Marplan® (isocarboxazid) Tablets Clinical Trials
Treatment-Resistant Major Depression*
The treatment of major depression is difficult in itself. But, when a patient has been treated with a series of different antidepressant medications and still experiences only minimal symptom relief, the situation can become particularly frustrating for both the physician and the patient. ECT has long been considered an option in such cases, but high rates of relapse, cognitive side effects, and poor patient acceptability make this option problematic1,2.
Monoamine oxidase inhibitors MAO Inhibitors, such as Marplan® (isocarboxazid) Tablets, have been used as an effective alternative for treatment-resistant depression.3,4
Marplan® (isocarboxazid) Tablets therapy has been utilized successfully since the 1950's but in recent years the publication of new meta-analyses has underscored its level of effectiveness,4 and newer dietary data has shown that patients can benefit from Marplan® (isocarboxazid) Tablets' symptom-relieving MAO Inhibitor action while enjoying a much wider range of fresh or pasteurized foods5.
For patients who have failed to respond to first-line antidepressant drugs, Marplan® (isocarboxazid) Tablets may be the answer3.
MAO Inhibitors regulate the monoamine content of the central nervous system, but, unlike other types of antidepressants, MAO Inhibitors raise the levels of all three of the neurotransmitters in the brain responsible for mood elevation (norepinephrine, serotonin, and dopamine)2.
Marplan® (isocarboxazid) Tablets is FDA-approved for patients with treatment-resistant* major depression who have failed treatment with first line agents3.
The MAO Inhibitor power of Marplan® (isocarboxazid) Tablets treatment: Meta-Analyses of Marplan® (isocarboxazid) Tablets Clinical Trials
The clinical efficacy of Marplan® (isocarboxazid) Tablets is detailed in the contemporary and rigorous meta-analyses performed in the mid-1990's to review the clinical data gathered from Marplan® (isocarboxazid) Tablets studies conducted from the 1960's through the 1980's4.
It is important to note that Marplan® (isocarboxazid) Tablets has the largest body of placebo-controlled efficacy and safety data of all irreversible MAO Inhibitors4.
Summary of Meta-Analysis of Marplan® (isocarboxazid) Tablets Efficacy in Depression
- Authors: Thase et al6
- Publication Date: 1995
- Studies Analyzed: 12 randomized controlled trials
- Number of Patients: 434
- Using the "intent to treat" sample method, authors concluded that Marplan® (isocarboxazid) Tablets exhibited a 41.3% average difference vs. placebo.
- "Intent to treat" samples in 5 of these 12 studies revealed a Marplan® (isocarboxazid) Tablets efficacy rate of 60.1%.
- In 8 of these 12 studies, the "Adequate Treatment" sample method showed a Marplan® (isocarboxazid) Tablets efficacy rate of 68.2% among patients receiving at least a minimum number of weeks of treatment.
- In one of 7 placebo-controlled studies in the meta-analysis, Giller et al (1984) as cited in Thase, 16 out-patients who were crossed over from placebo (due to lack of response) achieved a 69% response rate with Marplan® (isocarboxazid) Tablets treatment.
- At the close of this 2-stage trial, 18% of patients on placebo and 92% of Marplan® (isocarboxazid) Tablets-treated patients had improved (11 of 12 patients who were fair to poor responders to tricyclics). Recalculating this result on a base of the full 16 patients originally crossed over, the improvement on Marplan® (isocarboxazid) Tablets was 69% as cited in the Thase et al meta-analysis6.
The MAO Inhibitor power of Marplan® (isocarboxazid) Tablets treatment: Individual Marplan® (isocarboxazid) Tablets Clinical Trials
In the Giller, Bialos, Riddle and Waldo study7, a 1988 24-week multi-axial open-label outcome assessment of Marplan® (isocarboxazid) Tablets' effectiveness in 43 adult outpatients with major depressive disorder, 4 outcome areas were evaluated: symptoms, work, family functioning, and social functioning.
In addition to depression, patients in this study experienced one or more of the following symptoms: anxiety, somatic complaints, phobia, or panic.
- After 6 weeks on Marplan® (isocarboxazid) Tablets therapy, the 'symptoms' outcome area improved the most.
- Among patients who completed the full 24 weeks of the study, all four outcome areas improved beyond their 6-week levels, and "study completers" who began to improve at week 6 continued to improve through week 24.
- Improvement in "work functioning" reached statistical significance among study completers (p=0.0001).
- In contrast to the early-on improvement in "symptoms", the bulk of improvement in work functioning occurred between weeks 6 and 24 (not during the first 6 weeks) prompting the authors to comment that the need to continue Marplan® (isocarboxazid) Tablets therapy beyond initial symptom improvement "cannot be underestimated".
The effectiveness of Marplan® (isocarboxazid) Tablets in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Marplan® (isocarboxazid) Tablets for extended periods should periodically evaluate the long-term usefulness of the drug for the individual patient.
In the earlier (1984) Giller et al study8 30 outpatients diagnosed as having major depressive disorder with melancholia were entered into a 6-week trial that was placebo controlled during the first 3 weeks then followed by an open phase where 16 symptomatic placebo patients were given Marplan® (isocarboxazid) Tablets.8
Marplan® (isocarboxazid) Tablets dosage was titrated to 40mg per day by the end of the first week, and then increased until 90% of platelet MAO Inhibition was achieved (or a maximum dosage of 80mg per day was reached). **Recommended max dose is 60mg per day.
- Authors observed a significant clinical improvement in the Marplan® (isocarboxazid) Tablets-treated patients (56%) vs. patients given placebo (18%).
- Data for the 24 patients who completed the full 6-weeks (3-week placebo phase and 3 week open phase) of the study showed that 92% of the Marplan® (isocarboxazid) patients improved vs. 18% of the patients on placebo.
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.