Mood disorders are characterized by a disturbance in the regulation of mood, behavior, and affect; subdivided into (1) depressive disorders, (2) bipolar disorders (depression plus manic or hypomanic episodes), and (3) depression in association with medical illness or alcohol and substance abuse (see Chaps. 202: Alcohol Use Disorder , 203 , and 204 ).

Major Depression


Affects 15% of the general population at some point in life; 6–8% of all outpatients in primary care settings satisfy diagnostic criteria. Diagnosis is made when five (or more) of the following symptoms have been present for 2 weeks (at least one of the symptoms must be #1 or #2 below):

  1. Depressed mood
  2. Loss of interest or pleasure
  3. Change in appetite or weight
  4. Insomnia or hypersomnia
  5. Psychomotor agitation or retardation
  6. Fatigue or loss of energy
  7. Feelings of worthlessness or inappropriate guilt
  8. Decreased ability to concentrate and make decisions
  9. Recurrent thoughts of death or suicide

A small number of pts with major depression will have psychotic symptoms (hallucinations and delusions) with their depressed mood. Negative life events can precipitate depression, but genetic factors influence the sensitivity to these events.

Onset of a first depressive episode is typically in early adulthood, although major depression can occur at any age. Untreated episodes generally resolve spontaneously in a few months to a year; however, a sizable number of pts suffer from chronic, unremitting depression, or from a partial treatment response. Half of all pts experiencing a first depressive episode will go on to a recurrent course. Untreated or partially treated episodes put the pt at risk for future problems with mood disorders. Within an individual, the nature of episodes may be similar over time. A family history of mood disorder is common and tends to predict a recurrent course. Major depression can also be the initial presentation of bipolar disorder (manic depressive illness).


Approximately 4–5% of all depressed pts will commit suicide, and most will have sought help from a physician within 1 month of their death. Physicians must always inquire about suicide when evaluating a pt with depression.


Virtually every class of medication can potentially induce or worsen depression. Antihypertensive drugs, anticholesterolemic agents, and antiarrhythmic agents are common triggers of depressive symptoms. Among the antihypertensive agents, β-adrenergic blockers and, to a lesser extent, calcium channel blockers are most likely to cause depressed mood. Iatrogenic depression should also be considered in pts receiving glucocorticoids, antimicrobials, systemic analgesics, antiparkinsonian medications, and anticonvulsants.

Between 20% and 30% of cardiac pts manifest a depressive disorder. Tricyclic antidepressants (TCAs) are contraindicated in pts with bundle branch block, and TCA-induced tachycardia is an additional concern in pts with congestive heart failure. Selective serotonin reuptake inhibitors (SSRIs) appear not to induce ECG changes or adverse cardiac events, and thus, are reasonable first-line drugs for pts at risk for TCA-related complications. SSRIs may interfere with hepatic metabolism of warfain, however, causing increased anticoagulation.

In cancer, the prevalence of depression is 25%, but it occurs in 40–50% of pts with cancers of the pancreas or oropharynx. Extreme cachexia from cancer may be misinterpreted as depression. Antidepressant medications in cancer pts improve quality of life as well as mood.

Diabetes mellitus is another consideration; the severity of the mood state correlates with the level of hyperglycemia and the presence of diabetic complications. Monoamine oxidase inhibitors (MAOIs) can induce hypoglycemia and weight gain. TCAs can produce hyperglycemia and carbohydrate craving. SSRIs, like MAOIs, may reduce fasting plasma glucose, but they are easier to use and may also improve dietary and medication compliance.

Depression may also occur with hypothyroidism or hyperthyroidism, in neurologic disorders, in HIV-positive individuals, and in chronic hepatitis C infection. Some chronic disorders of uncertain etiology, such as chronic fatigue syndrome and fibromyalgia, are strongly associated with depression.

Treatment: Major Depression

  • Pts with suicidal ideation require treatment by a psychiatrist and may require hospitalization.
  • Most other pts with an uncomplicated unipolar major depression (a major depression that is not part of a cyclical mood disorder, such as a bipolar disorder) can be successfully treated by a nonpsychiatric physician.
  • Vigorous intervention and successful treatment appear to decrease the risk of future relapse.
  • Pts who do not respond fully to standard treatment should be referred to a psychiatrist.
  • Antidepressant medications are the mainstay of treatment, although combined treatment with psychotherapy improves outcome. Symptoms are ameliorated after 6–8 weeks at a therapeutic dose in 60–70% of pts.
  • A guideline for the medical management of depression is shown in Fig. 199-1 .
  • Once remission is achieved, antidepressants should be continued for 6–9 months. Pts must be monitored carefully after termination of treatment since relapse is common.
  • Pts with two or more episodes of depression should be considered for indefinite maintenance treatment.
  • Electroconvulsive therapy is generally reserved for treatment-resistant depression unresponsive to medication or for pts in whom the use of antidepressants is medically contraindicated.
  • Transcranial magnetic stimulation (TMS) is approved for treatment-resistant depression.
  • Vagus nerve stimulation (VNS) has been approved for treatment-resistant depression as well, but its degree of efficacy is controversial.
  • Other emerging approaches for refractory depression include low intensity transcranial current stimulation (tCS), intravenous or intranasal forms of ketamine, and deep brain stimulation of the internal capsule and cingulate region.
FIGURE 199-1
A guideline for the medical management of major depressive disorder. SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

Bipolar Disorder (Manic Depressive Illness)


A cyclical mood disorder in which episodes of major depression are interspersed with episodes of mania or hypomania; 1.5% of the population is affected. Most pts initially present with a manic episode in adolescence or young adulthood. Antidepressant therapy may provoke a manic episode; pts with a major depressive episode and a prior history of “highs” (mania or hypomania—which can be pleasant/euphoric or irritable/impulsive) and/or a family history of bipolar disorder should not be treated with antidepressants, but instead referred promptly to a psychiatrist.

With mania, an elevated, expansive mood, irritability, angry outbursts, and impulsivity are characteristic. Specific symptoms include (1) unusual talkativeness, (2) flight of ideas and racing thoughts, (3) inflated self-esteem that can become delusional, (4) decreased need for sleep (often the first feature of an incipient manic episode), (5) increase in goal-directed activity or psychomotor agitation, (6) distractibility, and (7) excessive involvement in risky activities (buying sprees, sexual indiscretions). Pts with full-blown mania can become psychotic. Hypomania is characterized by attenuated manic symptoms and is greatly underdiagnosed, as are “mixed episodes,” where both depressive and manic or hypomanic symptoms coexist simultaneously.

Untreated, a manic or depressive episode typically lasts for several weeks but can last for 8–12 months. Variants of bipolar disorder include rapid and ultrarapid cycling (manic and depressed episodes occurring at cycles of weeks, days, or hours). In many pts, especially females, antidepressants trigger rapid cycling and worsen the course of illness. Bipolar disorder has a strong genetic component; the concordance rate for monozygotic twins approaches 80%.

Treatment: Bipolar Disorder

  • Bipolar disorder is a serious, chronic illness that requires lifelong monitoring by a psychiatrist.
  • Acutely manic pts often require hospitalization to reduce environmental stimulation and to protect themselves and others from the consequences of their reckless behavior.
  • The recurrent nature of bipolar disorder necessitates maintenance treatment.
  • Mood stabilizers (lithium, valproic acid, second-generation antipsychotic drugs, carbamazepine) are effective for the resolution of acute episodes and for prophylaxis of future episodes.

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