Major Depressive Disorder

Subtypes of depression may be defined by the presence of psychotic features (delusions, hallucinations), catatonia (motor disturbances, such as immobility or agitation, stereotyped movements, mutism), melancholy (weight loss, insomnia, morning worsening) or atypism (hypersomnia, hyperphagia), or postpartum onset of depression.

In epidemiologic studies, the 12-month and lifetime prevalence of MDD are, respectively, 5% to 7% and 13% to 18%, and the prevalence seems to be largely unrelated to ethnicity or geography (region of the country or urbanicity). In a recent U.S. epidemiologic survey, being female; Native American; widowed, separated, or divorced; being unemployed or disabled or having low income was significantly associated with higher rates of MDD. The mean age at onset for MDD is in the early 30s. The hazard for childhood onset MDD is relatively low, increases sharply between ages 12 and 16 years, and continues to increase, albeit more gradually, up to the early 40s. The diagnosis of MDD is associated with the presence of one or more psychiatric disorders during one’s lifetime in nearly 75% of cases, including anxiety disorders (60%), substance use disorders (25%), and impulse control disorders (30%).

The neurobiologic basis and pathophysiology of MDD continue to be enigmatic. This is likely due in part to the heterogeneity of MDD, which may represent a group of disorders with several underlying pathologies, in which both genetic and environmental factors play a role. Studies have investigated disturbances in several neurotransmitters (serotonin [5-HT, i.e., 5-hydroxytryptamine], norepinephrine [NE], and dopamine, and more recently glutamate); in neuroendocrine and neuroimmune mechanisms, in particular, the hypothalamic-pituitary-adrenal axis involved in the response to stress; and in neurotrophic factors regulating plasticity in the brain. It is important to emphasize that neurotransmitters and hormones are integrated in anatomic and functional circuitry interacting at several levels. Imaging and postmortem studies suggest that MDD patients have structural and subtle cellular and molecular alterations within a complex neural network involving the prefrontal cortex, subgenual cingulate cortex, hippocampus, and amygdala.

MDD genetics are complex and multifactorial; this disorder frequently occurs in families, having an estimated heritability of approximately 40%. Through linkage, association, and genome-wide association studies, several candidate genes and regions of the genome are identified that may contribute to MDD; however, these findings are not consistent in variable studies. Each individual gene probably contributes only to a very small proportion of the variance, interacting with environmental factors.

Initial treatment modality choices in MDD are influenced by a number of factors, including symptom severity, co-occurring psychiatric or medical conditions, psychosocial stressors, and the patient’s preference. Antidepressant medications include selective serotonin reuptake inhibitors (SSRIs), usually used as a first choice, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and others, including bupropion, nefazodone, trazodone, and mirtazapine. The choice of an antidepressant is based on side-effect profile, tolerability, safety, and history of prior response to treatment.

After an initial phase of pharmacologic treatment of 2 to 3 months, aimed at achieving full remission of symptoms, pharmacotherapy is typically continued for approximately 4 to 9 months to prevent early relapse. Psychotherapy, alone or combined with medications, may also be considered as initial treatment for patients with mild-to-moderate MDD. Electroconvulsive therapy (ECT) is a potentially very successful treatment option for patients who are more severely ill, present psychotic features or catatonia, and for those who are acutely suicidal.

Only gold members can continue reading. Log In or Register to continue