Tricyclic antidepressants

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:

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 tricyclicMay be used to treatExamples of brand names
AmitriptylineSevere depression, neuropathic pain, PTSDEndep, Entrip
ClomipramineSevere depression, obsessive-compulsive disorder, phobias, panic disorderAnafranil, Placil
Dosulepin (dothiepin)Severe depression with anxietyDothep
DoxepinSevere depression, neuropathic painDeptran, Sinequan
ImipramineSevere depression, generalised anxiety disorder, panic disorderTofranil, Tolerade
NortriptylineSevere depression, neuropathic painAllegron, 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.

References

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2. Mayo Clinic. Tricyclic antidepressants and tetracyclic antidepressants (updated 28 Jun 2016). http://www.mayoclinic.com/health/antidepressants/MH00071 (accessed Jul 2018).
3. NPS Medicinewise. Antidepressant medicines explained (31 Jan 2017). https://www.nps.org.au/medical-info/consumer-info/antidepressant-medicines-explained (accessed Jul 2018).
4. Beyondblue. Antidepressant medication (updated Dec 2016). http://resources.beyondblue.org.au/prism/file?token=BL/0125 (accessed Jul 2018).
5. NHS Choices. Antidepressants (updated 14 Oct 2015). https://www.nhs.uk/conditions/antidepressants/ (accessed Jul 2018).
6. Lampe L. Drug treatment for anxiety. Australian Prescriber 2013;36:186-9 (2 Dec 2013). https://www.nps.org.au/australian-prescriber/articles/drug-treatment-for-anxiety (accessed Jul 2018).
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