Amitriptyline Contraindications and Precautions
- acute myocardial infarction
- AV block
- bundle-branch block
- ileus
- intravenous administration
- QT prolongation
- tricyclic antidepressant hypersensitivity
- abrupt discontinuation
- agranulocytosis
- alcoholism
- anticholinergic medications
- asthma
- bipolar disorder
- breast-feeding
- carbamazepine hypersensitivity
- cardiac arrhythmias
- cardiac disease
- children
- closed-angle glaucoma
- contact lenses
- diabetes mellitus
- driving or operating machinery
- elderly
- gastroesophageal reflux disease (GERD)
- GI disease
- glaucoma
- hematological disease
- hepatic disease
- hyperthyroidism
- hypothyroidism
- intramuscular injections
- mania
- myocardial infarction
- Parkinson’s disease
- pregnancy
- prostatic hypertrophy
- radiographic contrast administration
- respiratory depression
- seizure disorder
- seizures
- suicidal ideation
- sunlight (UV) exposure
- surgery
- thrombocytopenia
- tobacco smoking
- urinary retention
Amitriptyline Contraindications and Precautions
Tricyclic antidepressants are known to produce an allergic response in some patients. There appears to be cross-sensitivity, and caution should be used when changing from one tricyclic antidepressant to another. Alternative therapy should be considered in those patients with tricyclic antidepressant hypersensitivity. Patients allergic to tricyclic antidepressants may also display cross-sensitivity to carbamazepine (i.e., use caution in patients with carbamazepine hypersensitivity), maprotiline, or amoxapine.
Intravenous administration of amitriptyline injection is contraindicated; the injection is for intramuscular administration only. Use intramuscular injections of amitriptyline only when the oral route is not appropriate for dosing.
Following prolonged therapy with high doses, abrupt discontinuation of the tricyclic antidepressant should be avoided because it could precipitate symptoms of cholinergic rebound such as nausea, vomiting, or diarrhea. This is particularly true for the tertiary amine tricyclic antidepressants: amitriptyline, imipramine, clomipramine, trimipramine, and doxepin.
All effective antidepressants can transform depression into mania or hypomania in predisposed individuals (e.g., some patients with bipolar disorder). If a patient develops manic symptoms, amitriptyline should be held and appropriate therapy initiated to treat the manic symptoms. Also use TCAs with caution in patients with psychotic disorders (e.g., schizophrenia), as the antidepressant may activate psychotic symptoms in some individuals.
Amitriptyline is not FDA-approved for the treatment depression in pediatric patients. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary psychiatric disorder. Patients with suicidal ideation, including both adult and pediatric patients, should be closely supervised, whether or not they are taking an antidepressant. In addition, all antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n=4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Based on these data, FDA has determined that the following points are appropriate for inclusion in the boxed warning: antidepressants increase the risk of suicidal thinking and behavior (suicidality) in pediatric patients with MDD and other psychiatric disorders (OCD, social anxiety disorder); anyone considering the use of an antidepressant in a pediatric patient for any clinical use must balance the risk of increased suicidality with the clinical need; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose increases or decreases; such observation would generally include at least weekly face-to-face contact with patients, family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks; additional contact by telephone may be appropriate between face-to-face visits; adults with MDD or co-morbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes; families and caregivers should be advised to closely observe the patient (adult or child) on a daily basis for the emergence of agitation, irritability, unusual changes in behavior, emergence of suicidality, and to communicate immediately with the prescriber. It is unknown if the suicidality risk in pediatric patients extends to longer-term therapy (i.e., beyond several months) or to adult patients. In patients who exhibit changes in symptoms (see Adverse Events), worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described represent such a conversion is unknown. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that amitriptyline is not approved for use in treating bipolar depression.
TCAs are contraindicated for concomitant use in patients receiving MAO inhibitor therapy (see Drug Interactions). The TCA should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI, to allow for return of monoamine oxidase function.
Amitriptyline can induce significant sedation, particularly during the initiation of treatment. Patients should use caution when driving or operating machinery until they are aware of the effects of the medication. Tricyclic antidepressants should be used with caution in patients with a history of alcoholism or who may use alcohol or other sedative medications because the depressant effects on the CNS can be potentiated. Decreased mental alertness can occur.
Some authors have recommended against the use of amitriptyline in the elderly because of the strong sedative and anticholinergic properties of the drug. Although manufacturers have not identified differences in clinical responses between elderly and younger adults, amitriptyline dose selection should generally be cautious in the elderly patient. Starting at the low end of the dosage range is recommended. Geriatric patients are particularly sensitive to the peripheral and central anticholinergic side effects of tricyclic antidepressants. Elderly patients taking amitriptyline may be at increased risk for falls. Slow dosage titration and careful observation are warranted in the geriatric population.
Tricyclic antidepressants should be used with caution in patients with any cardiac disease (e.g., heart failure, history of myocardial infarction), because of the alterations in ECG patterns or heart rhythm that may occur with the administration of these drugs. Although the risk of cardiovascular adverse events is higher after acute overdose, patients with cardiovascular disease should be closely monitored via ECGs and clinical exams. Amitriptyline may cause orthostatic hypotension, particularly in the initial titration of dosing. Do not administer tricyclic antidepressants to patients with QT prolongation or familial histories of long-QT syndromes or in those patients with cardiac conduction defects (e.g., cardiac arrhythmias, AV block, bundle-branch block). Many adverse cardiovascular effects are associated with the use of tricyclic antidepressant drugs, and they can lead to complete cardiac collapse and sudden death. Tricyclic antidepressants should not be given to patients who are in the acute recovery phase following acute myocardial infarction; this could cause sudden death.
The anticholinergic effects of tricyclic antidepressants contraindicate their use in patients with decreased GI motility. Tricyclic antidepressants can induce or exacerbate hiatal hernia, and can cause paralytic ileus or constipation. Patients who have increased intraocular pressure or closed-angle glaucoma, benign prostatic hypertrophy, GI disease, gastroesophageal reflux disease (GERD), or urinary retention should be treated with caution because of the anticholinergic activity of tricyclic antidepressants. The anticholinergic effects of amitriptyline may be significant and are additive with other anticholinergic medications. Anticholinergic effects appear most frequently and cause the greatest morbidity in geriatric patients.
The anticholinergic effects of amitriptyline may increase lens discomfort for wearers of contact lenses. Mydriasis, disturbance of accommodation, and dry eyes may contribute to blurred vision and lens intolerance. The use of lubricating drops may be necessary.
Tricyclic antidepressants (TCAs) should be used with extreme caution in patients with a preexisting seizure disorder because these drugs can lower the seizure threshold. If seizures occur during therapy with the tricyclic antidepressant, then the TCA should be discontinued.
Tricyclic antidepressants should be used with caution in patients with Parkinson’s disease. Tricyclic antidepressants rarely can induce or worsen extrapyramidal symptoms. In addition, involuntary movements, which appear to be similar to tardive dyskinesia, can occur.
Patients with respiratory depression should be treated cautiously with tricyclic antidepressants because of the CNS-depressant effects of this class of drugs. Asthma can be aggravated by administering tricyclic antidepressants to patients with the disease.
Tricyclic antidepressant therapy should be discontinued several days before elective surgery because of the risk of hypertensive episodes.
On rare occasions, agranulocytosis, thrombocytopenia, eosinophilia, leukopenia, or purpura have been reported with tricyclic antidepressants. Any patient with symptoms of blood dyscrasia (sore throat, fever, bruising, etc.) should have immediate laboratory studies performed and suitable therapy initiated. Use tricyclic antidepressants cautiously in patients with preexisting hematological disease.
Tricyclic antidepressants should be used with caution in patients with hepatic disease. These agents have caused hepatitis and jaundice, which are reversible on discontinuation of the drug. Hepatic failure and death have occurred when tricyclic antidepressants were continued. Liver-function tests should be performed and the drug discontinued if there is persistent elevation of enzymes. Metabolism of tricyclic antidepressants may be altered in patients with hepatic impairment.
Patients may be more prone to sunburn during therapy with a tricyclic antidepressant. Suitable precautions should be taken prior to sunlight (UV) exposure, such as wearing long-sleeved clothing and a hat, and using sunscreens.
Tricyclic antidepressants should be used with caution in patients who have hyperthyroidism or are receiving thyroid drugs. Concomitant use with thyroid drugs can produce cardiac arrhythmias. Hypothyroidism that is untreated will prevent adequate response to antidepressant therapy. Thyroid agents also can accelerate the onset of the response to tricyclic antidepressants.
Tricyclic antidepressants affect blood glucose concentrations because of their effect on the endocrine system, so they should be used with caution in patients with diabetes mellitus.
Tricyclic antidepressants lower the seizure threshold. Because of a potential increased risk of seizures, tricyclic antidepressants should not be used during intrathecal radiographic contrast administration. Tricyclic antidepressant therapy should be discontinued 48 hours before and not restarted for at least 24 hours after myelography.
Tricyclic antidepressants are not recommended for use during pregnancy, unless the possible benefits outweigh the risks. Amitriptyline is classified in FDA pregnancy risk category D. Patients should be told about the risks to the neonate: possible fetal abnormality, delayed development, or withdrawal symptoms at birth.
Because tricyclic antidepressants are excreted into breast milk, the benefits and risks of breast-feeding should be carefully weighed if tricyclic antidepressants are needed in the mother. Amitriptyline is listed by the American Academy of Pediatrics as a drug whose effect on the nursing infant is not known but may be of concern, particularly with prolonged exposure.
There is limited information on the safety and efficacy of amitriptyline in children and adolescents. In general, amitriptyline has undergone limited study as a treatment for attention-deficit-hyperactivity disorder (ADHD), enuresis, depression, and anxiety in school-age children. Amitriptyline should be used with caution in children and adolescents with a known family history of heart disease, or in children who are taking other medications concomitantly that might cause drug interactions (see Drug Interactions). QTc interval prolongation, tachycardias, and other side effects have been reported in children who have taken TCAs; there are rare reports of deaths due to cardiovascular side effects. Routine cardiovascular monitoring has been suggested for children receiving tricyclic antidepressants due to the potential of these agents to produce adverse cardiac effects. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients (see Contraindications, suicidal ideation). Pediatric patients should be monitored closely for the risk of suicide with any antidepressant medication. Among the antidepressants, only fluoxetine is approved for use in treating depression in pediatric patients. Fluoxetine, sertraline, fluvoxamine, and clomipramine are approved for OCD in pediatric patients. None of the drugs is approved for other psychiatric indications in children. Pediatric patients being treated with antidepressants for any indication should be observed daily by caregivers for clinical worsening, as well as agitation, irritability, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. If concerns arise, contact with health care providers should be made immediately. Antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. A patient medication guide about using antidepressants in children and adolescents is available for amitriptyline. Health care providers should instruct patients and caregivers to read the guide and discuss any questions with them.
Tobacco smoking has been shown to increase the clearance of TCAs by inducing hepatic microsomal enzymes. The effect of tobacco on hepatic microsomal enzymes is not related to the nicotine component, so sudden smoking cessation may result in a reduced clearance of TCAs and increased TCA effects, despite the initiation of nicotine replacement products.
[ Last revised: 1/28/2005 5:17:00 PM ]
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