Methods for treating ADHD and bipolar disorder using a membrane potential ratio test

A method of optimizing a drug treatment therapy for a human patient with bipolar disorder (BD), comprising:

• obtaining a ratio of a mean membrane potential from a first population of cells from the human patient incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the human patient incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+, following treatment of the human patient with a drug therapy for BD;
• comparing the ratio to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have BD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) a BD control ratio of a mean membrane potential of BD control human cells known to have BD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the BD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• wherein each mean membrane potential is determined by incubating the cells in vitro in buffer comprising a potential-sensitive dye, resuspending the cells in potential-sensitive dye free-buffer, and measuring cell fluorescence;
• and
• identifying an optimal effective drug therapy for treatment of the human patient with BD when the ratio obtained is not significantly different from the control ratio in (a) and/or is significantly lower than the BD control ratio in (b);
• adjusting the drug therapy for BD to the optimal effective drug therapy identified;
• and
• administering the optimal effective drug therapy to the human patient with BD.

A method of optimizing a drug therapy treatment for a human patient with attention-deficit/hyperactivity disorder (ADHD), comprising the steps of:

• performing a drug therapy treatment for the patient with ADHD with at least one drug;
• obtaining at least one sample from the patient with ADHD which is collected after the drug therapy treatment with at least one drug;
• performing on each sample, a mean membrane potential test comprising:
• obtaining a ratio of a mean membrane potential from a first population of cells from the sample incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the sample incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• comparing the ratio of the mean membrane potential to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) an ADHD control ratio of a mean membrane potential of ADHD control human cells known to have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the ADHD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• modifying at least one drug in the drug therapy treatment based on the mean membrane potential test;
• identifying an optimal effective drug therapy treatment for the human patient with ADHD when the ratio of the mean membrane potential obtained is not significantly different from the control ratio in (a) and/or is significantly higher than the ADHD control ratio in (b);
• and
• administering the optimal effective drug therapy treatment to the human patient with ADHD.

A method of optimizing a drug therapy treatment for a human patient with bipolar disorder (BD), comprising the steps of:

• performing a drug therapy treatment for the patient with BD with at least one drug;
• obtaining at least one sample from the patient with BD which is collected after the drug therapy treatment with at least one drug;
• performing on each sample, a mean membrane potential test comprising:
• obtaining a ratio of a mean membrane potential from a first population of cells from the sample incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the sample incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• comparing the ratio of the mean membrane potential to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) a BD control ratio of a mean membrane potential of BD control human cells known to have BD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the BD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• modifying at least one drug in the drug therapy treatment based on the mean membrane potential test;
• identifying an optimal effective drug therapy treatment for the human patient with BD when the ratio of the mean membrane potential obtained is not significantly different from the control ratio in (a) and/or is significantly lower than the BD control ratio in (b);
• and
• administering the optimal effective drug therapy treatment to the human patient with BD.

A method of optimizing a drug dosage for treatment of a human patient with attention-deficit/hyperactivity disorder (ADHD), comprising:

• obtaining a ratio of a mean membrane potential from a first population of cells from the human patient incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the human patient incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+, following treatment of the human patient with a drug dosage for ADHD;
• comparing the ratio to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) an ADHD control ratio of a mean membrane potential of ADHD control human cells known to have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the ADHD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• wherein each mean membrane potential is determined by incubating the cells in vitro in buffer comprising a potential-sensitive dye, resuspending the cells in potential-sensitive dye free-buffer, and measuring cell fluorescence;
• identifying an optimal drug dosage effective for treatment of the human patient with ADHD when the ratio obtained is not significantly different from the control ratio in (a) and/or is significantly higher than the ADHD control ratio in (b);
• adjusting the drug therapy treatment of the human patient with ADHD to the optimal effective drug dosage identified;
• and
• administering the optimal effective drug dosage to the human patient with ADHD.

A method of optimizing a drug dosage for treatment of a human patient with bipolar disorder (BD), comprising:

• obtaining a ratio of a mean membrane potential from a first population of cells from the human patient incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the human patient incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+, following treatment of the human patient with a drug dosage for ADHD;
• comparing the ratio to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) a BD control ratio of a mean membrane potential of BD control human cells known to have BD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the BD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• wherein each mean membrane potential is determined by incubating the cells in vitro in buffer comprising a potential-sensitive dye, resuspending the cells in potential-sensitive dye free-buffer, and measuring cell fluorescence;
• and
• identifying an optimal drug dosage effective for treatment of the human patient with BD when the ratio obtained is not significantly different from the control ratio in (a) and/or is significantly lower than the BD control ratio in (b);
• adjusting the drug therapy treatment of the human patient with BD to the optimal effective drug dosage identified;
• and
• administering the optimal effective drug dosage to the human patient with BD.

A method of optimizing a drug dosage for treatment of a human patient with attention-deficit/hyperactivity disorder (ADHD), comprising the steps of:

• treating the human patient with a dosage of a drug for ADHD;
• obtaining at least one sample from the human patient which is collected after the treating step;
• performing on each sample, a mean membrane potential test comprising:
• obtaining a ratio of a mean membrane potential from a first population of cells from the sample incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the sample incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• comparing the ratio of the mean membrane potential to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) an ADHD control ratio of a mean membrane potential of ADHD control human cells known to have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the ADHD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• modifying the drug dosage based on the mean membrane potential test;
• identifying an optimal effective drug dosage for treating the human patient with ADHD when the ratio of the mean membrane potential obtained is not significantly different from the control ratio in (a) and/or is significantly higher than the ADHD control ratio in (b);
• and
• administering the optimal effective drug dosage to the human patient with ADHD.

A method of optimizing a drug dosage for treatment of a human patient bipolar disorder (BD), comprising the steps of:

• treating the human patient with a dosage of a drug for BD;
• obtaining at least one sample from the human patient which is collected after the treating step;
• performing on each sample, a mean membrane potential test comprising:
• obtaining a ratio of a mean membrane potential from a first population of cells from the sample incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the sample incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• comparing the ratio of the mean membrane potential to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) a BD control ratio of a mean membrane potential of BD control human cells known to have BD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the BD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• modifying the drug dosage based on the mean membrane potential test;
• identifying an optimal effective drug dosage for treating the human patient with BD when the ratio of the mean membrane potential obtained is not significantly different from the control ratio in (a) and/or is significantly lower than the BD control ratio in (b);
• and
• administering the optimal effective drug dosage to the human patient with BD.

A method of treating a human patient with attention-deficit/hyperactivity disorder (ADHD), comprising:

• obtaining a ratio of a mean membrane potential from a first population of cells from the human patient incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the human patient incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+, following treatment of the human patient with a drug dosage for ADHD;
• comparing the ratio to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) an ADHD control ratio of a mean membrane potential of ADHD control human cells known to have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the ADHD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• wherein each mean membrane potential is determined by incubating the cells in vitro in buffer comprising a potential-sensitive dye, resuspending the cells in potential-sensitive dye free-buffer, and measuring cell fluorescence;
• adjusting the drug dosage for ADHD to an effective drug dosage for treating the human patient such that the ratio obtained is not significantly different from the control ratio in (a) and/or is significantly higher than the ADHD control ratio in (b);
• and
• administering the effective drug dosage to the human patient with ADHD.

A method of treating a human patient with bipolar disorder (BD), comprising:

• obtaining a ratio of a mean membrane potential from a first population of cells from the human patient incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the human patient incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+, following treatment of the human patient with a drug dosage for BD;
• comparing the ratio to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have BD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) a BD control ratio of a mean membrane potential of BD control human cells known to have BD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the BD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• wherein each mean membrane potential is determined by incubating the cells in vitro in buffer comprising a potential-sensitive dye, resuspending the cells in potential-sensitive dye free-buffer, and measuring cell fluorescence;
• adjusting the drug dosage for BD to an effective drug dosage for treating the human patient such that the ratio obtained is not significantly different from the control ratio in (a) and/or is significantly lower than the BD control ratio in (b);
• and
• administering the effective drug dosage to the human patient with BD.

A method of treating a human patient with attention-deficit/hyperactivity disorder (ADHD), comprising the steps of:

• treating the human patient with a dosage of a drug for ADHD;
• obtaining at least one sample from the human patient which is collected after the treating step;
• performing on each sample, a mean membrane potential test comprising:
• obtaining a ratio of a mean membrane potential from a first population of cells from the sample incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the sample incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• comparing the ratio of the mean membrane potential to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) an ADHD control ratio of a mean membrane potential of ADHD control human cells known to have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the ADHD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• adjusting the drug dosage for ADHD to an effective drug dosage for treating the human patient such that ratio of the mean membrane potential obtained is not significantly different from the control ratio in (a) and/or is significantly higher than the ADHD control ratio in (b);
• and
• administering the effective drug dosage to the human patient with ADHD.

A method of treating a human patient with bipolar disorder (BD), comprising the steps of:

• treating the human patient with a dosage of a drug for BD;
• obtaining at least one sample from the human patient which is collected after the treating step;
• performing on each cell sample, a mean membrane potential test comprising:
• obtaining a ratio of a mean membrane potential from a first population of cells from the cell sample incubated in vitro in the presence of a compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential from a second population of cells from the cell sample incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• comparing the ratio of the mean membrane potential to (a) and/or (b):
• (a) a control ratio of a mean membrane potential of control human cells known to not have ADHD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the control human cells incubated in vitro in the absence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+,
• (b) a BD control ratio of a mean membrane potential of ADHD control human cells known to have BD incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the absence of K+, to a mean membrane potential of the BD control human cells incubated in vitro in the presence of the compound that alters Na+K+ ATPase activity and in the presence or absence of K+;
• adjusting the drug dosage for BD to an effective drug dosage for treating the human patient such that ratio of the mean membrane potential obtained is not significantly different from the control ratio in (a) and/or is significantly lower than the BD control ratio in (b);
• and
• administering the effective drug dosage to the human patient with BD.