Major Research Findings

The selegiline transdermal system (STS) is the first transdermal antidepressant medication approved by the US FDA for the treatment of major depressive disorder. 4 Its unique delivery system ensures a steady release of selegiline over 24 hours, minimizing fluctuations in blood serum levels. 4 This allows for sufficient concentrations in the central nervous system to achieve antidepressant effects without significantly inhibiting Monoamine oxidase-A in the gastrointestinal and hepatic systems, thereby reducing the risk of tyramine-induced hypertensive crises, especially at lower doses. 4 The convenience of once-daily application compared to multiple daily doses required for oral counterparts could theoretically improve patient adherence. 4 Clinical trials have established that doses between 6 and 12 mg over 24 hours are effective for major depressive disorder and well-tolerated by patients. 4 Hypertensive crises with STS have been minimally reported to date. 4 Overall, STS appears to be an effective treatment for major depressive disorder when evaluated against regulatory standards and post-marketing analyses. 4 This paper reviews the pharmacologic characteristics of STS and results of studies investigating its clinical efficacy and safety.

Research comparing oral and transdermal selegiline in rats found antidepressant-like effects in both modes of administration, as assessed by the forced swim test. 11 Transdermal administration, bypassing first-pass metabolism, allows for lower doses compared to oral administration. 11 An 8-week double-blind placebo-controlled flexible-dose titration trial demonstrated the efficacy, safety, and tolerability of STS in treating major depressive disorder (MDD) within a dose range of 6 mg/24 hours to 12 mg/24 hours. 7

A double-blind placebo-controlled parallel-group study in outpatients investigated the efficacy and safety of transdermal selegiline in adult outpatients with major depressive disorder. 1

STS, a formulation of the selective MAO-B inhibitor selegiline, has shown evidence of also inhibiting MAO-A in the human brain when administered via transdermal patches, bypassing first-pass metabolism. 9 This suggests that STS might target MAO-A in the brain while minimizing inhibition of MAO-A in the gastrointestinal tract, potentially reducing the risk of tyramine-induced hypertensive crises. 6 This characteristic implies that STS could achieve the necessary inhibition of MAO-A in the brain at lower doses, significantly reducing the risk of tyramine-induced hypertensive crises. 6

A double-blind placebo-controlled trial in patients with major depressive disorder confirmed the safety and efficacy of STS, even without dietary restrictions. 8 The trial demonstrated that STS was safe and effective without requiring dietary restrictions. 8

STS holds potential as an effective treatment option for patients with major depressive disorder, particularly those who have not responded well to first-line therapies. 10 STS bypasses first-pass metabolism by delivering the medication directly into the circulatory system, minimizing inhibition of MAO-A in the gastrointestinal tract and significantly reducing the risk of tyramine-related adverse events. 10 Additionally, STS maintains stable drug levels over 24 hours, eliminating the need for dietary restrictions at the minimum effective dose of 6 mg/24 hours, potentially improving patient adherence. 10

Benefits and Risks

Benefit Summary

The selegiline transdermal system (STS) offers several benefits in treating major depressive disorder. First, the convenience of once-daily application compared to multiple daily doses required for oral counterparts could theoretically improve patient adherence. 4 Additionally, STS bypasses first-pass metabolism by delivering the medication directly into the circulatory system, minimizing inhibition of MAO-A in the gastrointestinal tract and significantly reducing the risk of tyramine-related adverse events. 10 STS maintains stable drug levels over 24 hours, minimizing fluctuations in blood serum levels. 4 Furthermore, STS achieves sufficient concentrations in the central nervous system for antidepressant effects without significantly inhibiting Monoamine oxidase-A in the gastrointestinal and hepatic systems, thereby reducing the risk of tyramine-induced hypertensive crises, especially at lower doses. 4 Clinical trials have established that doses between 6 and 12 mg over 24 hours are effective for major depressive disorder and well-tolerated by patients. 4

Risk Summary

The primary risks associated with STS include irritation at the patch site and insomnia. 13 For higher-dose patches, dietary restrictions are recommended to minimize the risk of tyramine-induced hypertensive crises. 13 STS should be avoided in combination with certain pain medications, antidepressants, muscle relaxants, and any sympathomimetic amines, which include amphetamines, cold products containing pseudoephedrine, phenylephrine, phenylpropanolamine, ephedrine, and stimulant-containing weight-reduction agents. 13

Comparison between Studies

Similarities

All these studies consistently demonstrate that STS is effective and safe for treating major depressive disorder. 4 7 1 8 Moreover, they all suggest that STS offers greater patient convenience and a reduced risk of tyramine-induced hypertensive crises compared to oral medications. 4 11 6 10

Differences

These studies differ in their methodologies for evaluating STS's efficacy, including the study population's age, severity of depression, and duration of the study. 4 7 1 8 Some studies provide a more detailed analysis of the advantages of STS over oral medications. 11 6 10

Consistency and Contradictions

The results of these studies consistently show that STS is effective and safe for treating major depressive disorder. 4 7 1 8 However, they differ in their methodologies, study populations, and duration of the studies. 4 7 1 8 Therefore, further research is needed to generalize these findings.

Considerations for Real-World Application

While STS holds promise as an effective treatment option for major depressive disorder, some considerations are important. First, STS should be avoided in combination with certain pain medications, antidepressants, muscle relaxants, and any sympathomimetic amines. 13 Dietary restrictions are recommended for higher-dose patches to minimize the risk of tyramine-induced hypertensive crises. 13 It's crucial to consult with your physician before starting STS to determine the appropriate dosage and usage for your specific condition.

Limitations of Current Research

While these studies provide valuable information about STS's effectiveness and safety in treating major depressive disorder, they have some limitations. 4 7 1 8 First, they are relatively short-term studies involving a limited number of patients. 4 7 1 8 Therefore, further research is needed to generalize these findings. 4 7 1 8 Additionally, these studies don't provide comprehensive information on the long-term effects and safety of STS. 4 7 1 8 Therefore, further research is necessary to investigate the long-term effects and safety of STS.

Future Research Directions

Future research should investigate the long-term effects and safety of STS, its comparison with other antidepressants, and its impact on different patient populations. 4 7 1 8 These studies will help us better understand STS's role in treating major depressive disorder.

Conclusion

These studies consistently demonstrate that STS is effective and safe for treating major depressive disorder. 4 7 1 8 STS offers greater patient convenience and a reduced risk of tyramine-induced hypertensive crises compared to oral medications. 4 11 6 10 However, these studies are relatively short-term and involve a limited number of patients. 4 7 1 8 Further research is necessary to investigate the long-term effects and safety of STS. 4 7 1 8 If you are struggling with depression, consulting your doctor to find the right treatment option for you is essential.