Monoamine oxidase inhibitors (MAOIs) have proven efficacy for treating depression and for decades have been a preferred treatment for patients with atypical depression, high levels of anxiety, anergic bipolar depression, and treatment-resistant depression. However, MAOIs are infrequently used due to safety and tolerability concerns and the need for dietary restrictions. Current guidelines, which are reviewed here, recommend MAOIs as third-, fourth-, or fifth-line treatments due to these concerns. However, a transdermal formulation of selegiline limits the need for dietary restrictions and has fewer side effects than many more widely used antidepressants. The availability of a safer and more tolerable formulation gives clinicians another option in their armamentarium for treating depression.
"Monoamine oxidase inhibitors have been used for decades in the treatment of depression and their antidepressant properties result from selective MAO-A inhibition in the central nervous system, which could lead to increased brain levels of 5-HT, NE, and DA [42, 43]. Recently, selegiline, an MAO-B inhibitor, has been used with success in the treatment of patients that are refractory to other antidepressant in a pharmaceutical transdermal preparation to avoid food interactions [44, 45]. We also investigated the involvement of the MAO in the possible antidepressant-like effect of I. paraguariensis. "
[Show abstract][Hide abstract] ABSTRACT: In this study, we investigated the possible antidepressant-like effect of I. paraguariensis in rats. Rats were treated for four weeks with an aqueous extract of I. paraguariensis in drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours of I. paraguariensis intake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile of I. paraguariensis extract. I. paraguariensis reduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect of I. paraguariensis was observed in rats through the elevated plus-maze test. The antidepressant-like effect of I. paraguariensis was not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract of I. paraguariensis decreases the time of immobility in rats suggesting an antidepressant-like effect.
BioMed Research International 05/2014; 2014:958209. DOI:10.1155/2014/958209 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: Difficult-to-treat depression (eg, depression with atypical or anxious symptoms, treatment-resistant depression, or depression with frequent recurrence) is a challenging real-world health issue. This critical review of the literature focuses on monoamine oxidase inhibitor (MAOI) therapy and difficult-to-treat forms of depression. Data Sources: A literature search was performed in November 2012 and refreshed through January 2013 with no date restrictions using key search terms including MAO inhibitor therapy or MAOI and depression and anxiety, atypical, treatment-resistant, recurrent, relapse, or refractory. Study Selection: Articles were selected to summarize the current needs in difficult-to-treat depression as well as the use of MAOI therapies in this area. Results: Two strategies have fallen out of favor in the care of patients with major depressive disorder. The first is the use of MAOI therapy and the second is the proactive recognition of difficult-to-treat depression that may not respond as well to more frequently used antidepressants. The infrequent use of MAOIs stems from the perception that other oral therapies for depression are safer and easier to use than oral MAOIs; however, transdermal delivery is one potential strategy to improve the safety of this class of agents. Although food-related interactions with transdermal delivery of MAOI therapy can be lessened, clinicians still need to be vigilant for drug-drug interactions and serotonin syndrome. Conclusions: Clinicians should consider MAOIs for patients who have had several unsuccessful trials of antidepressants. Guidelines generally reserve MAOIs as third- and fourth-line treatments due to concerns over safety and tolerability; however, transdermal delivery of an MAOI may allay some of the safety and tolerability concerns. Patients should be provided education about MAOIs and their risks.
[Show abstract][Hide abstract] ABSTRACT: We investigated patient and disease characteristics predictive of relapse of MDD during a 52-week placebo controlled trial of selegiline transdermal system (STS) to identify patient characteristics relevant for STS treatment.
After 10 weeks of open-label stabilization with STS, 322 remitted patients with MDD were randomized to 52-weeks of double-blind treatment with STS (6mg/24h) or placebo (PLB). Relapse was defined as Hamilton Depression Rating Scale (HAMD-17) score of ≥14 and a CGI-S score of ≥3 with at least 2-point increase from the beginning of the double blind phase on 2 consecutive visits. Cox's proportional hazards regression was used to examine the effect of potential predictors (age, sex, age at onset of first MDD, early response pattern, number of previous antidepressant trials, severity of index episode, number of previous episodes, melancholic features, atypical features and anxious feature) on outcome. Exploratory analyses examined additional clinical variables (medical history, other psychiatric history, and individual items of HAM-D 28) on relapse.
For all predictor variables analyzed, treatment Hazard Ratio (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than PLB). Age of onset was significantly predictive of relapse. Type, duration, and severity of depressive episodes, previous antidepressant trials, or demographic variables did not predict relapse. In additional exploratory analysis, eating disorder history and suicidal ideation were significant predictors of relapse after controlling for the effect of treatment in individual predictor analysis.
While age of onset, eating disorder history and suicidal ideation were significant predictors, the majority of clinical and demographic variables were not predictive of relapse. Given the post-hoc nature of analysis, the findings need confirmation from a prospective study. It appears that selegiline transdermal system was broadly effective in preventing relapse across different subtypes and symptoms clusters of MDD.
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