Adverse Findings Observed in Short-Term, Placebo-Controlled Trials
Systematically collected data are available from only 86 patients exposed to Marplan, of whom only 52 received doses of ≥50 mg/day, including only 11 who were dosed at ≥60 mg/day. Because of the limited experience with systematically monitored patients receiving Marplan at the higher end of the currently recommended dose range of up to 60 mg/day, caution is indicated in patients for whom a dose of 40 mg/day is exceeded (see WARNINGS).
The table that follows enumerates the incidence, rounded to the nearest percent, of treatment emergent adverse events that occurred among 86 depressed patients who received Marplan at doses ranging from 20 to 80 mg/day in placebo-controlled trials of 6 weeks in duration. Events included are those occurring in 1% or more of patients treated with Marplan and for which the incidence in patients treated with Marplan was greater than the incidence in placebo-treated patients.
The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.
The commonly observed adverse event that occurred in Marplan patients with an incidence of 5% or greater and at least twice the incidence in placebo patients were nausea, dry mouth, and dizziness (see Table).
In three clinical trials for which the data were pooled, 4 of 85 (5%) patients who received placebo, 10 of 86 (12%) who received <50 mg of Marplan per day, and 1 of 52 (2%) who received ≥50 mg of Marplan per day prematurely discontinued treatment. The most common reasons for discontinuation were dizziness, orthostatic hypotension, syncope, and dry mouth.
Treatment-Emergent Adverse Events Incidence in Placebo-Controlled Clinical Trials with Marplan Doses of 40 to 80 mg/day21
|PLACEBO (N=85)||MARPLAN <50 mg (N=86)||MARPLAN ≥50 mg (N=52)22|
|Central Nervous System|
Other Events Observed During the Postmarketing Evaluation of Marplan
Isolated cases of akathisia, ataxia, black tongue, coma, dysuria, euphoria, hematologic changes, incontinence, neuritis, photosensitivity, sexual disturbances, spider telangiectases, and urinary retention have been reported. These side effects sometimes necessitate discontinuation of therapy. In rare instances, hallucinations have been reported with high dosages, but they have disappeared upon reduction of dosage or discontinuation of therapy. Toxic amblyopia was reported in one psychiatric patient who had received isocarboxazid for about a year; no causal relationship to isocarboxazid was established. Impaired water excretion compatible with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported.
Rediscover efficacy in Treatment-Resistant* Major Depression
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*Treatment failure with first-line antidepressants.
Please see Full Prescribing Information including BOXED WARNINGS regarding increased risk of suicidality in children and adolescents. MAO Inhibitors are contraindicated with certain drugs. Potential hypertensive crises may occur with foods that contain tyramine. As with all antidepressants, patients should be observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of treatment.
Suicidality and Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Marplan® (isocarboxazid) Tablets 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. Marplan® (isocarboxazid) Tablets is not approved for use in pediatric patients. (See Warnings: Clinical Worsening and Suicide Risk, Precautions: Information for Patients, and Precautions: Pediatric Use).
Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of 9 antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.