Why maximum tolerated dose?

Area of Science:

• Pharmacology
• Clinical Medicine
• Drug Dosing

Background:

• The traditional "start low and go slow" approach to drug dosing is often abandoned in clinical practice.
• Clinicians frequently prescribe the maximum tolerated dose (MTD) for acute and severe conditions, and sometimes even for prevention (e.g., hypercholesterolemia).
• There is a lack of robust evidence demonstrating that MTD improves patient outcomes compared to other dosing strategies.

Purpose of the Study:

• To explore the historical origins of prescribing medications at MTD.
• To identify potential problems and drawbacks associated with the MTD approach.
• To evaluate alternative dosing guidance, such as the effective dose 50 (ED50), for optimizing drug therapy.

Main Methods:

• Literature review and critical analysis of existing pharmacological and clinical guidelines.
• Examination of the evidence base supporting MTD prescribing in various disease states.
• Discussion of the theoretical underpinnings and practical implications of MTD.

Main Results:

• The MTD approach is prevalent but often lacks strong empirical support for superior efficacy or improved outcomes.
• Potential risks and adverse effects may be increased when prescribing at MTD without clear benefit.
• The effective dose 50 (ED50) is presented as a potentially useful metric for achieving a better balance between therapeutic efficacy and patient safety.

Conclusions:

• The routine prescription of maximum tolerated doses (MTD) in clinical practice warrants critical re-evaluation.
• Evidence supporting the universal benefit of MTD over other dosing strategies is limited, particularly in preventive care.
• The effective dose 50 (ED50) offers a promising alternative for guiding drug selection to optimize the balance between efficacy and safety in pharmacological treatment.