Meg Barbor, MPH

November 03, 2017

NEW ORLEANS ― Methadone can save the lives of patients with opioid use disorder, but it can also destroy those lives, so how do prescribers determine optimal candidates for treatment?

Here at the Institute of Psychiatric Services (IPS): The Mental Health Services 2017 Conference, Margaret Chaplin, MD, and Vania Modesto-Lowe, MD, MPH, discussed the role of medication-assisted treatment for opioid use disorder, and more specifically, the important role of methadone.

Methadone maintenance treatment (MMT) is a comprehensive treatment plan that involves the prescribing of methadone as an alternative to the opioid on which the client is dependent.

Dr Chaplin noted that the opioid epidemic has played a role in creating "an enormous treatment gap" in the United States. There are far more people in need of treatment than there are people accessing it.

"Clearly there's a huge role for psychiatry to play in this," said Dr Chaplin, a psychiatrist in New Britain, Connecticut. "Pharmacology is actually the crucial piece in the management of opioid use disorder. There's been a big shift in understanding that this is a medical illness that requires medical treatment."

But the flip side, she warned, is that the medications used to treat opioid use disorder can have severe consequences if prescribed improperly.

"It's important to conquer our fears of that," she said. "It's also important to understand that, even though medication is the mainstay of treatment, medication in isolation is not going to be enough to break the cycle of addiction."

Comprehensive Treatment Is Key

Dr Modesto-Lowe, a psychiatrist in Middletown, Connecticut, said the first thing to consider when prescribing methadone is whether or not the patient meets federal guidelines for MMT.

The individual must have demonstrated opioid dependency for more than 1 year (exceptions include patients who are pregnant, have been released from incarceration within the past 6 months, or who have received treatment at a methadone clinic within the past 2 years). Patients must be aged 18 years or older but can be younger in the event that two previous treatment episodes have failed and they have received the consent of a guardian.

The patient must be evaluated for contraindications, which include allergy or hypersensitivity to methadone; pulmonary heart disease; inflammation of the colon; selegiline use; intestinal obstruction; and chronic obstructive pulmonary disease (COPD). For patients with COPD, methadone can still be used, but clinicians should proceed with caution, she noted. The patient should be evaluated with respect to psychosocial status and environmental risk and protective factors.

"I think with methadone use, intention matters when it comes to outcomes," she added.

Methadone treatment is a double-edged sword. It is a full agonist of the mu-opioid receptor and produces morphinelike effects, such as analgesia, euphoria, constipation, sedation, and, importantly, respiratory depression. Effects are detectable at 30 minutes and take from 2 to 4 hours to peak.

"But its long and variable half-life is the double-edged part," she said. Its long half-life allows for once-a-day dosing for the treatment of addiction (not for pain), but methadone accumulates in the liver. When this occurs too fast, toxicity and respiratory depression can occur.

When it comes to induction, "start low, go slow," she said. The initial dose should be 10 to 30 mg daily. The dose should be increased by 5 to 10 mg every 3 to 5 days. Dosage should be determined on the basis of how the patient feels after 2 to 4 hours, not by how long the effects last, and the patient should be monitored for withdrawal symptoms.

"Remember the rule of thumb is that half of yesterday's dose is still circulating in the plasma," she noted. Depending on half-life, methadone reaches a steady state in 3 to 5 days.

Dr Modesto-Lowe urged healthcare providers to know clinically relevant drug interactions. Agents known to be associated with pharmacokinetic interactions include 3A4 inhibitors and inducers, 2D6 inhibitors, cocaine, St John's wort, and grapefruit juice.

Pharmacodynamic interactions include respiratory depression (due to concomitant use of benzodiazepines, barbiturates, alcohol, or fentanyl), constipation (due to use of antihistamines, selective serotonin reuptake inhibitors [SSRIs], and anticholinergics), sedation (due to use of atypical antipsychotics, trazodone, antihistamines, and tricyclic antidepressants), and QTc prolongation (due to use of atypical antipsychotics, SSRIs, and macrolides).

"Perhaps most important is the QTc prolongation," she said. "Although not too common, methadone does have the ability to increase QTc, particularly at high doses, and if the patient is taking other medications that increase QTc, that could be a problem." She suggested a cardiology consult to avoid this interaction.

She advised that attention should be paid to general physiologic status, because patients with a low potassium or magnesium level may be at increased risk for adverse reactions.

Follow-up Care

To ensure quality care after initiating treatment with methadone, the patient should be monitored for efficacy, side effects, self-reported use, and adherence. Collateral input regarding the patient's psychosocial standing should be sought from the patient's family, therapist, or case manager, said Dr Chaplin.

"There's this conception that being on methadone is a crutch, or sometimes it's seen as 'not really' recovery, so we try to address that," she said. "But if you had diabetes, you would not expect your doctor to say, 'You've been on insulin for 5 years. Don't you think it's about time your pancreas started working?,' but that's really the experience our patients face, that they shouldn't have to take this medication long term.

"We really try to encourage our patients to think of this as a chronic illness, and this medication is one tool towards their recovery," she continued. "This is worthwhile and necessary work. A lot of people need these medications, and they really do make a significant difference in people's lives."

Dr Chaplin and Dr Modesto-Lowe have disclosed no relevant financial relationships.

Institute of Psychiatric Services (IPS): The Mental Health Services 2017 Conference. Presented October 20, 2017.

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