Imipramine Disease Interactions

Tricyclic and tetracyclic antidepressants (TCAs) have anticholinergic activity, to which elderly patients are particularly sensitive. Tertiary amines such as amitriptyline and trimipramine tend to exhibit greater anticholinergic effects than other agents in the class. Therapy with TCAs should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. In patients with angle-closure glaucoma, even average doses can precipitate an attack. Glaucoma should be treated and under control prior to initiation of therapy with TCAs, and intraocular pressure monitored during therapy.

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Tricyclic and tetracyclic antidepressants (TCAs) may cause orthostatic hypotension, reflex tachycardia, syncope, and dizziness, particularly during initiation of therapy or rapid escalation of dosage. Imipramine appears to have the greatest propensity to induce these effects, while secondary amines such as nortriptyline may do so less frequently. Tolerance to the hypotensive effects often develops after a few doses to a few weeks. Rarely, collapse and sudden death have occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include tachycardia, arrhythmias, heart block, hypertension, thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with TCAs should be avoided during the acute recovery phase following myocardial infarction, and should be administered only with extreme caution in patients with hyperthyroidism, a history of cardiovascular or cerebrovascular disease, or a predisposition to hypotension. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. Many of the newer antidepressants, including bupropion and the selective serotonin reuptake inhibitors (SSRIs), are considerably less or minimally cardiotoxic and may be appropriate alternatives.

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Tricyclic and tetracyclic antidepressants (TCAs) may potentiate the effects of circulating catecholamines. Enhanced sympathetic activity can provoke hypertensive crises in patients with pheochromocytoma or other tumors of the adrenal medulla, such as some neuroblastomas. Therapy with TCAs should be administered cautiously in patients with these tumors.

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The use of most tricyclic antidepressants is contraindicated in patients that are going through the acute recovery period after a myocardial infarction.

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Tricyclic antidepressants should be used with extreme caution in patients with evidence of cardiovascular disease because of the possibility of fluctuations in the blood pressure, arrhythmias, conduction defects, tachycardia, myocardial infarction and stroke. This also applies to patients who have family history of sudden death, cardiac dysrhythmias, or conduction disturbances. In some cases a gradual dose titration is recommended.

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Tricyclic antidepressants (TCAs), can lower the seizure threshold and trigger seizures. These drugs should be used with extreme caution in patients with a history of seizures, or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism. Daily dose restrictions might apply for specific antidepressants. Physicians are encouraged to get additional dosing recommendations on the manufacturer's prescribing information.

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The use of tricyclic and tetracyclic antidepressants (TCAs) has rarely been associated with bone marrow suppression. Leukopenia, agranulocytosis, thrombocytopenia, anemia, eosinophilia, purpura, and pancytopenia have been reported with some TCAs. Patients with preexisting bone marrow suppression or blood dyscrasias receiving TCAs should be monitored closely during therapy for further decreases in blood counts.

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Both elevation and lowering of blood sugar levels have been reported with the use of some tricyclic antidepressants (TCAs). Rarely, these effects have also occurred with maprotiline, a tetracyclic antidepressant. Patients with diabetes should be monitored for worsening control of blood glucose when treated with these agents, particularly during dosage escalation or whenever dosage has been altered.

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Tricyclic and tetracyclic antidepressants (TCAs) are known to undergo metabolism in the liver. Some of the metabolites, such as those of imipramine, clomipramine and desipramine, may be pharmacologically active. Many of the metabolites are also excreted by the kidney. There are very limited data concerning the use of TCAs in patients with renal and/or liver disease. Therapy with TCAs should be administered cautiously in patients with significantly impaired renal or hepatic function. Dosage adjustments may be necessary.

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Tricyclic antidepressants (TCAs) may aggravate symptoms of psychosis in schizophrenic patients, particularly those with paranoid symptomatology. Depressed patients, usually those with bipolar disorder, may experience a switch from depression to mania or hypomania. These occurrences have also been reported rarely with the tetracyclic antidepressant, maprotiline. Therapy with these agents should be administered cautiously in patients with schizophrenia, bipolar disorder, or a history of mania.

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Tricyclic and tetracyclic antidepressants (TCAs) have anticholinergic activity, to which elderly patients are particularly sensitive. Tertiary amines such as amitriptyline and trimipramine tend to exhibit greater anticholinergic effects than other agents in the class. As with other drugs that possess anticholinergic activity, TCAs may aggravate tardive dyskinesia or induce previously suppressed symptoms. Patients with tardive dyskinesia requiring therapy with TCAs should be monitored for exacerbation of the condition.

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Tricyclic antidepressants can enhance the response to alcohol. In patients who may use alcohol excessively, it should be borne in mind that the potentiation may increase the danger inherent in any suicide attempt or overdosage.

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A major depressive episode can be the initial presentation of bipolar disorder. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment with a tricyclic antidepressant. This screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that tricyclic antidepressants are not approved for use in treating bipolar depression.

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Tricyclic antidepressants as other type of antidepressants have an effect on pupil size causing dilation. This effect can potentially narrow the eye angle resulting in increased intraocular pressure and angle closure glaucoma, especially in predisposed patients. These drugs should be used with caution in patients with anatomically narrow angle or history of glaucoma. Doxepin hydrochloride capsules are contraindicated in patients with glaucoma.

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There have been reports of both elevation and lowering of blood sugar levels in patients receiving tricyclic antidepressants. These drugs should be used with caution in patients with hypoglycemia, hyperglycemia or diabetes. Monitoring sugar levels is recommended.

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In general, tricyclic antidepressants should be used with caution in patients with liver or renal disease, as these drugs are metabolized and excreted through the liver and kidneys. Dose selection, especially in the elderly patients that might have liver or renal dysfunction, should usually be limited to the smallest effective total daily dose. Some tricyclic antidepressants such as clomipramine and nortriptyline have occasionally been associated with elevations in SGOT (AST) and SGPT (ALT), and other hepatic adverse events such as jaundice. Although serious liver injury has only been reported rarely, therapy with these drugs should be administered cautiously in patients with preexisting liver disease and periodic monitoring of liver enzyme levels is recommended.

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The use of some tricyclic antidepressants has been associated with neutropenia (ANC < 500/mm3) and agranulocytosis (ANC < 500/mm3). Leukocyte and differential blood counts should be performed in patients that develop fever and sore throat during treatment. Therapy should be discontinued if there is evidence of pathologic neutrophil depression.

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Some tricyclic antidepressants have shown to cause activation or exacerbation of psychosis in schizophrenic patients. A dosage reduction might be required.

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Most tricyclic antidepressants should be administered with caution in hyperthyroid patients or those receiving thyroid medication as they may develop arrhythmias when these drugs are given.

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Due to their anticholinergic properties, tricyclic antidepressants should be administered with caution in patients with history of urinary retention. Particularly doxepin hydrochloride capsules are contraindicated in patients with tendency to urinary retention.

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