Revitalizing monoamine oxidase inhibitors: a call for action

Abstract

This statement represents the view of the "International MAOI Expert Group" which is a group of clinicians, academics, and researchers with a special interest in monoamine oxidase inhibitors (MAOIs). This group was formed in March 2018 to promote actions aimed at: improving education; stimulating research; increasing clinical usage; and assuring continued availability of MAOIs worldwide. Non-selective irreversible MAOIs, including tranylcypromine, phenelzine, isocarboxazid, and the Selegiline Transdermal System (STS), can be dramatically effective for patients with biological depressive illnesses (e.g., melancholia and bipolar depression). It has been established by more than 50 years of research, including randomized double-blind studies, and clinical experience, that these medications can induce full remission when other antidepressants, combinations, and augmentation strategies, and even electroconvulsive therapy (ECT), have failed. 1-4 Because of their unique pharmacological properties, the efficacy of non-selective irreversible MAOIs is superior, in a proportion of patients, to more recently developed medications, including moclobemide, a reversible inhibitor of MAO-A, or MAO-B-selective doses of selegiline. Patients may experience fewer side effects with MAOIs than with other antidepressants; for example, the low rates of weight gain, cognitive dysfunction and sexual side effects with tranylcypromine and selegiline (STS) are a major advantage for many patients. 5,6 Despite these valuable attributes these vital life-saving antidepressant drugs are becoming unaffordable (because the cost has inexplicably escalated by about 50-fold), less available, or even unavailable, in many countries around the world.

Commentary letter on “Revitalizing monoamine oxidase inhibitors: a call for action”

“…ECT is available only in 1–2 University Hospital, and 2–3 other public or private facilities nationwide. This is in contrast with all other countries, as covered by the report by Gillman et al 1 , where stable prescription rates of ECT partially counterbalance the lack of MAOIs. While neuromodulatory interventions such as repetitive transcranial magnetic stimulation (rTMS) are gaining popularity even in Italy, there is no conclusive EBM, neither clinical consensus supporting their efficacy for resistant cases of MDD or BD (Fornaro M. et al “The concept and management of acute episodes of treatment-resistant bipolar disorder: a systematic review and exploratory meta-analysis of randomized controlled trials,” submitted for publication).…”

“…The contribute entitled: “Revitalizing monoamine oxidase inhibitors: a call for action” 1 deserves appraisal about the prescribing pattern in Italy and the lack of further effective interventions besides the monoamine oxidase inhibitor (MAOI) drugs.…”

“…The plea for attention toward the MAOIs made by Gillman et al 1 seems even more compelling for those prescribing clinicians based in Italy. The last available MAOI for prescription in Italy, namely the nonselective and irreversible inhibitor tranylcypromine, is not available anymore since the year 2018.…”

Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure‐Activity Relationships

“…Currently, selective serotonin reuptake inhibitors (SSRIs) and serotonin‐norepinephrine reuptake inhibitors (SNRIs) are first‐line treatment for major depressive disorders [11–12] which inhibit the reuptake of serotonin (5‐HT) and norepinephrine (NE) released from nerve cells in the brain. Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are also an important class of antidepressants but are mostly used as second‐line drugs [13,14] . MAOIs inhibit the MAO enzyme, thereby inhibiting the oxidative metabolism of monoamine neurotransmitters, [15] whereas TCAs prevent the reuptake of acetylcholine along with 5‐HT and NE in the nerve cells [16,17] …”

On the limited availability of classic MAOIs in Belgium: the “call for action” extended

“…(1) I have read with considerable interest the article by Gillman et al regarding the growing unavailability of classic monoamine oxidase inhibitors (MAOIs) and their regrettable underuse in current psychiatric practice 1 ; this is certainly the case in Belgium: Willaert et al's overview (2014) of the waning obtainability of MAOIs on the Belgian market shows that tranylcypromine (TCP) was commercialized/registered only up until 1965; isocarboxazid (ISO) up until 1991-leaving only phenelzine (PLZ)… 2 But then the Marketing Authorization Holder (MAH) of PLZ reported production problems on February 26, 2019 3a ; and, subsequently, the (temporary?) cessation of commercialization of PLZ on June 17.…”