Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations.

Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.

Selective inhibitors of monoamine oxidase type B and the "cheese effect".

Potentiation of the cardiovascular and other effects of dietary tyramine by monoamine oxidase (MAO) inhibitors (cheese effect) has been a major limitation to clinical use of these drugs. The discovery that MAO exists in two distinct isoforms, MAO-A and MAO-B, together with the development of selective inhibitors of each isoform, enabled the understanding that selective inhibition of MAO-A, or inhibition of both isoforms, will cause cheese effect, but selective inhibition of MAO-B can be elicited without dangerous pressor reaction. This development has permitted the introduction of selective MAO-B inhibitors to clinical medicine for treatment of Parkinson's disease. This review describes the basic mechanisms involved in cheese effect, as well as providing information on tyramine levels in a variety of foodstuff, and surveys clinical information from tyramine pressor testing with the selective MAO-B inhibitors, selegiline and rasagiline.

Drug interactions and fluoxetine: a commentary from a clinician's perspective.

This commentary suggests that clinicians require an additional perspective to that expressed in Wernicke's review. Clinicians must consider the relative risks, because even small differences may be a reason to adjust usage of a particular drug. As early as 1993, reviews noted a 'serious' interaction potential. Also, the product information requires supplementation because it does not provide the emphasis on predictable interactions that clinicians require. An extensive basis in experimental pharmacology provides the foundations for our knowledge of cytochrome P450 interactions which predict the effects on the levels of other drugs. This work has been confirmed in human studies. Adverse outcomes related to fluoxetine interactions are relatively frequent and sometimes fatal. Patients may suffer serious and irreversible ill-effects from the increased risk of many manifestations of toxicity, and the cost of resultant medico-legal settlements is considerable. A clinician who balances risks may use fluoxetine less frequently.