Treatment-resistant depression
The combination medicine dextromethorphan/bupropion is approved for treatment-resistant major depressive disorder due to its action on the NMDA receptor. Available forms
Dextromethorphan is available alone in the form of cough syrup and pills as well as in combination with other agents. As a pharmaceutical drug, it is available as dextromethorphan/quinidine (Nuedexta) for the treatment of pseudobulbar affect and as dextromethorphan/bupropion (Auvelity) for treatment-resistant major depressive disorder. Contraindications
Because dextromethorphan can trigger a histamine release (allergic reaction), atopic children, who are especially susceptible to allergic reactions, should be administered dextromethorphan only if absolutely necessary, and only under the strict supervision of a healthcare professional. Adverse effects
Side effects of dextromethorphan at normal therapeutic doses can include:

A rare side effect is respiratory depression. Neurotoxicity
Dextromethorphan was once thought to cause Olneys lesions when administered intravenously; however, this was later proven inconclusive, due to lack of research on humans. Tests were performed on rats, giving them 50 mg or more every day for as long as a month. Neurotoxic changes, including vacuolation, have been observed in posterior cingulate and retrosplenial cortices of rats administered other NMDA receptor antagonists such as PCP, but not with dextromethorphan. Dependence and withdrawal
In many documented cases, dextromethorphan has produced psychological dependence in people who used it recreationally. It is considered less addictive than other common cough suppressants, such as the weak opiate codeine. Since dextromethorphan also acts as a serotonin reuptake inhibitor, users report that regular recreational use over a long period of time can cause withdrawal symptoms similar to those of antidepressant discontinuation syndrome.
A resolution of the two isomers of racemorphan with tartaric acid was published in 1952, and dextromethorphan was successfully tested in 1954 as part of US Navy and CIA-funded research on nonaddictive substitutes for codeine. Dextromethorphan was approved by the FDA in 1958 as an over-the-counter antitussive. As had been initially hoped, dextromethorphan was a solution for some of the problems associated with the use of codeine phosphate as a cough suppressant, such as sedation and opiate dependence, but like the dissociative anesthetics phencyclidine and ketamine, dextromethorphan later became associated with nonmedical use.During the 1960s and 1970s, dextromethorphan became available in an over-the-counter tablet form by the brand name Romilar. In 1973, Romilar was taken off the shelves after a burst in sales because of frequent misuse. A few years later, products with an unpleasant taste were introduced (such as Robitussin, Vicks-44, and Dextrotussion), but later the same manufacturers began producing products with a better taste. The advent of widespread internet access in the 1990s allowed users to rapidly disseminate information about dextromethorphan, and online discussion groups formed around use and acquisition of the drug. As early as 1996, dextromethorphan hydrobromide powder could be purchased in bulk from online retailers, allowing users to avoid consuming dextromethorphan in syrup preparations.FDA panels considered moving dextromethorphan to prescription status due to its potential for abuse, but voted against the recommendation in September 2010, citing lack of evidence that making it prescription-only would curb abuse.