Feeling Good: The New Mood Therapy
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serotonin antagonists, including trazodone (Desyrel) and nefazodone (Serzone)
hyperpyretic crisis (serotonin syndrome)
mirtazapine (Remeron)
hypertensive crisis (noradrenergic syndrome)
venlafaxine (Effexor)
hypertensive crisis (noradrenergic syndrome)
Asthma Medicines
Drug
Comment
ephedrine, a bronchodilator contained in Marax, Quadrinal, and other asthma drugs
hypertensive crisis
inhalants which contain albuterol (Proventil, Ventolin), metaproterenol (Alupent, Metaprel), or other beta-adrenergic bronchodilators
blood pressure elevations and a rapid heart; beclomethasone and other nonsystemic steroid inhalers are generally safer
theophylline (Theo-Dur), a common ingredient in asthma drugs
rapid heart and anxiety
Cold, Cough, Allergy, Sinus, Decongestant, and Hay Fever Medications (including tablets, drops, or sprays)
Drug
Comment
antihistamines: terfenadine (Seldane-D)
can cause an increase in MAOI blood levels
dextromethorphan can be found in many cold and cough medications, especially any drug with DM or Tuss in its name. These include Bromarest-DM or -DX, Dimetane-DX cough syrup, Dristan Cold & Flu, Phenergan with Dextromethorphan, Robitussin-DM, several Tylenol cold, cough, and flu preparations, and many others
hyperpyretic crisis (serotonin syndrome); may also cause brief episodes of psychosis or bizarre behavior
ephedrine can be found in Bronkaid, Primatene, Vicks Vatronol nose drops and several other asthma and cold medications.
hypertensive crisis (noradrenergic syndrome)
oxymetazoline (Afrin) nose drops or sprays used to treat nasal decongestion
hypertensive crisis (noradrenergic syndrome)
phenylephrine can be found in Dimetane, Dristan decongestant, Neo-Synephrine nasal spray and nose drops, and many other similar preparations, including some eye drop medications
hypertensive crisis (noradrenergic syndrome)
phenylpropanolamine is contained in Alka-Seltzer Plus Cold and Night-Time Cold medicine, Allerest, Contac decongestants, Coricidin D decongestants, Dexatrim appetite pills, Dimetane-DC Cough syrup, Ornade Spansules, Robitussin-CF, Sinarest, St. Joseph Cold Tablets, Tylenol Cold medicine, and many others
hypertensive crisis (noradrenergic syndrome)
pseudoephedrine can be found in Actifed, Allerest No Drowsiness formula, Benadryl combinations, CoAdvil, Dimetane-DX Cough syrup, Dristan Cold Maximum Strength, Robitussin-DAC syrup, Robitussin-PE, Seldane-D tablets, Sinarest No Drowsiness, Sinutab, Sudafed, Triaminic Nite Light, and numerous Tylenol allergy, sinus, flu, and cold preparations, as well as several Vicks products including NyQuil, to mention just a few
hypertensive crisis (noradrenergic synarome)
Diabetes Medications
Drug
Comment
insulin
may cause a greater drop in blood sugar
oral hypoglycemic agents
as above
Medications for Low Blood Pressure (for patients in shock)
Drug
Comment
sympathomimetic amines including:
• dopamine (Intropin)
• epinephrine (Adrenalin)
• isoproterenol (Isuprel)
• metaraminol (Aramine)
• methyldopa (Aldomet)
• norepinephrine (Levophed)
hypertensive crisis (noradrenergic syndrome) because these drugs cause blood vessels to constrict
Medications for High Blood Pressure
Drug
Comment
guanadrel (Hylorel) guanethidine (Ismelin) hydralazine (Apresoline) methyldopa (Aldomet) reserpine (Serpasil)
These blood-pressure medications may cause a paradoxical increase in blood pressure when combined with MAOIs.
beta-blockers
may be more potent when combined with MAOIs, leading to a greater-than-expected drop in blood pressure and dizziness when standing
calcium channel blockers
appear to be reasonably safe when combined with MAOIs. Check with your doctor and monitor blood pressure closely. Watch for a greater-than-expected drop in blood pressure
diuretics
watch for a greater-than-expected drop in blood pressure. May increase blood level of MAOI
Mood Stabilizers
Drug
Comment
carbamazepine (Tegretol)
hyperpyretic crisis (serotonin syndrome); MAOI may cause carbamazepine levels to fall, so epileptics may experience seizures
lithium (Eskalith)
can cause hyperpyretic crisis (serotonin syndrome) in animal studies
Painkillers and Anesthetics
Drug
Comment
anesthetics: general
Tell your anesthesiologist you are on an MAOI. If possible, discontinue the MAOI two weeks before elective surgery
Muscle relaxants such as succinylcholine and tubocurarine may have a more pronounced or prolonged effect. General anesthetics such as halothane may lead to excitement, excessive depression of the brain, or hyperpyretic reactions
anesthetics: local
Some contain epinephrine or other sympathomimetics—make sure you tell your dentist you are taking an MAOI
Pain Medications and Anesthetics cont.
Drug
Comment
cyclobenzaprine (Flexeril) (a muscle relaxant used to treat muscle spasm)
hyperpyretic crisis (serotonin syndrome) or severe seizures
meperidine (Demerol)
A single injection can cause seizures, coma, and death (serotonin syndrome). Most other narcotics, including morphine and codeine, have been used safely with MAOIs
Sedatives and Tranquilizers
Drug
Comment
alcohol
May have enhanced sedative effects, especially when combined with phenelzine (Nardil). This could be hazardous when driving or operating dangerous machinery
barbiturates (such as phenobarbital)
enhanced sedative effects as described above
buspirone (BuSpar)
enhanced sedative effects as described above
major tranquilizers (neuroleptics)
enhanced sedative effects as described above; some neuroleptics may cause a drop in blood pressure when combined with MAOIs
minor tranquilizers (benzodiazepines) such as alprazolam (Xanax), diazepam (Valium) and others
enhanced sedative effects as described above
sleeping pills
enhanced sedative effects as described above
L-tryptophan
hyperpyretic crisis (serotonin syndrome); blood pressure elevations; disorientation, memory impairment, and other neurologic changes
Stimulants (Pep Pills) and Street Drugs
Drug
Comment
amphetamines (speed or crank)
cocaine
benzedrine
benzphetamine (Didrex)
dextroamphetamine (Dexedrine)
methamphetamine (Desoxyn)
methylphenidate (Ritalin)
the hypertensive crisis (noradrenergic syndrome) is possible; methylphenidate is considered somewhat less risky than the amphetamines
Weight-Loss and Appetite-Suppression Medications
Drug
Comment
pemoline (Cylert)
drug interactions have not been studied in humans; great caution should be used; some experts report that pemoline has been combined with MAOIs in some cases1
fenfluramine (Pondimin)
hyperpyretic crisis (serotonin syndrome)
phendimetrazine (Plegine)
hypertensive crisis (noradrenergic syndrome)
phentermine and some over-the-counter meds
hypertensive crisis (noradrenergic s
yndrome)
phenylpropanolamine (Acutrim)
hypertensive crisis (noradrenergic syndrome)
stimulants (listed above)
hypertensive crisis (noradrenergic syndrome)
Other MAOI Drug Interactions
Drug
Comment
caffeine (in coffee, tea, soda, chocolate)
Probably safe in moderate amounts; avoid large amounts; may cause blood pressure elevations, a racing heart, and anxiety
disulfiram (Antabuse) (used to treat alcoholism)
Severe reactions when mixed with an MAOI
L-dopa (Sinemet) (used to treat Parkinson’s disease)
hypertensive crisis (noradrenergic syndrome)
aInformation in this table was obtained from several sources including the Manual of Clinical Psychopharmacology1 and Psychotropic Drugs Fast Facts.17 These excellent references are highly recommended.
bMany patients have been successfully treated with a combination of an MAOI and a tricyclic antidepressant under close observation, but such drug combinations are dangerous and require a high level of expert supervision.
Drugs that are categorized as sympathomimetics are particularly dangerous because they are contained in many over-the-counter drugs for common ailments such as colds. They are called sympathomimetics because they tend to mimic the effects of the sympathetic nervous system, which is involved in the control of blood pressure.
Several sympathomimetic drugs are found in large numbers of prescription and over-the-counter cold preparations, cough medicines, decongestants, and hay fever medications. These include ephedrine, phenylephrine, phenylpropanolamine and pseudoephedrine. For example, ephedrine can be found in Bronkaid, Primatene, Vicks’ Vatronol nose drops, and several other cold and asthma medications. Phenylephrine can be found in Dimetane, Dristan decongestants, Neo-Synephrine nasal spray and nose drops, and many other similar preparations. Phenylpropanolamine is contained in Alka-Seltzer Plus Cold Medicines, Contac decongestants, Coricidin D decongestants, Dexatrim appetite suppressant pills, Dimetane-DC Cough syrup, Ornade Spansules, Robitussin-CF, Sinarest, St. Joseph Cold Tablets, and many other cold medicines. Pseudoephedrine can be found in Actifed, Advil Cold & Sinus, Allerest No-Drowsiness formula, Benadryl combinations, Dimetane-DX Cough syrup, Dristan Cold Maximum Strength, Robitussin-DAC syrup, Robitussin-PE, Seldane-D tablets, Sinarest No Drowsiness, Sinutab, Sudafed, Triaminic Nite Light, and numerous Tylenol allergy, sinus, flu, and cold preparations, as well as several Vicks products including NyQuil, to mention just a few.
Some cold and cough preparations contain dextromethorphan. This is not a sympathomimetic drug, but a cough suppressant. Dextromethorphan is on the list of forbidden medications because it can cause a hyperpyretic crisis. Dextromethorphan can be found in any drug with “DM” or “Tuss” in its name, as well as many preparations without these suffixes. A few examples are Bromarest-DM or -DX, Dimetane-DX Cough syrup, Dristan Cold & Flu, Phenergan with Dextromethorphan, Robitussin-DM, several Tylenol cold, cough, and flu preparations, and many other medications as well.
Because so many common over-the-counter medications contain sympathomimetics or dextromethorphan, it is nearly impossible to keep up with all of them. You can best protect yourself by reading the warning labels that come with these medications and by checking with your doctor or pharmacist before you combine any with an MAOI.
Diabetics taking MAOIs need to know that the MAOIs may also cause blood levels of insulin as well as some oral hypoglycemic agents to increase. As a result, your blood sugar may fall more than expected. This can cause a hypoglycemic reaction, with dizziness, faintness, sweating, and so forth, because your brain does not get enough sugar from your blood. Your doctor may have to adjust the doses of your diabetic medications if you are on an MAOI.
Any of the MAOIs can lower your blood pressure, and so they can intensify the effects of other blood-pressure medications your doctor has prescribed, including diuretics and beta-blockers. The MAOIs can also cause the blood levels of a number of blood-pressure medications to increase. This also tends to intensify their effects. As noted above, some blood-pressure medications can have the paradoxical effect of causing an increase in blood pressure if you are taking an MAOI. Make sure you let your doctor know about the MAOI. Many major tranquilizers (neuroleptics) can also cause blood pressure to fall, and MAOIs can increase this effect as well.
Some painkillers must be avoided if you are taking an MAOI. For example, a single injection of the painkiller meperidine (Demerol) has been known to cause seizures, coma, and death in patients taking MAOIs. Other opiates, including morphine, are thought to be safer. Most mild nonprescription painkillers, such as aspirin or Tylenol, are also thought to be safe as long as they contain no caffeine. However, cyclobenzaprine (Fiexeril), which is commonly used to treat local muscle spasm, can cause fever, seizures, and death. This drug should be avoided entirely.
Many local and general anesthetics can also interact with the MAOIs. Some local anesthetics contain epinephrine or other sympathomimetic drugs that can create hypertensive reactions. Inform your dentist that you are taking an MAOI so she or he can choose a local anesthetic that will be safe for you. If you require elective surgery while on an MAOI, it would be best to discontinue the MAOI for one or two weeks prior to the surgery. Some general anesthetics, such as halothane, can cause excitement or excessive sedation as well as hyperpyretic reactions when combined with an MAOI. The muscle relaxants used by anesthesiologists, such as succinylcholine or tubocurarine, may also have more potent effects. Make sure you inform your anesthesiologist if you are taking an MAOI.
Sedative drugs, including alcohol, major tranquilizers (neuroleptics) and minor tranquilizers, barbiturates and sleeping pills, can interact with MAOIs. This is especially true for phenelzine (Nardil). Because phenelzine also tends to be sedating, it can enhance the effects of any other sedative agent. You should try to avoid combining MAOIs with sedative drugs because the sleepiness you experience could be hazardous, especially if you are driving or operating dangerous machinery.
L-tryptophan is another sedative agent that should not be combined with MAOIs because it can cause a hyperpyretic crisis (serotonin syndrome). L-tryptophan is an essential amino acid that is present in certain foods such as meats and dairy products. It used to be available in health food stores and has been actively promoted as a natural sedative agent to help people with insomnia. It has also been used as a treatment for depression, but the evidence for its antidepressant effects is meager at best. Following ingestion, L-tryptophan rapidly accumulates in the brain, where it is converted into serotonin. If the dose of L-tryptophan is large enough, you will begin to feel sleepy. If you are taking an MAOI, the increase in brain serotonin may be massive. This is because your brain cannot metabolize the excess serotonin when you are on an MAOI, so the levels of serotonin can escalate to dangerous levels, triggering the serotonin syndrome.
However, some researchers have purposely treated depressed patients with an MAOI plus 2 to 6 grams per day of L-tryptophan in an attempt to make the MAOI treatment more effective. The purpose of these augmentation strategies is to convert a drug nonresponder into a drug responder. Some studies have indicated that this combination can be more potent than treatment with an MAOI alone. Such a treatment is somewhat dangerous, and should probably be administered by experts and reserved for patients with very difficult, resistant depressions.20 Dr. Jonathan Cole and his colleagues have given doses of 3 to 6 grams of L-tryptophan to patients who had been taking an MAOI for several weeks or more.1 They observed some early signs of the serotonin syndrome in these patients, suggesting the potential benefits of this drug combination may not be worth the risk.
In animal studies, the combination of lithium with an MAOI can also cause the serotonin syndrome. This is because lithium causes L-tryptophan to enter the brain more rapidly. L-tryptophan is present in the foods we eat, and a large meal can contain as much as 1 gram of L-tryptophan. If you combin
e lithium with an MAOI, you may get a large increase in serotonin in your brain following meals. However, some doctors have added lithium to an MAOI if the MAOI has not been effective, in just the same way they might add L-tryptophan to try to augment the antidepressant effect of the MAOI. If you receive lithium plus an MAOI, you must be monitored closely to make sure you do not develop any symptoms of the serotonin syndrome, such as fever, tremor, jerking of the muscles, or confusion.
MAOIs are often combined with lithium for another reason. Bipolar patients with abnormal episodic mood elevations as well as depression are often maintained indefinitely on lithium or another mood stabilizer, as described below. During the depressed phase of the cycle, many bipolar patients will need an antidepressant as well as lithium to reverse the depression. The MAOIs, as well as many other kinds of antidepressants, have been used safely and successfully in this way. However, patients need to be monitored closely for signs of hyperpyretic crises as well as episodes of mania, which can occur on rare occasions when bipolar patients receive antidepressants.
Stimulants, pep pills, and weight-loss pills are especially dangerous when combined with MAOIs. Some of these drugs are categorized as sympathomimetics, and they can cause hypertensive crises. For example, methylphenidate (Ritalin), which is widely used for the treatment of attention deficit disorder in children and adults, is a sympathomimetic that could have this effect. Several commonly abused street or prescription drugs are also sympathomimetics. These include the amphetamines such as Benzedrine, Dexedrine, and Methedrine (also known as “speed” or “crank”) and cocaine. Amphetamines used to be prescribed for weight loss, but their abuse potential is so high that most doctors no longer prescribe them for this purpose. However, a number of the newer popular weight-loss drugs can also be quite dangerous when mixed with MAOIs. For example, phentermine (Adipex; Fastin) can cause hypertensive reactions and fenfluramine (Pondimin), the controversial weight-loss drug that was recently in vogue, can lead to hyperpyretic crises.