Dextromethorphan

Dextromethorphan

Common Trade Names: Robitussin, Dexalone, Pediacare, St. Joseph, Robafen Cough, Delsym, Miltuss, Simply Cough, Vicks 44, Babee Cof Syrup, Creomulsion, Nycoff

Other Names: Dextromethorphan hydrobromide monohydrate, (1S,9S,10S)-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene;hydrate;hydrobromide

Dextromethorphan (DXM) is an FDA-approved, over-the-counter cough suppressant. DXM is not considered an addictive or habit-forming medication, but at supratherapeutic doses, it can have dissociative hallucinogenic effects which carry a potential for abuse. Long-term misuse of DXM can lead to addiction. Read on to know more about DXM addiction below.

A Brief History of Dextromethorphan

Dextromethorphan was first tested in 1954 as part of a series of research studies on nonaddictive alternatives for codeine, which was then largely used as an antitussive. DXM proved to be an important substitute for codeine as it did not come with the unfavorable side effects commonly associated with codeine use such as opiate dependence and respiratory depression. DXM was granted a US FDA approval as an over-the-counter cough suppressant in 1958. An over-the-counter tablet form under the brand name Romilar became available in the 1960s.

Later on, cases of DXM misuse started to rise. In 1973, Romilar was pulled out of the market because of reports of misuse. Several manufacturers began to produce DXM with a bitter taste, such as Robitussin, to help combat the growing problem. FDA panels also considered making DXM a prescription-only medication but the recommendations were denied in 2010. To help curb the cases of DXM abuse, several US states have placed restrictions on DXM purchases. For example, the states of California and Oregon prohibit the sale of DXM to minors unless a doctor’s prescription is presented.

How Does Dextromethorphan Work in the Human Body?

The mechanism of action of dextromethorphan is not fully understood. However, there are theories suggesting that DXM acts on the nucleus tractus solitarius, a structure located in the brainstem that is thought to be the first relay nucleus in the cough reflex pathway. DXM is also structurally similar to alkaloid opioids such as codeine but DXM does not seem to activate mu-opioid receptors.

DXM has also demonstrated agonist activity on the sigma-1 receptor and antagonist activity on the N-methyl-D-aspartate (NMDA) receptor. This particular pharmacodynamic effect of DXM is similar to other psychoactive agents such as ketamine and lysergic acid diethylamide (LSD), making DXM a potentially addictive medication. In fact, at supratherapeutic doses, DXM can act as a dissociative hallucinogen.

DXM is FDA-approved as a cough suppressant and as treatment for pseudobulbar affect (PBA) in combination with quinidine. PBA is a neurologic condition that impairs emotional expressions and is typically characterized by episodes of uncontrollable laughing or crying.

Apart from the aforementioned, there are other potential indications for the use of DXM. These include the following:

  • Stroke
  • Depression
  • Seizure
  • Traumatic brain injury (TBI)
  • Pain
  • Parkinson’s Disease
  • Methotrexate toxicity
  • Autism

While the use of DXM in these conditions is still under investigation, existing clinical studies have demonstrated the benefits of DXM.

The only absolute contraindication to the use of DXM is a history of hypersensitivity, allergic or idiosyncratic to it or any of its components.

How Is Dextromethorphan Taken or Administered?

DXM comes in various formulations, including the following:

Tablet
● 15mg

Capsule
● 15mg

Gel, Oral
● 7.5mg/5mL

Liquid, Oral
● 7.5mg/5mL
● 10mg/5mL
● 15mg/5mL

Syrup, Oral
● 5mg/5mL
● 7.5mg/5mL
● 10mg/5mL
● 15mg/5mL
● 20mg/15mL

Liquid, Extended-Release
● 30mg/5mL

Lozenge
● 5mg
● 7.5mg
● 15mg

Strip, Oral
● 7.5mg

The recommended doses of DXM as a cough suppressant are as follows:

Extended-Release: 60mg every 12 hours, up to a maximum of 120mg every 24 hours
Lozenges: 5-15mg every 1 to 4 hours, up to a maximum of 120mg per day
Strips: 30mg every 6 to 8 hours, up to a maximum of 120mg per day
Liquid and Syrup: 10-20mg every 4 hours or 30mg every 6 to 8 hours
Oral gel: 30mg every 6 to 8 hours, up to a maximum of 120mg every 24 hours

What Are the Immediate and Long-Term Effects of Dextromethorphan Use?

DXM is a relatively safe antitussive medication with only a few mild side effects. Some side effects associated with DXM use are:

  • Nausea and vomiting
  • Gastrointestinal upset
  • Drowsiness
  • Dizziness

Occasionally, DXM can lead to:

  • Fatigue
  • Itching
  • Vertigo

At doses higher than 4mg/kg, DXM can induce psychoactive effects, including:

  • Euphoria
  • Visual hallucinations
  • Delusions
  • Feeling “high”

Abrupt withdrawal from DXM after long-term misuse or abuse can also lead to the development of withdrawal symptoms, such as the following:

  • Diarrhea
  • Anxiety
  • Weight loss
  • Insomnia
  • Increased sweating
  • Depression
  • Hallucinations

Signs of Dextromethorphan Use Disorder

As mentioned above, DXM carries a potential for abuse because of its similar pharmacodynamic effect to other psychoactive agents such as ketamine and LSD. Recent studies have shown that cases of DXM abuse have been consistently rising particularly among adolescents who are taking it as a psychoactive drug. DXM’s cheap price and wide availability contribute further to these cases.

While DXM is not considered an addictive substance, long-term misuse of DXM can eventually lead to tolerance and dependence, and when left untreated, can result in addiction. The Diagnostic and Statistical Manual of Mental Disorders – 5th Edition (DSM-5) Criteria for Substance Use Disorders (SUD) has identified four main pathological behavioral patterns associated with all substance use disorders, including abuse of DXM.

  1. Impaired control
  2. Social impairment
  3. Risky use
  4. Pharmacological indicators (tolerance and withdrawal)

These behavioral patterns are further broken down into the following criteria. These criteria are necessary for the diagnosis of SUDs:

Impaired Control

  1. Taking higher doses of DXM or taking it for a longer time than prescribed
  2. Being unable to stop using DXM despite many attempts
  3. Spending most of one’s time getting, using, or recovering from DXM use
  4. Feeling strong cravings for or urges to take DXM

Social Impairment

  1. DXM use keeps one from fulfilling work, family, and other social obligations
  2. DXM use causes problems in social and personal relationships
  3. DXM use causes one to miss recreational and other social activities

Risky Use

  1. Continued use of DXM in potentially hazardous situations, such as while driving a vehicle or operating a motor vehicle or heavy machinery
  2. Continued use of DXM despite it worsening existing medical conditions or causing new ones

Physical Tolerance

  1. Requiring a higher dose of DXM to achieve its desired effects in the body (tolerance)
  2. Stopping DXM use leads to withdrawal syndrome (withdrawal)

Rehab and Treatment for Dextromethorphan Use Disorder

DXM is an over-the-counter medication that is cheap and widely available. These characteristics make DXM easily accessible to most people and increase its potential for abuse. Because DXM is not a prescription drug, patients do not even need to buy DXM from illicit sellers or illegal sites to acquire DXM. As a consequence, patients also do not have the benefit of having a professional to educate them about DXM’s abuse potential or to monitor them for signs of addiction.

Chronic DXM use can lead to drug misuse, which can eventually result in DXM use disorder. The DSM-5 criteria are a helpful guide to evaluate whether one has developed DXM use disorder. Prompt recognition of the signs listed in the DSM-5 criteria is one of the key steps in successful drug rehab, because it will allow for the early initiation of intervention. In general, drug rehab programs begin with the detoxification process.

Detoxification, or detox for short, refers to the process of flushing out toxic substances from the body in order to reverse the damage brought on by long-term misuse. Detox may be done by slowly titrating the dose of DXM downward over a period of several weeks. Abrupt withdrawal from DXM is not recommended under any circumstance as this may lead to the development of withdrawal symptoms. For DXM, there is no prescribed rate of downward titration. The goal is to identify the minimum dose required to achieve its therapeutic effects. After a successful titration, physicians may shift to another cough suppressant with the same efficacy and safety profile but with a much lower abuse potential to completely eliminate drug dependence.

There are also several nonpharmacologic interventions that may be utilized to manage DXM use disorder. Some examples are counselling, psychotherapy, and group therapy. These programs may be participated in either on an outpatient or inpatient basis, depending on factors such as the severity of the patient’s addiction and their financial capabilities.

It has been well-established in many clinical studies that the adjunctive use of nonpharmacologic treatments with pharmacologic strategies is the best approach in the management of substance use disorders, including abuse of DXM. Combination therapy using both strategies has shown significantly higher recovery rates than monotherapy alone.

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