Amoxapine
Amoxapine
Definition
Amoxapine is an oral dibenzoxazepine-derivative tricyclic antidepressant. Formerly sold in the United States under the brand name Asendin, it is now manufactured and sold only under its generic name.
Purpose
Amoxapine is used primarily to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants of this chemical and pharmacological class, amoxapine has also been used in limited numbers of patients to treat panic disorder, obsessive-compulsive disorder, attention deficit/hyperactivity disorder, enuresis (bed-wetting), eating disorders such as bulimia nervosa , cocaine dependency, and the depressive phase of bipolar (manic-depressive) disorder. It has also been used to support smoking cessation programs.
Description
Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Amoxapine acts primarily by increasing the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, by blocking the action of another brain chemical, acetylcholine. Amoxapine shares most of the properties of other tricyclic antidepressants, such as amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline, and trimipramine. Studies comparing amoxapine with these other drugs have shown that amoxapine is no more or less effective than other antidepressants of its type. Its choice for treatment is as much a function of physician preference as any other factor.
The therapeutic effects of amoxapine, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug. People taking amoxapine should be aware of this and continue taking the drug as directed even if they do not see immediate improvement.
Recommended dosage
As with any antidepressant, amoxapine must be adjusted by the physician to produce the desired therapeutic effect. Amoxapine is available as 25-mg, 50-mg, 100-mg, and 150-mg oral tablets. Therapy is usually started at 100 to 150 mg per day and increased to 200 to 300 mg daily by the end of the first week. If no improvement is seen at this dose after two weeks, the physician may increase the dose up to 400 mg per day in outpatients and up to 600 mg per day in hospitalized patients. Doses up to 300 mg may be given in single or divided doses. Doses of more than 300 mg per day should be divided in two or three doses daily.
Because of changes in drug metabolism of older patients, starting at about age 60, the initial dose of amoxapine should be adjusted downward to 50 to 75 mg per day and increased to 100 to 150 mg daily by the end of the first week. Some older patients may require up to 300 mg daily, but doses should never be increased beyond that.
Precautions
Like all tricyclic antidepressants, amoxapine should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy, urinary retention, and glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if amoxapine is the right antidepressant for them.
A common problem with tricyclic antidepressants is sedation (drowsiness, lack of physical and mental alertness). This side effect is especially noticeable early in therapy. In most patients, sedation decreases or disappears entirely with time, but until then patients taking amoxapine should not perform hazardous activities requiring mental alertness or coordination.
The sedative effect is increased when amoxapine is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take amoxapine in combination with these substances. Amoxapine may increase the possibility of having seizures. Patients should tell their physician if they have a history of seizures, including seizures brought on by the abuse of drugs or alcohol. These people should use amoxapine only with caution and be closely monitored by their physician.
Amoxapine may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases where patients with cardiovascular disease must receive amoxapine, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.
Side effects
Amoxapine shares side effects common to all tri-cyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, and decreased coordination. As with most side effects associated with tricyclic antidepressants, the intensity is highest at the beginning of therapy and tends to decrease with continued use.
Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.
Men with prostate enlargement who take amoxapine may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect. People who think they may be experiencing any side effects from this or any other medication should tell their physicians.
Interactions
Dangerously high blood pressure has resulted from the combination of tricyclic antidepressants, such as amoxapine, and members of another class of antidepressants known as monoamine oxidase inhibitors (MAOI). Because of this, amoxapine should never be taken in combination with MAOIs. Patient taking any MAOIs, for example Nardil (phenelzine sulfate) or Parmate (tranylcypromine sulfate), should stop the MAOI then wait at least 14 days before starting amoxapine or any other tricyclic antidepressant. The same holds true when discontinuing amoxapine and starting an MAOI.
KEY TERMS
Acetylcholine —A naturally occurring chemical in the body that transmits nerve impulses from cell to cell. Generally, it has opposite effects from dopamine and norepinephrine; it causes blood vessels to dilate, lowers blood pressure, and slows the heartbeat. Central nervous system well-being is dependent on a balance among acetylcholine, dopamine, serotonin, and norepinephrine.
Anticholinergic —Related to the ability of a drug to block the nervous system chemical acetylcholine. When acetylcholine is blocked, patients often experience dry mouth and skin, increased heart rate, blurred vision, and difficulty urinating. In severe cases, blocking acetylcholine may cloud thinking and cause delirium.
Benign prostate hypertrophy —Enlargement of the prostate gland.
Norepinephrine —A neurotransmitter in the brain that acts to constrict blood vessels and raise blood pressure. It works in combination with serotonin.
Serotonin —A widely distributed neurotransmitter that is found in blood platelets, the lining of the digestive tract, and the brain, and that works in combination with norepinephrine. It causes very powerful contractions of smooth muscle, and is associated with mood, attention, emotions, and sleep. Low levels of serotonin are associated with depression.
Amoxapine may decrease the blood pressure-lowering effects of clonidine. Patients who take both drugs should be monitored for loss of blood-pressure control and the dose of clonidine increased as needed.
The sedative effects of amoxapine are increased by other central nervous system depressants such as alcohol, sedatives, sleeping medications, or medications used for other mental disorders such as schizophrenia. The anticholinergic effects of amoxapine are additive with other anticholinergic drugs such as benztropine, biperiden, trihexyphenidyl, and antihistamines.
See alsoNeurotransmitters.
Resources
BOOKS
American Society of Health-System Pharmacists. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002.
DeVane, C. Lindsay, Pharm.D. “Drug Therapy for Mood Disorders.” In Fundamentals of Monitoring Psychoactive Drug Therapy. Baltimore: Williams and Wilkins, 1990.
Jack Raber, Pharm.D.
Amoxapine
Amoxapine
Definition
Amoxapine is an oral tricyclic antidepressant. Formerly sold in the United States under the brand name Asendin, it is now manufactured and sold only under its generic name.
Purpose
Amoxapine is used primarily to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants of this chemical and pharmacological class, amoxapine has also been used in limited numbers of patients to treat panic disorder , obsessive-compulsive disorder , attention-deficit/hyperactivity disorder , enuresis (bed-wetting), eating disorders such as bulimia nervosa , cocaine dependency, and the depressive phase of bipolar (manic-depressive) disorder. It has also been used to support smoking cessation programs.
Description
Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Amoxapine acts primarily by increasing the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, by blocking the action of another brain chemical, acetylcholine. Amoxapine shares most of the properties of other tricyclic antidepressants, such as amitriptyline , clomipramine , desipramine , imipramine , nortriptyline , protriptyline , and trimipramine . Studies comparing amoxapine with these other drugs have shown that amoxapine is no more or less effective than other antidepressants of its type. Its choice for treatment is as much a function of physician preference as any other factor.
The therapeutic effects of amoxapine, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug. People taking amoxapine should be aware of this and continue taking the drug as directed even if they do not see immediate improvement.
Recommended dosage
As with any antidepressant, amoxapine must be adjusted by the physician to produce the desired therapeutic effect. Amoxapine is available as 25-mg, 50-mg, 100-mg, and 150-mg oral tablets. Therapy is usually started at 100 to 150 mg per day and increased to 200 to 300 mg daily by the end of the first week. If no improvement is seen at this dose after two weeks, the physician may increase the dose up to 400 mg per day in outpatients and up to 600 mg per day in hospitalized patients. Doses up to 300 mg may be given in single or divided doses. Doses of more than 300 mg per day should be divided in two or three doses daily.
Because of changes in drug metabolism of older patients, starting at about age 60, the initial dose of amoxapine should be adjusted downward to 50 to 75 mg per day and increased to 100 to 150 mg daily by the end of the first week. Some older patients may require up to 300 mg daily, but doses should never be increased beyond that.
Precautions
Like all tricyclic antidepressants, amoxapine should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy, urinary retention, and glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if amoxapine is the right antidepressant for them.
A common problem with tricyclic antidepressants is sedation (drowsiness, lack of physical and mental alertness). This side effect is especially noticeable early in therapy. In most patients, sedation decreases or disappears entirely with time, but until then patients taking amoxapine should not perform hazardous activities requiring mental alertness or coordination. The sedative effect is increased when amoxapine is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take amoxapine in combination with these substances. Amoxapine may increase the possibility of having seizures . Patients should tell their physician if they have a history of seizures, including seizures brought on by the abuse of drugs or alcohol. These people should use amoxapine only with caution and be closely monitored by their physician.
Amoxapine may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases in which patients with cardiovascular disease must receive amoxapine, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.
Side effects
Amoxapine shares side effects common to all tricyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, and decreased coordination. As with most side effects associated with tricyclic antidepressants, the intensity is highest at the beginning of therapy and tends to decrease with continued use.
Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.
Men with prostate enlargement who take amoxapine may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect. People who think they may be experiencing any side effects from this or any other medication should tell their physicians.
Interactions
Dangerously high blood pressure has resulted from the combination of tricyclic antidepressants, such as amoxapine, and members of another class of antidepressants known as monoamine oxidase (MAO) inhibitors. Because of this, amoxapine should never be taken in combination with MAO inhibitors. Patient taking any MAO inhibitors, for example Nardil (phenelzine sulfate) or Parmate (tranylcypromine sulfate), should stop the MAO inhibitor then wait at least 14 days before starting amoxapine or any other tricyclic antidepressant. The same holds true when discontinuing amoxapine and starting an MAO inhibitor.
Amoxapine may decrease the blood pressure–lowering effects of clonidine . Patients who take both drugs should be monitored for loss of blood-pressure control and the dose of clonidine may be increased as needed.
The sedative effects of amoxapine are increased by other central nervous system depressants such as alcohol, sedatives, sleeping medications, or medications used for other mental disorders such as schizophrenia . The anticholinergic effects of amoxapine are additive with other anticholinergic drugs such as benztropine , biperiden , trihexyphenidyl , and antihistamines.
Resources
BOOKS
American Society of Health-System Pharmacists. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002.
DeVane, C. Lindsay, Pharm.D. "Drug Therapy for Mood Disorders." In Fundamentals of Monitoring Psychoactive Drug Therapy. Baltimore: Williams and Wilkins, 1990.
Jack Raber, Pharm.D.