MAJOR PSYCHIATRIC DISORDERS (AXIS I DIAGNOSES)
MOOD DISORDERS (MAJOR AFFECTIVE DISORDERS)
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
                CLINICAL FEATURES              
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):
- Depressed mood
 - Loss of interest or pleasure
 - Change in appetite or weight
 - Insomnia or hypersomnia
 - Psychomotor agitation or retardation
 - Fatigue or loss of energy
 - Feelings of worthlessness or inappropriate guilt
 - Decreased ability to concentrate and make decisions
 - 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).
                SUICIDE              
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.
                DEPRESSION WITH MEDICAL ILLNESS              
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
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)
                CLINICAL FEATURES              
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
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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Citation
Kasper, Dennis L., et al., editors. "MAJOR PSYCHIATRIC DISORDERS (AXIS I DIAGNOSES)." Harrison's Manual of Medicine, 20th ed., McGraw Hill Inc., 2020. harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623494/all/MAJOR_PSYCHIATRIC_DISORDERS__AXIS_I_DIAGNOSES_. 
MAJOR PSYCHIATRIC DISORDERS (AXIS I DIAGNOSES). In: Kasper DLD, Fauci ASA, Hauser SLS, et al, eds. Harrison's Manual of Medicine. McGraw Hill Inc.; 2020. https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623494/all/MAJOR_PSYCHIATRIC_DISORDERS__AXIS_I_DIAGNOSES_. Accessed November 4, 2025.
MAJOR PSYCHIATRIC DISORDERS (AXIS I DIAGNOSES). (2020). In Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., & Loscalzo, J. (Eds.), Harrison's Manual of Medicine (20th ed.). McGraw Hill Inc.. https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623494/all/MAJOR_PSYCHIATRIC_DISORDERS__AXIS_I_DIAGNOSES_
MAJOR PSYCHIATRIC DISORDERS (AXIS I DIAGNOSES) [Internet]. In: Kasper DLD, Fauci ASA, Hauser SLS, Longo DLD, Jameson JLJ, Loscalzo JJ, editors. Harrison's Manual of Medicine. McGraw Hill Inc.; 2020. [cited 2025 November 04]. Available from: https://harrisons.unboundmedicine.com/harrisons/view/Harrisons-Manual-of-Medicine/623494/all/MAJOR_PSYCHIATRIC_DISORDERS__AXIS_I_DIAGNOSES_.
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