Mood and Psychotic Disorders

Major Depressive Disorder

Major depressive disorder is a very significant and common psychiatric disorder that usually begins in early adulthood. Physicians of all specialties encounter it frequently in many different guises. Major depressive disorder accounts for 5% of total disability worldwide in adults; comparatively, cardiovascular disease represents 6.6% and cancer 5.6%. Women have a higher prevalence. There is no gender difference in symptoms, course, or consequences of illness. When depression affects men, the long-term risk of suicide is more common. Familial clustering is apparent, especially for earlier onset and recurrent episodes; heritability is approximately 40%. Chronic medical conditions are associated with an increased risk of major depressive disorder. In addition, the risk of some chronic medical conditions (i.e., obesity, diabetes, cardiovascular disease) is increased in the setting of major depressive disorder; these interactions are bidirectional.

Certain medical conditions may provoke or mimic major depressive disorder. These can include adrenal insufficiency, neurodegenerative disorders, hypothyroidism, vitamin deficiencies, stroke, multiple sclerosis, cancers, obstructive sleep apnea, systemic lupus erythematosus, certain toxins, or brain injury. There are no reliable laboratory screening tests to diagnose major depressive disorder. Rather, laboratory examination should be guided by the medical history and physical examination (e.g., head imaging with focal neurologic deficits on exam).

Major depressive disorder presents clinically as a 2-week period of sad mood or anhedonia (loss of pleasure from normally enjoyable experiences), with at least five or more associated symptoms of impaired energy or concentration, insomnia, loss of appetite, feelings of worthlessness or guilt, or recurrent thoughts of death or suicide. The presence of predominant diurnal mood fluctuation—feeling worse in the morning—is almost pathognomonic of major depressive disorder. It is not uncommon to find disturbed sleep architecture with shortened rapid eye movement latency.

Suicidal ideation or suicide attempts are a major concern in the care of patients with major depressive disorder ( Fig. 41.1 ). Although overt suicide attempts are notoriously difficult to predict, physicians must maintain a heightened sense of alertness to assessing suicide risk. Screening tools and assessment instruments are available that can support the clinical examination (e.g., Columbia-Suicide Severity Rating Scale). One must always stand by to offer help and intervene when necessary, especially with the patient having significant suicidal risk factors—previous suicide attempts, substance use, being male, intense anxiety or agitation, social isolation, advanced age, or psychosis.

Major depressive disorder has graded levels of severity from mild, moderate, to severe. The severe form is characterized by increasing numbers of symptoms or the presence of psychosis. The psychotic phenomena are typically characterized by delusions that are “affect consonant”—for example, delusions of poverty, moral depravity, or life-threatening illness. The recognition of psychotic thinking in the depressed patient has very definite therapeutic consequences. This subgroup of patients typically fails to respond to standard antidepressant medications and can instead benefit more robustly from electroconvulsive therapy or a combination of antidepressant and antipsychotic medication ( Fig. 41.2 ).

Treatment of major depressive disorder combines specific pharmacologic medications with psychotherapy. Studies have repeatedly demonstrated the superiority of combined pharmacologic and psychotherapeutic intervention to either intervention alone. Goals of treatment of a major depressive episode are symptom remission and improving function. Treatment outcomes can be commonly monitored with patient reported or provider administered questionnaires and scales that are increasingly incorporated into general practice (e.g., Patient Health Questionnaire-9, Montgomery-Asberg Depression Rating Scale, and Beck Depression Inventory).

There are various psychological frameworks describing depression in individuals. Aaron Beck introduced the cognitive triad of depression, linking an individual's negative view of the world, pessimism of the future, and negative view of himself or herself. These elements provide a basis for the direct psychological interventions of cognitive-behavioral therapy (CBT), a validated and effective psychological treatment for major depressive disorder.

Serotonin reuptake inhibitors (SRIs) are the preferred pharmacologic agents for initial treatment. Other pharmacologic agents have demonstrated equal efficacy to SRIs, although with varying mechanisms of action that modulate combinations of monoamines: serotonin and norepinephrine reuptake inhibitors (SNRIs), norepinephrine and dopamine reuptake inhibitors (NDI), and serotonergic agonists or alpha-2 inhibitors. Newer agents with more specific receptor profiles continue to be developed. Large, multicentered pharmacologic trials have demonstrated the relative efficacy of these agents in the treatment of major depressive disorder.

Older agents, including tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs), remain efficacious; unfortunately these agents have an increasing burden of side effects, including lethal toxidromes, cardiac conduction abnormalities, and a narrow therapeutic index. However, these agents may be useful in specific situations of major depression with comorbid illness (e.g., tricyclic use for a migrainous patient or selegiline for a patient with Parkinson disease).

Patients who have only a partial response to pharmacologic treatment may sometimes respond to various other therapeutic maneuvers. These include a switch to a different class of antidepressant, addition of a second antidepressant of a different class, or augmentation with lithium, triiodothyronine (T3), or atypical antipsychotic agent. However, likelihood of symptom remission is reduced with each subsequent failed therapeutic trial.

Bipolar disorder may be present in at least 10% of individuals presenting with what appears at first to be unipolar, major depressive disorder; this creates a unique diagnostic challenge. A heightened level of suspicion for the presence of underlying bipolar disorder is necessary for anyone with a family history of bipolar disorder, childhood onset of depressive illness, or poor therapeutic response to past antidepressant treatments. Similarly, if the patient experiences a sudden or immediate response to initiation of antidepressant medication—that is, “switching”—rather than following the usual delayed therapeutic response, a bipolar disorder requires further consideration. Efforts should be made to limit the exposure of patients with known or suspected bipolar disorder to the usual antidepressant medications.

Additional somatic therapies for major depressive disorder include electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), bright light therapy, and vagus nerve stimulation (VNS). ECT is indicated for severely depressed individuals or those who fail medication trials. It has more than a 90% response rate in well-selected populations. ECT is also the first-line treatment for severe major depressive disorder with psychotic features, intense suicidal ideation, and otherwise medically ill patients. Unilateral electrode placement can diminish the occurrence of post-ECT confusion. Although rTMS can be used in major depressive disorder and may have a less severe side-effect profile than ECT, it has not been adopted as a first-line treatment due to modest benefits from this treatment. Patients who get depressed in the winter (i.e., major depressive disorder with seasonal component) can respond to bright light therapy, typically at 10,000 lux daily for 20–30 minutes/day. Surgical VNS placement can be used for treatment-resistant major depressive disorder. However, controversy as to its effectiveness continues.

It is important to recognize that depression is a chronic illness with a propensity for recurrence. Therefore a maintenance and prophylactic treatment protocol should be considered at the time of diagnosis for each patient. Active treatment for first episodes should last at least 6 months, preferably 1 year. After three episodes, indefinite lifelong prophylaxis with full-dose antidepressant medication is indicated.