Side Effects of Pamelor (nortriptyline)

Pamelor (nortriptyline) is a tricyclic antidepressant (TCA) used to treat depression.

Individuals with depression may have an imbalance in neurotransmitters, chemicals that nerves make and use to communicate with other nerves. Like all TCAs, Pamelor increases levels of the neurotransmitters norepinephrine and serotonin, and blocks the action of acetylcholine, another neurotransmitter. It is believed that by restoring the balance of these different neurotransmitters in the brain depression is alleviated.

Common side effects of Pamelor include

• fast heart rate,
• blurred vision,
• urinary retention,
• dry mouth,
• constipation,
• weight gain or loss,
• low blood pressure, 
• dizziness on standing, and
• rash and hives (rare).

Serious side effects of Pamelor include

• seizures,
• hepatitis,
• elevated pressure in the eyes of some patients with glaucoma,
• life-threatening abnormal heart rhythms or seizures with overdoses, and
• increased risk of suicidal thinking and behavior in children and adolescents with depression and other psychiatric disorders.

If Pamelor is discontinued abruptly, withdrawal symptoms, such as headache, nausea, and general discomfort may occur. 

Drug interactions of Pamelor include monoamine oxidase inhibitors (MAOIs) because of the possibility of hyperpyretic crises (high fever), convulsions, and even death.

• Cimetidine, propafenone, flecainide, quinidine, and fluoxetine can increase blood levels of Pamelor in the blood by interfering with the breakdown of Pamelor by the liver.
• Increased levels of Pamelor may possibly lead to side effects.
• Pamelor exaggerates the effects of other medications and drugs that slow the activity of the brain, such as alcohol, barbiturates, benzodiazepines, and narcotics.
• Reserpine stimulates the brain when given to patients taking Pamelor.
• Combining Pamelor or other TCAs with anticholinergic drugs can cause constipation and even paralyze the intestine (paralytic ileus).
• Dangerous elevations in blood pressure may occur if TCAs are combined with clonidine.

Safe use of Pamelor during pregnancy has not been established. Doctors may use Pamelor in pregnant women if its benefits are deemed to outweigh its potential but unknown risks.

Safe use of Pamelor during lactation has not been established. It is not known if Pamelor is secreted in breast milk. Consult your doctor before breastfeeding.

The most commonly encountered side effects associated with nortriptyline include:

• Fast heart rate
• Blurred vision
• Urinary retention
• Dry mouth
• Constipation
• Weight gain or loss
• Low blood pressure on standing (orthostatic hypotension)

Rare side effects include:

• Rash
• Hives
• Seizures
• Hepatitis

Nortriptyline also can cause elevated pressure in the eyes of some patients with glaucoma.

Overdoses of nortriptyline can cause life-threatening abnormal heart rhythms or seizures.

If nortriptyline is discontinued abruptly, headache, nausea, and general discomfort may occur. Therefore, it is recommended that the dose of antidepressant be reduced gradually when therapy is discontinued.

Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children and adolescents with depression and other psychiatric disorders. Anyone considering the use of nortriptyline or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be closely observed for clinical worsening, suicidal thinking or behavior, and unusual changes in behavior.

Note

Included in the following list are a few adverse reactions that have not been reported with this specific drug. However, the pharmacologic similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when nortriptyline is administered.

Cardiovascular

Hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, stroke.

Psychiatric

Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia, panic, nightmares; hypomania; exacerbation of psychosis.

Neurologic

Numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures, alteration in EEG patterns; tinnitus.

Anticholinergic

Dry mouth and, rarely, associated sublingual adenitis; blurred vision, disturbance of accommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract.

Allergic

Skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); edema (general or of face and tongue), drug fever, cross-sensitivity with other tricyclic drugs.

Hematologic

Bone marrow depression, including agranulocytosis; eosinophilia; purpura; thrombocytopenia.

Gastrointestinal

Nausea and vomiting, anorexia, epigastric distress, diarrhea, peculiar taste, stomatitis, abdominal cramps, blacktongue.

Endocrine

Gynecomastia in the male, breast enlargement and galactorrhea in the female; increased or decreased libido, impotence; testicular swelling; elevation or depression of blood sugar levels; syndrome of inappropriate ADH (antidiuretic hormone) secretion.

Other

Jaundice (simulating obstructive), altered liver function; weight gain or loss; perspiration; flushing; urinary frequency, nocturia; drowsiness, dizziness, weakness, fatigue; headache; parotid swelling; alopecia.

Withdrawal Symptoms

Though these are not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.

Postmarketing Experience

The following adverse drug reaction has been reported during post-approval use of Pamelor. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency.

Cardiac Disorders - Brugada syndrome

Eye Disorders - angle-closure glaucoma

Administration of reserpine during therapy with a tricyclic antidepressant has been shown to produce a “stimulating” effect in some depressed patients.

Close supervision and careful adjustment of the dosage are required when Pamelor is used with other anticholinergic drugs and sympathomimetic drugs.

Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressant. The patient should be informed that the response to alcohol may be exaggerated.

A case of significant hypoglycemia has been reported in a type II diabetic patient maintained on chlorpropamide (250 mg/day), after the addition of nortriptyline (125 mg/day).

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 coadministration 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.