classesTetracyclic Antidepressants

Tetracyclic Antidepressants: Uses, most common brand names, and safety information

Medically reviewed by Jamie Winn, PharmD

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Tetracyclic antidepressants (TeCAs) are a class of antidepressant drugs that were first introduced in the 1970s. They were one of the first antidepressants developed. Tetracyclic antidepressants are named after their four-ring (tetracyclic) chemical structure. They are similar in structure and function to tricyclic antidepressants (TCAs). Tetracyclic antidepressants are not commonly used as first-line therapy because of the increased incidence of side effects when compared to newer antidepressants.

The list below includes tetracyclic antidepressants approved by the U.S. Food and Drug Administration (FDA) and their pricing:

List of Tetracyclic Antidepressants

Drug name	Indication
Remeron (mirtazapine)	Remeron is indicated to treat depression, PTSD, insomnia, and hot flashes.
Remeron SolTab (mirtazapine)	Remeron SolTab is indicated to treat depression, PTSD, insomnia, and hot flashes.
Ludiomil (maprotiline)	Ludiomil is indicated to treat depression and anxiety associated with depression.

Some other medications that are sometimes classified as tetracyclic antidepressants include:

Asendin (amoxapine)
Tolvon (mianserin)
Tecipul (setiptiline)

What are tetracyclic antidepressants?

Tetracyclic antidepressants, which are named because of their chemical structure, are closely related to tricyclic antidepressants (TCAs). Together, they are known as cyclic antidepressants. Tetracyclic antidepressants have varied pharmacology and differ from TCAs in multiple ways.

They are typically used to treat several mental health disorders such as severe or treatment-resistant depression or as add-on therapy with other psychiatric medications. Tetracyclic antidepressants are effective in reducing symptoms of depression but can cause significantly more side effects than SSRIs and SNRIs. They are usually used when other treatments have failed.

How do tetracyclic antidepressants work?

Tetracyclic antidepressants work similarly to other antidepressants including TCAs. They are an antagonist at central presynaptic alpha-2 adrenergic receptors which increases norepinephrine and serotonin activity. Tetracyclic antidepressants also block certain neurotransmitter receptors such as serotonin, adrenergic, and histamine. Serotonin and norepinephrine play a key role in regulating sleep, digestion, mood, memory, and behavior. Their activity at histamine receptors may be the reason why they commonly cause sedation. Tetracyclic antidepressants have a low affinity for muscarinic receptors and tend to have few anticholinergic side effects.

What conditions are tetracyclic antidepressants used to treat?

Tetracyclic antidepressants are a class of medications used in the treatment of depression and other conditions such as:

Major depressive disorder
Severe or treatment-resistant depression
Obsessive-compulsive disorder (OCD)
Post-traumatic stress disorder
Anxiety associated with depression

Are tetracyclic antidepressants safe?

The use of tetracyclic drugs is relatively safe and effective when taken as prescribed. Your prescribing physician should be aware of your medical conditions, including:

Heart disease
Arrhythmias
Increased heart rate
Bipolar disorder
Narrow-angle glaucoma
Benign prostatic hyperplasia (BPH) or other prostate issues
Thyroid disease
Lung disease
Low sodium levels
Are pregnant or plan on becoming pregnant as they may cause fetal harm and/or death

You should also make sure they are aware of all the medications you take, including prescription drugs, over-the-counter medications, and supplements, as they may cause drug interactions:

Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as Cymbalta (duloxetine) and Effexor XR (venlafaxine)
Selective serotonin reuptake inhibitors (SSRIs) such as Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), and Lexapro (escitalopram)
Monoamine oxidase inhibitors (MAOI) such as Emsam (selegiline) and Nardil (phenelzine)
Tricyclic antidepressants (TCAs) such as Elavil (amitriptyline), Desyrel (trazodone), Anafranil (clomipramine), Vivactil (protriptyline), Surmontil (trimipramine), Sinequan (doxepin), Norpramin (desipramine), Tofranil (imipramine), and Pamelor (nortriptyline)
St. John’s wort, antipsychotics, and any other antidepressant medications that increase serotonin
Blood thinners or any medication that affects coagulation such as aspirin and Coumadin (warfarin)
Antipsychotics such as Risperdal (risperidone)
Medications for Parkinson’s disease such as Sinemet (levodopa/carbidopa)
Dilantin (phenytoin)
Sedating medications such as Valium (diazepam)

Can you take tetracyclic antidepressants while you are pregnant or breastfeeding?

The use of tetracyclic antidepressants during pregnancy should be used only if the benefits outweigh the risks to the mother and fetus. There is a registry that monitors outcomes in women exposed to antidepressants during pregnancy. You can register by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/

Tetracyclic antidepressants can be found in breast milk. The health benefits of breastfeeding should be considered along with any possible adverse events for the infant.

You should always discuss the risks and benefits of any medication you need with your healthcare provider if you are pregnant, plan on becoming pregnant, or are breastfeeding.

What are the common side effects of Tetracyclic antidepressants?

Some common adverse effects of Tetracyclic antidepressants include:

Constipation
Dizziness
Dry mouth
Blurred vision
Anxiety
Nervousness
Confusion
Weakness
Nausea
Weight gain
Drowsiness
Fatigue
Blurred vision.
Orthostatic hypotension (low blood pressure upon standing)
Nausea
Urinary retention.
Sexual dysfunction.

Tetracyclic antidepressants can rarely cause serious side effects, including:

Serotonin syndrome, which can be life-threatening
Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults (aged <24 years)
Low white blood cell count
Arrhythmias
Seizures
Manic episodes
Angle-closure glaucoma
Low blood sodium levels

This is not a complete list of side effects and we encourage you to consult with your healthcare professional for medical advice about any possible side effects.

How much do Tetracyclic antidepressants cost?

Tetracyclic antidepressants are expensive with an average cost of around $500 per year.

You can purchase Tetracyclic antidepressants for $49 per month from NiceRx if eligible for assistance. Prices at the pharmacy vary by location, strength, and quantity, as well as your insurance status.

Related resources for Tetracyclic antidepressants

The content on this website is intended for information purposes only. It does not constitute medical advice. The information on this website should not be relied upon and is not a substitute for professional medical advice. You should always speak to your doctor regarding the risks and benefits of any treatment.