This chapter reviews the antidepressant drugs that are combined norepinephrine dopamine reuptake inhibitors (NDRIs) and selective norepinephrine reuptake inhibitors (NRIs), and that are currently available to clinicians. NDRIs are considered first-line treatment, and NRIs are often second-line. Each drug in these classes is reviewed. The aim of this chapter is to familiarize the reader with these options for treating depression.

SSRI: selective serotonin reuptake inhibitors. NDRI: norepinephrine dopamine reuptake inhibitors. SNRI: serotonin norepinephrine reuptake inhibitors. SDA: serotonin dopamine antagonists. α 2 antagonist: alpha 2 antagonists. NRI: selective norepinephrine reuptake inhibitors. TCA: tricyclic antidepressants. SARI: serotonin 2A antagonist/reuptake inhibitors. MAOI: monoamine oxidase inhibitors. 5HT1A: serotonin 1A partial agonists. BZ: benzodiazepines. DPA: dopamine partial agonists. MTHF: L-5-methyl-tetrahydrofolate. T3/T4: thyroid hormone. ECT: electroconvulsive therapy. IPT: interper-sonal therapy. VNS: vagus nerve stimulation.

Bupropion may be useful in treating nicotine addiction due to its ability to occupy DATs in the striatum and nucleus accumbens, mitigating cravings but not becoming abusable itself. Bupropion was originally marketed in the United States only, and in an immediate-release formulation. Recent formulations have been developed in twice-daily (bupropion SR) and once-daily doses (bupropion XR). These advances not only provide convenience but are also beneficial in reducing the risk of seizures at peak plasma drug levels associated with the original formulation. Bupropion is generally a stimulating agent, and does not appear to cause sexual dysfunction that may be associated with use of other antidepressants. Bupropion has been very useful for patients who experience reduced positive affect, or the “dopamine-deficiency syndrome” (see Fig. 1.35). Oftentimes, augmentation with bupropion to an existing SSRI or SNRI can be useful for patients who have not responded to previous serotonergic-focused treatment.