"What are tricyclic antidepressants, and how do they work?
Tricyclic antidepressants (TCAs) are a class of antidepressant medications that share a similar chemical structure and biological effects. Scientists believe that patients "...
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Details with Side Effects
Adverse reactions reported in controlled studies in the United States are categorized with respect to incidence below. Following this is a listing of reactions known to occur with other antidepressant drugs of this class.
Incidence Greater Than 1%
The most frequent types of adverse reactions occurring with amoxapine (amoxapine (amoxapine tablets) tablets) in controlled clinical trials were sedative and anticholinergic: these included drowsiness (14%), dry mouth (14%), constipation (12%), and blurred vision (7%).
Less frequently reported reactions are:
Endocrine: elevation of prolactin levels.
Incidence Less Than 1%
CNS and Neuromuscular: tingling, paresthesias of the extremities, tinnitus, disorientation, seizures, hypomania, numbness, incoordination, disturbed concentration, hyperthermia, extrapyramidal symptoms, including, tardive dyskinesia. Neuroleptic malignant syndrome has been reported. (See WARNINGS.)
Drug Relationship Unknown
The following reactions have been reported rarely, and occurred under uncontrolled circumstances where a drug relationship was difficult to assess. These observations are listed to serve as alerting information to physicians.
Anticholinergic: paralytic ileus.
CNS and Neuromuscular: hallucinations.
Gastrointestinal: parotid swelling.
Endocrine: change in blood glucose levels.
Additional Adverse Reactions
The following reactions have been reported with other antidepressant drugs.
CNS and Neuromuscular: delusions.
Gastrointestinal: stomatitis, black tongue.
Read the Amoxapine (amoxapine tablets) Side Effects Center for a complete guide to possible side effects
See CONTRAINDICATIONS about concurrent usage of tricyclic antidepressants and monoamine oxidase inhibitors. Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic drugs. Amoxapine (amoxapine (amoxapine tablets) tablets) may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. Serum levels of several tricyclic antidepressants have been reported to be significantly increased when cimetidine is administered concurrently. Although such an interaction has not been reported to date with amoxapine (amoxapine (amoxapine tablets) tablets) , specific interaction studies have not been done, and the possibility should be considered.
Drugs Metabolized by P450 2D6
The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of caucasians are so called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).
In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).
Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.
Concurrent administration with electroshock therapy may increase the hazards associated with such therapy.
Last reviewed on RxList: 7/1/2008
This monograph has been modified to include the generic and brand name in many instances.
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