Stadol, Stadol NS is a Solution of Butorphanol Tartrate, an Opioid Substance

What Are Opioids?

As the name suggests, opioids are drugs that act on the body and brain in the same basic ways as opium and its many derivatives. Opioids can offer relief from severe, unresponsive pain, can bring sleep to the weary and, unfortunately, can also result in drug dependency if overused or abused.

Opium is an extract of the seeds of the oriental poppy and contains morphine and codeine along with many other active compounds. For decades, researchers have sought to develop new opium-like compounds that might offer the pain relief of the natural narcotics with fewer of their risks and side effects. Oxycodone, methadone, and butorphanol are examples of synthetic or semisynthetic opioids.

Opium-like substances do not come only from poppies and pharmaceutical companies. The body produces its own pleasure-giving and pain-relieving chemicals, such as the endorphins. Opium and opioid drugs work because they act on the same sites in the brain and nervous system as the endorphins. Problems in the body's own opioid system may be a factor in some cases of migraine, although the evidence to support this theory is still limited.

Opioid drugs do not all act in exactly the same way on the brain, however. For example, oxycodone and methadone act primarily on one class of opioid receptor (a "gatekeeper" molecule that triggers responses within brain cells), while targets a different class of receptor. Effects and side effects can vary accordingly.

When Are Opioids Used to Treat Headache?

There is a growing number of non-narcotic medications available to stop a migraine attack or blunt its pain. These range from over-the-counter Excedrin Migraine to DHE-45 and the triptans. Some patients cannot take either the triptans or the ergot drugs (ergotamine or DHE-45) because of contraindications such as a past heart attack or uncontrolled high blood pressure. A few patients with severe, prolonged headaches may not achieve adequate pain relief with any of the standard treatments. In these situations, physicians will occasionally prescribe short-acting opioids for use when other treatments fail and the headache is severe.

Several prescription pain relievers combine moderate doses of a short-acting opioid with aspirin, acetaminophen and/or caffeine. Codeine combinations are the opioids most often prescribed for relieving severe, unresponsive headache. These include Fioricet with codeine, Tylenol with codeine and Fiorinal with codeine. (Fioricet and Fiorinal also contain butalbital, a barbiturate). Propoxyphene combinations (Darvocet, Darvon) and oxycodone combinations (Percocet, Percodan) can also be used with caution and strict rationing. Physicians often set a limit on use for all these opioid medications, allowing only a specified number of tablets per month, with non-refillable prescriptions.

These are short-acting opioids-they are generally prescribed for "breakthrough" headaches-for use after a non-narcotic analgesic has failed to be effective. Because they produce sedation and drowsiness, many people find they cannot take them at work or school. Also, the individual should not drive a car or operate dangerous machinery for at least one hour after taking the dose. Alcohol use should be avoided.

Butorphanol (Stadol) nasal spray is a viable alternative to the opioid combinations that are taken by mouth. Stadol's primary advantage over opioids taken by mouth is its onset of action-often within 15 minutes. When properly used with patient education by the drug manufacturer and strict limits on refills, to prevent overuse, butorphanol is a reasonable choice for controlling severe headaches. For patients who have vomiting or significant nausea with their migraine attacks, a nasal spray offers advantages over drugs taken by mouth.

How Are Opioids Used to Prevent Headache?

Sufferers who have four or more severe headaches per month are often given a trial of a prophylactic (preventive) medication. Preventive treatments are generally taken daily to reduce the number or severity of the headaches. Patients with seasonal cluster headaches or menstrual migraine can often limit use to their headache-prone times.

A number of different medications have been shown to be effective in reducing headache frequency or severity, including beta blockers, several antidepressants, and divalproex (Depakote). None of these drugs will work for all patients, and a few may find their headaches are resistant to standard preventive approaches. In these instances, long-acting opioids may be tried as a daily preventive.

Steady use of short-acting opioids heightens the potential for drug dependency. Long-acting opioids offer more prolonged pain control, reducing the need for dosing to one to two administrations a day in carefully selected and monitored patients. These drugs are formulated so that the opioid enters the bloodstream relatively slowly, lessening the side effects and reducing the risk of tolerance.

The use of long-acting opioids for prevention of chronic daily headache is controversial. The safety and efficacy of this approach are still being studied with small groups of patients at major headache referral centers.

What Are the Risks and Side Effects?

Opioids have significant side effects. Although the side effect profile of each drug is different, there are a number of common effects, such as constipation, sedation, itching, drowsiness, lightheadedness, dizziness, and mood changes. use or avoid alcohol altogether.

Many physicians advise their patients to have someone with them when taking an opioid for the first time, in case some undetected health condition or drug interaction results in more serious respiratory depression.

Some migraine sufferers will find that the nausea or vomiting they experience with their attacks is relieved by opioid treatment. Because opioids have complex effects on the gastrointestinal system, they can also produce nausea or vomiting as side effects.

The mood changes caused by opioid medication are not all enjoyable. While some drugs do cause euphoria (a pleasant state of consciousness), they can also bring on negative, restless or anxious feelings (called dysphoria, the opposite of euphoria). Either mood change can potentially interfere with thinking and concentration on tasks. For some the mood changes will be minor and improve as therapy continues.

Could I Become Addicted?

The most important concern for both doctors and patients is the fear of becoming addicted to the drugs.

Both doctors and patients often misunderstand addiction and misuse the term. Addiction is best defined as psychological dependence. Someone who is psychologically dependent becomes obsessed with obtaining the drugs, uses them for recreation not pain control, and shows an overall loss of control over drug use. Usually their relationships and work performance have deteriorated as a result of their obsession with drug use.

It's important not to confuse addiction with two other potential effects of continued opioid treatment: tolerance and physical dependence. Tolerance means that ever-higher doses are needed to achieve an effect. Some degree of tolerance usually develops after the first few opioid doses but should not escalate if the drug is used properly. Physical dependence involves changes in the nervous system that create withdrawal symptoms if drug use is abruptly stopped. Withdrawal symptoms can include restlessness, sweating, cramping, diarrhea, weakness, anxiety, depression and increased pain-none of them pleasant, but all time-limited and reversible. It is possible to develop physical dependence and to have withdrawal symptoms when treatment is stopped without being addicted.

Patients who take opioids as prescribed to control pain have a very low risk of significant tolerance, physical dependence or psychological dependence as long as the doctor and the patient have had sufficient information and warning about usage from the drug manufacturer.

Signs of psychological dependence can develop with the opioids, or with any pain medication. Headache patients often come to fear headache and become preoccupied with avoiding and relieving pain. They may then become anxious or agitated if their doctor limits their supply of narcotic medication. This behavior is often called pseudoaddiction. The individual is not abusing drugs recreationally but fear of pain is expressed in drug-seeking behavior. Behavioral therapy can help the individual understand the fear and learn better coping strategies.

When Do Doctors Decide Opioids Are Indicated?

Responsible physicians must be conservative in electing to use opioid drugs for chronic pain conditions such as headache. The risk of physical or psychological dependency with overuse is one major concern. Also, the sedation or drowsiness and the mood changes produced by opioids can interfere with normal activities. The physician and the headache sufferer must be convinced that the standard non-narcotic treatments are unsatisfactory after being tried at the appropriate dosage and for an appropriate length of time.

This is not always simple to do. Many preventive drugs may need adjustments in dosage and a trial of two to three weeks before they will begin to show an effect. Sometimes combinations of different acute and preventive treatments produce much better results than any one drug used alone. Most importantly, some headache sufferers who have failed to get relief from many different medications are actually experiencing rebound headache from medication overuse.

Drug rebound headache is a form of chronic daily headache that is triggered by daily or near-daily use of pain relief medicines, either prescription or over-the-counter analgesics, including short-acting opioids. Caffeine in coffee, tea or sodas can also contribute to drug rebound headache in some people. Some evidence suggests that tolerance to common non-narcotic analgesics can develop, with withdrawal symptoms (including headache) when their use is stopped.

In most instances, patients who develop drug rebound headache have been taking more frequent doses or larger doses than the labeling for the medications advise. However, a few susceptible individuals may develop a chronic daily headache in response to moderately heavy use of analgesics and caffeine.

Drug rebound headache can only be treated by stopping all the pain medications under a physician's supervision. Other preventive medications, including opioids, will not work until the analgesics have been discontinued. Unfortunately, stopping analgesics will bring on more severe headaches and other withdrawal symptoms. It may take up to two months for the headaches to improve, although some people will note improvement within two or three weeks.

It is important to realize that preventive opioid therapy is not always effective, and the side effects may prove difficult to tolerate. One headache clinic has reported results on 42 patients with severe, treatment-resistant chronic daily headache who were treated with methadone for six months. Between 60% and 86% reported significant improvement in quality-of-life indicators such as relationships and work performance. All reported moderate to excellent relief from their severe chronic daily headaches. However, another 106 patients in the same clinic discontinued methadone treatment because of side effects or ineffectiveness. While long-acting opioids have significant risks and limitations, they can improve quality of life for a small minority of patients whose severe daily or near-daily headaches do not respond to other treatments.

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