Cracking Addiction

On Cracking Addiction this week

Illicitly used opioids are the third most common form of illicit drug use worldwide and in most high income countries less than 1% of population has used illicit opioids in the last year. Opioids can be associated with overdose, deaths and other health harms but contributes to less of the global burden of disease than licit substances like alcohol and tobacco.

In a local context more people die of prescription drug overdose in Victoria than all the illegal drugs combined. Prescribed opioids were the third largest cause for overdose deaths (usually in combination with other medications).

Opioids include naturally occurring opiate compounds such as morphine an alkaloid of opium obtained from the poppy plant Papaver somniferum as well as synthetic chemicals. Other examples of opioids include: morphine, methadone, buprenorphine, oxycodone, pethidine, codeine, diacetylmorphine (heroin), fentanyl, pentazocine, hydromorphone, dextropropoxyphene

Opioids act on opioid receptors in CNS to produce analgesia and varying amounts of euphoria and sedation. There are three main types of opioid receptors and they produce the following effects:

• mu receptors: euphoria, sedation, analgesia, miosis, reduced GI motility, respiratory depression and physical dependence

• kappa: (spinal cord, basal ganglia and temporal lobes) drowsiness and dysphoria

• delta: analgesia and cardiovascular effects (hypotension and bradycardia)

The simulation of mu (and delta) receptors are involved in reward systems.

On Cracking Addiction this week

Legacy patients on high dose opioids or on combination hypno-sedatives including the combination of opioids and benzodiazepines are at an elevated risk of death. The OPQRST mnemonic can be used to conceptualise the strategies that help to mitigate legacy patients’ risk of death and to trend them towards a position of safer prescribing.

• O= opioid antagonist therapy: take home naloxone

• P = pharmacotherapy

• Q = quantity: reduced

• R = referral to allied health and or psychology

• R = rotation of opioids

• S = staged supply

• T = tapering

Opioid antagonist therapy.
Opioid antagonist therapy in the form of naloxone is available as “Narcan” vials, “Prenoxad” prefilled syringes and as “Nyxoid” nasal spray.

The Pennington institute’s community overdose prevention education program (COPE) provides useful resources and advice regarding the use of naloxone in the management of accidental opioid overdose. It should at this point be stated that naloxone therapy should not be reserved for patients with opioid substance use disorders, but rather should be a widely available therapy for all patients who are at risk of opioid overdose.

Regarding this point, Jauncey and Nielson stated in their 2017 paper that “Regardless of whether opioid use is licit or illicit, anyone at risk of opioid overdose should be considered for naloxone.” It is the author’s opinion therefore, that any patient who is prescribed a total opioid load of more than 50 mg oral morphine equivalent per day should be prescribed naloxone and that they and their carers should be provided with training on its use.

Pharmacotherapy
Suboxone pharmacotherapy can be considered as one option for the treatment of those patients on high dose prescription opioids who meet the diagnostic criteria for an opioid use disorder as defined DSM 5. The distinction needs to be made between physiological dependence and opioid use disorder. Any patient on long term prescribed opioids has the potential to become physiologically dependent on their opioid medication and can therefore present to their clinician requesting higher doses of opioids to treat an apparently worsening pain.

This group of patients can be dealt with by various interventions including a reassessment of underlying medical conditions, alternative pain management interventions (pharmacological or otherwise) opioid rotation or opioid tapering (if deemed appropriate). They must also be distinguished from those patients who present with aberrant behaviours. Such behaviours have been extensively described and include the following.

• Medically unsanctioned use of prescription medication including use of higher doses, unsanctioned indications (non-pain indications e.g. a “bad day”) and unsanctioned routes of ingestion (e.g. snorting or injecting crushed tablets)

• Prescription forgery

• Selling medication

• Doctor shopping

Patents who demonstrate aberrant behaviours with regard to their prescription opioids should be considered for long term pharmacotherapy either with methadone or buprenorphine (with or without naloxone). Each state in Australia has its own rules and regulations regarding the accreditation of clinicians to provide pharmacotherapy and it behoves clinicians to consider their own local requirements before prescribing pharmacotherapy.

Quantity: reduced
It is not mandatory to prescribe quantities as per the original pack size. Smaller quantities of medication should be prescribed per prescription by clinicians who are concerned about the supply of hypno-sedative drugs to their patients.

Referral
Referrals to allied health practitioners and or psychologists should be encouraged as part of a multimodal system of chronic pain management in which the provision of psychological and physical therapies supersede the emphasis on prescribing.

Rotation of opioids
Opioid rotation provides a rapid and effective means of reducing the total daily oral morphine equivalent (OME) daily dose. For patients on more than 100 mg OME, opioid rotation can be used to rapidly reduce the OME to less than 100 mg. It relies on the fact that patients do not usually demonstrate cross tolerance between opioids so converting a patient from one opioid to another necessitates a reduction in dose of the second opioid to approximately fifty percent of the equivalent dose of the first opioid. For instance, if a patient has been prescribed 60 mg b.d. of “Targin” this equates to approximately 200 mg OME. If the patient were to be transferred to 200 mg daily of a long acting morphine, e.g. “MS Contin” or “Kapanol” the patient would likely suffer an overdose because of the lack of cross tolerance between opioids. Therefore, as per the usual practice of only prescribing 50% of the calculated OME for the second opioid, the patient should be started on only 100 mg daily of long acting morphine. It can be seen in this example that converting from oxycodone to morphine has reduced the overall OME from 200 mg to 100 mg. A reduction in OME is an important step in trending the legacy patient to a position of reduced risk of death.

Staged supply
Staged supply denotes the practice of requiring that a patient attend a pharmacy or other dosing point on a regular basis to receive a daily dose of the medication in question. Clinicians can arrange staged supply of any drug, not just Suboxone or methadone. Therefore, staged supply of opioids would be entirely reasonable as part of a plan to manage high dose or high-risk opioid prescribing.

Tapering of opioids
Patients can be weaned off high doses of opioids by gradually reducing their dose over weeks to months. This process, called tapering, is usually done in conjunction with opioid rotation.

The process of tapering involves the following steps.

• The daily dose of short acting opioids is incorporated into a long acting dose of equivalent opioid.
• If multiple opioid combinations are used, then all opioids are converted into an oral morphine equivalent and an opioid rotation is performed as described above.
• One long acting opioid is commenced
• The taper starts at a rate of approximately ten percent per week of the original starting dose
• The use of short acting opioids or prn doses is strictly limited.

The recommended taper rate is a reduction of ten per cent of the original dose of opioid per week or fortnight such that over a period of ten to twenty weeks patients can be completely weaned off their opioids if appropriate or otherwise weaned down to a dose of less than 100 mg OME.

On Cracking Addiction this week

The natural history of opioid use is characterised by the development of dependence relatively rapid after 6-8 weeks of regular use or many years of intermittent use and once dependent users may struggle to control their use for substantial proportions of their lives.

 The terms dependence and addiction are often used interchangeably but theses terms actually refer to two different phenomena. Dependence refers to a physiological response and is characterised by tolerance to a substance and withdrawal symptoms when one cannot access this substance. It is characterised by a neuroadaptation to this substance.

 Addiction refers compulsive and uncontrollable use of a substance even in negative circumstances and even when harms are occurring due to this substance usage. Thus one can be dependent on a substance and not addicted and one can use opioids prescribed or illicitly and not have an opioid use disorder.

 The criteria for opioid use disorder is listed below and:

• meeting 2-3 criteria characterises mild opioid use disorder

• meeting 4-5 criteria characterises moderate opioid use disorder

• meeting 6-11 criteria characterises severe opioid use disorder

Opioid use disorder (DSM-5)

2-3 criteria mild, 4-5 moderate, 6-11 severe opioid use disorder

• 1. impaired control over use

• 2. Great deal of time spent obtaining, using or recovering from effects of opioids

• 3. Craving or compulsion to use

• 4. Unsuccessful attempts to cut down on use

• 5. Preoccupation with opioid use to the detriment of all other responsibilities

• 6. Continued opioid use despite negative repercussions

• 7. Social, occupational or recreational activities abandoned due to opioid use

• 8. Recurrent opioid use in physically hazardous situations

• 9. Tolerance

• 10. Withdrawal or use of opioids to prevent withdrawal

• 11. Persistent use despite clear evidence of physical or psychological adverse consequences

The ICD 11 criteria for substance dependence recognises that this is a disorder of regulation and requires that two out of three of the following themes need to be present for a diagnosis of substance dependence to be made and that is:

• impaired control

• increasing priority of substance use over all other priorities

• presence of some physiological features whether that be tolerance, withdrawal or neuroadaptation.

Thus one can see that dependence and addiction are two quite different phenomena and how important it is to be clear in our definition and language when discussion both addiction and dependence.

On Cracking Addiction this week

Methadone was developed in Germany in 1941 as a synthetic opioid agonist. It was in 1961 that Dole and Nyswander suggested it could be used as opioid agonist therapy in the treatment of heroin addiction.

Methadone is an extensively investigated treatment in opioid agonist therapy. A 30 year observational study by Grella and his colleagues in 2011 found that 25% of patients on Methadone decreased their heroin use quite rapidly and stopped using heroin in 10-20 years, 15% achieved a modest decrease in their heroin usage but also subsequently stopped using heroin in the next 10-20 years and another 25% decreased their heroin usage.

Methadone has also been found to reduce the frequency of injecting and the sharing of injecting equipment thus also decreasing the risks of transmission of blood borne viruses.

Methadone maintenance treatment improves health, reduces illicit heroin usage, reduces infectious diseases transmission and overdose death. However it’s effectiveness is compromised if low maintenance doses of Methadone are used. Studies have shown that those receiving greater than or equal to 60mg daily doses of Methadone are 70% more likely to remain in treatment than those on doses less than 60mg daily. Degenhardt and his colleagues in 2009 found that Methadone decreases mortality by 29% in this cohort of patients.

Thus in summary Methadone is of vital importance in the optimal treatment of patients in opioid agonist therapy.

On Cracking Addiction this week

Methadone has a number of benefits that extend from not only the person taking it but also society as a whole. Methadone decreases criminality with the overall reduction in convictions and cautions estimated to be at 10% for each six months enrolled in methadone maintenance therapy with patients in continuous treatment receiving the best outcomes.

Generally patients receiving a daily dose of 60 mg or more have better treatment outcomes than those receiving less than 60 mg in terms of:
• Retention in treatment
• Unsanctioned opioid use
• Criminal activity

Methadone is also cost effective with evidence from the National Institute on Drug Abuse in America from 2018 revealing that every dollar invested in addiction treatment programs yields a return of between $4 and $7 in reduced drug-related crime, criminal justice costs, and theft. When savings related to healthcare are included the total savings can exceed costs by a ratio of 12 to 1.

More local evidence from the ‘Final Report of the National Ice Taskforce’ in 2015 in Australia revealed that:
• For every $1 invested in treatment services, more than $7 is returned to the community through health and social benefits.
• For every $1 spent on needle and syringe exchange programs, the community saves $27 in future cost.

Thus in summary Methadone is a cost effect and effective treatment for opioid use disorder that has significant benefits to society as a whole.

On Cracking Addiction this week

Taking an accurate substance use history is of great importance in the management of addiction. There are a number of strategies that one could use but the most important part of history taking is that of demeanour and empathy. The best results and most accurate information are often obtained when one treats one’s patients with human empathy and in a non-judgemental manner. There is a quote by Walt Whitman ‘be curious and not judgemental’ which I try and use as my guiding principle when I am taking a substance use history.
A good tool for taking a comprehensive substance use history is the DUDIT .
Dr Ferghal Armstrong usually utilises his own mnemonic ‘TARCD’ when taking a substance use history:

Timing
• First use
• Last use
• Frequency of use
• Time within the day
• Periods of abstinence

Amounts (and overdoses)

Routes
• Oral nasal intravenous etc

Risk
• Drug specific risks e.g. seizures with alcohol withdrawal
• Access to Needle syringe programs
• Transmission of BBV

Costs
• Financial
• Relationships
• Loss of activities and hobbies

Dependency Factors
• DSM 5 criteria – CHEW THAT COP

A question that is not frequently asked but is of great importance is a simple one: ‘What do the drugs do for you?’. This question asks not about dependence or withdrawal but rather what reason is the person taking drugs and from personal experience can cause some quite profound revelations or open up some deep emotions or profound hurts that have caused the individual to start using drugs.

In summary it is very important to be empathetic, non-judgemental when conducting a substance use history regardless of the actual technique used to elicit the history-the non-verbal cues the patient perceives will be vital in the accuracy of the history obtained.

In this episode of Lifestyle Matters.

This week Dr Ferghal and I explore one of the most common addictive habits known to mankind – smoking. Back in the 50s-60s, smoking was considered the epitome of fashion and glamour. It was around then too when they started discovering the ill effects of smoking due to the various carcinogenic components, tar and carbon monoxide found in cigarettes. Of course, nicotine itself has deleterious effects on our health as it constricts our blood vessels, but the main offending agents are the other components that make up cigarettes.

We know that 2/3 of long-term smokers will cut their life expectancy by 10 years compared to non-smokers and will die of a smoking related disease.

The following include some but not all the health issues that we are at a higher risk of should we smoke regularly:
• Heart disease
• Stroke
• Peripheral vascular disease –e.g. clots in legs (Deep Vein Thrombosis), poor blood flow to our extremities resulting in poor wound healing, ulceration, poor exercise tolerance
• Eye disease e.g., macular degeneration
• Diabetes i.e., 30-40% higher risk in a smoker
• Lung disease e.g., chronic obstructive pulmonary disease (COPD)
• Cancers e.g., lung cancers, throat, mouth, stomach, liver etc.

Nicotine is a highly addictive substance as it binds to the nicotinic receptors in our brain causing the release of a good feeling hormone called Dopamine. Once nicotine wears off, we understandably crave for more. This is where the various therapies come into play such as:
• Nicotine replacement therapy – gum, patches, inhalers
• Pharmacological therapy – Vareniciline (Champix) and Bupropion ( Zyban)
• Vaping – which has nicotine but not the other more harmful substances

Whichever therapy a patient chooses, the success rate is markedly increased when it is combined with some form of counselling, especially cognitive behaviour therapy. Caffeine is another factor that needs to be taken into consideration when quitting smoking as our body does not metabolise it as quickly as it would when smoking. What this means is that the effects of caffeine our body when quitting smoking can be increased by up to 50%. Hence reducing caffeine consumption would be highly advisable during this period to reduce the risk of agitation and insomnia.

Having a supportive network and not giving up despite a relapse are important factors in increasing success in smoking cessation. Reaching out to your GP would be a great starting point in this journey.

On Cracking Addiction this week

There are a whole range of drugs of concern that one can become dependent upon or become addicted to and this list can seem daunting. The list of drugs that a ‘use disorder’ can be appended to under the DSM 5 criteria is similarly long. Dr Ferghal Armstrong though provides us with a useful mnemonic to remember these drugs ‘COCA SHITS’.

• Cocaine
• Opioids
• Cannabis
• Alcohol
• Stimulants
• Hallucinogens
• Inhalants
• Tobacco
• Sedatives

Similarly an alternative classification system of drugs of dependence making it easier to remember these drugs is as follows:

The Legals
Alcohol tobacco
The prescribed
Opiates benzodiazepines quetiapine pregabalin stimulants
The uppers
Cocaine amphetamine methamphetamine
Downers
Heroin cannabis
Party drugs
MDMA LSD magic mushrooms GHB

Identifying those patients who may be ta risk of prescription drug aberrancy can be difficult and is an area that can leave a doctor feeling quite fraught. A useful set or patterns of behaviours to be aware of can be remembered through Dr Armstrong’s mnemonic ‘USE TALK’

Urgency
Unscheduled medical appointments
Splitting
“You are the only one who can help”
Efficacy
“Nothing else works for me”
Timing
Saturday afternoon and I have run out of my medication – no option for cross checking with other agencies
Allergies
“I am intolerant of all other pharmacological options”
Lost
Lost prescriptions that trigger requests for further replacement prescriptions
Knowledge
High degree of knowledgeability surrounding the drug in question

On Cracking Addiction this week

Most women presenting with opioid dependence are of child-bearing age with chaotic drug use predisposes to amenorrhoea. The initiation of opioid substitution therapy (OST) facilitates stability and reinstatement of regular menstrual cycles and thus OST is a risk factor for unplanned pregnancy. Contraception needs to be discussed with all female patients of child bearing age who present to OST treatment services.

Substance use disorder in pregnancy mandates referral to a specialist services with best practice including involvement in a multidisciplinary drug and alcohol antenatal clinic. This multidisciplinary team should include: midwives, Obstetricians, Paediatricians, social workers and Addiction Medicine specialists.

Counselling needs to be provided regarding the risks and benefits of OST during pregnancy and lactation. There is a significant risk of miscarriage if doses of OST missed/opioid withdrawal occurs. Pregnant patients may be reluctant to engage with antenatal services or OST treatment programs because of chaotic lifestyles, stigma or concerns about child protective services and removal of their child from them post birth. By focussing on the health of the baby this may promote engagement with treatment services.

Suboxone, Subutex and Methadone are all Category C drugs in pregnancy. However inadequately treated opioid use disorder is a significant risk to the viability of the pregnancy. Opioid withdrawal in the first trimester can cause uterine contractions and does increase the risk of miscarriage in the first trimester and opioid withdrawal in the third trimester increases the risk of intrauterine growth restriction as well as risk of premature labour.

Another concern about OST in pregnancy is adequately dosing the pregnant woman. The half life of Methadone is reduced in pregnancy from 22-24 hours in non-pregnant women to 8.1 hours in pregnant women. Methadone metabolism is accelerated due to increased CYP3A4 expression by liver, intestine, and placenta and methadone clearance increases with advancing gestational age. As a result of this higher doses and split dosing of Methadone may be required.

An optimal dose of methadone remains controversial with doses of 80-120mg per day not inappropriate. Twice or thrice daily dosing can result in more sustained plasma levels, fewer withdrawal symptoms, and less illicit drug use and less suppression of foetal movement and breathing.

Thus in summary it is important to adequately treat women who are pregnant with opioid use disorder to prevent harms to both the woman and foetus.

On Cracking Addiction this week

Post birth the patient’s usual oral methadone dose can be continued in the peripartum and post partum period. There is a theoretical concern in the postpartum period of over-sedation as methadone levels may increase as plasma volume and hepatic clearance normalise post the delivery of the child. Women should be closely monitored during this time period to guard against complications.

There are three approaches to manage this potential problem including: stay on the same dose of Methadone with close monitoring, decrease the Methadone dose by 10-20% or reduce the methadone dose by 20 to 40 percent immediately postpartum and closely monitor and follow up the woman to ensure the patient is not in significant withdrawal.

Most women who undergo buprenorphine maintenance therapy will not experience large dose adjustments during their pregnancies and may continue the same doses after delivery

Breast feeding should be promoted with confidence unless active substance use is occurring or otherwise contraindicated. Breastfeeding may reduce the severity of neonatal withdrawal syndrome in the neonate. With Methadone about 1-3% of maternal dosage will be transferred into the breast milk and with buprenorphine the amount of buprenorphine in breast milk is <1 percent of maternal dose. There is a low oral bioavailability with significant absorption unlikely.

Neonatal abstinence syndrome (NAS) is a phenomena when the infant withdraws from drugs that they have been exposed to in utero. NAS is not unique to opioids and can occur with benzodiazepines, nicotine and also SSRI and SNRIs. Methadone causes a withdrawal syndrome in 60–80% of cases with symptoms occurring usually between 48 to 72 hours after birth but also up to five days. In rare circumstances symptoms can be delayed by up to a month. The severity of NAS is not related to the maternal dose of Methadone.

There are lower rate of NAS with buprenorphine compared to methadone which is thought to be secondary to: lower bioavailability, lower transplacental passage and partial agonism. The risk of NAS with buprenorphine is also not dose dependent. However overall the risks of opioid withdrawal during pregnancy are greater to the foetus than those of NAS to the infant so it is important to adequately treat the pregnant woman with opioid use disorder rather than be concerned about the risks of NAS.