Prevention of accumulated tolerance to stimulant medication for the treatment of ADHD

A method of treating or reducing, in a human being, carry-over tolerance of methylphenidate and emergence of accumulated tolerance of methylphenidate that undermines long-term efficacy of methylphenidate, methylphenidate having effectiveness against attention-deficit/hyperactivity disorder (ADHD), the method comprising:

• administering once daily to the human being a pharmaceutical composition in a single dosage form, the pharmaceutical composition comprising:
• a first component comprising a dose of methylphenidate having effectiveness against ADHD, wherein methylphenidate causes acute tolerance to methylphenidate when administered daily as a once-a-day formulation with a drug delivery profile to maintain efficacy, wherein failure of the acute tolerance to methylphenidate to dissipate between daily administrations results in the carry-over tolerance which accumulates as the accumulated tolerance and emerges over time as long-term tolerance to methylphenidate;
• and
• a second component comprising a delayed-release formulation of mazindol or modafinil that improves attention and wakefulness, wherein the mazindol or modafinil does not elicit acute tolerance to the mazindol or modafinil and allows the acute tolerance to the methylphenidate to dissipate fully each day;
• wherein when administered once daily, the pharmaceutical composition maintains effectiveness against ADHD and allows the accumulated tolerance to the methylphenidate to dissipate before the next daily administration without the carry-over tolerance to the methylphenidate, which maintains the efficacy of the methylphenidate during long-term treatment;
• and
• wherein administrating the pharmaceutical composition daily effectively treats ADHD symptoms for a similar time frame as the methylphenidate administered daily as the once-a-day formulation with the drug delivery profile.

A method of treating or reducing, in a human being, carry-over tolerance and/or tachyphylaxis of methylphenidate having effectiveness against ADHD and to prevent, in the human being, emergence of accumulated tolerance of methylphenidate that undermines long-term efficacy of methylphenidate the stimulant drug-against attention-deficit/hyperactivity disorder (ADHD), the method comprising:

• administering once daily a pharmaceutical composition in a single dosage form, the pharmaceutical composition comprising:
• a first component comprising a dose of methylphenidate, having the effectiveness against ADHD, wherein methylphenidate causes the carry-over tolerance and/or the tachyphylaxis when administered daily as a once-a-day formulation with a drug delivery profile to maintain efficacy;
• and
• a second component comprising a delayed-release formulation of mazindol or modafinil that improves attention and wakefulness, wherein the mazindol or modafinil does not elicit acute tolerance to the mazindol or modafinil and allows the carry-over tolerance and/or the tachyphylaxis to the methylphenidate to dissipate fully each day;
• wherein when administered once daily, the pharmaceutical composition maintains effectiveness against ADHD and allows the carry-over tolerance and/or the tachyphylaxis to the methylphenidate to dissipate before the next daily administration without the carry-over tolerance and/or tachyphylaxis to the methylphenidate, which maintains the efficacy of the methylphenidate during long-term treatment.