The concurrent administration of a MAO inhibitor and buproprion hydrochloride (Wellbutrin® , and Zyban® , Glaxo Wellcome) is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with buproprion hydrochloride.
Marplan should not be administered in combination with any SSRI. There have been reports of serious, sometimes fatal, reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation and confusion progressing to delirium and coma) in patients receiving fluoxetine (Prozac® , Lilly) in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued fluoxetine and are then started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Fluoxetine and other SSRIs should therefore not be used in combination with Marplan, or within 14 days of discontinuing therapy with Marplan. As fluoxetine and its major metabolite have very long elimination half-lives, at least 5 weeks should be allowed after stopping fluoxetine before starting Marplan. At least 2 weeks should be allowed after stopping sertraline (Zoloft® , Pfizer) or paroxetine (Paxil® , SmithKline Beecham Pharmaceuticals) before starting Marplan. In addition, there should be an interval of least 10 days between discontinuation of Marplan and initiation or fluoxetine or other SSRIs.
Marplan should not be used in combination with buspirone HCL (Buspar® , Bristol Myers Squibb); several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone HCL. At least 10 days should elapse between the discontinuation of Marplan and the institution of buspirone HCL. Serious reactions may also occur when MAO inhibitors are given with serotoninergic drugs (e.g., dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxine).
Marplan should not be administered in combination with sympathomimetics, including amphetamines, or with over-the-counter drugs such as cold, hay fever, or weight-reducing preparations that contain vasoconstrictors.
During Marplan therapy, it appears that some patients are particularly vulnerable to the effects of sympathomimetics when the activity of metabolizing enzymes is inhibited. Use of sympathomimetics and compounds such as guanethidine, methyldopa, methylphenidate, reserpine, epinephrine, norepinephrine, phenylalanine, dopamine, levodopa, tyrosine, and tryptophan with Marplan may precipitate hypertension, headache, and related symptoms. The combination of MAO inhibitors and tryptophan has been reported to cause behavioral and neurologic symptoms, including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyperreflexia, shivering, ocular oscillations, and Babinski signs.
Meperidine should not be used concomitantly with MAO inhibitors or within 2 or 3 weeks following MAO therapy. Serious reactions have been precipitated with concomitant use, including coma, severe hypertension or hypotension, severe respiratory depression, convulsions, malignant hyperpyrexia, excitation, peripheral vascular collapse, and death. It is thought that these reactions may be mediated by accumulation of 5-HT (serotonin) consequent to MAO inhibition.
Marplan should not be used in combination with dextromethorphan. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior.
Hypertensive crises have sometimes occurred during Marplan therapy after ingestion of foods with a high tyramine content. In general, patients should avoid protein foods in which aging or protein breakdown is used to increase flavor. In particular, patients should be instructed not to take foods such as cheese (particularly strong or aged varieties), sour cream, Chianti wine, sherry, beer (including non-alcoholic beer), liqueurs, pickled herring, anchovies, caviar, liver, canned figs, raisins, bananas or avocados (particularly if overripe), chocolate, soy sauce, sauerkraut, the pods of broad beans (fava beans), yeast extracts, yogurt, meat extracts, meat prepared with tenderizers, or dry sausage.
Patients taking Marplan should not undergo elective surgery requiring general anesthesia. Also, they should not be given cocaine or local anesthesia containing sympathomimetic vasoconstrictors. The possible combined hypotensive effects of Marplan and spinal anesthesia should be kept in mind. Marplan should be discontinued at least 10 days before elective surgery.
Marplan should not be used in combination with some central nervous system depressants, such as narcotics, barbiturates, or alcohol.
Marplan should not be used in combination with antihypertensive agents, including thiazide diuretics. A marked potentiating effect on these drugs has been reported, resulting in hypotension.
Excessive use of caffeine in any form should be avoided in patients receiving Marplan.
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 of nine antidepressant drugs (SSRIs) and others) 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 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk 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. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.
|Age Range||Drug-Placebo Difference in Number of Cases of Suicidality Per 1000 Patients Treated|
|Increases Compared to Placebo|
|<18||14 additional cases|
|18 to 24||5 additional cases|
|Decreases Compared to Placebo|
|25 to 64||1 fewer case|
|>65||6 fewer cases|
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 casual 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 health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for MARPLAN should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
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