OMED 17 OCTOBER 7-10 PHILADELPHIA, PENNSYLVANIA 29.5 Category 1-A CME credits anticipated ACOFP / AOA s 122 nd Annual Osteopathic Medical Conference & Exposition Joint Session with ACOFP, ACONP and AOAAM: Headache Treatment and Addiction J. Mark Bailey, DO, PhD, FACN The American College of Osteopathic Family Physicians is accredited by the American Osteopathic Association Council to sponsor continuing medical education for osteopathic physicians. The American College of Osteopathic Family Physicians designates the lectures and workshops for Category 1-A credits on an hour-for-hour basis, pending approval by the AOA CCME, ACOFP is not responsible for the content.
Headache and Addiction Mark Bailey, DO, PhD, FACN Professor Neurology and Anesthesiology
Disclosures Dr. Bailey has no relevant financial conflicts of interest or disclosures.
Objectives Review the overlap symptoms common to headache and addiction Review the details of medication-overuse headache and its treatments Review new treatments for headache, including pharmacologic, psychological, and neuromodulation.
Medication-Overuse Headache (MOH) Present on at least 15 days per month. Developed or markedly worsened during medication overuse. Resolves or reverts to its previous pattern within two months of discontinuing overused medication. Regular overuse for three months or more of one of the following drugs for headache: Has taken triptans, opioids, ergots or combination preparations on at least 10 days per month. Has taken paracetamol, aspirin (or other non-steroidal anti-inflammatory drugs (NSAIDs)) or combinations of these on at least 15 days per month. For definite diagnosis the headache must resolve (or revert to its previous pattern) within two months of cessation of overuse if the diagnosis is to be definite. Prior to this happening the diagnosis is 'probable MOH'.
Migraine Background Chronic HA
Causes of MOH Common Agents: Opiate-containing medications Fioricet / Fiorinal / Midrin Triptans Ergotamine. NSAIDs are less likely to cause MOH but can do so. For this reason ten days a month or more of triptan or opiate use is considered to be overuse, whereas fifteen days or more a month of NSAID use is considered as overuse. (Chronic Pain Patients?) It is a combination of frequency AND regularity of medication use which seems to trigger the problem. The level of medication use which can lead to MOH is variable, but it is more likely to occur with use for more than three consecutive days per week for several weeks.
Medication-overuse headache is a dull constant headache which is often worse in the morning. It is present on most days or part of every day. It is possible to have medication headaches most days with episodic migraine pain superimposed on the headache. Only people who are prone to headaches develop this syndrome, generally those with migraine or a family history of migraine. It is generally not seen in people taking painkillers for reasons other than headaches, such as arthritis or back pain. The overuse of acute migraine drugs can also stop preventative migraine medications from working and long-term use of acute drugs may be damaging to the liver and kidneys. The only way of treating this condition is to stop the medication. (and using topiramate)
Schuman E. Another Comment on Drug Induced Refractory Headache. Headache: 2008;48(8):1242
Withdrawal of Agent
Chemical Withdrawal Withdrawal refers to the physical problems and emotions you experience if you are dependent on a substance (such as alcohol, prescription medicines, or illegal drugs) and then suddenly stop or drastically reduce your intake of the substance. Symptoms of withdrawal are caused by decreased amounts of alcohol or drugs in the blood or tissues of a person who has grown accustomed to prolonged heavy use and who then suddenly stops. Withdrawal syndrome is a set of symptoms that occur when you decrease or stop drinking or using drugs after using alcohol or drugs for a long time. - WebMD
Physical Withdrawal Symptoms Sweating Racing heart Palpitations Muscle tension Tightness in the chest Difficulty breathing Tremor Nausea, vomiting, or diarrhea Seizures (benzos not opioids)
Emotional Withdrawal Symptoms Anxiety Restlessness Irritability Insomnia Headaches Poor concentration Depression Social isolation
New Treatments for Migraine Medications Psychological Neuromodulation
Acute Migraine Treatment Calcitonin Gene Related Peptide (CGRP) Released into jugular blood during migraine CGRP infusion produces migraine Serum CGRP levels increased during migraine CGRP receptor antagonists abort migraine but are too hepatotoxic for chronic use
CGRP Receptor Antibody Specificity of antibodies to targets indicates primary role for CGRP and its receptor in migraine Not hepatotoxic and used as preventative agent Presumably, these antibodies do not cross the BBB Macromolecules require SQ / IV but at infrequent intervals (q2 week / monthly / quarterly) Indicate a mechanism of action that is either peripheral or in CNS regions outside BBB Anti-CGRP monoclonal antibodies in migraine: current perspectives. Giamberardino MA, et al, Intern Emerg Med. 2016 Dec;11(8):1045-1057. Epub 2016 Jun 23.
Preventative Treatment 2012 AAN Guidelines have been revised concerning butterbur Despite butterbur s potential efficacy, doubts are increasing about the long-term safety of this supplement given of the risk of liver damage and the lack of an actively regulated preparation. Due to the mounting concerns, the American Headache Society is currently evaluating a position statement cautioning against its use. CGRP targeting agents
Ongoing Phase 2 Trials
Pituitary adenylate cyclase activating polypeptide and migraine Alessandro S Zagami, 1 Lars Edvinsson, 2 and Peter J Goadsby Ann Clin Transl Neurol. 2014 Dec; 1(12): 1036 1040. Acute Migraine Treatment Pituitary Adenylate Cyclase Activating Peptide (PACAP) Infusion triggers migraine in susceptible individials Blood levels elevated in migraine and cluster and reduced following treatment with sumitriptan Co-localized with CGRP in human trigeminocervical regions A potential target for future theraputics
Lasmiditan Phase III trials - Lilly 5HT 1F receptor antagonist First-in-class "neurally acting anti-migraine agent" Receptors not on blood vessels Does not produce vasoconstriction in animal models Effective as abortive therapy in migraine Side effect profile indicates CNS activity dizziness, vertigo, paresthesia and fatigue Lasmiditan for the treatment of migraine. Capi M, et al. Expert Opin Investig Drugs. 2017 Feb;26(2):227-234. doi: 10.1080/13543784.2017.1280457.
Behavioral Treatment of Migraine
Neuromodulation Transcranial Magnetic Stim Occipital Nerve Stim Supraorbital Transcutaneous Stim Sphenopalantine Ganglion Stim
Transcranial Magnetic Stim Early treatment of Migraine with aura Lipton, R. B., Dodick, D.W., Silberstein, S.D., Saper, J.R., Aurora, S.K., Pearlman, S.H., Fischell, R.E., Ruppel, P.L., Goadsby, P.J. (2010). Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomized, double-blind, parallel-group, sham controlled trial. Lancet Neurology, 9(4):373-380. Doi: 10.1016/s1474-4422(1)70054-5.
stms
Occipital Nerve Stim Outcomes generally favour ONS over sham controls but quantitative analysis was hampered by incomplete publication and reporting of trial data. Lead migration and infections are common and often require revision surgery. Open-label follow-up of RCTs and case series suggest longterm effectiveness can be maintained in some patients but evidence is limited. Occipital Nerve Stimulation for Chronic Migraine A Systematic Review https://www.ncbi.nlm.nih.gov NCBI Literature PubMed Central (PMC) by YF Chen - 2015
Supraorbital Transcutaneous Stim Double-blind, sham-controlled trial n=67 Applied daily for 20 minutes during three months Monthly migraine attacks, monthly headache days, and monthly acute antimigraine drug intake were all significantly reduced No reported side effects. FDA approved. "This study provides Class III evidence that treatment with a supraorbital transcutaneous stimulator is effective and safe as a preventive therapy for migraine," Cefaly Device Migraine prevention with a supraorbital transcutaneous stimulator: a randomized controlled trial. Schoenen J. Neurology. 2013 Feb 19;80(8):697-704. doi: 10.1212/WNL.0b013e3182825055. Epub 2013 Feb 6.
Sphenopalatine Ganglion Stim Studied primarily in the acute management of cluster HA Autonomic Technologies Sphenopalatine Ganglion Stimulator Treats Cluster Headaches August 24, 2013 by David Prutchi Pain relief was achieved in 67.1% of full stimulationtreated attacks at 15 min following the start of stimulation, compared with 7.4% of sham-treated attacks (p < 0.0001). A reduction in cluster attack frequency of at least 50% compared with baseline without any increase in preventive drugs was observed in 43% of patients
Summary There is considerable overlap in the presentation of addiction and headache Medication overuse headache is common and responds to stopping the offending agent. There are new and novel approaches to headache management being studied and approved.
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Contact Information UAB Highlands 1201 11 th Avenue South Suite 3800 Birmingham, AL 35205 (205) 930-8400 office (205) 930-8900 fax markbailey@uabmc.edu www.uab.edu/neuropain