Ultram was administered to 550 patients during the double-blind or open-label extension periods in U.S. studies of chronic nonmalignant pain. Of these patients, 375 were 65 years old or older. TABLE 1 reports the cumulative incidence rate of adverse reactions by 7, 30 and 90 days for the most frequent reactions (5% or more by 7 days). The most frequently reported events were in the central nervous system and gastrointestinal system. Although the reactions listed in the table are felt to be probably related to Ultram administration, the reported rates also include some events that may have been due to underlying disease or concomitant medication. The overall incidence rates of adverse experiences in these trials were similar for Ultram and the active control groups, Tylenol with Codeine #3 (acetaminophen 300 mg with codeine phosphate 30 mg), and aspirin 325 mg with codeine phosphate 30 mg. (TABLE 1)

Table 1 – Tramadol HCl, Adverse Reactions

Cumulative Incidence of Adverse Reactions for Ultram (tramadol HCl)

In Chronic Trials of Nonmalignant Pain

———————————————————————–

Up to 7 Days Up to 30 Days Up to 90 Days

———————————————————————–

Dizziness/Vertigo 26% 31% 33%

Nausea 24% 34% 40%

Constipation 24% 38% 46%

Headache 18% 26% 32%

Somnolence 16% 23% 25%

Vomiting 9% 13% 17%

Pruritus 8% 10% 11%

“CNS Stimulation” 7% 11% 14%

Asthenia 6% 11% 12%

Sweating 6% 7% 9%

Dyspepsia 5% 9% 13%

Dry Mouth 5% 9% 10%

Diarrhea 5% 6% 10%

———————————————————————–

1 “CNS Stimulation” is a composite of nervousness, anxiety, agitation,

tremor, spasticity, euphoria, emotional lability and hallucinations.

Incidence less than 5% possibly casually related: TABLE 2 lists adverse reactions that occurred with an incidence of less than 5% in clinical trials, and for which the possibility of a casual relationship with Ultram exists. Reactions are separated according to whether the incidence was greater than 1%. (TABLE 2)

Table 2 – Tramadol HCl, Adverse Reactions

Possibly Ultram Related Adverse Reactions

with an Incidence of Less Than 5%

———————————————————————–

Incidence of Adverse Reaction

————————————————

Body System From 1% to <5% Less Than 1%

———————————————————————–

Body as a Whole Malaise Allergic reaction;

Accidental injury;

Weight loss

Cardiovascular Vasodilation Syncope; Orthostatic

hypotension; Tachycardia

Central Nervous System Anxiety; Confusion; Seizure (see WARNINGS);

Coordination Paresthesia; Cognitive

disturbance; dysfunction;

Euphoria; Nervous- Hallucinations; Tremor;

ness; Sleep dis- Amnesia; Difficulty in

order concentration; Abnormal

gait

Gastrointestinal Abdominal pain;

Anorexia; Flatulence

Musculoskeletal Hypertonia

Respiratory Dyspnea

Skin Rash Urticaria, Vesicles

Special Senses Visual disturbance Dysgeusia

Urogenital Urinary retention; Dysuria; Menstrual dis-

Urinary frequency; order

Menopausal symptoms

Other adverse experiences, casual relationship undetermined: A variety of other adverse events were reported infrequently in patients taking Ultram during clinical trials. A casual relationship between Ultram and these events has not been determined. However, the most significant events are listed below as alerting information to the physician.

Body as a whole: Suicidal tendency.

Cardiovascular: Abnormal ECG, hypertension, myocardial ischemia, palpitations.

Central Nervous System: Migraine

Gastrointestinal: Gastrointestinal bleeding, hepatitis, stomatitis.

Laboratory abnormalities: Creatinine increase, elevated liver enzymes, hemoglobin decrease, proteinuria.

Sensory: Cataracts, deafness, tinnitus.

DRUG ABUSE AND DEPENDENCE
Although tramadol can produce drug dependence of the µ-opioid type (like codeine or dextropropoxyphene) and potentially may be abused, there has been little evidence of abuse in foreign clinical experience. In clinical trials, tramadol produced effects similar to an opioid, and at supratherapeutic doses was recognized as an opioid in subjective/behavioral studies. Tolerance development has been reported to be relatively mild and withdrawal when present, is not considered to be as severe as that produced by other opioids. Part of tramadol’s activity and some extension of the duration of µ-opioid activity. Delayed µ-opioid activity is believed to reduce a drug’s abuse liability.

An assay for tramadol is not included in routine urine screens for drugs of abuse.

Tramadol Precautions

Respiratory Depression When large doses of Ultram are administered with anesthetic medications or alcohol, respiratory depression may result. Cases of intraoperative respiratory depression, usually with large intravenous doses of tramadol and with concurrent administration of respiratory depressants, have been reported in foreign experience. Such cases should be treated as overdoses (see OVERDOSAGE). Ultram should be administered cautiously in patients at risk for respiratory depression.

Increased Intracranial Pressure or Head Trauma Ultram should be used with caution in patients with increased intracranial pressure or head injury. Pupillary changes (miosis) from tramadol may obscure the existence, extent or course of intracranial pathology. Clinicians should also maintain a high index of suspicion for adverse drug reaction when evaluating mental status in these patients if they are receiving Ultram.

Acute Abdominal Conditions The administration of Ultram may complicate the clinical assessment of patients with acute abdominal conditions.

Patients Physically Dependent on Opioids Ultram is not recommended for patients who are dependent on opioids. Patients who have recently taken substantial amounts of opioids may experience withdrawal symptoms. Because of the difficulty in assessing dependence in patients who have previously received substantial amounts of opioid medication, caution should be used in the administration of Ultram to such patients.

Use in Renal and Hepatic Disease Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite M1. In patients with creatinine clearances of less than 30 ml/min dosing reduction is recommended (see DOSAGE AND ADMINISTRATION).

Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of the liver. In cirrhotic patients, dosing reduction is recommended (see DOSAGE AND ADMINISTRATION).

With the prolonged half-life in these conditions, achievement of steady state is delayed, so that it may take several days for elevated plasma concentrations to develop.

Information for Patients Patients being treated with Ultram should receive the following information:

Ultram may impair mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.

Carcinogenesis, Mutagenesis, Impairment of Fertility Tramadol was not mutagenic in the following assays: Ames Salmonella microsomal activation test, CHO/HPRT mammalian cell assay, mouse lymphoma assay (in the absence of metabolic activation), dominant lethal mutation tests in mice, chromosome aberration test in Chinese hamsters, and bone marrow micronucleus tests in mice and Chinese hamsters. Weakly mutagenic results occurred in the presence of metabolic activation in the mouse lymphoma assay and micronucleus test in rats. Overall, the weight of evidence from these tests indicates that tramadol does not pose a genotoxic risk to humans.

A slight, but statistically significant, increase in two common murine tumors, pulmonary and hepatic, was observed in a mouse carcinogenicity study, particularly in aged mice (dosing orally up to 30 mg/kg for approximately two years, although the study was not done with the Maximum Tolerated Dose). This finding is not believed to suggest risk in humans. No such finding occurred in a rate carcinogenicity study.

No effects on fertility were observed for tramadol at oral dose levels up to 50 mg/kg in male rats and 75 mg/kg in female rats.

Teratogenic Effects: Usage in Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Ultram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Tramadol has been shown to be embryotoxic and fetotoxic in mice, rats and rabbits and maternally toxic doses 3 to 15 times the maximum human dose or higher (120 mg/kg in mice, 25 mg/kg or higher in rats and 75 mg/kg or higher in rabbits), but was not teratogenic at these dose levels. No harm to the fetus due to tramadol was seen at doses that were not maternally toxic.

No drug-related teratogenic effects were observed in progeny of mice, rats or rabbits treated with tramadol by various routes (up to 140 mg/kg for mice, 80 mg/kg for rats or 300 mg/kg for rabbits). Embryo and fetal toxicity consisted primarily of decreased fetal weights, skeletal ossification and increased supemumerary ribs at maternally toxic dose levels. Transient delays in developmental or behavioral parameters were also seen in pups in rat dams allowed to deliver. Embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit.

In peri- and post-natal studies in rats, progeny of dams receiving oral (gavage) dose levels of 50 mg/kg or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (6 to 10 times the maximum human dose). No toxicity was observed for progeny of dams receiving 8, 10, 20, 25 or 40 mg/kg. Maternal toxicity was observed at all dose levels, but effects on progeny were evident only at higher dose levels where maternal toxicity was more severe.

Labor and Delivery Ultram should not be used in pregnant women prior to or during labor unless the potential benefits outweigh the risks, because safe use in pregnancy has not been established. Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor.

The effect of Ultram, if any, on the later growth, development, and functional maturation of the child is unknown.

Nursing Mothers Ultram is not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. Following a single 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours postdose was 100 µg of tramadol (0.1% of the maternal dose) and 27 µg of M1.

Pediatric Use The pediatric use of Ultram (tramadol hydrochloride) is not recommended because safety and efficacy in patients under 16 years of age have not been established.

Use in the Elderly In subjects over the age of 75 years, serum concentrations are slightly elevated and the elimination half-life is slightly elevated and the elimination half-life is slightly prolonged. The aged also can be expected to vary more widely in their ability to tolerate adverse drug effects. Daily doses in excess of 300 mg are not recommended in patients over 75

Pharmacodynamics Ultram is a centrally acting synthetic analgesic compound that is not derived from natural sources nor is it chemically related to opiates. Although its mode of action is not completely understood from animal tests, at least two complementary mechanisms appear applicable; binding to µ-opioid receptors and inhibition of reuptake of norepinephrine and serotonin. Ultram opioid activity derives from low affinity binding of the parent compound to µ-opioid receptors and higher affinity binding of the M1 metabolite. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding. The contribution to human analgesia of tramadol relative to M1 is unknown.

Tramadol-induced antinociception is only partially antagonized by the opiate naloxone in several animal tests. In addition, tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro, as have some other opioid analgesics. These latter mechanisms may contribute independently to the overall analgesic profile of Ultram. Onset of analgesia in humans is evident within one hour after administration and reaches a peak in approximately two to three hours. peak plasma concentrations are reached about two hours after administration, which correlates closely with the time to peak pain relief.

Apart from analgesia, Ultram administration may produce a constellation of symptoms (including dizziness, somnolence, nausea, constipation, sweating and pruritus) similar to that of an opioid. However, tramadol causes significantly less respiratory depression than morphine. In contrast to morphine, tramadol has not been shown to cause histamine release. At therapeutic doses, Ultram has no effect on heart rate, left-ventricular function or cardiac index. Orthostatic changes in blood pressure have been observed.

Pharmacokinetics Absorption: Racemic tramadol is rapidly and almost completely absorbed after oral administration. The mean absolute bioavailability of a 100 mg oral dose is approximately 75%. Oral administration of Ultram with food does not significantly affect its rate or extent of absorption. Therefore, Ultram can be administered without regard to food. The mean peak (± SD) plasma concentration of racemic tramadol is 308 ± 78 ng/ml and occurs at approximately two hours after a single 100 mg oral dose in healthy subjects. At this dose the mean peak plasma concentration of the active mono-O-desmethyl metabolite, racemic M1 is 55 ± 20 ng/ml and occurs approximately three hours post-dose. The separate [+]- and [-]-enantiomers of tramadol generally follow a parallel time course in plasma after a single 100 mg oral dose of Ultram. Following 100 mg oral administration of tramadol the maximum plasma concentrations of the [-]-enantiomer of tramadol are somewhat lower than those of the [+]-enantiomer (148 ± 33 vs. 168 ± 36 ng/ml respectively). The [-]-M1 enantiomer is present at slightly higher plasma concentrations than the [+]-M1 enantiomer (35 ± 10 vs. 26 ± 13 ng/ml respectively). At steady state following a 100 mg q.i.d. regimen of tramadol, 3 out of 18 subjects formed relatively low amounts of [+]-M1, while their [-]-M1 formation remained similar to that of other subjects. This is believed not to be clinically significant.

Plasma concentrations of racemic tramadol are predictable over a 50 mg to 100 mg single-dose range. This is also true under multiple-dose conditions. Steady state is achieved after two days of dosing Ultram by a 100 mg q.i.d. regimen (maximum plasma concentration was 592 ± 177 ng/ml). The plasma half-life of tramadol following a single and multiple dosing was 6 and 7 hours, respectively. This increase in half-life upon multiple dosing is not considered to be clinically significant or to warrant dosage adjustment for chronic use.

Mean plasma racemic tramadol and racemic M1 concentration-versus-time profiles following a single 100 mg oral dose of Ultram and following twenty-nine 100 mg doses four times daily.

Distribution: The volume of distribution of tramadol was 2.6 and 2.9 liters/kg in male and female subjects respectively following a 100 mg intravenous dose. The binding of tramadol to human plasma proteins is approximately 20% and binding also appears to be independent of concentration up to 10 µg/ml. Saturation of plasma protein binding occurs only at concentrations outside the clinically relevant range. Although not confirmed in humans, tramadol has been shown in rats to cross the blood-brain barrier.

Metabolism: Tramadol is extensively metabolized after oral administration. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites. The remainder is excreted either as unidentified or an unextractable metabolites. The major metabolic pathways appear to be N- and O-demethylation and glucuronidation or sulfation in the liver. Only the one metabolite (mono-O-desmethyltramadol denoted M1) is pharmacologically active. Production of M1 is dependent on the CYP2D6 isoenzyme of cytochrome P-450.

Elimination: The mean terminal plasma elimination half-lives of racemic tramadol and racemic M1 are 6.3 ± 1.4 and 7.4 ± 1.4 hours respectively. The plasma elimination half-life of racemic tramadol increased from approximately six hours to seven hours upon multiple dosing.

Special Populations: Renal: Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite M1. In patients with creatinine clearances of less than 30/ml/min adjustment of the dosing regimen is recommended (see DOSAGE AND ADMINISTRATION). The total amount of tramadol and M1 removed during a dialysis period is less than 7% of the administrator dose.

Hepatic: Metabolism of tramadol and M1 is reduced in patients with advanced cirrhosis of the liver resulting in a larger area under the serum-concentration-versus-time to curve tramadol and longer tramadol and M1 elimination half-lives (13 hrs. for tramadol and 19 hrs. for M1). In cirrhotic patients adjustment of the dosing regimen is recommended (see DOSAGE AND ADMINISTRATION).

Age: Healthy elderly subjects aged 65 to 75 years have plasma tramadol concentrations and elimination half-lives comparable to those observed in healthy subjects less than 65 years of age. In subjects over 75 years maximum serum concentrations are slightly elevated (208 vs. 162 ng/ml) and the elimination half-life is slightly prolonged (7 vs. 6 hours) compared to subjects 65 to 75 years of age. Adjustment of the daily dose is recommended for patients older than 75 years (see DOSAGE AND ADMINISTRATION).

Gender: The absolute bioavailability of tramadol was 73% in males and 79% in females. The plasma clearance was 6.4 ml/min/kg in males and 5.7 ml/min/kg in females following a 100 mg IV dose of tramadol. Following a single oral dose, and after adjusting for body weight, females had a 12% higher peak tramadol concentration and a 35% higher area under the concentration-time curve compared to males. This difference may not be of any clinical significance.

Clinical Studies: Ultram (tramadol hydrochloride) has been given in single oral doses of 50, 75, 100, 150 and 200 mg to patients with pain following surgical procedures (orthopedic, gynecological, cesarean section) and pain following oral surgery (extraction of impacted molars).

In single-dose models of pain following oral surgery, pain relief was demonstrated in some patients at doses of 50 mg and 75 mg. A dose of 100 mg Ultram tended to provide analgesia superior to codeine sulfate 60 mg, but it was not effective as the combination of aspirin 650 mg with codeine phosphate 60 mg. In single-dose models of pain following surgical procedures, 150 mg provided analgesia generally comparable to the combination of acetaminophen 650 mg with propoxyphene napsylate 100 mg, with a tendency toward later peak effect.

Ultram (tramadol hydrochloride) has been studied in three long-term controlled trials involving a total of 820 patients with 530 patients receiving Ultram. Patients with chronic conditions such as low back pain, cancer, neuropathic pain and orthopedic and joint conditions entered a double-blind phase of one to three months. Average daily doses of approximately 250 mg of Ultram in divided doses produced analgesia comparable with five doses of acetaminophen 300 mg with codeine phosphate 30 mg (Tylenol® with Codeine #3) daily five doses of aspirin 325 mg with codeine phosphate 30 mg daily and with two to three doses of acetaminophen 500 mg with oxycodone hydrochloride 5 mg (Tylox®) daily. Following the double-blind period, some patients took Ultram in an open period for up to two years.

Tension Headache Medications

Pain-Relievers 

• Mixed analgesics – These medicines are pain-relievers that contain more than one active ingredient. For example, Excedrin contains acetaminophen, aspirin and caffeine, and Fiorinal contains butalbital and aspirin. You may take these if mild analgesics are not strong enough to relieve your headache pain or if you headache is more severe. Some

Preventive medications
Certain medications taken at regular intervals may reduce the frequency and severity of attacks. Your doctor may prescribe these if you have frequent headaches or have tension headaches that aren’t relieved by acute medication and nondrug therapy such as stress management. Your doctor also may recommend preventive medication if your headache pain becomes disabling or causes you to overuse acute medication, or if you can’t take acute medication because of other medical conditions.

Doctors may prescribe antidepressants to prevent tension headache, especially the chronic form. These drugs aren’t painkillers. Rather, they work to stabilize the levels of brain chemicals such as serotonin, which may be involved in the development of a headache. You don’t have to have depression in order to use these drugs.

Preventive medications may include:

• Tricyclic antidepressants. Tricyclic antidepressants, including amitriptyline and nortriptyline (Pamelor), are the most commonly used medications to prevent tension headache. They’re effective against both the episodic and chronic forms. Side effects of these medications may include weight gain, drowsiness and dry mouth.
• Selective serotonin reuptake inhibitors (SSRIs). Antidepressants such as paroxetine (Paxil), venlafaxine (Effexor) and fluoxetine (Prozac, Sarafem) produce fewer side effects than do the tricyclic antidepressants but generally aren’t considered effective for tension headaches.
• Other medications. Other medications that may prevent tension headache include anticonvulsants, such as topiramate (Topamax) and gabapentin (Neurontin), and muscle relaxants, such as tizanidine (Zanaflex).

Preventive medications may require several weeks or more to build up in your nervous system before they take effect. So don’t get frustrated if you haven’t seen improvements shortly after you begin taking the drug — it may take a couple of months or longer. Also be aware that overusing caffeine or painkillers for acute relief may reduce the effect of a preventive drug.

To obtain the greatest benefit from preventive medication, keep your use of acute pain relievers to a minimum. Your doctor will monitor your treatment to see how the preventive medication is working. If your headaches are under control, your dose of medication may be reduced gradually over time.

Preventive, or “prophylactic,” medicines are taken every day to prevent headaches from starting. They are used to treat chronic headaches that occur more than twice a week and/or are extremely painful. They are also prescribed when other headache medicines or remedies do not work or cannot be used. More commonly-used medicines include:

• Tricyclic anti-depressants (TCAs) – These medicines were originally used to treat depression and related disorders. However, headache experts have learned that TCAs can also help prevent and relieve chronic TTH. A TCA such as amitriptyline (Elavil) is often the first medicine of choice for preventing chronic TTH. TCAs are often begun at lower doses and are slowly increased. In addition to relieving pain, TCAs may improve sleep and decrease depression in people who have it. Other TCAs given for chronic TTH include nortriptyline (Pamelor), desipramine (Norpramin), doxepin (Sinequan) and clomipramine (Anafranil).

• Anti-convulsants – These medicines were originally used to treat seizures (convulsions or epilepsy). Now, certain anti-convulsants are also used to help prevent chronic TTH. Your health care provider may give you an anti-convulsant if TCAs failed to relieve your headaches. Examples include valproic acid (Depakote), gabapentin (Neurontin) and topiramate (Topamax).

Other Medicines

• Muscle relaxants – These medicines are also called “anti-spasmodics.” They given to relax tight muscles. They may be given alone, but medical research shows that they are more effective when given together with a medicine such as a TCA. Examples of muscle relaxants are tizanidine (Zanaflex) and metaxalone (Skelaxin). More research needs to be done on the effectiveness of muscle relaxants as a treatment for TTH.

Migraine treatment is aimed at relieving symptoms and preventing additional attacks. Quick steps to ease symptoms may include napping or resting with eyes closed in a quiet, darkened room; placing a cool cloth or ice pack on the forehead, and drinking lots of fluid, particularly if the migraine is accompanied by vomiting. Small amounts of caffeine may help relieve symptoms during a migraine’s early stages.

Drug therapy for migraine is divided into acute and preventive treatment. Acute or “abortive” medications are taken as soon as symptoms occur to relieve pain and restore function. Preventive treatment involves taking medicines daily to reduce the severity of future attacks or keep them from happening. The U.S. Food and Drug Administration (FDA) has approved a variety of drugs for these treatment methods. Headache drug use should be monitored by a physician, since some drugs may cause side effects.

Acute treatment for migraine may include any of the following drugs.

• Triptan drugs increase levels of the neurotransmitter serotonin in the brain. Serotonin causes blood vessels to constrict and lowers the pain threshold. Triptans-the preferred treatment for migraine-ease moderate to severe migraine pain and are available as tablets, nasal sprays, and injections.
• Ergot derivative drugs bind to serotonin receptors on nerve cells and decrease the transmission of pain messages along nerve fibers. They are most effective during the early stages of migraine and are available as nasal sprays and injections.
• Non-prescription analgesics or over-the-counter drugs such as ibuprofen, aspirin, or acetaminophen can ease the pain of less severe migraine headache.
• Combination analgesics involve a mix of drugs such as acetaminophen plus caffeine and/or a narcotic for migraine that may be resistant to simple analgesics.
• Nonsteroidal anti-inflammatory drugs can reduce inflammation and alleviate pain.
• Nausea relief drugs can ease queasiness brought on by various types of headache.
• Narcotics are prescribed briefly to relieve pain. These drugs should not be used to treat chronic headaches.

Taking headache relief drugs more than three times a week may lead to medication overuse headache (previously called rebound headache), in which the initial headache is relieved temporarily but reappears as the drug wears off. Taking more of the drug to treat the new headache leads to progressively shorter periods of pain relief and results in a pattern of recurrent chronic headache. Headache pain ranges from moderate to severe and may occur with nausea or irritability. It may take weeks for these headaches to end once the drug is stopped.

Everyone with migraine needs effective treatment at the time of the headaches. Some people with frequent and severe migraine need preventive medications. In general, prevention should be considered if migraines occur one or more times weekly, or if migraines are less frequent but disabling. Preventive medicines are also recommended for individuals who take symptomatic headache treatment more than three times a week. Physicians will also recommend that a migraine sufferer take one or more preventive medications two to three months to assess drug effectiveness, unless intolerable side effects occur.

Several preventive medicines for migraine were initially marketed for conditions other than migraine.

• Anticonvulsants may be helpful for people with other types of headaches in addition to migraine. Although they were originally developed for treating epilepsy, these drugs increase levels of certain neurotransmitters and dampen pain impulses.
• Beta-blockers are drugs for treating high blood pressure that are often effective for migraine.
• Calcium channel blockers are medications that are also used to treat high blood pressure treatment and help to stabilize blood vessel walls. These drugs appear to work by preventing the blood vessels from either narrowing or widening, which affects blood flow to the brain.
• Antidepressants are drugs that work on different chemicals in the brain; their effectiveness in treating migraine is not directly related to their effect on mood. Antidepressants may be helpful for individuals with other types of headaches because they increase the production of serotonin and may also affect levels of other chemicals, such as norepinephrine and dopamine. The types of antidepressants used for migraine treatment include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants (which are also used to treat tension-type headaches).

Natural treatments for migraine include riboflavin (vitamin B2), magnesium, coenzyme Q10, and butterbur.

Non-drug therapy for migraine includes biofeedback and relaxation training, both of which help individuals cope with or control the development of pain and the body’s response to stress.

Lifestyle changes that reduce or prevent migraine attacks in some individuals include exercising, avoiding food and beverages that trigger headaches, eating regularly scheduled meals with adequate hydration, stopping certain medications, and establishing a consistent sleep schedule. Obesity increases the risk of developing chronic daily headache, so a weight loss program is recommended for obese individuals.

Physical Therapies

Bracing yourself for the next headache attack can result in tight, tense muscles. Your health care provider may suggest physical therapy (PT) if you have problems with muscle tension. A therapist may use techniques to relax your muscles and increase normal movement. These include:

• Electrotherapy such as TENS 
• Heat and cold treatments
• Manual (“hands on”) therapy such as head and neck massage
• Stretching exercises

Exercising at home or at the local gym can also be an important part of your headache treatment program. Exercise can include aerobic reconditioning and stretching exercises. Regular aerobic exercise may help decrease how severe and how often people get headaches such as migraine. Muscle tightness and tenderness that bothers many people with chronic headache can be decreased with stretching exercises.