DXM is very well tolerated with few side effects when taken at the same doses as recommended for cough (up to 120 mg/day). Dextromethorphan is considered to induce fewer side effects than other NMDA antagonists. The rate of side effects was minimal if a high dose is divided into smaller portions. Interestingly, 55% of the patients that reported side effects were females compared with 45% males. Subjects in the age range of 26-40 yr/old had the highest rate.

Research studies have evaluated a range of doses of DXM for both pain management and opioid tolerance reduction. Unfortunately, dosing standards have not been established. As such, the usual rule for medication dosing applies: Start low, Go slow. Dosing as recommended for cough, up to 120mg/day, in divided doses is a good place to start. In a study evaluating opioid tolerance and DXM, daily doses up to 480 mg/day were generally well-tolerated, limited to drowsiness and no clinically serious side effects. One unusual side effect of DXM is pruritis (itching), a consequence of histamine release – a characteristic shared by some opioids.



Side effects are generally dose-related: as dosing goes up, the frequency and severity of possible side effects follows:

Doses of < 1.5 mg/kg body weight (< 100mg for a 150 lb person):

Few if any side effects, possibly mild drowsiness or nausea

Doses of 1.5-2.5 mg/kg body weight (100mg to 175mg for a 150 lb person):



Increased alertness

Restlessness

Visual and auditory sensitivity

Generalized euphoria

Doses of 2.5-7.5 mg/kg body weight (175 mg to 525 mg for a 150 lb person):

Exaggerated auditory and visual sensativity

Imbalance and dizziness



Feeling drunk

Hallucinations

Increased energy and excitability

Doses of 7.5-15 mg/kg body weight (525 mg to 1050 mg for a 150 lb person):

Visual and auditory disturbances

Periods of semi-consciousness

Impaired thinking

Manic and/or panic

Partial disassociative psychosis

Doses of >15 mg/kg body weight (> 1050 mg for a 150 lb person):

Complete disassociative psychosis

Hallucinations and delusions

Ataxia (impaired coordination)

Full List of Possible Side Effects

confusion giddiness slow breathing nausea vomiting agitation nervousness restlessness unsteadiness dizziness vision changes shortness of breath fast heart rate hallucinations (seeing or hearing things that do not exist) seizures coma

Dextromethorphan Products (OTC)

Delsym®

Delsym® is an over-the-counter (OTC) medication recommended for cough. It is available in a 12-hour time release formulation of 30mg/5ml (or 30mg/tsp) with a maximum recommended dose of 60mg (10ml or 2 tsp) every 12 hours for cough. As noted above, higher doses may be required for pain management with caution regarding the potential for more side effects at higher doses.



Robitussin DM®

Robitussin DM® is another over-the-counter (OTC) medication recommended for cough. Like Delsym®, it contains DM but it also contains guaifenesin, an expectorant believed to thin cough secretions making them easier to cough up (expectorate). Guaifenesin may also have NMDA receptor antagonist activity but a trial evaluating guaifenesin in 20 patients with fibromyalgia over a 12–month observational period showed no difference in outcomes.

Robitussin DM® is available in many formulations containing up to 7.5mg/tsp of DM, but the multiple avaialable products contain an array of other active ingredients – always check the label for dosing instructions. It is recommend not to exceed the maximum recommended DM dose of 120mg/day (4 tsp four times/day) withoust consulting a physician. As noted above, higher doses may be required for pain management with caution regarding the potential for more side effects at higher doses.

Dextromethorphan Products (Rx)

Nuedexta® (Dextromethorphan-20mg/Quinidine -10mg)



Nuedexta is a prescription medication that combines dextromethorphan (20mg) with quinidine (10mg). The quinidine is included because it inhibits the liver enzymes (Cyp2D6) that metabolize (break down) dextromethorphan, thus prolonging the action of dextromethorphan. It is FDA approved for treatment of Pseudobulbar Affect disorder (PBA), “a neurologic disorder of emotional expression characterized by frequent, sudden, involuntary outbursts of crying and/or laughing disproportionate or unrelated to the patient’s underlying mood, occurring in settings of neurologic disease or injury. PBA is commonly associated with conditions such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), traumatic brain injury, stroke, Alzheimer’s disease, and Parkinson’s disease and is thought to affect as many as 7 million people in the U.S.



Studies indicate that Nuedexta is generally safe and well tolerated, with no evidence of clinically relevant cardiac or respiratory effects. Nuedexta has also been evaluated for the potential for drug-drug interaction (DDI) with memantine, another NMDA receptor antagonist. Minimal pharmacokinetic and pharmacodynamic interactions were observed between memantine and Nuedexta, suggesting they can be administered together without dose adjustment.



Use of Nuedexta or dextromethophan for pain or opioid management related conditions would be considered “off-label”but studies indicate they are safe and well tolerated.

Dextromethorphan Withdrawal Syndrome

With prolonged use, especially with high doses, a physical withdrawal syndrome can occur. Physical withdrawal symptoms are generally mild and may include intermittent vomiting, night sweats, muscle aches, diarrhea, restlessness, insomnia, and anxiety. The DXM dependence and physical withdrawal may be secondary to serotonergic and sigma-1 opioidergic properties of the drug although DXM affinities for these receptors is considered to be minimal.



