What Are Tetracyclic Antidepressants?

Tetracyclic antidepressants are a type of medication distinguished by the four atom rings within each molecule. Generally, they tend to impact, to greater or lesser degree, the brain chemicals dopamine, norepinephrine, and serotonin. Some of these medications are used to treat depression, anxiety disorders, and anorexia, but not all are approved for or frequently used for each. Not many of these drugs are currently in use.

Medications in this class have a close association to tricyclic antidepressants. They have similar action and most were developed at approximately the same time, in the late 1960s or early 1970s. There is also dispute on which drugs belong in this group, and some medications, like trazodone, can be listed as a tetracyclic antidepressant or considered in a different class.

The term "tetracyclic" comes from the structure of these different medications. Tricyclics (TCAs) have three atom rings within each molecule, while tetracyclic antidepressants contain four. It is often noted that many tetracyclic antidepressants work differently than TCAs and are less involved in reuptake inhibition of neurotransmitters, though there are exceptions. Many of these medications still increase key neurotransmitter levels, but they may accomplish this by other means, such as through indirect stimulation of production.

One medication in the class of tetracyclic antidepressants is mirtazapine. This drug is specifically approved for the treatment of depression, and is also used for anxiety disorders and for anorexia. It elevates norepinephrine and serotonin by inhibiting adrenergic receptors that prevent the release of these chemicals.

Trazodone might be considered a tetracyclic and is called an antidepressant, but may be more often used to promote sleep or to treat anxiety disorders and chronic pain. It increases serotonin levels by acting on other receptors. Amoxapine creates some elevation of serotonin and norepinephrine and might be used for depression, anxiety disorders, or to alleviate psychotic symptoms.

Mazindol typically is not used for depression but instead is used as a weight loss drug in the obese by acting on dopamine and serotonin. In this respect it differs from the other tetracyclic antidepressants, which are usually associated with weight gain. Maprotiline has anti-anxiety, antidepressant, antihistamine and sedative properties. It appears to most strongly affect norepinephrine levels.

Setiptiline impacts mostly serotonin and norepinephrine. Mianserin may be used to promote sleep, lower nausea, or as an antidepressant or anxiolytic. It acts most on norepinephrine.

The different actions of tetracyclic antidepressants means that the medications will have varied side effects. One common side effect is that they can make especially teenagers and young adults more prone to develop suicidal thinking or behavior. They also may not be appropriate for older patients because they can risk cardiac side effects.

Tetracyclic antidepressants should never be combined with alcohol because the sedative effects of the drugs can be magnified. Other side effects that might also be encountered when taking these medications include headache, sleepiness or insomnia, weight gain, stomach upset, and dry mouth. Confusion and dizziness are also possible.

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