

What are tricyclic antidepressants used for?

Tricyclic antidepressants were among the first antidepressants developed. They have largely been superseded by newer antidepressants that have less side effects, although they may still suit certain people or be effective when other antidepressants have been ineffective.

In addition to depression, TCAs may also be used to treat a range of other conditions, for example:

  • Anxiety
  • Bed-wetting
  • Chronic nerve-related pain
  • Migraine prevention
  • Obsessive-compulsive disorder
  • Panic attacks
  • Post-traumatic stress disorder (PTSD).

Some reduction in symptoms may be noticed within one to two weeks; however, it may take six to eight weeks of treatment before the full effects are seen.

What are the differences between tricyclic antidepressants?

Although all TCAs are thought to act in the same way, with some slight variations in their effect on certain neurotransmitters, there are differences between individual TCAs with regards to how long they remain in the body, how they are metabolized, and their propensity for interactions with other medications, and their side effects. For example, amitriptyline, doxepin, imipramine and trimipramine are more likely to cause sedation than nortriptyline and desipramine.

Amitriptyline, doxepin, and imipramine have been associated with more weight gain than some other TCAs; nortriptyline and desipramine may be better tolerated.

Some TCAs, such as amoxapine, are often listed as a TCA, but are in fact tetracyclic antidepressants.

Generic name Brand name examples
amitriptyline Generic only
amoxapine Asendin
clomipramine Anafranil
desipramine Norpramin
doxepin Sinequan
imipramine Tofranil
nortriptyline Pamelor
protriptyline Vivactil
trimipramine Surmontil

Are tricyclic antidepressants safe?

When taken at the recommended dosage, tricyclic antidepressants are considered safe. However, they have been associated with a few severe side effects, some potentially fatal, such as:

  • An increase in suicidal thoughts and behaviors, particularly in children and young adults under the age of 25 years. This is most likely to occur when starting therapy
  • Serotonin syndrome – this is caused by excessive levels of serotonin in the body and is more likely to occur with higher dosages of SSRIs or when SSRIs are administered with other medications that also release serotonin. Symptoms include agitation, confusion, sweating, tremors, and a rapid heart rate
  • The precipitation of a manic episode in people with undiagnosed bipolar disorder
  • An increased risk of seizures in people with a history of seizures
  • An increased risk of arrhythmias, heart attacks, stroke, and other cardiovascular effects, particularly in people with pre-existing heart disease
  • The triggering of an angle closure attack in people with angle-closure glaucoma.

TCAs may also not be suitable for people with hyperthyroidism or receiving thyroid medications, or in those who use alcohol excessively.

What are the side effects of tricyclic antidepressants?

Some of the more commonly reported side effects with tricyclic antidepressants include:

  • A drop-in blood pressure when moving from a sitting to standing position
  • Blurred vision
  • Constipation
  • Disorientation or confusion
  • Drowsiness
  • Dry mouth
  • Excessive sweating
  • Increased or irregular heart beat
  • Sexual dysfunction (such as reduced desire or erectile dysfunction)
  • Tremor
  • Urine retention
  • Weight loss or weight gain.

For a complete list of side effects, please refer to the individual drug monographs.

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.

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 urine drug testing is quite important in cases of toxicity, overdose and other emergency situations.

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.

  • 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.

Under the CSA, all types of tricyclic antidepressants not in combination with any drug are not-controlled drugs.

Tricyclic Antidepressants Drug Type

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
  • 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:

  • 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
  • Stimulants
  • Oral contraceptive
  • Thyroid medications
  • Alcohol
  • Stimulants refer to amphetamine, methamphetamine and cocaine.

Tricyclic Antidepressant Brand Names

Some of the most common TCA prescribed today are:

Tricyclic Antidepressant Uses

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.

Approved by the Food and Drugs Administration (FDA), TCA is used for:

  • Treating several types of depression
  • Obsessive compulsive disorder
  • Bedwetting

For off-label uses (not FDA approved), TCA has been used for the management of:

  • Bulimia
  • Panic disorder
  • Chronic pain such as tension headache, migraine, diabetic neuropathy, neuralgia due to herpes
  • Phantom limb pain
  • Premenstrual symptoms
  • Chronic itching

Tricyclics Side Effects and Symptoms

All medications have side effects. However, not everyone feels the side effect or 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 of Tricyclic Antidepressants

Tricyclic antidepressants may cause a number of side effects, including:

  • Blurred vision
  • Dry mouth
  • Dizziness or lightheadedness
  • Drowsiness
  • Restlessness
  • Racing heartbeat
  • Urinary retention
  • Constipation
  • Tremor
  • 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
  • Sweating
  • 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 Tricyclic Antidepressants 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 conditions must not take tricyclic antidepressants:

  • 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 TCAs

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 effects 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
  • Dizziness
  • Flu-like symptoms
  • Sleep disturbance
  • Mood swings
  • Nauseous
  • Abdominal cramps
  • Diarrhea
  • 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.

History of Tricyclic Antidepressants

The 1950’s 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.

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.

Tricyclic antidepressants and tetracyclic antidepressants

Possible side effects and cautions

Because of the different ways cyclic antidepressants work, side effects vary somewhat from medication to medication. Some side effects may go away after a time, while others may lead you and your doctor to try a different medication. Side effects may also be dependent on the dose, with higher doses often causing more side effects.

Some common possible side effects include:

  • Blurred vision
  • Constipation
  • Dry mouth
  • Drowsiness
  • Drop in blood pressure when moving from sitting to standing, which can cause lightheadedness
  • Urine retention

Other possible side effects, among others, include:

  • Increased appetite leading to weight gain
  • Weight loss
  • Excessive sweating
  • Tremor
  • Sexual problems, such as difficulty achieving an erection, delayed orgasm or low sex drive

Generally speaking:

  • Amitriptyline, doxepin, imipramine and trimipramine are more likely to make you sleepy than other tricyclic antidepressants are. Taking these medications at bedtime may help.
  • Amitriptyline, doxepin and imipramine are more likely to cause weight gain than other tricyclic antidepressants are.
  • Nortriptyline and desipramine appear to have better tolerated side effects than other tricyclic antidepressants do.

Which antidepressant is best for you depends on a number of issues, such as your symptoms and any other health conditions you may have. Ask your doctor and pharmacist about the most common possible side effects for your specific antidepressant and read the patient medication guide that comes with the prescription.

What are tricyclic antidepressants?

Tricyclic antidepressants, such as amitriptyline and nortriptyline, were once widely used as antidepressants before being replaced by newer antidepressant medications with better side effect profiles. Other uses of tricyclic antidepressants include the treatment of insomnia, enuresis and chronic pain syndromes such as fibromyalgia.

The tricyclic antidepressants are finding a place in the treatment of chronic pain and itch associated with some dermatological conditions.

Tricyclic antidepressants are useful in reducing the symptoms of chronic pain in the following skin conditions:

  • Vulvodynia (vulval pain)
    • Vestibulodynia (pain with sexual intercourse)
    • Dyaesthetic vulvodynia (neuropathic pain)
  • Shingles and post-herpetic neuralgia
  • Trigeminal trophic syndrome

Pain arising from these conditions is defined as sympathetically maintained pain (SMP). The pain is usually described as having a burning sensation and is often in response to stimuli that do not ordinarily cause pain. This pain originates from the nervous system. Amitriptyline appears to be effective in reducing this type of neuropathic pain in doses lower than those used to treat depression.

Tricyclic medications may reduce the pain of chronic ulcers including:

  • Pyoderma gangrenosum
  • Polyarteritis nodosum
  • Venous ulceration
  • Epidermolysis bullosa.

Tricyclic antidepressants are sometimes successfully prescribed for pruritus (itch), especially when this is of neuropathic origin:

  • Notalgia paraesthetica
  • Brachioradial pruritus
  • Pruritus vulvae
  • Male genital dysaesthesia

Tricyclic medication has some antihistamine H1 blocking activity and may be useful in the treatment of urticaria even when conventional antihistamines have failed.

The dosage of tricyclic medications

Patients are usually started on tricyclic medications at a low dose of 5–10 mg daily, taken at night to minimise side effects. This is gradually increased to a maximum daily dose of 50–150 mg, depending on the response and tolerability of side effects by the patient. Patients need to be warned that pain/itch relief is not immediate as it may take several weeks for the drug to become fully effective.

Side effects of tricyclic medications

The side effects of amitriptyline and nortriptyline include:

  • Sedation
  • Drowsiness
  • Dry mouth (which could contribute to dental decay)
  • Blurred vision
  • Constipation
  • Increased sweating (hyperhidrosis)
  • Difficulty urinating
  • Dizziness due to a drop in blood pressure on standing up (postural hypotension)
  • Nausea, confusion or a headache due to hyponatraemia (sodium imbalance)
  • Weight gain
  • Heart rhythm disturbances.

Anticholinergic/antimuscarinic side effects may occur in up to 50% of patients and elderly patients are at greater risk. Intolerance of these effects often leads to discontinuation of the drug. Other tricyclic antidepressants such as desipramine and nortriptyline may be better tolerated than amitriptyline.

It may be dangerous to take a tricyclic medicine with a monoamine oxidase inhibitor (MAOI) antidepressant medication or within 14 days of discontinuing an MAOI. Adverse effects are likely to be worse with alcohol.

Tricyclic medications may not be suitable for people with certain medical conditions or taking certain medications such as anticholinergic agents. Tell your doctor if you have had any of the following health problems:

  • Heart disease
  • Seizures/epilepsy
  • Glaucoma
  • Urinary retention
  • Overactive thyroid gland
  • Drug-related hyperpyrexia.

It may be wise to under an electrocardiograph prior to treatment and have this repeated after a few weeks. Tricyclic medications are dangerous in overdose.

New Zealand approved datasheets are the official source of information for these prescription medicines, including approved uses and risk information. Check the individual New Zealand datasheet on the Medsafe website.

TCA urine test (tricyclic antidepressants)

Description

This strip is made for the detection in human urine of tricyclic antidepressants.

Tricyclic antidepressants are used to treat obsessive compulsive disorders, behavioral problems, or to treat depression.

Like other pharmaceutical mollecules, they are often diverted from legal medical cricuit, and are misused by some people, especially to help reduce stress. Much use without medical supervision have also been identified in the workplace, or even the school environment and students.

This test is a qualitative assay (type “NO / YES”), and thus delivers a “NEGATIVE” or “POSITIVE” result.

Technical data

Cut-off : 1 000 ng/ml
This test will be positive if the sample tested contains at least 1 000 nanograms of one of the medications in this class of pharmacopoeia per milliliter of urine, or negative if the sample contains less or not at all.

Detection time of tricyclic antidepressants in urine :

  • 5 days after consumption

NarcoCheck® Tricyclic antidepressants test (TCA 1000)

compounds cut-off (ng/ml)
Nortriptyline 1 000
Amitriptyline 1 000
Chlorpromazine 3 500
Clomipramine 10 000
Cyclobenzaprine 1 500
Desipramine 500
Diphenyldramine 20 000
Doxepine 1 000
Imipramine 800
Nordoxepine 1 000
Opipramol 4 000
Protriptyline 3 000
Perphenazine 25 000
Promazine 200
Promethazine 40 000
Trimipramine 2 500



Available test formats

Dipstick

The test is immersed directly into the urine sample, which prevents any liquid handling.
Currently on this page.

Cassette + pipette

Few microliters of sample are collected using a disposable pipette (provided with each test) and then introduced directly into the test.
Available only on special order.
Ask for a quotation



Tricyclic antidepressants (also called tricyclics or TCAs) are named for their chemical structure (3 rings). They are among the earliest antidepressants developed and first came into widespread use in the 1950s. Some of the available tricyclics include imipramine, amitriptyline, clomipramine and nortriptyline.

Tricyclics are currently available in Australia for the treatment of depression, certain anxiety disorders and chronic pain.

Tricyclic antidepressants tend to have more unpleasant and serious side effects than newer antidepressants (such as SSRIs). However, they can be very effective in treating depression and other illnesses, and are often prescribed when other medicines or treatments have not been helpful.

What are tricyclics used for?

Tricyclics are commonly used to treat depression when other medicines have not been effective. They may also be used in people who have not tolerated other antidepressant medicines due to side effects.

Tricyclics can also be used in the treatment of certain anxiety disorders, including:

  • obsessive-compulsive disorder (OCD);
  • panic disorder;
  • generalised anxiety disorder;
  • phobias; and
  • post-traumatic stress disorder (PTSD).

Tricyclics are not usually the first choice medicine for anxiety disorders, but may be helpful when other medicines have not controlled symptoms.

Tricyclics also have a pain-relieving effect that is separate from their antidepressant effect, and may be especially useful in relieving neuropathic pain (nerve pain). They can also sometimes be used in the treatment of chronic pain (ongoing pain) that is not due to nerve pain.

Tricyclic antidepressants in Australia

There are several different tricyclic antidepressants available in Australia. They can be taken as tablets or capsules. See the table below for a list of the different tricyclics, what they are commonly used to treat and their brand names.

Tricyclic antidepressants
Type of tricyclic May be used to treat Examples of brand names
Amitriptyline Severe depression, neuropathic pain, PTSD Endep, Entrip
Clomipramine Severe depression, obsessive-compulsive disorder, phobias, panic disorder Anafranil, Placil
Dosulepin (dothiepin) Severe depression with anxiety Dothep
Doxepin Severe depression, neuropathic pain Deptran, Sinequan
Imipramine Severe depression, generalised anxiety disorder, panic disorder Tofranil, Tolerade
Nortriptyline Severe depression, neuropathic pain Allegron, NortriTABS

Amitriptyline is the most commonly used tricyclic antidepressant for treating neuropathic pain (such as sciatica); doxepin or nortriptyline may be used as alternatives.

How tricyclics work

Tricyclic antidepressants allow more of the brain chemicals serotonin and noradrenaline to be available to nerve cells. This helps nerve signalling in the brain, which can help relieve depression.

Unfortunately, as well as making more serotonin and noradrenaline available, tricyclic antidepressants also affect the amounts of other chemicals, such as histamine and acetylcholine, which are involved in other nerve signalling systems that are responsible for a wide range of other bodily processes. Because of this, tricyclics have a variety of side effects.

Side effects of tricyclics

As with all medicines, side effects are possible, but you may not experience any side effects at all. If you do get side effects, they may go away after a week or so of treatment.

Side effects of tricyclics can include:

  • drowsiness;
  • difficulty urinating;
  • dizziness when standing up (due to a sudden drop in blood pressure);
  • dry mouth;
  • blurred vision;
  • constipation;
  • sweating (especially at night);
  • palpitations (an awareness of your heart beating or pounding);
  • changes in sexual function (including reduced libido, difficulty having an orgasm, problems ejaculating);
  • change in appetite; and
  • weight gain or weight loss.

If you are getting these side effects from one tricyclic you may not get them from another, as each one is different.

Some side effects can be mistaken for some of the symptoms of depression, so it is very important to talk to your doctor about any side effects you experience — your doctor may need to change the dose or change the medicine altogether.

If tricyclic antidepressants are not taken according to your doctor’s instructions (if too many are taken) they can cause confusion, seizures and dangerous heart rhythm problems. Taking too much of this type of medicine is dangerous to your health.

Taking tricyclics

When you begin treatment with a tricyclic antidepressant your doctor will recommend starting with a low dose. The dose is then gradually increased over several days. Because tricyclics can make you sleepy (some more than others), your doctor may recommend you take them at bedtime to help with sleep and to minimise drowsiness during the day.

People younger than 25 years of age with depression may have a slightly increased risk of suicidal thoughts and behaviour when they first start taking antidepressants. So close monitoring is needed in any young person taking antidepressants, especially when they are first started. Get help straight away if you experience any suicidal thoughts.

It’s important that you don’t stop taking tricyclic antidepressants suddenly as this can cause withdrawal symptoms. Talk to your doctor, and if your medicine needs to be stopped, they the dose should generally be reduced slowly.

Tricyclics, alcohol and driving

If you are prescribed a tricyclic, you should avoid alcohol. Alcohol can increase the sedative effects of the medicine and you should not drink and drive while taking tricyclics.

Your doctor may advise you not to drive or operate machinery until they can judge whether you are suffering from any sedating side effects.

People taking tricyclics should not take cannabis as it can make you very unwell.

Who should not take tricyclic antidepressants?

Tricyclic antidepressants can be dangerous or cause problems if taken by people with:

  • heart problems;
  • prostate enlargement;
  • glaucoma;
  • thyroid problems;
  • diabetes;
  • liver disease;
  • epilepsy or a history of seizures; or
  • a history of head injury.

Tricyclics can also interact with other medicines. When medicines interact, the effects of either medicine can be changed. Some of the medicines that tricyclics interact with include:

  • other antidepressants, including monoamine oxidase inhibitors and SSRIs;
  • lithium;
  • antiarrhythmic medicines (used to control heart rhythm);
  • some medicines for high blood pressure; and
  • certain medicines for sleep disturbances.

Some complementary medicines, such as St John’s wort, also interact with antidepressants. Always tell your doctor if you are taking any other medicines before starting on tricyclics, as interactions between medicines can be dangerous to your health. Also, some tricyclics interact with grapefruit, grapefruit juice and cranberry juice – ask your doctor about whether you need to adjust your diet.

Pregnancy and breast feeding

If you are pregnant or planning a pregnancy, let your doctor know, as it will impact on the type of medicine that your doctor prescribes. Your doctor will weigh up the risks and benefits of treatment for both you and your baby. Breast feeding is not recommended if you are taking tricyclic antidepressants.

Tetracyclic antidepressants

Tetracyclic antidepressants (which have 4 rings in their chemical structure) are among the oldest types of antidepressants. Mianserin (brand name Lumin) is a tetracyclic antidepressant available in Australia.

Mianserin can be used to treat depression, and may be useful in people whose symptoms include insomnia (difficulty sleeping) or weight loss.

When taking mianserin you need to have several blood tests to check for a rare and dangerous side effect called agranulocytosis. This is where the number of white blood cells (which fight infection) decrease, which can increase your risk of serious infections.

Changing antidepressants

If you are changing antidepressants, your doctor will usually recommend slowly stopping the first medicine and then having a break before starting the new one. This is called a ‘washout period’, and it’s important because it prevents the antidepressants interacting, which can cause serious harm.

Depending on the antidepressants you are stopping and starting, the washout period may need to last for days or weeks. The main concern is serotonin toxicity (also known as serotonin syndrome), which is an overload of serotonin in the brain.

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Last Reviewed: 21/07/2018

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  • Albers LJ, Reist C, Vu RL, Fujimoto K, Ozdemir V, Helmeste D, et al. Effect of venlafaxine on imipramine metabolism. Psychiatry Res. 2000;96:235–243.
  • Amitai Y, Frischer H. Excess fatality from desipramine and dosage recommendations. Ther Drug Monit. 2004;26:468–473.
  • Amitai Y, Frischer H. Excess fatality from desipramine in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2006;45:54–60.
  • Amsterdam JD, Garcia-Espana F, Rosenzweig M. Clomipramine augmentation in treatment-resistant depression. Depress Anxiety. 1997;5:84–90.
  • Anderson IM. SSRIS versus tricyclic antidepressants in depressed inpatients: a meta- analysis of efficacy and tolerability. Depress Anxiety. 1998;7 Suppl 1:11–17.
  • Anderson IM. Meta-analytical studies on new antidepressants. Br Med Bull. 2001;57:161–178.
  • Anon British National Formulary 2005Pharmaceutical Press: London; ISBN 9780853696698
  • Bassetti C. Narcolepsy. Curr Treat Opt Neurol. 1999;1:291–298.
  • Baumann P, Hiemke C, Ulrich S, Gaertner I, Rao ML, Eckermann G, et al. Therapeutic monitoring of psychotropic drugs: an outline of the AGNP-TDM expert group consensus guideline. Ther Drug Monit. 2004;26:167–170.
  • Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts of interest in biomedical research: a systematic review. JAMA. 2003;289:454–465.
  • Bertilsson L, Dahl ML, Dalen P, Al-Shurbaji A. Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol. 2002;53:111–122.
  • Bezchlibnyk-Butler KZ, Jeffries JJ. Clinical Handbook of Psychotropic Drugs 2005Hogrefe and Huber: Toronto; 15 edn
  • Blier P, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Debonnel G. Effects of different doses of venlafaxine on serotonin and norepinephrine reuptake in healthy volunteers. Int J Neuropharmacol. 2007;10:41–50.
  • Bogni A, Monshouwer M, Moscone A, Hidestrand M, Ingelman-Sundberg M, Hartung T, et al. Substrate specific metabolism by polymorphic cytochrome P450 2D6 alleles. Toxicol In Vitro. 2005;19:621–629.
  • Bolden-Watson C, Richelson E. Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci. 1993;52:1023–1029.
  • Bonnet U. Moclobemide: therapeutic use and clinical studies. CNS Drug Rev. 2003;9:97–140.
  • Brosen K. Some aspects of genetic polymorphism in the biotransformation of antidepressants. Therapie. 2004;59:5–12.
  • Brunton LL, Lazo JS, Parker KL. Goodman and Gilman’s The Pharmacologicl Basis of Therapeutics 2006McGraw-Hill: New York; 11th edn
  • Buckley N. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ. 2002;325:1332–1333.
  • Buckley NA, Mcmanus PR. Can the fatal toxicity Of antidepressant drugs be predicted with pharmacological and toxicological data. Drug Saf. 1998;18:369–381.
  • Carlsson A, Lindqvist M. Central and peripheral monoaminergic membrane-pump blockade by some addictive analgesics and antihistamines. J Pharm Pharmacol. 1969;21:460–464.
  • Chalon SA, Granier LA, Vandenhende FR, Bieck PR, Bymaster FP, Joliat MJ, et al. Duloxetine increases serotonin and norepinephrine availability in healthy subjects: a double-blind, controlled study. Neuropsychopharmacology. 2003;28:1685–1693.
  • Christensen M, Tybring G, Mihara K, Yasui-Furokori N, Carrillo JA, Ramos SI, et al. Low daily 10-mg and 20-mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19) Clin Pharmacol Ther. 2002;71:141–152.
  • Coppen A, Ghose K, Swade C, Wood K. Effect of mianserin hydrochloride on peripheral uptake mechanisms for noradrenaline and 5-hydroxytryptamine in man. Br J Clin Pharmacol. 1978;5 Suppl 1:13S–17S.
  • Cowen PJ. New drugs, old problems: revisiting pharmacological management of treatment-resistant depression. Adv Psychiatr Treat. 2005;11:11–27.
  • Danie WA, Syrek M, Rylko Z, Wojcikowski J. Effects of antidepressant drugs on the activity of cytochrome P-450 measured by caffeine oxidation in rat liver microsomes. Pol J Pharmacol. 2001;53:351–357.
  • Dawson AH. The tricyclic antidepressants Med Toxicol 2004Lippincott Williams & Wilkins: Baltimore; 851–861.In: Dart RC (ed)vol. 1, 3rd edn, pp
  • de Leon J, Armstrong SC, Cozza KL. Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics. 2006;47:75–85.
  • DeBattista C, Sofuoglu M, Schatzberg AF. Serotonergic synergism: the risks and benefits of combining the selective serotonin reuptake inhibitors with other serotonergic drugs. Biol Psychiatry. 1998;44:341–347.
  • Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P. Differential physiological effects of a low dose and high doses of venlafaxine in major depression. Int J Neuropharmacol. 2007;10:51–61.
  • Doggrell SA, Woodruff GN. Effects of antidepressant drugs on noradrenaline accumulation and contractile responses in the rat anococcygeus muscle. Br J Pharmacol. 1977;59:403–409.
  • Dostert P, Castelli MG, Cicioni P, Strolin Benedetti M. Reboxetine prevents the tranylcypromine-induced increase in tyramine levels in rat heart. J Neural Transm. 1994;41:149–153.
  • Ellis P. Australian and New Zealand clinical practice guidelines for the treatment of depression. Aust NZ J Psychiatry. 2004;38:389–407.
  • Fineberg NA, Gale TM. Evidence-based pharmacotherapy of obsessive-compulsive disorder. Int J Neuropharmacol. 2005;8:107–129.
  • Furman KD, Grimm DR, Mueller T, Holley-Shanks RR, Bertz RJ, Williams LA, et al. Impact of CYP2D6 intermediate metabolizer alleles on single-dose desipramine pharmacokinetics. Pharmacogenetics. 2004;14:279–284.
  • Geister U, Gaupp M, Arnold P, Schaarschmidt D, Doser K, Renner J. Bioavailability investigation of two different oral formulations of doxepin. Arzneimittelforschung. 2001;51:189–196.
  • Ghose K, Coppen A, Turner P. Autonomic actions and interactions of mianserin hydrochloride (Org. GB 94) and amitriptyline in patients with depressive illness. Psychopharmacology (Berl) 1976;49:201–204.
  • Gillman PK. Linezolid and serotonin toxicity. Clin Infect Dis. 2003;37:1274–1275.
  • Gillman PK. Comment on: serotonin syndrome due to co-administration of linezolid and venlafaxine. J Antimicrob Chemother. 2004;54:844–845.
  • Gillman PK. Drug interactions and fluoxetine: a commentary from a clinician’s perspective. Expert Opin Drug Saf. 2005a;4:965–968.
  • Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth. 2005b;95:434–441.
  • Gillman PK. A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biol Psychiatry. 2006a;59:1046–1051.
  • Gillman PK. A systematic review of the serotonergic effects of mirtazapine: implications for its dual action status. Hum Psychopharmacol. 2006b;21:117–125.
  • Gillman PK. Serotonin syndrome: history and risk. Fund Clin Pharmacol. 1998;12:482–491.
  • Gillman PK, Whyte IM. Serotonin Syndrome. Oxford University Press: Oxford; 2004.
  • Goodman NW. Who will challenge evidence-based medicine. J R Coll Physicians London. 1999;33:249–251.
  • Gruetter CA, Lemke SM, Anestis DK, Szarek JL, Valentovic MA. Potentiation of 5-hydroxytryptamine-induced contraction in rat aorta by chlorpheniramine, citalopram and fluoxetine. Eur J Pharmacol. 1992;217:109–118.
  • Gupta RK, Tiller JW, Burrows GD. Dual action antidepressants and some important considerations. Aust NZ J Psychiatry. 2003;37:190–195.
  • Harvey AT, Rudolph RL, Preskorn SH. Evidence of the dual mechanisms of action of venlafaxine. Arch Gen Psychiatry. 2000;57:503–509.
  • Hirschfeld RM, Montgomery SA, Aguglia E, Amore M, Delgado PL, Gastpar M, et al. Partial response and nonresponse to antidepressant therapy: current approaches and treatment options. J Clin Psychiatry. 2002;63:826–837.
  • Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 2005;5:6–13.
  • Jiang Z, Dragin N, Jorge-Nebert LF, Martin MV, Guengerich FP, Aklillu E, et al. Search for an association between the human CYP1A2 genotype and CYP1A2 metabolic phenotype. Pharmacogenet Genomics. 2006;16:359–367.
  • Jiang ZP, Shu Y, Chen XP, Huang SL, Zhu RH, Wang W, et al. The role of CYP2C19 in amitriptyline N-demethylation in Chinese subjects. Eur J Clin Pharmacol. 2002;58:109–113.
  • Jo SH, Youm JB, Lee CO, Earm YE, Ho WK. Blockade of the HERG human cardiac K(+) channel by the antidepressant drug amitriptyline. Br J Pharmacol. 2000;129:1474–1480.
  • Johansson I, Lundqvist E, Bertilsson L, Dahl ML, Sjoqvist F, Ingelman-Sundberg M. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc Natl Acad Sci USA. 1993;90:11825–11829.
  • Keller T, Schneider A, Tutsch-Bauer E. Fatal intoxication due to dothiepin. Forensic Sci Int. 2000;109:159–166.
  • Khalifa M, Daleau P, Turgeon J. Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. J Pharmacol Exp Ther. 1999;291:280–284.
  • Kongsamut S, Kang J, Chen XL, Roehr J, Rampe D. A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs. Eur J Pharmacol. 2002;450:37–41.
  • Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology. 2003;28:519–526.
  • Lamba JK, Lin YS, Thummel K, Daly A, Watkins PB, Strom S, et al. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics. 2002;12:121–132.
  • Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data. Clin Infect Dis. 2006;42:1578–1583.
  • Leucht S, Hackl HJ, Steimer W, Angersbach D, Zimmer R. Effect of adjunctive paroxetine on serum levels and side-effects of tricyclic antidepressants in depressive inpatients. Psychopharmacology (Berl) 2000;147:378–383.
  • Lopez-Munoz F, Alamo C, Rubio G, Cuenca E. Half a century since the clinical introduction of chlorpromazine and the birth of modern psychopharmacology. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:205–208.
  • Mann K, Hiemke C, Schmidt LG, Bates DW. Appropriateness of therapeutic drug monitoring for antidepressants in routine psychiatric inpatient care. Ther Drug Monit. 2006;28:83–88.
  • Mason J, Freemantle N, Eccles M. Fatal toxicity associated with antidepressant use in primary care. Br J Gen Pract. 2000;50:366–370.
  • McManus P, Mant A, Mitchell P, Birkett D, Dudley J. Co-prescribing of SSRIs and TCAs in Australia: how often does it occur and who is doing it. Br J Clin Pharmacol. 2001;51:93–98.
  • Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B. Evidence b(i)ased medicine – selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications. BMJ. 2003;326:1171–1173.
  • Meyer JH, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an DASB positron emission tomography study. Am J Psychiatry. 2004;161:826–835.
  • Millan MJ, Gobert A, Rivet JM, Adhumeau-Auclair A, Cussac D, Newman-Tancredi A, et al. Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of alpha2-adrenergic and serotonin2C receptors: a comparison with citalopram. Eur J Neurosci. 2000;12:1079–1095.
  • Mizutani T. PM frequencies of major CYPs in Asians and Caucasians. Drug Metab Rev. 2003;35:99–106.
  • Nelson JC, Mazure CM, Jatlow PI, Bowers MB, Jr, Price LH. Combining norepinephrine and serotonin reuptake inhibition mechanisms for treatment of depression: a double-blind, randomized study. Biol Psychiatry. 2004;55:296–300.
  • Nelson JC, Portera L, Leon AC. Are there differences in the symptoms that respond to a selective serotonin or norepinephrine reuptake inhibitor. Biol Psychiatry. 2005;57:1535–1542.
  • Nicholson GM, Blanche T, Mansfield K, Tran Y. Differential blockade of neuronal voltage-gated Na(+) and K(+) channels by antidepressant drugs. Eur J Pharmacol. 2002;452:35–48.
  • Nielsen KK, Flinois JP, Beaune P, Brosen K. The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther. 1996;277:1659–1664.
  • Oates JA, Sjoerdsma A. Neurologic effects of tryptophan in patients receiving a monoamine oxidase inhibitor. Neurology. 1960;10:1076–1078.
  • Pare CM, Kline N, Hallstrom C, Cooper TB. Will amitriptyline prevent the ‘cheese’ reaction of monoamine-oxidase inhibitors. Lancet. 1982;2:183–186.
  • Parker G, Roy K, Wilhelm K, Mitchell P. Assessing the comparative effectiveness of antidepressant therapies: a prospective clinical practice study. J Clin Psychiatry. 2001;62:117–125.
  • Patten SB, Beck C. Major depression and mental health care utilization in Canada: 1994 to 2000. Can J Psychiatry. 2004;49:303–309.
  • Preskorn S, Flockhart D. 2006 guide to psychiatric drug interactions. Primary Psychiatry. 2006a;13:35–64.
  • Preskorn SH. Tricyclic antidepressant plasma level monitoring: an improvement over the dose-response approach. J Clin Psychiatry. 1986;47 Suppl 1:24–30.
  • Preskorn SH. Reproducibility of the in vivo effect of the selective serotonin reuptake inhibitors on the in vivo function of cytochrome P450 2D6: an update (part I) J Psychiatr Pract. 2003;9:150–158.
  • Preskorn SH, Baker B, Klick-Davis A, Ramadan M, Coyner L, Flockhart DA, et al. The effect of duloxetine, escitalopram, and sertraline on CYP 2D6 function. Clin Pharmacol Ther. 2006b;79:52.
  • Richelson E. Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984;23:94–102.
  • Richelson E. Biological basis of depression and therapeutic relevance. J Clin Psychiatry. 1991;52:4–10.
  • Richelson E. Pharmacology of antidepressants. Mayo Clin Proc. 2001;76:511–527.
  • Richelson E. Interactions of antidepressants with neurotransmitter transporters and receptors and their clinical relevance. J Clin Psychiatry. 2003;64 Suppl 13:5–12.
  • Rossi S. Australian Medicines Handbook 2007 2007(Ed.)Adelaide ISBN 0-9757919-5-8
  • Rudorfer MV, Potter WZ. Metabolism of tricyclic antidepressants. Cell Mol Neurobiol. 1999;19:373–409.
  • Sala M, Coppa F, Cappucciati C, Brambilla P, d’allio G, Caverzasi E, et al. Antidepressants: their effects on cardiac channels, QT prolongation and Torsade de Pointes. Curr Opin Investig Drugs. 2006;7:256–263.
  • Sanchez C, Hyttel J. Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cell Mol Neurobiol. 1999;19:467–489.
  • Schulz M, Schmoldt A. Successful physostigmine treatment of acute dothiepin intoxication. Pharmazie. 1994;49:614.
  • Schulz M, Schmoldt A. Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie. 2003;58:447–474.
  • Seppala T, Linnoila M, Soundergaard I, Elonen E, Mattila MJ. Tyramine pressor test and cardiovascular effects of chlorimipramine and nortriptyline in healthy volunteers. Biol Psychiatry. 1981;16:71–77.
  • Shah RR. Drug-induced QT interval prolongation – regulatory guidance and perspectives on hERG channel studies. Novartis Found Symp. 2005;266:251–280.
  • Sharpley AL, Vassallo CM, Cowen PJ. Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT(2C) receptors in vivo. Biol Psychiatry. 2000;47:468–470.
  • Shen WW. A history of antipsychotic drug development. Compr Psychiatry. 1999;40:407–414.
  • Shimoda K, Jerling M, Bottiger Y, Yasuda S, Morita S, Bertilsson L. Pronounced differences in the dispositon of clomipramine between Japanese and Swedish patients. J Clin Psychopharmacol. 1999;19:393–400.
  • Shin JG, Park JY, Kim MJ, Shon JH, Yoon YR, Cha IJ, et al. Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug Metab Dispos. 2002;30:1102–1107.
  • Sim SC, Ingelman-Sundberg M. The human cytochrome P450 Allele Nomenclature Committee Web site: submission criteria, procedures, and objectives. Methods Mol Biol. 2006a;320:183–191.
  • Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther. 2006b;79:103–113.
  • Skinner MH, Kuan HY, Pan A, Sathirakul K, Knadler MP, Gonzales CR, et al. Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. Clin Pharmacol Ther. 2003;73:170–177.
  • Smith D, Dempster C, Glanville J, Freemantle N, Anderson I. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry. 2002;180:396–404.
  • Smith RL. The Paton Prize Award. The discovery of the debrisoquine hydroxylation polymorphism: scientific and clinical impact and consequences. Toxicology. 2001;168:11–19.
  • Sola CL, Bostwick JM, Hart DA, Lineberry TW. Anticipating potential linezolid-SSRI interactions in the general hospital setting: an MAOI in disguise. Mayo Clin Proc. 2006;81:330–334.
  • Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, et al. Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004;5:895–931.
  • Sotelo J. Regulation of clinical research sponsored by pharmaceutical companies: a proposal. PLoS Med. 2006;3:e306.
  • Stein DJ, Spadaccini E, Hollander E. Meta-analysis of pharmacotherapy trials for obsessive-compulsive disorder. Int Clin Psychopharmacol. 1995;10:11–18.
  • Szegedi A, Wetzel H, Leal M, Hartter S, Hiemke C. Combination treatment with clomipramine and fluvoxamine: drug monitoring, safety, and tolerability data. J Clin Psychiatry. 1996;57:257–264.
  • Szewczuk-Boguslawska M, Kiejna A, Beszlej JA, Orzechowska-Juzwenko K, Milejski P. Doxepin inhibits CYP2D6 activity in vivo. Pol J Pharmacol. 2004;56:491–494.
  • Taylor JJ, Wilson JW, Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006;43:180–187.
  • Teschemacher AG, Seward EP, Hancox JC, Witchel HJ. Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline. Br J Pharmacol. 1999;128:479–485.
  • Thanacoody HK, Thomas SH. Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev. 2005;24:205–214.
  • Thase ME. Depression and sleep: pathophysiology and treatment. Dialogues Clin Neurosi. 2006;8:217–226.
  • Turcotte JE, Debonnel G, de Montigny C, Hebert C, Blier P. Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects. Neuropsychopharmacology. 2001;24:511–521.
  • Ullmann U, Lehnfeld R, Bliesath H, Birkel M, Gebbing H, Grave M, et al. Relative bioavailability of imipramine (Tofranil) coated tablets in healthy volunteers. Int J Clin Pharmacol Ther. 2001;39:271–276.
  • Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ. Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004;55:320–322.
  • Vandel S, Bertschy G, Baumann P, Bouquet S, Bonin B, Francois T, et al. Fluvoxamine and fluoxetine: interaction studies with amitriptyline, clomipramine and neuroleptics in phenotyped patients. Pharmacol Res. 1995;31:347–353.
  • Vignatelli L, D’Alessandro R, Candelise L. Antidepressant drugs for narcolepsy. Cochrane Database Syst Rev. 2005;3:CD003724.
  • Vincent S, Bieck PR, Garland EM, Loghin C, Bymaster FP, Black BK, et al. Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation. 2004;109:3202–3207.
  • von Moltke LL, Greenblatt DJ, Court MH, Duan SX, Harmatz JS, Shader RI. Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. J Clin Psychopharmacol. 1995;15:125–131.
  • Westlind-Johnsson A, Hermann R, Huennemeyer A, Hauns B, Lahu G, Nassr N, et al. Identification and characterization of CYP3A4*20, a novel rare CYP3A4 allele without functional activity. Clin Pharmacol Ther. 2006;79:339–349.
  • Whyte IM. Serotonin uptake inhibitors Med Toxicol 2004Lippincott Williams & Wilkins: Baltimore; 843–851.In: Dart RC (ed)vol. 1, 3rd edn, pp
  • Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. Q J Med. 2003;96:369–374.
  • Wijkstra J, Lijmer J, Balk FJ, Geddes JR, Nolen WA. Pharmacological treatment for unipolar psychotic depression: systematic review and meta-analysis. Br J Psychiatry. 2006;188:410–415.
  • Witchel HJ, Hancox JC, Nutt DJ. Psychotropic drugs, cardiac arrhythmia, and sudden death. J Clin Psychopharmacol. 2003;23:58–77.
  • Yue QY, Zhong ZH, Tybring G, Dalen P, Dahl ML, Bertilsson L, et al. Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes. Clin Pharmacol Ther. 1998;64:384–390.

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