Treatment of headaches (Cohen) Flashcards
what the patients want
Most physicians think headache patients seek pain relief
This is wrong! Numerous public opinion polls show:
Most patients seek an explanation for the headache and then seek pain relief
What we need to do
It is important to:
Establish a diagnosis
Educate patients about their condition and its treatment
Establish realistic expectations
Encourage patients to participate in their own management
Discuss treatment / medication preferences
PRESCRIBING OPIOIDS FOR THE PRIMARY HEADACHE DISORDERS IS NEARLY ALWAYS COUNTER-PRODUCTIVE
number one thing to remember about PHARMACOLOGIC TREATMENT OF MIGRAINE
Individualize management (stratified care)
Treatment choice depends on
Attack frequency and severity Presence and degree of disability Associated symptoms Prior response to medications Comorbid and coexistent conditions
ABORTIVE TREATMENT FOR PATIENTS
Over-the-counter medications
Analgesics (eg, aspirin, Tylenol®, Excedrin® Migraine)
Anti-inflammatory medications (eg, Advil®, Aleve®, Motrin®)
Migraine-specific medications prescribed by a doctor
Caffeine, including dark chocolate or cola drinks
*acetominophen is seldom useful
Triptans- history
Triptans are the most effective prescription drug for aborting a migraine headache
Sumatriptan (Imitrex) came first, approved as an injection in the United States in 1993
A. Developed as a serotoninergic agonist, at 5HT1 receptors, by Humphreys in England, who presumed that this would stop a migraine through vasoconstriction
B. However, sumatriptan seems to cause no more than 7% vasoconstriction in cerebral arterioles
C. We later learned there are multiple 5HT1 receptors, including 1d and 1f, which are neuronal inhibitory autoreceptors, and 1b, which are located on arterioles (b for blood vessels)
The triptans- mechanism
It was well known that patients secrete serotonin during a migraine, and triptans work by binding to auto-receptors at the ends of axons releasing 5HT, PREVENTING FURTHER RELEASE OF THIS TRANSMITTER AND OTHERS, INCLUDING SUBSTANCE P, NEUROKININ A, AND CALCITONIN GENE RELATED PEPTIDE
triptans- half lives, contraindicated
These drugs have similar mechanisms, and are all studied clinically in their ability to ACHIEVE RELIEF OF HEADACHE PAIN IN TWO HOURS
Injectable sumatriptan, as well as oral rizatriptan and oral eletriptan, can achieve 2 hour pain relief in 80% of patients, although oral sumatriptan is effective in 55%
These drugs all work on two or three of the 5HT1b, 1d and 1f receptors
Oral sumatriptan has a half life of only two hours and a bioavailability of only 14%
Newer triptans have slightly longer half lives and better availability.
Contraindicated in patients with stroke or acute coronary syndromes, due to slight vasoconstriction of cerebral and coronary arteries
Contraindicated in pregnant patients, but few if any reports of fetal harm
ERGOTAMINES
can be effective in aborting migraines, but are not used as much anymore since the development of triptans
The drugs work on multiple receptors besides 5HT1d, and they really do cause significant vasoconstriction, vasospasm, and can raise the blood pressure
A. Part of this may be by blocking alpha receptors on arterial walls
Ergotamine with caffeine, which may have added to the effectiveness of ergotamine alone (called Cafegot) is no longer available in the United States
DIHYDROERGOTAMINE, or DHE, is still available and is very effective as an INTRAVENOUS or INTRAMUSCULAR injection, especially for migraines that have been going on for many hours or even days
A. Half life is about 9 hours
Dihydroergotamine designed for NASAL ABSOPTION (Migranal) is not as effective as parenteral DHE, working about 50% of the time
Migraine treatments in the emergency department
generally do not include triptans, because most patients have had a migraine for many hours
A. Emergency room doctors are trying NOT to use opioids such as morphine, to discourage addicts
Drugs which block dopamine receptors can be effective, although how they might work is unexplained
There are very few studies showing benefit from dopamine blockers, such as the antipsychotic haloperidol (Haldol), or dugs used entirely for nausea, including promethazine (Phenergan), prochloperazine (Compazine) and metoclopramide (Reglan)
A. These drugs may work on other receptors, such as blocking muscarinic acetylcholine receptors, and can be sedating
B. They certainly do limit the NAUSEA of migraine, and somehow can limit the pain
C. The antihistamine diphenhydramine (Benadryl) is also sometimes effective for migraine headaches
Calcitonin Gene Related Peptide Receptor antagonists
have been shown to be just as effective as the serotoninergic triptans, but because of unexpected hepatic damage, will probably never be approved
monoclonal antibodies to CGRP receptors
are showing great results in clinical studies, and may soon be approved as PREVENTATIVE drugs for migraines
Although CGRP can cause vasodilation, these drugs do NOT cause vasoconstriction, perhaps because CGRP is far more important in nociceptive (pain related) neuronal activity in the brain
Preventative drugs for migraine
At least one third of migraine patients get more than two attacks per month, and have insufficient benefit from abortive drugs
These patients may benefit from a daily medication which limits the number of migraines per month.
All of the drugs currently used were originally developed for other conditions, such as depression or tachycardia or epilepsy, but were subsequently found to be effective in migraine prophylaxis
They are not “cures,” for migraines, but patients can often reduce their monthly frequency from 3 or even more migraines per month, to one or two
Patients must accept some side effects, and they have to be compliant with daily medications
MIGRAINE PREVENTATIVE DRUGS
by effectiveness
GREAT: Amitriptyline, Propanolol* , Topiramate*
GOOD: Gabapentin, Valproic acid,* Timolol*
- drugs approved by the FDA
It is unclear how these drugs could limit migraines.
They may limit action potential generation and synaptic transmission in neurons.
PROPANOLOL
A. Developed in the 1950s as a treatment for coronary artery disease, found later to be effective in preventing migraines
B. FDA approved. Other beta blockers are generally less effective as migraine preventatives, although timolol is also FDA approved
C. The half life is approximately 4 to 6 hours, so it has to be taken about three times per day, generally 10 – 20 mg tid
D. Most physicians use a long acting, once daily formulation, 60 – 160mg every morning
E. Relatively contraindicated in patients with asthma or congestive heart failure, or bradycardia due to heart blocks
AMITRIPTYLINE
One of the first tricyclic antidepressants, preventing synaptic reuptake of serotonin and noradrenaline
However, other tricyclics seldom work as well as amitriptyline, and none of the tricyclic antidepressants is FDA approved for migraine
Sedating, perhaps by its antihistamine effects, and VERY ANTICHOLINERGIC
Given in low doses every evening, generally 10 – 50mg, far less than the 150mg dose usually needed for relief of depression
May cause tachyarrhythmias, and therefore can be the cause of suicide from overdose
Weight gain is also commonly experienced
TOPIRAMATE
Originally introduced as an anticonvulsant for epileptics, and it is still commonly used for this
FDA approved for prevention of seizures and migraines
Half life is approximately 18 – 20 hours, so most patients can take it only at bedtime, less often twice a day
Generally low doses are effective, from 50mg to 100mg qhs
Can cause difficulties with speech and cognition, so some have given it the nickname “DOPAMAX”
Side effects include anorexia and weight loss, and loss of sensation in the arms, perhaps by changes in serum acidity and therefore calcium solubility
VALPROIC ACID
A. Many likely mechanisms of action, including blocking Na+ channels and effects on gamma-aminobutyric acid
B. FDA approved for migraine prevention, epilepsy and bipolar disease
C. Variable half life of 10 -20 hours, but needs to be given at least twice a day for effectiveness in all three diseases
D. Doses for migraine are generally 500 – 100mg total per day
E. Side effects include weight gain, lowering of platelet counts, tremor, and hair loss…all of which limit its value
Botulinum toxin as a migraine preventative
In 2010 the US FDA approved botulinum toxin, or Botox, for migraine prevention.
Roughly, one half of the patients had a 50% reduction in days of migraines each month
Botulinum toxin is injected over many sites in the scalp every three months
The mechanism is probably more than inhibition of acetylcholine release; perhaps botulinum somehow inhibits sensory neurons, also
Expensive, wears off in less than 3 months, may cause muscle weakness and muscle wasting
Treatment of tension type headache
Again, most patients with these headaches do not seek medical help, and many of them do not need pharmacologic treatments
Correct diagnosis and reassurance by the doctor are often the best treatments
Patients need to be considered for more serious causes or headaches, most of all
Patients may already be treating their headaches with over the counter drugs, which may be useful and safe if not done more than once or twice per week, BUT IF THESE DRUGS ARE USED MORE OFTEN THAN THIS THE PATIENT MUST LIMIT OR STOP THEIR USE
Treatment of frequent tension type headaches
- Co-morbidities…hypertension, depression, anxiety, insomnia, diabetes/hypoglycemia, other sources of pain, including the neck
- Is there analgesic abuse, or prescription drugs for pain?
- Manipulation of the upper cervical spine, sometimes acupuncture can be vey effective for frequent tension-type headaches
- Prophylactic drugs: amitriptyline, protriptyline, topiramate, but only rarely
TREATMENT OF CLUSTER HEADACHE
Cluster headache is usually daily, and often more than once daily, for weeks or months, so BOTH PREVENTATIVE AND ABORTIVE TREATMENTS ARE INDICATED
Rarely can a change in lifestyle be helpful, although for many patients drinking alcoholic beverages causes more headaches
ABORTIVE TREATMENTS FOR CLUSTER:
Injectable or nasal sumatriptan, nasal zolmitriptan
Inhaled oxygen at high flow rates
PREVENTATIVE TREATMENT OF CLUSTER HEADACHE
VERAPAMIL, an older calcium channel blocker, sometimes high doses, 240 -480mg/day
A. May cause hypotension, constipation
LITHIUM, with its unclear effects on postsynaptic synaptic transmission, up to as much as 1500mg/day
A. Low therapeutic index, so dangerous in suicidal patients, also causes renal and thyroid disease
PREDNISONE, 60-80mg/day, works quickly, mechanism in cluster headache is unknown
A. Its many side effects limit its use when the “season” of cluster headache is many months in individual patients
For dug resistant patients with cluster headache
DEEP BRAIN STIMULATION is being studied, as is the use of an implanted OCCIPITAL NERVE STIMULATOR
Mechanisms of these invasive treatments remain unknown
MEDICATION OVERUSE HEADACHE
These patients have a headache, whether it is migraine or tension type, nearly every day, or at least 15 days per months
Nearly all of the patients are using over the counter or prescription drugs on a nearly daily basis, from acetaminophen to NSAIDs, to opioids
The first step is to inform them that their headaches will NEVER stop as long as they continue to take these medications so often, or even more than once per week
PREVENTATIVE DRUGS FOR MIGRAINE OR TENSION TYPE HEADACHE WILL NOT WORK AS LONG AS PATIENTS TAKE SO MANY ANALGESIC PAIN PILLS
TRIGEMINAL NEURALGIA
treatment
Consider MRI scanning, especially if there is an abnormal neurological examination, since some patients may have vascular anomalies or even tumors
Responsive to CARBAMAZEPINE (Tegretol) in @ 80% of patients, so this is the drug of first choice, at 200 – 400mg bid or occasionally tid
Somewhat less responsive to gabapentin (Neurontin) or phenytoin (Dilantin)
May require RADIOLOGICAL OR SURGICAL ABLATION of the trigeminal nerve via gamma knife, injection of glycerol, or electrical ablation
A. Usually safe, and vey effective for dug resistant patients, but permanent facial numbness can result
