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Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Tuesday, March 1, 2011

Opioid Therapy: Chronic Pain Relief

This section was originally part of the "therapeutic uses" page, however while reformatting the blog's main pages, I've had to re-publish this section to provide it a space of its own.

Those who are ethically or ideologically opposed to the idea of long term narcotherapy for non-cancer pain often tend to cite the lack of placebo controlled long term trials or peer reviewed studies in this particular field. These individuals, whether they be doctors or laypeople, tend to emphasize this lack of definitive evidence and characterize this ambiguity itself as evidence to refute the validity of this practice. What they fail to acknowlege, perhaps out of willful density, is simple - The self-reported experience of countless individuals who will adamantly testify to the significant relief of symptoms provided by chronic use of narcotics. Such anecdotal evidence lacks the empirical objectivity to which one could apply a standardized means of measurement. These patient reported benefits include cognitive and emotional improvement, restored sense of passion for life, improvement in function, increased social & economic productivity, restoration of physical energy, improvement in interpersonal relationships and a reduced degree of suffering overall.

Criteria for Opioid Therapy: Palliative opioid therapy as a pain treatment, is generally most likely to be considered by Doctors under the following conditions.

a) Has been present for weeks, months, or years, lasting at least 12 hours per day at an intensity of at least 5 on a10-point pain scale.

b) Interferes with sleep, self grooming or hygeine, independence, employment, and other tasks deemed essential to a productive lifestyle.

c) Exacerbates an unrelated condition such as heart disease, severe depression, etc; or interferes with the course of treatment for such an underlying condition.

d) Has resulted in a marked deterioration of physical or emotional health.

e) Some of the more gracious Doctors will consider a deterioration in quality of life itself as sufficient indication for chronic opioids, assuming one is currently capable of giving informed consent.

The Case for Opioid Therapy

Narcotics are not given to "cure" pain or to "fix" the source of pain. They are not effective in doing either - but this by no means negates their value. The phenomena of pain is more complex than some would have us believe. To debate the merits of narcotics for pain is not as simple as debating whether they treat the source or mask the symptoms. Ignorant opponents of chronic opioid use maintain the misconception that opioids merely cloud the perception of pain, and claim that pain is merely a symptom which in itself does not merit a potentially 'habit forming' treatment. This is a mistruth. Pain in its simplest and acute sense is indeed a symptom - often secondary to an injury or illness - and even so, for pain as a symptom to be denied treatment, especially over irrational fears of 'addiction', is pointless, idiotic and inhumane. The simplistic view that "pain is pain is pain", is especially senseless. It must be established that pain occurs in many different forms under many different circumstances. Pain is a complex biological state, of which our understanding is still in its infancy, and manifests as far more than just a symptom. Pain can range from a symptom, to a condition, to a chronic disorder in itself. When chronic pain is considered by its clinical definition, the implication that chronic pain is merely a symptom is completely false.

Chronic pain (or CP) is a state of disorder typically involving the central nervous system. The very fact that CP is often a "symptom of nothing", is the basis for its classification by some as a medical 'disorder'. In the case of chronic pain, what once may have been a symptom has remained long past healing time of the original injury or illness. 

Chronic pain targets the pain pathways within the dorsal horn of the spinal cord. What often begins as symptomatic pain may develop into chronic pain over time if the pain itself is not well controlled. The untreated pain with time leads to neuroplastic changes involving ascending C-fiber pathways and descending modulatory pain feedback pathways - a process known as long term potentiaton. In effect - Pain pathways within the spinal cord continue transmitting pain in the absence of any actual damage or inflammation.

Given for acute pain, opioids change the perception of pain, inhibit the reaction to pain, and calm the pain transmission (i.e. nociception) itself at the spinal level - this prevents the aforementioned adaptive changes in which lead to chronic pain. When symptomatic pain is left untreated to become chronic, this is where pain becomes much more complicated to manage and to treat.

In any discussion of acute or chronic pain, one must acknowledge the naturally occurring painkillers of the body - the endogenous opioids (i.e. endorphins). "Endorphin" is often used as a broad term to cover a spectrum of naturally occurring neurotransmitters in the body, which act in the same way & at the same receptors as narcotic drugs like morphine and heroin - i.e. binding to opioid receptors and inhibiting the transmission of pain from one neuron to the next. Endorphins are released into the bloodstream and spinal fluid, and naturally relieve pain and distress during injury, illness, or stressful experience. 

Opioid drugs (i.e. narcotics) are known as exogenous opioids, as their source is outside of the body. During symptomatic pain, narcotics are given when the pain is too great for endorphins to manage. During chronic pain, endorphins are produced and released, but the pain has long since exceeded the point of responding to endorphins. Furthermore, as discussed prior, chronic pain becomes a full blown dysfunction, without a source which can be repaired or healed. The only possible treatments will target the central nervous system - i.e. the pain pathways of the spinal cord, the physical response to pain by the brain, and the perception of pain by the brain. The opioids target all three elements.

To clarify further; research is still in its infancy in regards to fully characterizing the mechanisms underlying the deep rooted neurobiological changes present in chronic pain. However, opioids do in fact attack the pathological product of such changes, by countering the transmission of such seeming source-less nociceptive stimulus. In the process of doing so, the narcotics are effective in treating the many problematic physiological, psychological, emotional & behavioral impacts of chronic pain (which will be covered in more detail below).

Purposes of Opioid Therapy for Chronic Pain:

First and foremost; to reduce the flow of pain transmission to the brain and calm the physiological reaction to pain.

To increase one's tolerance to pain and to alter the perception of pain and reduce its negative impact on emotions. Opioids cause euphoria or have a positive effect on mood in many individuals. Some pain may be present, but will be much less bothersome.

Prevent the complications of long term pain on physical health. Untreated pain may cause or worsen high blood pressure, other cardiovascular conditions, interfere with vital functions such as rest, sleep, and food intake, lead to major weight changes, reduce physical energy, and in some cases lead to heart attack, stroke, and death.

Prevent the complications of pain on mental health - as untreated pain may directly or indirectly lead to anxiety or depressive disorders, complicate underlying mental illness, impair cognitive function and social skills, and in some cases lead to nervous breakdown or suicide.

Restore and maintain an adequate state of physical and psychological function.

Increasing function!! Opioids will lead to increased mobility, better function, employability and financial productivity, energy, hygeine, excersize and independence.

Quality of life!! Improvement in mood, motivation, and a restored interest in personal passions, thus allowing a better quality of life.

An ideal approach to chronic opioid therapy may also include the following:

Regular visits to assess and re-assess the efficacy and response to opioids, to review the patient's med use and med reactions, and to make any changes needed. A good doctor will counsel the patient adequately regarding the major points of narcotic therapy - physical dependence, tolerance, proper use, serious side effects, and other limitations.

Quality documentation of pain patterns and responses to treatment. Keeping a pain journal or diary, and periodic assesment of pain on a graded scale - this over time will allow a doctor to become more familiarized with an individuals personal pain scale, and to analyze progress and assess future goals.
Physical therapy when necessary to promote fitness and use of the body and maintain further function, mobility, and independence.

Adjuvant analgesics or analgesic techniques; i.e. gabapentin, pregabalin, SRI's or NRI's; steroid injections; local anaesthetics or nerve blocks; NMDA antagonists to slow tolerance + enhance analgesia; icing, wrapping, massage, or heating techniques; acupuncture.

Psychosocial therapy never hurts; even for those in perfect health. Periodic individual or group type counseling helps many people to remain socially engaged, in tune with others, and may promote or maintain a healthy relationship with their opioid medications (and family or friends). Talking with others is generally beneficial for most individuals, in one way or another.

Regular primary care to address physical health as a whole and to treat any unrelated underlying conditions such as heart disease, obesity, diabetes, asthma, etc. This may include monitoring of testosterone levels, enzyme levels, neuroendocrine function, digestive function, and reproductive function - such functions specifically might require attention to address the common opioid side effects, which can easily by treated/managed.

Diet and lifestyle changes, emphasis on nutrition, excersize, sleep habits. Emphasize the importance of a healthy lifestyle and nutritional balance; incorporate this into any treatment plan.

Any ongoing (or necessary) psychiatric care - including initiation or maintenance of any current psych meds for underlying mood disorders such as OCD, ADHD, major depressive or anxiety disorders, sleep disorders, etc.

What to expect with chronic opioid therapy:

Initiation of chronic narcotic therapy is often referred to by doctors as an opioid trial. The trial phase will likely involve induction with a short acting narcotic, usually morphine, given in a modest dose every 4 hour; this will be supplemented with additional rescue doses, which are taken intermittently "as needed". 

Rescue doses may be taken as often as needed, as frequently as every hour - keep in mind this is the trial phase. The dose is assessed each day or two and pain relief is assessed. Once a consistent level of relief is observed at a given dose (with pain measured on a 10 point scale) the total daily dose, including the rescue doses which were required, is established. This process of "low base dose + rescue dosing" allows both doctor and patient to establish the lowest effective dose without guessing and "shooting high". In some cases, a number on the pain scale would already have been selected beforehand to represent the pain-relief goal; determined by the level of pain which the patient believes would be manageable. 

The proper level will be the dose which gives the most effective relief while producing the fewest adverse effects; generally sedation and somnolence. 

Once the proper dose is established, the total daily dose is given as either an ER or IR formulation of the same opioid, or converted to a new opioid in an equianalgesic dose. Whether a long or short acting medication is used will depend upon the nature of the pain.

Relieving Chronic-Consistent Pain:

If the drug is being considered for chronic-consistent pain which is present throughout most if not all of the day, it is standard practice to use a long acting opioid - this may be a traditional semi-synthetic opiate in a contolled release form, or it may be a regular non modified form of a naturally longer acting opioid. The typical first choice of most doctors is morphine as an extended release formulation such as MS Contin, Kadian, Avinza, or Embeda, (the latter of which contains an inactive opiate antagonist to prevent misuse of the pill) - MSContin is designed to last 8 to 12 hours, Kadian lasts 12 or more hours, Avinza lasts 24 hours, and Embeda lasts 24 hours. If morphine is inadequate or inappropriate due to poor pain relief, adverse effects, or hypersensitivity/allergy, the common second options are 12-hour oxycodone (OxyContin), 12-hour oxymorphone (Opana ER), or a transdermal fentanyl patch which is applied every 2-3 days. One possibility is a newer once daily hydromorphone tablet called Exalgo, but like every narcotic pain medication introduced after 2010, doctors must jump through some bureaucratic hoops to become registered to prescribe it; which leaves the two third tier options. Methadone and levorphanol. Both are available as generics. Methadone is the cheapest opioid available price-wise, and is taken a few times daily. Individuals vary in their reactions to methadone, so selecting a dosing interval is trial and error. Levorphanol is available as a generic from only one manufacturer, and is more costly than methadone. It is generally taken at an interval of anywhere from every 6 to 12 hours.

Long acting morphine: A common initial dose for MS Contin is 15 to 30mg every 8-12 hours for an opiate naiive individual. Certain products such as avinza can be taken once daily at doses up to around 60mg. Individuals requiring more than 60mg morphine daily are clinically considered opiate tolerant.

OxyContin is the only long acting oxycodone available. In those who are not switching from morphine or another opioid, it's given in doses of 10-20mg every 8-12 hours, depending on how quickly it wears off in a given individual. Individuals requiring more than 30-45mg of oxycodone per day are clinically considered opioid tolerant.

Oxymorphone ER is generally given only to opioid tolerant individuals. A typical starting dose is dependent upon their previous dose of a given opioid. For a patient who had previously taken 60mg morphine, or 40mg oxycodone, twice daily, Opana ER would ideally be started at 20-30mg every 12 hours.

The transdermal fentanyl patch is reserved for opioid tolerant individuals - even the 25ug/hour patch is reserved for those taking well over 100mg morphine around the clock. A dosing chart is included below. Note that according to medical standards: "Patients considered opioid tolerant are those who are taking around-the-clock medicine consisting of at least 60 mg of oral morphine daily, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oral oxycodone daily, at least 8 mg oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer."

Methadone dosing is typically trial and error. Potency is inconsistent between individuals, but as doses increase, its morphine relative potency multiplies - in other words, it has a non linear, upward curve in dose-effect. Most doctors are cautious, starting with 2.5 to 5mg every 8 to 12 hours, taken as needed during induction. Once a steady dose is acheived, methadone is given every 6 or 8 hours around the clock. However, intervals up to 12 hours are sometimes appropriate in the elderly, who often exhibit lower hepatic and renal clearance. In any case, methadone lingers in soft muscle tissues and plasma - to the extent that blood levels in those maintained on the drug may reach several times those seen with a single dose - therefore, doses may be tapered down significantly once one is stabilized on methadone.

Levorphanol is reccomended primarily for tolerant individuals, however this is not always the case. A typical starting dose is 2mg every 6 to 8 hours, given around the clock in cases of consistent CP. Higher doses may be given in tolerant individuals; every 4mg of oral levorphanol is comparable to 30mg oral morphine, and intervals are generally the same. In any case, levorphanol lingers in plasma - to the extent that blood levels in those maintained on the drug may reach 5x those seen with a single dose - therefore, doses are often tapered down significantly once one is stabilized on levorphanol.

Once daily hydromorphone (i.e. Exalgo) may be used by doctors who have acquired the proper registration, however the doses available in the US are unreasonably low for almost any opioid tolerant individual, the highest dose tablet available contains 16mg. Individuals taking this product may require multiple tablets per day. An alternate approach would involve the addition of a second opioid with an incomplete cross tolerance to hydromorphone, to create drug synergy & a subsequent sparing effect.

Buprenorphine has been around for ages, yet its use in the US for chronic pain is fairly new - a 7 day transdermal skin patch is the only american buprenorphine medication approved for pain at this time. BuTrans is applied to the skin like the fentanyl patch, and is changed every 5 to 7 days. Buprenorphine is over 30x more potent than morphine, and 1/3 as potent as fentanyl and is used in microgram doses ranging from 5 to 20ug per hour in the case of BuTrans. In this dose range, buprenorphine produces typical morphine-like effects, with an agonist dose response curve which does not exhibit a plateau in response. Also owing to its agonist properties in low doses, buprenorphine can be supplemented with opioid agonists such as morphine, oxycodone, hydromorphone, etc.

Relieving Chronic-Intermittent Pain:

There is an entirely different approach to medicating chronic cases of intermittent pain. Such cases can include chronic renal colic (i.e. recurring kidney stones), migraine attacks, cluster headaches, and severe tension headaces. In this case, a short acting opioid is usually given to be taken as needed. This may amount to the occasional 'here and there', or at certain times each day as a result of certain physical activities, or as frequently as several times each day. A short acting opioid for this purpose is ideally equally quick to take effect. Pain relief is always best when medications are taken right away, at the first sign of pain, or before a certain activity in anticipation of pain.

Doctors may start off providing compounded meds such as hydrocodone w/ acetaminophen (Vicodin, Norco, Lortab) or oxycodone w/ acetaminophen or aspirin (Percocet, Percodan, Endocet). Either way, there will likely reach a point that drug tolerance has increased to where one is taking up to 12 tablets daily, the maximum number recommended as acetaminophen is toxic in higher doses. At this point, traditional single entity narcotics are given. Morphine and oxycodone are the most popular in the US. Hydromorphone (i.e. Dilaudid) may be a first choice when particularly rapid relief is desired. Oxymorphone immediate release in the form of Opana IR is comparable to morphine & oxycodone in its onset, peak, and duration, and is used as another alternative to morphine. Opana is twice as potent as oxycodone by milligram when swallowed.

Norco, Vicodin, Lortab (hydrocodone compounds): common dosing is 5-10mg every 3 to 4 hours, or 10-20mg every 4 to 6 hours. No more than 4,000 mg acetaminophen in 24 hours. Up to 120mg of hydrocodone can be taken per day. This translates to 12 Norco tablets containing 10mg hydrocodone w/ 325mg acetaminophen.

Percocet, Endocet (oxycodone compounds): common dose is 5-10mg every 3 to 4 hours, or 10-20mg every 4-6 hours. 120mg of oxycodone can be taken per day before exceeding the ceiling for acetaminophen - this is equal to 12 percocet tablets containing 10mg oxycodone w/ 325mg acetaminophen.

Morphine oral: Common starting dose is usually 15 to 30mg every 3 to 6 hours. There is no limit on dosing for tolerant individuals. Chronic users may reach daily doses of several hundred milligrams to several grams per day.

Oxycodone oral: Common dose is initially 10-15mg every 3 to 6 hours, which can be increased to 30mg if required. No dose limit for tolerant individuals.

Hydromorphone oral: Common dose is usually 2-4mg every 3-4 hours, which can be increased to 8mg if needed. No dose limit with dilaudid.

Oxymorphone oral: A common starting point is 10-20mg every 4-6 hours. With its low oral bioavailability, this is equivalent to 1-2mg by injection every few hours.

Some key points to keep in mind:

Dosing at regular intervals (around-the-clock) is preferable to dosing as needed. With chronic treatment, analgesics are almost always most effective when the analgesic is given preventatively, meaning before pain develops.

If pain is infrequent or intermittent however, chronic migraine or tension headache for instance - analgesics should be taken immediately at the very first indication of oncoming pain.

When taking an opioid for around the clock pain control (i.e. baseline analgesia), many doctors will supply a supplemental narcotic for sudden onset flares of pain, known as 'breakthrough' or 'rescue' medication. Ideally this will be a rapid acting and perhaps short acting narcotic, which is suited for quick relief of sudden onset pain. Popular narcotics for this purpose (in the US) are oral oxycodone, oral hydromorphone, oral oxymorphone, oral hydrocodone with acetaminophen, and sometimes buccal or sublingual fentanyl. Given elsewhere around the world for this purpose may also be oral or injectable morphine or diamorphine, injectable buprenorphine, dipipanone, dextromoramide, and nicomorphine.

Your doctor may be empathetic and compassionate, and may be happy to help you manage your pain. Your doctor may be a family physician you've seen for years. But the fact remains that the majority of doctors fear police investigation, prosecution, and career ending sanctions. Those taking opioids for true chronic pain who are fortunate enough to have access through a good doctor, should always take care to avoid ruining a great situation. Doctors are hyper-vigilant for what they refer to as abbarrent drug related behaviors - Avoid dropping red flags. Just use some common sense.

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