Also Known As: Zofran, Ondansetron

Ondansetron (INN) is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic (to treat nausea and vomiting), often following chemotherapy. Its effects are thought to be on both peripheral and central nerves. Ondansetron reduces the activity of the vagus nerve, which deactivates the vomiting center in the medulla oblongata, and also blocks serotonin receptors in the chemoreceptor trigger zone. It has little effect on vomiting caused by motion sickness, and does not have any effect on dopamine receptors or muscarinic receptors.

The 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting (CINV). A common use case is to give them intravenously about 30 minutes before commencement of a chemotherapy treatment. Ondansetron is also effective in controlling post-operative nausea and vomiting (PONV) and post-radiation nausea and vomiting, and is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis.

Although it is highly effective, the high cost of the brand-name version had limited its use to controlling PONV and CINV. It is also used off-label to treat hyperemesis gravidarum in pregnant women, but there is no conclusive data available on its safety in pregnancy, especially during the first trimester. It is also used to treat cyclic vomiting syndrome; although there have been no formal trials to confirm efficacy, case reports suggests it can be helpful in some cases. The drug is administered 1–3 times daily, depending on the severity of nausea and/or vomiting. The normal oral dose for adults and children over the age of 12 is 8 mg initially, followed by a second dose of 8 mg eight hours later. The drug is then administered once every 12 hours, usually for not more than 2–3 days. Following oral administration, it takes about 1.5 to 2 hours to reach maximum plasma concentrations. This drug is removed from the body by the liver and kidneys.

The clinical effect of ondansetron (and other drugs from the same group) can be potentiated by combining it with dexamethasone.

Investigational and off-label

Neuropsychiatric disorders

A 2006 double-blind, randomized controlled trial indicated that ondansetron may have value in the treatment of schizophrenia, as an adjunct to haloperidol. The study found the combination to significantly improve negative schizophrenia symptoms, and people taking both drugs experienced fewer of the adverse effects commonly associated with haloperidol.[2] An earlier, smaller, open-label trial had found ondansetron to be useful in treating antipsychotic-induced tardive dyskinesia in people with schizophrenia, and the study patients also showed significant improvement in the disease's symptoms.[3][4]

Early studies have also examined ondansetron as a possible treatment for psychosis resulting from advanced Parkinson's disease.[5] Its apparent benefits despite a lack of any significant antagonistic properties at dopamine receptors or the 5-HT2A receptor raises interesting questions about the etiology of psychosis.

Hewlett and others found that the treatment of obsessive compulsive disorder with Ondansetron 1 mg three times daily was associated with a significant decrease in the Yale Brown Obsessive Compulsive scores in a small (n=8), 8-week, open-label study.[6]

Substance use

Ondansetron lowers the cravings for alcohol, especially in early-onset alcoholics. In one cognitive-behavioral therapy study, ondansetron patients with early-onset alcoholism had fewer drinks per day and reported more days without drinking at all, as compared to the other groups in the study. Also of note, individuals with the LL genotype show significant improvements in alcohol misuse when treated with ondansetron, compared with individuals with the other genotypes of the 5HTTLPR polymorphism, who showed no improvement over placebo.[7][8][9]

Researchers at the Stanford University School of Medicine have demonstrated that ondansetron might be useful and effective for treating withdrawal symptoms of opioid addictions.[10] Unlike the existing treatments methadone and buprenorphine, it is not itself an opioid.[10] Additionally, it does not require continued supervision like treatment with clonidine.[10]

The original experiment used mice who were injected with increasing doses of morphine, assayed with naloxone and then underwent haplotypic analysis to isolate a gene candidate.[11] HTR3A which codes for the 5-HT3 receptor emerged as the primary candidate, which suggested 5-HT3 antagonist ondansetron as a possible treatment.[11] The researchers were then able to show using an acute morphine administration model the efficacy in withdrawal symptom control in humans.[11]

Irritable bowel syndrome

Ondansetron blocks the 5-HT3 receptor in the enteric nervous system, and thereby reduces colonic contractions, sensory perception, and motility. A large number of drugs in this category, 5-HT3 antagonists, have been shown to have this effect, which positively impacts irritable bowel syndrome with diarrhea (IBS-D). Thus, ondansetron has been effective in treating diarrhea-predominant IBS in initial studies, and is being used off label for this exact effect.[12]

Postanesthetic shivering

Two small, placebo-controlled trials have been conducted to assess the efficacy of ondansetron for postanesthetic shivering, a common occurrence after surgery. Ondansetron was found to be as effective as pethidine (meperidine, Demerol) when given as a single IV dose before anesthesia.[13]

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