Category Archives: Medications

Prialt

PRIALT (Ziconotide Intrathecal Infusion) for Severe Chronic Pain in patients for whom intrathecal (IT) therapy is warranted, and who are intolerant of or refractory to other treatment, such as systemic analgesics, adjunctive therapies or IT morphine.

PRIALT is a Novel Non-Narcotic Treatment Based on Marine Snail Peptide Blocks Pain Signals.

PRIALT(R) is Approved for use only in the Medtronic SynchroMed(R) EL, SynchroMed(R) II Infusion System and Simms Deltec Cadd Micro(R) External Microinfusion Device and Catheter.

Prialt selectively blocks the nerve channels responsible for transmitting pain signals. This drug is part of a new class known as N-type calcium channel blockers. It is known chemically as ziconotide.

Prialt has been studied in patients with cancer, AIDS and other chronic pain, such as back pain. More than 1,200 patients took part in three clinical trials.

There are side effects, and the FDA is including a “black box” warning – the government’s strongest warning short of a ban. The four most frequently reported adverse events associated with PRIALT were dizziness, nausea, confusion, and headache. When PRIALT was used with an external pump, there was a higher incidence of meningitis.

PRIALT has been evaluated as an IT infusion in more that 1,200 patients participating in chronic pain trials. The longest treatment duration to date is more than seven years. Severe psychiatric symptoms and neurological impairment may occur during treatment with PRIALT. Patients with a pre-existing history of psychosis should not be treated with PRIALT. All patients should be monitored frequently for evidence of cognitive impairment, hallucinations, or changes in mood or consciousness. PRIALT therapy can be interrupted or discontinued abruptly without evidence of withdrawal effects in the event of serious neurological or psychiatric signs or symptoms.

The idea for the drug came from a snail called the Conus magus that lives in the South Pacific, which paralyzes its victims with venom after capturing them, the company said. Researchers set out learning how to develop a drug based on this venom and eventually copied the amino acid sequence.

http://www.elan.com/

Pain Management & Appropriate Care Of The Terminally Ill: Headache/ Migraine and Chronic Daily

The UCSD CMA Pain Management and Appropriate Care of the Terminally Ill: Headache/ Migraine and Chronic Daily program features a series of pain case conferences in which physicians present interesting and challenging cases to a multidisciplinary pain panel of experts knowledgeable in treating the type of pain each patient presents. The patient’s physician provides the history, examination, labs and radiology, and diagnosis along with other pertinent information to the panel. Experts give brief presentations on topics specific to the case. The panel discussions include the overall assessment, anatomy, etiology, prevalence, patient education procedures, treatment options and patient monitoring.

This program meets the requirement of California Assembly Bill AB487, which requires physicians to complete 12 hours in Pain Management by the end of 2006. To earn CME credit for the program, go to http://www.ab487.com or call UCSD CME 1-888-229-6263. Series: “UCSD CMA Pain Management and Appropriate Care of the Terminally Ill

Sugar treatments for chronic musculoskeletal pain

News 10 has an article about Prolotherapy, which is use a dextrose (sugar water) solution, which is injected into the ligament or tendon where it attaches to the bone. This causes a localized inflammation in these weak areas which then increases the blood supply and flow of nutrients and stimulates the tissue to repair itself.

Part of the theory is the injections cause an inflammation that causes healing, and anti-inflammatory drugs stop healing process.

They also list this link to Magaziner Center in Cherry Hill, N.J. and a phone number at Information on Prolotherapy Injections for Chronic Pain: (856) 424-8222

History of Medicare’s Prolotherapy Coverage Policy

The Coverage Issues Manual (CIM) ’35-13, “Prolotherapy, Joint Sclerotherapy, and Ligamentous Injections with Sclerosing Agents – Not Covered,” states that the medical effectiveness of these therapies has not been verified by scientifically controlled studies, and therefore, cannot be covered by the Social Security Act, ‘1862(a)(1), as a “reasonable and necessary” treatment. This policy of non-coverage along with an erroneous Administrative Law Judge (ALJ) opinion issued in favor of Irwin Abraham, MD, in December 1997, on behalf of a Medicare beneficiary, prompted Dr. Abraham to request a national coverage decision reversing the current policy of non-coverage.

Prolotherapy was last examined for coverage by the Health Care Financing Administration (HCFA) in September 1992. The request had been generated by a beneficiary claiming a benefit from the prolotherapy treatments she had been receiving. HCFA received a number of anecdotal accounts of significant benefit derived from prolotherapy treatments, but when a literature search was conducted it failed to produce any scientifically sound studies on which to base a coverage decision.

The ALJ decision in favor of Dr. Abraham was based on Dr. Abraham’s ability to successfully bill HCFA under the CPT code 20550, “Injection, tendon sheath, ligament, trigger points or ganglion cyst” in the past. However, after the carrier identified the treatment of Dr. Abraham’s patient as prolotherapy, the carrier denied further payment. The ALJ reasoned that because the treatment had been paid for in the past, the carrier was estopped from further payment for the same procedure on the same patient who claims a benefit from the treatment. The ALJ further reasoned that payment for this treatment in the past and the teaching of this method in some medical schools is sufficient evidence that HCFA had modified its policy regarding prolotherapy. Unfortunately, the ALJ did not address the possibility that the carrier had mistakenly paid for the treatment before recognizing it as the non-covered prolotherapy. Furthermore, because the carrier failed to submit evidence that prolotherapy was indeed experimental and investigational, the ALJ determined that without advance notice to the beneficiary that the procedure was non-covered, Medicare would cover the treatment as reasonable and necessary.



HCFA conducted a new electronic literature search using MEDLINE and Ovid. The results only provided editorial articles devoid of any new scientific research. Also, HCFA staff searched the internet and contacted the American Association of Osteopaths for a complete list of current scientific evidence on the efficacy of prolotherapy. None of these efforts produced significant evidence to support the coverage request.

Analysis of Scientific Evidence

In light of the aforementioned ALJ decision, Dr. Abraham’s confusion regarding the policy here is just; however, an ALJ decision is neither binding nor precedent setting on HCFA’s national coverage decisions. Dr. Abraham supplied HCFA with five articles, two of which are clinical trials that support his request for coverage of prolotherapy. Neither of these articles contain sufficient evidence to persuade HCFA to alter the policy now in place.



The Ongley et al. article: “A New approach to the Treatment of Chronic Low Back Pain,” published in The Lancet, July 1987, studied 81 patients with chronic low back pain with an average duration of ten years in a double-blinded study to compare prolotherapy injections with a non-proliferant injectable course of therapy. Forty of the 81 patients received a regimen of forceful spinal manipulation and injections of a dextrose-glycerine-phenol solution. The 41 patients in the placebo group received less extensive initial local anesthesia (<10 ml 0.5% lignocaine compared with infiltration of 60 ml 0.5% lignocaine in treatment group), a non-forceful manipulation and saline as a substitute for the proliferant used in the experimental group. Also, the experimental group on the first day received a regimen including infiltration of triamcinolone (an anti-inflammatory) into the gluteus medius origin, whereas the placebo group only received lignocaine into the gluteus medius origin. The program included exercises in both groups to encourage the synthesis of the new cells with existing connective tissue. While the authors concluded that "the experimental regimen is a safe and effective treatment for chronic low back pain that has not responded to other conservative forms of treatment," they write earlier in the body of the results section of the paper that "(i)ndependent evaluation of physical signs revealed no significant differences between the groups after treatment."


The Ongley study fails to support the coverage of prolotherapy for a number of reasons. The authors report a subjective improvement in pain amelioration, but they fail to supply any persuasive objective criteria on which to base a coverage decision that must be grounded in scientifically valid evidence. Even the authors acknowledge in their conclusion “(f)uture studies may be needed to analyse [sic] the relative import of each component of the overall procedure.” Since the authors chose to provide the participants with manipulation, exercises and anesthesia in addition to the proliferant and saline injections, it is difficult, if not impossible, to isolate the component of the treatment which gave the participants the reported relief.




Establishing a link between the subjective improvement in pain management and a particular regimen is problematical because the participants in the experimental group received a different preparation course with more anesthesia and a forceful manipulation as opposed to the placebo group’s faux manipulation. Since the study did not treat the proliferant injections as a single variable, there is no way to positively identify prolotherapy as the cause of the pain relief rather than the forceful manipulation. Also, because Medicare currently covers forceful manipulation and massage therapy by a qualified provider, HCFA would need evidence that the addition of another variable, such as prolotherapy, to a patient’s course of treatment would provide greater benefit than that which is currently covered. Furthermore, even if the results concluded that the benefit in pain reduction could be positively attributed to prolotherapy, the sample size of 81 patients is really an insufficient number on which to base a positive national coverage decision.




The more recent study submitted by Dr. Abraham also falls short of the requisite level of evidence needed for a national coverage decision. The Klein et al. study, “A Randomized Double-Blind Trial of Dextrose-Glycerine-Phenol Injections for Chronic, Low Back Pain” published in 1993, fails in much the same way as the Ongley study before it. Again, the number of participants is small; therefore it would be difficult to use the results in support of a newly crafted national coverage decision.

The Klein study was comprised of 79 patients, 39 of which were placed in the proliferant group. Thirty of 39 patients in the proliferant group achieved a 50% or greater diminution in subjective pain or disability. The control group was not a true placebo because “the patients received four of the five active interventions of the full treatment regimen and demonstrated statistically significant within-group improvements compared to baseline disability and pain scores.” Twenty-one of 40 patients in the placebo group reported a 50% or greater diminution in subjective pain and disability scores. A response of more than 50% of patients in the control group reporting improvement suggests that an actual treatment effect rather than a pure placebo response occurred. Even the authors note, “(t)he interventions shared by both treatment groups, including exercises, injection of local anesthetics, repeated needling, and manipulation may all enhance the success of the procedure, but the relative contribution of each intervention requires further study.”

The authors identify that further studies are needed to show greater improvement in treating pain with prolotherapy because “the statistical significance was only borderline” when the experimental group was compared to the control group. Also, “objective testing of range of motion, isometric strength, and velocity of movement showed significant improvements in both groups following treatment, but did not favor either” the proliferant or the control group. Further, “the MRI and CT scans showed significant abnormalities in both groups, but these did not correlate with subjective complaints and were not predictive of response to treatment.”

A total of 160 patients studied over the past twelve years, with only 79 of the patients receiving the proposed treatment, is not a large enough sample to support a change in the coverage policy. More studies with larger control and experimental groups must be evaluated using regimens designed to isolate variables and correlate them to positive results. Ideally, these studies would consist of improvements in both objective and subjective measurement tools. However, substantial and statistically significant improvements in subjective pain scores could be persuasive if HCFA could attribute the patient benefit to the prolotherapy regimen.

ClinicalTrials.gov shows an closed study “Joint Injections for Osteoarthritic Knee Pain” to determine whether prolotherapy can decrease pain and disability from knee osteoarthritis.

Two teens died after applying Duragesic 25 patch

I thought this was weird. The girl was prescribed Duragesic for chronic headache and was “discovered unresponsive and with respiratory depression” 21 hours after the patch was first applied. The boy, who was prescribed the drug for throat pain due to mononucleosis, was found in respiratory arrest 14 hours after the patch was first applied. This is from Health Canada.

Some doctors seem to go now to the other extreme and prescribe morphine for every day illnesses? And to such young kids. And I can’t believe their parents agreed to this.

CRPS treatment with ketamine

From a press release: Thirty-three patients with unrelenting CRPS (Complex Regional Pain Syndrome, also known as Reflex Sympathetic Dystrophy – RSD) were treated using this novel approach developed by Dr. Graeme E. Correll, BE, MBBS, in Mackay, Queensland, Australia. Pain relief and the duration of this relief appeared impressive. After only one treatment, there was complete relief in 76% (25) of the group. 54% of the patients remained free of pain for more than three months, 31% for more than six months. Although the relief of pain did not last indefinitely, it was noted that following a second treatment given to 12 of the patients, the outcome was improved. In this retreated group 58% remained pain free for more than a year and almost 33% experienced relief for over three years.

Vioxx pulled from the market

Vioxx was pulled from the market by its maker after a study found it doubled the risk of heart attacks and strokes.

Experts advised patients to immediately stop taking Vioxx and talk to their doctors about alternatives, which may include generic pain relievers -ibuprofen and aspirin, as well as Celebrex.

A Merck study led to warnings about heart risks being placed on the drug’s label in 2002, and the FDA has been monitoring problems that have been reported since then.

Participants taking Vioxx for more than 18 months were found to be twice as likely as those given dummy pills to suffer a heart attack, stroke or other heart complications. But there is no evidence that the elevated risk of heart attack persists after a patient has stopped taking the drug.

In the study that was halted, 45 of the 1,287 people taking Vioxx had heart attacks or other cardiovascular problems versus 25 of the 1,299 who got dummy pills, Merck reported.

Patients with leftover pills could mail them back to Merck for a refund.

What are opioids?

There are at least two important ways to answer this question. Unfortunately, the most scientific definition, while straightforward, is so disarmingly simple, that it doesnít tell us nearly all of what we need to know about these medications, because it ignores the important cultural forces that influence our use of these medications: the opioids comprise a class of medications that have been employed to relieve pain for well over one hundred years. Their use is so routine in certain settings (after surgery, in the Emergency Room, for labor and delivery, for cancer and in the laboratory) that they are regarded as the standard against which all other pain-killing drugs (analgesics) are compared. These drugs, previously referred to as ìnarcoticsî are derived from or are chemically related to opium, the main constituent of the poppy plant (papaver somniferum), which has been used as a pain killer since biblical times. Science has only recently demonstrated that the human body makes substances that possess a similar structure and function. These endorphins, enkephalins and other molecules, referred to as ìendogenous opioids,î are thought to be responsible for the so-called ìrunnerís high.î

While the above explanation is accurate, it does not even begin to portray the raging controversy that exists surrounding the contemporary use of opioids. While the term ìopioidî is awkward at first, it is preferred to the term ìnarcotic.î Contemporary authorities including the authors of our most important pharmacology textbook, Goodman and Gillmanís The Pharmacologic Basis of Therapeutics have advised that we abandon the term narcotic. It is so culturally and socially laden with references to drug abuse that its has use a chilling effect on prescribers and patients alike, interfering with appropriate treatment of pain. The lurid images of back alley abuse conjured by the term narcotic eclipse its scientific meaning, and as a result, the term opioid is strongly preferred.

In the midst of the tremendous progress that has been made generally in medicine and specifically in our understanding of pain and its treatment it is practically unthinkable that the individual who has done the most to advance our thinking about this issue is Jack Kevorkian. It has taken, arguably a fanatic, if not a lunatic (this authorís thoughts) to bring to our attention that despite the most sophisticated health care delivery system in the world, many Americans inappropriately are led to seek an early death because their pain is not adequately addressed. Since medical science is by no means perfect, those who suffer are not necessarily entitled to relief of their pain, but they are certainly at least entitled to our best efforts to achieve improvement, and by no means should they be subjected to humiliation or derision for seeking the relief of suffering. Although when ignored, unrelieved pain like any other chronic illness leads to depression, pain is almost always fundamentally a medical problem, so we should no more coerce the sufferer to ìtough it outî than we would encourage a diabetic to withhold taking their insulin as a means to ìbuild their character.î While we donít readily admit it, modern medicine actually cures very little of todayís maladies: diabetes and hypertension are not eradicated, but are managed, and thus the mandate to manage chronic pain over a patientís lifetime should not be a surprise or a dilemma that we, as a culture, should shrink away from. These unfortunate individuals should certainly not be discarded as having ìfailedî our current treatments, rather we should acknowledge the shortcomings of current therapies. It is only recently that pain in patients with life threatening cancer has been treated more effectively, and although legislation exists to protect the rights of those with chronic pain (and the prescribing physician), in reality, one practically needs to be dying in this country in order to be assured of getting adequate pain relief.