Maprotiline

Maprotiline
	Black Box Warning
	Adult Indications & Dosage
	Pediatric Indications & Dosage
	Contraindications
	Warnings & Precautions
	Adverse Reactions
	Drug Interactions
	Use in Specific Populations
	Administration & Monitoring
	Overdosage
	Pharmacology
	Clinical Studies
	How Supplied
	Images
	Patient Counseling Information
	Precautions with Alcohol
	Brand Names
	Look-Alike Names

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Black Box Warning

Suicidality and Antidepressant Drugs

See full prescribing information for complete Boxed Warning.

Condition Name: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of maprotiline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Maprotiline is not approved for use in pediatric patients. (See warning: Clinical Worsening and Suicide Risk, precautions: Information for Patients and precautions: Pediatric Use.)

Overview

Maprotiline is a tetracyclic antidepressant that is FDA approved for the {{{indicationType}}} of bipolar disorder, depressed phase, depression, dysthymia, mixed anxiety and depressive disorder. There is a Black Box Warning for this drug as shown here. Common adverse reactions include constipation, xerostomia, dizziness , feeling nervous , myoclonus, somnolence, blurred vision, visual disturbance.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Bipolar disorder, depressed phase

Outpatients: 75 mg/day PO (2-3 divided doses) for 2 weeks; may increase in 25 mg increments up to a max of 225 mg/day in single or divided doses
Inpatients: 100-150 mg/day PO (2-3 divided doses) for 2 weeks; may increase in 25 mg increments up to a max of 225 mg/day in single or divided doses
Maintenance: 75-150 mg/day PO in single or divided doses

Depression

75 mg/day PO (2-3 divided doses) for 2 weeks; increase in 25 mg increments up to a max of 225 mg/day in single or divided doses
Inpatients: 100-150 mg/day PO (2-3 divided doses) for 2 weeks, increase in 25 mg increments up to a max of 225 mg/day in single or divided doses
Maintenance: 75-150 mg/day ORALLY in single or divided doses

Dysthymia

75 mg/day PO (2-3 divided doses) for 2 weeks, increase in 25 mg increments up to a max of 225 mg/day in single or divided doses
Inpatients: 100-150 mg/day PO (2-3 divided doses) for 2 weeks; may increase in 25 mg increments up to a MAX of 225 mg/day in single or divided doses
Maintenance: 75-150 mg/day ORALLY in single or divided doses

Mixed anxiety and depressive disorder

Outpatients 75 mg/day PO (2-3 divided doses) for 2 weeks, increase in 25 mg increments up to a max of 225 mg/day in single or divided doses
Inpatients: 100-150 mg/day PO (2-3 divided doses) for 2 weeks, increase in 25 mg increments up to a max of 225 mg/day in single or divided doses
Maintenance: 75-150 mg/day ORALLY in single or divided doses

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Maprotiline in adult patients.

Non–Guideline-Supported Use

Pain

There is limited information about Off-Label Non–Guideline-Supported Use of Maprotiline in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety has not been established below 18 years of age.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Maprotiline in pediatric patients.

Non–Guideline-Supported Use

There is limited information about Off-Label Non–Guideline-Supported Use of Maprotiline in pediatric patients.

Contraindications

Contraindicated in patients hypersensitive to maprotiline and in patients with known or suspected seizure disorders.
It should not be given concomitantly with monoamine oxidase (MAO) inhibitors.
A minimum of 14 days should be allowed to elapse after discontinuation of MAO inhibitors before treatment with maprotiline is initiated.
Effects should be monitored with gradual increase in dosage until optimum response is achieved.

Not recommended for use during the acute phase of myocardial infarction.

Warnings

Suicidality and Antidepressant Drugs

See full prescribing information for complete Boxed Warning.

Condition Name: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of maprotiline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Maprotiline is not approved for use in pediatric patients. (See warning: Clinical Worsening and Suicide Risk, precautions: Information for Patients and precautions: Pediatric Use.)

Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications.

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, 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. The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for maprotiline should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Screening Patients for Bipolar Disorder

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 above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that maprotiline is not approved for use in treating bipolar depression.

Seizures have been associated with the use of maprotiline

Most of the seizures have occurred in patients without a known history of seizures. However, in some of these cases, other confounding factors were present, including concomitant medications known to lower the seizure threshold, rapid escalation of the dosage of maprotiline, and dosage that exceeded the recommended therapeutic range. The incidence of direct reports is less than 1/10 of 1%. The risk of seizures may be increased when maprotiline is taken concomitantly with phenothiazines, when the dosage of benzodiazepines is rapidly tapered in patients receiving maprotiline or when the recommended dosage of maprotiline hydrochloride is exceeded. While a cause and effect relationship has not been established, the risk of seizures in patients treated with maprotiline may be reduced by (1) initiating therapy at a low dosage, (2) maintaining the initial dosage for 2 weeks before raising it gradually in small increments as necessitated by the long half-life of maprotiline (average 51 hours), and (3) keeping the dosage at the minimally effective level during maintenance therapy. (See dosage and administration.) Extreme caution should be used when this drug is given to:

patients with a history of myocardial infarction;
patients with a history or presence of cardiovascular disease because of the possibility of conduction defects, arrhythmias, myocardial infarction, strokes and tachycardia.

General precautions

The possibility of suicide in seriously depressed patients is inherent in their illness and may persist until significant remission occurs. Therefore, patients must be carefully supervised during all phases of treatment with maprotiline, and prescriptions should be written for the smallest number of tablets consistent with good patient management. Hypomanic or manic episodes have been known to occur in some patients taking tricyclic antidepressant drugs, particularly in patients with cyclic disorders. Such occurrences have also been noted, rarely, with maprotiline. Prior to elective surgery, maprotiline should be discontinued for as long as clinically feasible, since little is known about the interaction between maprotiline and general anesthetics. Maprotiline should be administered with caution in patients with increased intraocular pressure, history of urinary retention, or history of narrow angle glaucoma because of the drug's anticholinergic properties.

Adverse Reactions

Clinical Trials Experience

Central Nervous System

Drowsiness (16%), dizziness (8%), tremor (3%), and, rarely, numbness, tingling, motor hyperactivity, akathisia, seizures, EEG alterations, tinnitus, extrapyramidal symptoms, ataxia, and dysarthria.

Cardiovascular

Rare occurrences of hypotension, hypertension, tachycardia, palpitation, arrhythmia, heart block, and syncope have been reported with maprotiline.

psychiatric

Nervousness (6%), anxiety (3%), insomnia (2%), and agitation (2%); rarely, confusional states (especially in the elderly), hallucinations, disorientation, delusions, restlessness, nightmares, hypomania, mania, exacerbation of psychosis, decrease in memory, and feelings of unreality.

Gastrointestinal

Nausea (2%) and, rarely, vomiting, epigastric distress, diarrhea, bitter taste, abdominal cramps and dysphagia.

Hypersensitive Reactions

Rare instances of skin rash, petechiae, itching, photosensitization, edema, and drug fever.

Anticholinergic

Dry mouth (22%), constipation (6%), and blurred vision (4%); rarely, accommodation disturbances, mydriasis, urinary retention, and delayed micturition.

Miscellaneous

Weakness and fatigue (4%) and headache (4%); rarely, altered liver function, jaundice, weight loss or gain, excessive perspiration, flushing, urinary frequency, increased salivation, nasal congestion and alopecia.