The CYP2D6*1xN alleles (*1x2 and *1x鈮?) have been assigned as increased function alleles by CPIC. Patients carrying a *1xN allele in combination with a normal or increased function allele or a decreased function allele with an activity value of 0.5 may have increased imipramine dose requirements as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a *1xN allele with an activity value of 3 or greater in combination with a decreased function allele with an activity value of 0.25 or a no function allele may also have increased imipramine dose requirements as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying a *1xN allele with an activity value of 2 in combination with a decreased function allele with an activity value of 0.25 or a no function allele may have similar imipramine dose requirements as compared to patients with other alleles that result in a normal metabolizer phenotype. Other genetic and clinical factors may also influence imipramine dose requirements.