nefazodone
Meaning of nefazodone: An antidepressant kept in limited use because of a rare but severe effect on the liver.
Definition of nefazodone
Nefazodone is an antidepressant that acts on serotonin in two ways at once, blocking one type of serotonin receptor while weakly reducing the reuptake of serotonin from the gap between nerve cells. It was valued for causing less sexual dysfunction and less sleep disturbance than several alternatives. Reports of severe liver injury led to its withdrawal in a number of countries and to restricted use elsewhere.
How does it differ from more common antidepressants?
The widely used serotonin reuptake inhibitors raise serotonin levels across the board, and stimulation of one particular receptor subtype is thought to account for two of their most disliked effects: sexual difficulties and disrupted sleep. This drug blocks that receptor directly while adding only modest reuptake inhibition. The result is an antidepressant that tends to improve sleep quality rather than fragment it, and that carries a lower burden of sexual side effects.
Why is its use restricted?
| Concern | Detail |
|---|---|
| Liver injury | Rare but can progress to liver failure requiring transplant |
| Onset | Reported from weeks to months after starting |
| Regulatory response | Brand withdrawn in several countries; warnings elsewhere |
| Drug interactions | Blocks a major liver enzyme, raising levels of other medicines |
What does the liver risk mean in practice?
The injury is idiosyncratic, meaning it does not depend on dose and cannot be predicted from who takes it. Its rarity is set against its severity: the great majority of people are unaffected, but the cases that occur can be catastrophic and are not always reversible on stopping. Because the reaction gives little warning, the drug is generally reserved for situations where other treatments have failed, and liver function is monitored. Dark urine, yellowing of the skin or eyes, and unusual fatigue are the recognized warning signs, since they indicate the liver has already been affected.
What else limits it?
It strongly inhibits the CYP3A4 enzyme that clears a long list of other medicines, so levels of statins, certain sedatives, some heart drugs and several others can rise into a dangerous range when taken alongside. Sedation, dizziness and a drop in blood pressure on standing are common at the start. As with other drugs used for depression, the full effect takes weeks to develop, and abrupt discontinuation can produce withdrawal symptoms. The generic form remains available in some countries where the original brand was removed.
Also known as
Used in a sentence
Liver function tests were monitored throughout treatment with nefazodone.
Good to know
Rare but potentially fatal liver injury led to withdrawal of the original brand in several countries, and the reaction is unpredictable and independent of dose.