Methadone vs. Suboxone: Comparison

Methadone was originally developed in Germany during the 1930s as a synthetic alternative to opium.  Post World War II, the United States obtained all research records for the substance and noted that it was less sedating and less of a respiratory depressant than morphine.  In 1947, Methadone was approved by the FDA for the treatment of opioid dependence.

Methadone was considered a form of opioid replacement therapy and was used to help patients transition off of more addictive opioids like heroin.  Eventually “Methadone Clinics” began sprouting throughout the United States, offering treatment to those with opioid dependence.  Unfortunately, most individuals ended up becoming nearly as dependent upon the Methadone as illicit drugs like heroin.

For a long time, Methadone was considered the preeminent opioid replacement therapy option.  Eventually, Reckitt Benckiser Pharmaceuticals developed the drug Suboxone, a partial opioid agonist as a competitor to Methadone.  Suboxone hit the market in 2002 and is regarded as similar in efficacy to Methadone, but favorable in that it has a reduced potential for abuse.

Methadone vs. Suboxone Comparison Chart

Below is a chart comparing some general similarities and differences between Methadone and Suboxone.  As you can tell, Methadone is a much older drug that hit the market in the late 1940s, whereas Suboxone wasn’t released until the early 2000s.  Both drugs are synthetic opioids, but Suboxone is a partial opioid agonist, whereas Methadone is a full opioid agonist.

Methadone vs. Suboxone

	Methadone	Suboxone
Ingredients	Methadone Hydrochloride	Buprenorphine (~80%) + Naloxone (~20%)
Drug classification	Synthetic opioid (Full agonist)	Synthetic opioid (Partial agonist)
Approved medical uses	Opioid dependence.	Opioid dependence.
Formats	Dropper. Oral concentrate. Oral solution. Tablet.	Sublingual film. Sublingual tablet.
Dosages	Dropper: 30 ml of 10 mg/ml. Oral concentrate: 10 mg/ml. Oral solution: 5 mg/5ml or 10 mg/5ml. Tablet: 5 mg. 10 mg. 40 mg.	Sublingual film: 2 mg/0.5 mg or 4 mg/1 mg or 8 mg/2 mg or 12 mg/3 mg Tablet: 2 mg/0.5 mg or 8 mg/2 mg
Manufacturer	Eli Lilly & Company	Reckitt Benckiser Pharmaceuticals
Legal status	Schedule III (US)	Schedule III (US)
Mechanism of action	Functions as a long-acting full mu-opioid agonist and NMDA glutamate receptor antagonist. Exhibits a mechanism of action similar to morphine such that it may mimic endogenous opioids, enkephalins, and endorphins. This triggers the release of neurotransmitters such as: acetylcholine, norepinephrine, substance P, and dopamine.	Non-selective mixed agonist-antagonist opioid receptor modulator. Partial agonist at the mu-receptor. Antagonist at the kappa-receptor. Antagonist at the delta-receptor. Exhibits high affinity for the sigma-receptor and a minimal affinity for the nociceptin receptor. Buprenorphine also inhibits voltage-gated sodium channels. The Naloxone component of Suboxone has a high affinity for the mu-receptor as a competitive antagonist.  It also elicits antagonist effect upon the kappa and delta receptors.
Generic version (?)	Yes.	Yes.
Half-Life	8 to 59 hours.	24 to 42 hours.
Common side effects	Constipation. Dizziness. Drowsiness. Dry mouth. Lightheadedness. Nausea. Sweating. Vomiting.	Constipation. Dizziness. Drowsiness. Dry mouth. Lightheadedness. Nausea. Sweating. Vomiting.
Date approved	1947	2002 (October)
Duration of effect	24 to 36 hours (Analgesic: 6 to 8 hours)	24 hours (Analgesic: 8 to 12 hours)
Investigational uses	Chronic Pain.	Chronic Pain. Neonatal abstinence syndrome. Treatment-resistant depression. (Read: Suboxone for depression)

Methadone vs. Suboxone: What’s the difference?

Methadone and Suboxone are similar in that they are both synthetic opioids engineered as a replacement option for those addicted to illicit drugs like heroin.  Although the side effect profile associated with each drug is similar, there are many differences between the two drugs.  Methadone is regarded as a full mu-opioid receptor agonist, whereas Suboxone is considered a partial agonist.

The fact that Suboxone is a partial agonist makes it less potent than the full agonist that is Methadone.  Suboxone has less potential for abuse due to the fact that it was engineered with a ceiling effect.  This means that when taken at increasingly higher doses, a user will not derive any additional psychological euphoria from Suboxone, but they will from Methadone.

Abuse Potential

Upon comparison, the abuse potential of Methadone is greater than that of Suboxone.  Methadone is classified as a “Schedule II” controlled-substance, meaning it has significant potential for abuse and may result in dependence.  Users of Methadone often build up tolerance to the effects of the drug, meaning the therapeutic effect diminishes in time.

This results in users increasing their doses or taking more than necessary to maintain a sense of well-being.  Furthermore, when ingested at higher than recommended doses, Methadone can produce a “high.”  For this reason, a person is usually required to stay at a “Methadone Clinic” for awhile so that professionals can monitor their dosing – which prevents initial abuse.

The problem is that once users leave the Methadone Clinic and have a prescription for Methadone, they do not have the professional supervision to monitor their usage.  This may result in a person taking abnormally high doses in attempt to attain an opioid-induced euphoria.  By comparison, Suboxone isn’t regarded as having significant potential for abuse.

Suboxone was designed to have a “ceiling effect” to prevent users from abusing the drug.  This means that past a certain dose, a user will not be able to attain any additional effect or “high.”  In addition to the “ceiling effect,” Suboxone is only a partial opioid agonist, meaning its “high” isn’t considered as potent as that of Methadone, which leads to reduced potential for abuse.

By comparison, Suboxone is classified as a “Schedule III” controlled-substance.  Under this classification, it is thought to have a lower potential for abuse than “Schedule II” substances (e.g. Methadone).  Methadone clearly has greater potential for abuse due to its full opioid agonist effect and its lack of a ceiling effect.

Cost: Which is more expensive?

Those comparing Methadone to Suboxone may want to consider the prices of each drug.  Buying “brand name” Methadone is considerably cheaper than purchasing Suboxone.  Even generic Methadone is significantly less expensive than purchasing generic Suboxone.  For “Dolophine,” a brand name tablet form of Methadone, you’ll end up paying between $26 and $50 for 60 tablets.

For Methadose oral concentrate, the price ranges  between $60 and $75 for a 720 ml prescription. For Methadose tablet formats the prices range between $17 and $45 for 60 tablets.  Generic oral concentrate of Methadone can cost up to $60 for 950 ml, while the generic tablet form of Methadone costs between $13 and $35 for a supply of 120 tablets.

For a supply of 30 “brand name” Suboxone films, the price typically falls within the range of $130 and $470.  The cost for 30 generic sublingual Suboxone tablets (buprenorphine / naloxone) ranges from $75 to $185 and depends on the dosage.  The lower dose of 2 mg/0.5 mg is generally a bit cheaper than the higher dose of 8 mg/2 mg.

If you don’t have as much money to spend on prescriptions or have poor insurance, Methadone is by far the cheaper option.  That said, people often forget the total cost associated with staying at a Methadone Clinic.  Should you end up at a clinic, you may end up accruing additional costs ranging from $10 to $20 per day.

Dosage & Formats

Methadone is manufactured with more dosing options and formats than Suboxone.  Formats of Methadone administration include: liquid (dropper, oral concentrate, oral solution) and tablet.  Formats of administration for Suboxone include: sublingual film and tablet.  The “Dropper” is prescribed with 30 ml of 10 mg/ml, the “Oral concentrate” contains 10 mg/ml as well, and the “Oral solution” contains doses of 10 mg/5 ml or 5 mg/5 ml.

In tablet format, Methadone is manufactured in three dosing options of 5 mg, 10 mg, and 40 mg.  Suboxone is unique in that it is manufactured in a sublingual film – a strip that delivers the drug under the tongue.  The sublingual format of Suboxone is manufactured with dosing options of: 2 mg/0.5 mg, 4 mg/1 mg, 8 mg/2 mg, and 12 mg/3 mg; the first number indicates the amount of buprenorphine, while the second indicates the amount of naloxone.

Suboxone is also manufactured in tablet formats of 2 mg/0.5 mg and 8 mg/2 mg.  The dosing options are considered more limited for the tablet than they are for the sublingual film.  Many people prefer the novel sublingual delivery of Suboxone over the oral and tablet formats of Methadone.  Both Suboxone and Methadone are thought to provide sufficient dosing options for titration upwards or downwards.

Efficacy: Which drug is more effective?

Those who are attempting to use opioid replacement therapy as a way to overcome opioid dependence often want to know whether Methadone is more effective than Suboxone, or vice-versa.  A meta-analysis published in 2014 evaluated all randomized controlled trials of buprenorphine and methadone compared to a placebo for the management of opioid dependence.  The goal of this research was to determine whether one substance was safer and/or more effective than the other.

The researchers included 31 trials with a cumulative total of 5430 individuals.  The study authors determined that buprenorphine was effective in maintenance treatment of heroin dependence at doses above 2 mg.  It also suppressed illicit opioid usage when administered at doses exceeding 16 mg.

Methadone was considered more effective than Suboxone for treatment retention when used flexibly at low fixed quantities.  At medium and high doses, there was no significant difference in treatment retention and both drugs suppressed the usage of illicit opioids.  Due to the fact that doses are often used flexibly and are seldom “fixed” in clinical practice, the authors suggested that Methadone leads to greater treatment retention.

That said, both drugs were equally effective at suppressing illicit opioid use.  If you’re using Suboxone at a fixed medium or high dose, there shouldn’t be much of a difference in regards to treatment-retention or efficacy compared to Methadone.  However, if you’re using Suboxone at flexible doses, particularly within the range of 2 mg to 6 mg, treatment retention is often poorer compared to Methadone.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/18425880

Mechanisms of action

The mechanisms of action differ between Methadone and Suboxone.  Methadone is comprised of two enantiomers: levomethadone (R-methadone) and dextromethadone (S-methadone).  The levomethadone acts as a full mu-opioid receptor agonist.  It binds to the mu-receptor site and elicits effects akin to endogenous opioids, enkephalins, and endorphins.

This may produce a cascade effect that may stimulate the release of other neurotransmitters including: acetylcholine, norepinephrine, substance P, and dopamine.  Methadone also functions as an NMDA glutamate receptor antagonist, which may aid in decreasing pain.  It also has very minor effects as a nicotinic acetylcholine receptor antagonist.

By comparison, Suboxone acts as partial mu-opioid receptor agonist.  Technically, it is regarded as a non-selective, mixed agonist/antagonist opioid receptor modulator.  In addition to its agonist effect at the mu-receptor, it also acts as an angatonist at the kappa and delta opioid receptors.  It has a high affinity for the sigma receptor, and elicits minor effects on the nociceptin receptor.

While both drugs primarily target the mu-receptor, their secondary mechanisms differ in that Suboxone doesn’t act as an NMDA receptor antagonist.  Suboxone affects the kappa and delta receptors as an antagonist, whereas Methadone isn’t known to elicit this effect.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/22504149
• Source: http://www.ncbi.nlm.nih.gov/pubmed/12435410
• Source: http://www.ncbi.nlm.nih.gov/pubmed/24903063
• Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1070723/

Medical Uses

Medically, both Methadone and Suboxone are used to primarily treat opioid dependence and addiction.  They are also commonly prescribed off-label as analgesics for low-grade or moderate chronic pain.  The FDA recommended uses for Methadone and Suboxone aren’t subject to significant variation.

That said, investigative uses for Suboxone and Methadone are known to differ.  Methadone isn’t commonly prescribed off-label or utilized as an investigational treatment.  Suboxone has been investigated for the treatment of neonatal abstinence syndrome.  This is a condition affecting newborns that have been exposed to opioids during pregnancy that experience symptoms of withdrawal upon birth.

The usage is limited to FDA trials and is being used in a specifically calibrated neonatal formulation.  Another off-label use is that of Suboxone for treatment-resistant depression.  This is especially common among those who have refractory depression and a history of opioid dependence.

An offshoot of Suboxone called “ALKS-5461” (Buprenorphine / Samidorphan) is showing significant promise as an antidepressant augmentation strategy.  Due to the reduced potency and abuse potential of Suboxone compared to Methadone, it is more commonly utilized as an off-label treatment.

Popularity

As of 2013, Suboxone was estimated to be prescribed 9.3 million times.  There isn’t exact data for the number of Methadone prescriptions.  Estimates from the CDC (Centers for Disease Control) suggest that Methadone accounted for 2% of analgesic prescriptions in the United States in 2012.  It is thought that both drugs remain extremely popular among those involved in opioid replacement therapy.

Suboxone may have surpassed the popularity of Methadone in recent years due to the fact that it is a newer drug, is thought to be slightly less potent, with an equal comparative efficacy.  Doctors may prefer prescribing Suboxone due to its “ceiling effect” which mitigates its potential for abuse.  Patients may also prefer taking Suboxone in the form of sublingual film as opposed to the liquid formats of Methadone.

Among opioid addicts, Methadone is likely to be more popular due to the fact that it has a greater propensity for abuse.  Methadone does not have a ceiling effect and is therefore likely to produce a physical and psychological “high” when ingested at high doses.  Methadone also remains popular due to the fact that there are many “Methadone Clinics” throughout the United States, making the drug widely available.

Side Effects

The side effects associated with Methadone and Suboxone are nearly identical.  Common side effects associated with both drugs include: constipation, dizziness, drowsiness, dry mouth, lightheadedness, nausea, sweating, and vomiting.  Most side effects are subject to individual variation or how your physiology responds to the particular drug.

Differences in side effects may also be due to the slight differences in mechansim of action associated with Methadone and Suboxone.  Methadone may produce more severe and or different side effects due to the fact that it is a full mu-receptor agonist and NDMA receptor antagonist.  Suboxone is a partial mu-receptor agonist and has effects on a variety of other opioid receptors (e.g. kappa).

Withdrawal

Discontinuation of Methadone or Suboxone is likely to result in severe withdrawal symptoms.  These symptoms are often most severe within the first 1 to 2 weeks of discontinuation, but may persist for months after the drug has been discontinued as “post-acute withdrawal syndrome” or PAWS.  The degree of difficulty associated with discontinuation of Methadone and Suboxone largely depends on the time span over which the drug was taken and the dosage.

It could be argued that since Methadone is a full mu-receptor agonist, its discontinuation effects may be more pronounced than Suboxone.  In any regard, there are numerous anecdotal reports of Methadone withdrawal and Suboxone withdrawal that highlight their respective degrees of difficulty.  Since Methadone doesn’t have a “ceiling effect,” its withdrawal effects from high doses may be more pronounced than Suboxone.

Based on a comparison of the most addictive drugs, Street Methadone has an estimated addiction rating of “2.08” and Buprenorphine’s estimated addiction rating is “1.64” – meaning it should theoretically be tougher to discontinue Methadone.  Assuming no addiction or abuse of either substance, the difficulty of discontinuation may be relatively similar.  Individual physiology and subjectivity may dictate whether one is tougher than the other.

Similarities (Recap): Methadone vs. Suboxone

Below is a recap of the commonalities shared by Methadone and Suboxone.

• Drug type: Both drugs are classified as synthetic opioids and are considered first-line options for treating opioid dependence.
• Efficacy: Methadone and Suboxone are regarded as equally effective in reducing usage of illicit opioids like heroin.
• Generic availability: Each drug is available in generic formats of Methadone (methadone hydrochloride) and Suboxone (buprenorphine / naloxone).
• Medical uses: The FDA has approved Methadone and Suboxone for treating opioid dependence, opioid addiction, and chronic pain.
• Side effects: The side effects are regarded as similar among these drugs and include: constipation, dizziness, drowsiness, nausea, and vomiting.
• Withdrawal: Discontinuation from Methadone and Suboxone is regarded as being highly difficult, especially when utilized for a long-term and/or at a high dosage.

Differences (Recap): Methadone vs. Suboxone

Below are some differences between Methadone and Suboxone.

• Abuse potential: Methadone is considered to have a higher potential for abuse, whereas Suboxone has a lower abuse potential due to its built-in “ceiling effect.”
• Cost: Both brand name and generic formulations of Methadone are cheaper than brand name Suboxone. From a cost-perspective, Methadone is the better bargain.
• Duration of effect: The duration of effect for Suboxone is approximately 24 hours, whereas Methadone is thought to last between 24 and 36 hours. The window of analgesic effect from Suboxone is an estimated 8 to 12 hours, whereas that of Methadone is 6 to 8 hours.
• Formats: Although Methadone and Suboxone are both manufactured in tablet formats, Methadone is also prescribed in a liquid solution and Suboxone in a sublingual film.
• Half-life: The elimination half-life for Methadone is estimated between 8 and 59 hours, while Suboxone’s half-life is estimated between 24 and 42 hours.
• Ingredients: Methadone is comprised of “methadone hydrochloride” and Suboxone is comprised of Buprenorphine and Naloxone.
• Investigational uses: Methadone doesn’t have many investigational uses, while Suboxone has been investigated as an antidepressant and to treat neonatal abstinence syndrome.
• Legal status: Methadone is considered a “Schedule II” drug and Suboxone is a “Schedule III” drug.
• Manufacturers: Methadone is manufactured by Eli Lilly & Company and Suboxone is manufactured by Reckitt Benckiser Pharmaceuticals.
• Mechanisms of action: Methadone is considered a full mu-receptor agonist, while Suboxone is a partial mu-receptor agonist. Methadone also acts as an NMDA receptor antagonist (Suboxone doesn’t), and Suboxone acts on other opioid receptors (Methadone doesn’t).
• Popularity: Throughout the 1990s, Methadone became the most popular opioid replacement therapy option. However, since Suboxone’s approval in 2002, the number of prescriptions for Suboxone has continued to rise.  Methadone may have more appeal to addicts, whereas Suboxone is often considered safer by medical professionals.

Which drug is a better opioid replacement therapy? Methadone vs. Suboxone.

As was already mentioned, there appears to be no significant difference in the efficacy of Methadone and Suboxone for the treatment of opioid dependence.  They are both synthetic opioids that primarily act as agonists of the mu-receptor.  Certain individuals may prefer Methadone over Suboxone for its increased potency, while others may respond better to the mechanisms of Suboxone.

Some people may find that they both work equally well in managing opioid dependency and reducing their propensity to use illicit opioids.  The research shows that those receiving Methadone at flexible doses are more likely to adhere to treatment compared to those receiving Suboxone at flexible doses.  That said, both were found to have equal efficacy in terms of reducing illicit opioid usage.

Among individuals that may be likely to abuse Methadone, Suboxone may be preferred.  Suboxone’s ceiling effect mitigates additional opioid effects past a certain dosage.  Methadone can be abused, and some patients may take large quantities to “get high.”  Therefore, Methadone is more strictly regulated by professionals.

For this reason, patients generally need to stay at a “Methadone Clinic” in order to receive their medication.  Only when the patient is adhering to the treatment are they allowed to take their Methadone home for self-administration.  Anecdotal reports have suggested that Methadone may be better at combating physical symptoms of opioid replacement compared to Suboxone.

Those taking Suboxone may have an easier time dealing with side effects and withdrawal symptoms due to its slightly reduced potency.  For individuals with mild or moderate opioid dependence, Suboxone is usually the preferred option.  Methadone can be used for all levels of dependence, but may be better than Suboxone for severe forms.

Which drug do you prefer: Methadone or Suboxone?

If you have used both Methadone and Suboxone, feel free to share which one you found to be the better opioid replacement therapy.  Did one drug feel more potent than the other or do a better job at reducing cravings to use illicit opioids?  Mention any reasons that you prefer Methadone over Suboxone or vice-versa.

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