longer duration of depressive episodes. Finally, people with more severe depression and those who are suicidal are more likely to be nonresponsive to antidepressant treatment. Treatment There are three basic categories of drug treatment that can be used when a medication course is found to be ineffective. One option is to switch the patient to a different medication. Another option is to add a medication to the patient’s current treatment. This can include combination therapy: the combination of two different types of antidepressants, or augmentation therapy: the addition of a non-antidepressant medication that may increase the effectiveness of the antidepressant. Medication Antidepressants Dose increase Increasing the dosage of an antidepressant is a common strategy to treat depression that does not respond after adequate treatment duration. Practitioners who use this strategy will usually increase the dose until the person reports intolerable side effects, symptoms are eliminated, or the dose is increased to the limit of what is considered safe. Switching antidepressants Studies have shown a wide variability in the effectiveness of switching antidepressants, with anywhere from 25–70% of people responding to a different antidepressant. There is support for the effectiveness of switching people to a different SSRI; 50% of people that were non-responsive after taking one SSRI were responsive after taking a second type. Switching people with treatment-resistant depression to a different class of antidepressants may also be effective. People who are non-responsive after taking an SSRI may respond to moclobemide or tricyclic antidepressants, bupropion or an MAOI. However, the more antidepressants an individual had already tried, the less likely they were to benefit from a new antidepressant trial. Some off label antidepressants are low dose ketamine and highly serotonergic catecholamines (including very controlled use of MDMA in the treatment of PTSD and crippling depression/anxiety). For lethargic syndromes, dysthymia, or caffeine-resistant amotivation, a dopaminergic stimulant such as methlyphenidate, or even dextroamphetamine or methamphetamine can be helpful. Primarily dopaminergic or norepinephrine releasing stimulants, in low doses, have been used especially in the past, or in conjunction with a multidisciplinary therapy approach, although more targeted and "mild" agents, including modafinil and atomoxetine are considered first line for both childhood and adult lethargy and inattention disorders, due to their virtually nonexistent abuse potential (limited to one or two cases per 10 000), and higher selectivity, safety, and thus slightly broader therapeutic index. When depression is related or co-morbid to an inattention disorder, often ADHD,