Read Feeling Good: The New Mood Therapy Online
Authors: David D. Burns
Amoxapine (Asendin) has a distinct and troublesome type of side effect not shared with most other antidepressants. This is because one of its metabolites blocks dopamine receptors in the brain, much like antipsychotic drugs such as chlorpromazine (Thorazine) and many others which are used in the treatment of schizophrenia. Thus, patients who take amoxapine can in rare instances develop some of the same types of side effects that occur in patients who take antipsychotic drugs. For example, women may experience galactorrhea (the production of milk by the breast.) Any of several so-called “extrapyramidal” reactions can also develop. One of them, called akathisia, is a motor restlessness syndrome. This is an unusual kind of muscular “itchiness”—your arms or legs feel intensely restless and so you cannot sit still. You feel the compulsion to keep moving or pacing about. Akathisia is uncomfortable but not dangerous.
In rare instances amoxapine can also cause symptoms that mimic Parkinson’s disease. Symptoms include passive inactivity, a “pill-rolling” tremor of the thumb and fingers while at rest, decreased swinging of the arms when walking, stiffness, stooped posture, and others. If these symptoms develop, notify your doctor right away. She or he will probably want you to stop the drug and try an alternative medication. Although alarming, these symptoms are not dangerous and should disappear when you stop taking the amoxapine.
However, a more serious side effect of amoxapine (as well as many other antipsychotic drugs) is called “tardive dyskinesia.” Patients with tardive dyskinesia develop involuntary, repetitious movements of the face, especially the lips and tongue. The abnormal movements can also involve the arms and legs. Once it begins, tardive dyskinesia sometimes becomes irreversible or difficult to treat. The risk appears to be the highest among elderly women, but it can occur with any patient. The risk of tardive dyskinesia also increases the longer you have been on the drug, but it can develop after only a brief period of treatment at a low dose.
Table 20–3.
Side Effects of Tetracyclic Antidepressants
a
a
The + to + + + ratings in this table refer to the likelihood that a particular side effect will develop. The actual intensity of the side effect will vary among individuals and will also depend on how large the dose is. Reducing the dose can often reduce side effects without reducing effectiveness.
b
EPS = extrapyramidal symptoms (described in text) including akathisia and dystonic reactions and tardive dyskinesia.
C
NMS = neuroleptic malignant syndrome. This is a potentially fatal reaction that also occurs in reaction to antipsychotic drugs (also known as neuroleptics). The symptoms include increased fever, rigid muscles, altered mental status, irregular pulse or blood pressure, rapid heart, profuse sweating, and abnormal heart rhythms.
Finally, as if that weren’t enough to frighten you, amoxapine can, in rare cases, cause a dreaded complication known as neuroleptic malignant syndrome, or NMS. NMS consists of high fever, delirium, and muscle rigidity, along with changes in blood pressure, heart rate and rhythm, and sometimes death. All these risks should obviously be carefully balanced against any potential benefits of amoxapine; it may sometimes be difficult to justify using this medication when so many equally effective and safer drugs are readily available.
Tricyclic and Tetracyclic Antidepressant (TCA) Drug Interactions
. I described the problem of drug interactions in Chapter 19. Briefly, when you are taking more than one drug, there is a possibility that the drugs may interact in ways that will be detrimental to you. One drug may cause the level of the second drug to increase or decrease in your blood. As a result, the second drug may cause excessive side effects (if its blood level gets too high) or it may become ineffective (if its blood level falls). In addition, sometimes the interaction of two drugs can lead to toxic reactions that are quite dangerous.
A number of drug interactions for the tricyclic and tetracyclic antidepressants are listed in Table 20–4 on pages 540–547. This list is not comprehensive, but it does include many of the more common or important interactions. If you are taking any other medications along with a TCA, it would be wise to review this table. Note that both prescription and nonprescription drugs are listed, including many psychiatric and nonpsychiatric drugs as well. In addition,
you should ask your physician and pharmacist if there are any drug interactions among the drugs you are taking.
You can see in Table 20–4 that smoking cigarettes and drinking alcohol can both cause the blood level of a TCA to fall, thus reducing the likelihood that the drug will be effective. Your doctor may need to do a blood test to find out if your blood level is adequate. In addition, alcohol can enhance the sedative effects of the tricyclic antidepressants, a combination that can be quite hazardous if you are driving or operating dangerous machinery.
Certain antidepressants can be particularly hazardous for individuals with specific medical conditions. In particular, the tricyclics can be dangerous to individuals with cardiovascular disease, including those with a previous heart attack, abnormalities in heart rhythm, or high blood pressure. Special precautions should also be taken for individuals with thyroid disease. Make sure you mention any medical problems you have to the doctor who is prescribing your antidepressant so that she or he can take the proper precautions.
As noted above, several of the tricyclic and tetracyclic antidepressants can cause seizures in rare instances. An incidence of seizures as high as 1 percent to 3 percent has been reported with clomipramine, imipramine, and maprotiline.
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These estimates may be overly high. At any rate, the risk can be reduced by making sure the dose is not excessive and by raising the dose gradually. Nevertheless, these drugs should be used with caution, if at all, in individuals with a history of seizure disorders, head trauma, or other neurologic disorders associated with seizures. In addition, caution should be used if these drugs are combined with other drugs that can lower the seizure threshold, such as the major tranquilizers (neuroleptics) and others. Rapid withdrawal from sedative agents, such as alcohol, minor tranquilizers, and barbiturates can also trigger seizures, and so clomipramine, imipramine, and maprotiline should be used with great caution in combination with these agents.
Table 20–4.
Drug Interaction Guide for Tricyclic and Tetracyclic Antidepressants (TCAs)
a
Note: | |
Antidepresssants | |
Drug | Comment |
tricyclic and tetracyclic antidepressants | desipramine causes an ↑ in other TCAs—abnormal heart rhythms can result |
SSRIs | TCA levels can ↑ (as much as 2- to 10-fold); abnormal heart rhythms can result; SSRI levels can also ↑ |
MAOIs | serotonin syndrome |
serotonin antagonists, | nefazodone may cause low blood pressure |
bupropion (Wellbutrin) | ↑ in risk of seizures; extreme caution required |
venlafaxine (Effexor) | probably okay; in theory TCA could cause ↑ in venlafaxine blood levels |
mirtazapine (Remeron) | information not yet available |
Antibiotics | |
Drug | Comment |
chloramphenicol (Chloromycetin) | TCA levels and toxicity may ↑ |
doxycycline (Vibramycin) | TCA levels and effectiveness may ↓ |
isoniazid (INH, Nydrazid) | TCA levels and toxicity may ↑ |
Antifungal Agents | |
Drug | Comment |
imidazoles | TCA levels may ↑, especially nortriptyline |
griseofulvin (Fulvicin) | TCA levels may ↓ |
Diabetes Medications | |
Drug | Comment |
insulin | greater-than-expected drop in blood sugar |
oral hypoglycemic drugs | greater-than-expected drop in blood sugar |
Medical Conditions | |
Condition | Comment |
glaucoma | highly anticholinergic TCA can trigger attacks of narrow-angle glaucoma; symptoms include eye pain, blurred vision, and halos around lights |
heart disease | use TCA with extreme caution; may trigger abnormal heart rhythms |
liver disease | use TCA with caution; the metabolism by the liver may be impaired, with excessively high blood levels and increased side effects and toxic effects |
seizure disorder | use TCA with caution; TCA may cause ↑ in seizures (TCA lowers the seizure “threshold”) |
thyroid disease | use TCA with caution in patients with thyroid disease or those taking thyroid medication; may trigger abnormal heart rhythms |
Medications for Abnormal Heart Rhythms | |
Drug | Comment |
disopyramide (Norpace) | abnormal heart rhythms |
epinephrine | TCA may enhance the effects, leading to rapid heart, abnormal heart rhythms, and ↑ in BP |
quinidine | blood levels of quinidine and TCA may ↑; abnormal heart rhythms and weakened heart muscle can lead to congestive heart failure |
Medications for High Blood Pressure | |
Drug | Comment |
beta-blockers | beta-blockers may cause increased depression; TCA may cause greater-than-expected drop in BP |
clonidine (Catapres) | TCA [e.g., desipramine (Norpramin)] may reduce effectiveness of clonidine because blood levels ↓ |
calcium channel blockers | BP drop may be greater than expected |
guanethidine (Ismelin) | may lose antihypertensive effect when combined with TCA [e.g., desipramine (Norpramin)] |
methyldopa (Aldomet) | BP drop may be greater than expected, especially with amitriptyline (Elavil); some TCAs [e.g., desipramine (Norpramin)] may reduce the antihypertensive effect |
prazosin (Minipress) | BP may ↑ because levels of prazosin may ↓ |
reserpine (Serpasil) | may cause greater-than-expected drop in BP; may also cause excessive stimulation |
thiazide diuretics | blood-pressure drop may be greater than expected; effects of TCA may increase |
Medications for Low Blood Pressure (for patients in shock) | |
Drug | Comment |
epinephrine | TCA may enhance the effects, leading to rapid heart, abnormal heart rhythms, and ↑ in BP |
Mood Stabilizers and Anticonvulsants | |
Drug | Comment |
carbamazepine (Tegretol) | blood levels of TCA and carbamazepine may ↓; TCA can make seizures more likely |
lithium (Eskalith) | may enhance antidepressant effects |
phenytoin (Dilantin) | blood levels of TCA may ↑ or ↓; TCA can make seizures more likely |
valproic acid (Depakene) | ↑ in blood levels of amitriptyline (Elavil) and valproic acid |
Pain Medications and Anesthetics | |
Drug | Comment |
acetaminophen (Tylenol) | TCA levels may ↑; acetaminophen levels may ↓ |
aspirin | TCA levels may ↑ |
halothane (Fluothane) | TCA levels may ↑; TCA with strong anticholinergic effects may cause abnormal heart rhythms |
cyclobenzaprine (Flexeril) | may cause abnormal heart rhythms |
methadone (Dolophine) | may have greater-than-expected narcotic effect; for example, desipramine (Norpramin) may double the blood level of methadone |
meperidine (Demerol) | greater-than-expected narcotic effect; lower doses of meperidine or another painkiller may be needed |
morphine (MS Contin) | greater-than-expected narcotic effect and sedation; TCA levels may ↓ |
pancuronium (Pavulon) | abnormal heart rhythms, especially TCA with strong anticholinergic effects |
Sedatives and Tranquilizers | |
Drug | Comment |
alcohol | May have enhanced sedative effects. This could be hazardous when driving or operating dangerous machinery. May cause TCA levels to ↓ |
barbiturates | enhanced sedative effects; may cause TCA levels to ↓ |
buspirone (BuSpar) | enhanced sedative effects as described above |
chloral hydrate (Noctec) | TCA levels may ↓ |
ethchlorvynol (Placidyl) | Temporary mental confusion has been reported when combined with amitriptyline (Elavil), but could conceivably occur with other TCAs as well |
major tranquilizers (neuroleptics) | levels of TCA and phenothiazine neuroleptics [such as chlorpromazine (Thorazine)] may ↑, leading to more side effects and greater potency; abnormal heart rhythms have been observed with thioridazine (Mellaril), clozapine (Clozaril), and pimozide (Orap) |
minor tranquilizers (neuroleptics) | enhanced sedative effects |
Stimulants (Pep Pills) and Street Drugs | |
Drug | Comment |
amphetamines cocaine benzedrine benzphetamine (Didrex) dextroamphetamine (Dexedrine) methamphetamine (Desoxyn) methylphenidate (Ritalin) | These drugs may boost the blood levels and effects of some TCA [(e.g., imipramine (Tofranil), clomipramine (Anafranil), desipramine (Norpramin)] and vice versa; abnormal heart rhythms and increased blood pressure have been observed with cocaine. but seem possible when any stimulants are combined with TCA |
Weight-Loss and Appetite-Suppression Medications | |
Drug | Comment |
fenfluramine (Pondimin) | Possible serotonin syndrome when combined with clomipramine; increased TCA levels |
Other Medications | |
Drug | Comment |
antihistamines | increased drowsiness; it is safer to use antihistamines that are not sedative |
acetazolamide (Diamox) | TCA blood levels may ↑; blood pressure may fall |
birth control pills | TCA blood levels may ↑, with greater side effects; higher doses of estrogen may reduce the effects of TCA |
caffeine | TCA blood levels may ↑ |
charcoal tablets | TCA blood levels may ↓ due to poor absorption from the stomach and intestinal tract |
cholestyramine (Questran) | TCA blood levels may ↓ |
cimetidine (Tagamet) | TCA blood levels may ↑ (greater side effects) |
disulfiram (Antabuse) | TCA blood levels may ↑ (greater side effects); in two reported cases, disulfiram plus amitriptyline (Elavil) caused a severe brain reaction (organic brain syndrome) with mental confusion and disorientation |
ephedrine | TCA may block the ↑ in BP ordinarily caused by ephedrine; ephedrine levels and effects may ↓ |
high fiber diet | TCA blood levels may ↓ due to poor absorption from the stomach and intestinal tract |
liothyronine (T3, Cytomel) | can enhance the effects of TCA; abnormal heart rhythms can result; TCA blood levels may ↑ |
Drug | Comment |
prochlorperazine (Compazine) | TCA blood levels may ↑ with increased side effects and toxic effects |
psyllium (Metamucil) | TCA blood levels may ↓ due to poor absorption from the stomach and intestinal tract |
scopolamine (Transderm) | may cause ↑ in TCA blood levels |
L-dopa (Sinemet) | absorption of TCA from the stomach and intestinal tract into the blood may ↓; effects of both TCA and L-dopa may ↓ |
theophylline (Bronkaid) | TCA blood levels may ↑ |
tobacco (smoking) | TCA blood levels may ↓ |