Individuals suffering from Major Depressive Disorder seem to have a greater number of stressful life events than healthy individuals. Psychosocial stressors appear to have more significant impact early in the course of the depression and during the first episode. Psychosocial stressors appear to have less impact on later episodes and later during the course of the initial onset. Further, loss early in one's life has been linked to depression. This includes loss of a parent other than death. However, the link is considered weak and less impactful than recent events.

There are a number of approaches that have been found effective in the treatment of Major Depressive Disorder. Some theoretical approaches that seem to be helpful are cognitive-behavioral (CBT) and interpersonal psychotherapy (IPT). When patients exhibit mild or moderate symptoms, psychotherapy is the number one treatment. More severe depression appear to be most effectively treated with medication and psychotherapy. The primary reason for using a cognitive-behavioral approach is to help patients change their thinking and behavior. In the cognitive-behavioral school, it is believed that distorted cognitions and beliefs cause depression. The therapist helps the client to identify negative thoughts and assumptions and replace them with more positive beliefs.

Interpersonal therapy helps to refine social functioning. Social support is considered important in the development of depression. The goal of interpersonal therapy is to improve disturbed relationships, thereby improving adaptation to stress. The focus is on current relationships. However, earlier relationships are not ignored. Several problem areas are generally addressed in IPT. These areas are: 1) unresolved grief, 2) difficulties with role transitions, 3) interpersonal disputes, and 4) inadequate social skills. The first stage of treatment involves diagnosing, educating, and assessing interpersonal relationships. Treatment involves identifying problems and using specific here and now interventions. It should be noted that IPT is neither psychodynamic, nor cognitive-behavioral therapy, but it shares qualities of both.

Several forms of brief psychodynamic therapy are considered useful in the treatment of depression. These include "brief focal therapy", "short-term anxiety-provoking therapy", and "broad focus psychodynamic therapy". While these approaches are considered valuable, none have been significantly researched.

Both IPT and CBT have been researched and found effective in the treatment of depression. However, they have been researched largely by the creators of the therapies. Since they are concrete and can be "replicated" with some consistency, they lend themselves to research. Researchers have created manuals that are used by clinicians. They follow specific protocols and procedures. Psychodynamic approaches are less replicable and have generally not been studied with any consistency. Hence, they do not have the empirical backing of IPT and CBT. However, more research is being conducted by psychodynamic clinicians and researchers. In the future, other forms of therapy may be proven as effective as CBT and IPT.