Clinical Pearl Series from Yale-G First Aid: Crush USMLE Step 2CK & Step 3 by Yale Gong, MD, Sr. Medical Advisor at www.medicine.net (Copyrighted)
MOOD DISORDERS
Depressive Disorders
These include a group of mood disorders with depressive features. If episodes of mania, hypomania, and depression occur, it is considered bipolar disorder.
Disruptive Mood Dysregulation Disorder (DMDD)
DMDD (previously as a bipolar disorder) is a condition in which a child or adolescent experiences ongoing irritability, anger, and frequent, severe/intense temper outbursts that are grossly out of proportion to the situation at hand. The symptoms go beyond a “bad mood.” These occur, on average, more than 3 times each week for more than 1 year up to age 18 years. Youth with DMDD experience significant problems at home, at school, and often with peers. DMDD is at an increased risk of developing depression and anxiety in the future, but not adult bipolar disorder. It occurs more often in boys than girls and is treatable.
Essentials of diagnosis
1. Symptoms go far beyond temper tantrums in children to temper outbursts that are grossly out of proportion in intensity to the situation, which is severe enough for clinical attention.
2. Between outbursts, children display a persistently irritable or angry mood, most of the day and nearly every day.
3. A DMDD diagnosis requires the above symptoms to be present in at least two settings (at home, at school, or with peers) for 12 or more months, and symptoms must be severe in at least one of these settings. During this period, the child must not have gone 3 or more consecutive months without symptoms. The onset of symptoms must be before age 10, and a DMDD diagnosis should not be made for the first time before age 6 or after age 18.
Treatment
Individualized medications (atypical antipsychotics), psychotherapy and a combination of the two are effective therapies. Individuals also tend to require mental health care services, including physician visits and sometimes hospitalization.
Major Depressive Disorder (MDD)
It is also called major depression or unipolar depression, including single and recurrent episodes, defined as depressed mood or anhedonia (loss of pleasure or interest) more than 2 week’s course that changes from the patient’s previous level of functioning. The course is mostly between 2 weeks and 2 years. Prevalence is 15-25%; ratio between female and male is 2:1. Onset is usually 20-40 y/a. Suicide mortality is 10-15%. Subclasses are Single Episode and Recurrent MDD. The prognosis is better than other mood disorders if treated properly, and is worse if psychotic symptoms are present.
Etiology
Studies have shown that depression is influenced by both biological and environmental factors –associated with genetics (first degree relatives of patients with higher risk), low levels of serotonin (5-HT) and norepinephrine (NE), abnormal dopamine (DA), sex hormone imbalances, chronic diseases, stress (divorce, job loss), and loneliness.
Essentials of diagnosis
1. DSM-5 criteria: ≥ five of the following symptoms must have been present for 2 weeks: (1) Depressed mood (feeling sadness or emptiness) most of the day and nearly every day; (2) Loss of energy, anhedonia, or fatigue most of the day; (3) Reduced interest in activities that used to be enjoyed, sleep disturbances (insomnia or hypersomnia); (4) Difficulty concentrating, memorizing, or making decisions; (5) Feelings of worthlessness or guilt and recurrent suicide thoughts or intentions; (6) Others: psychomotor agitation or retardation; significant weight loss or gain. (7) Absence of a manic or hypomanic episode.
2. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
3. The episode is not attributable to the physiological effects of a substance/drug or to another medical condition (hypothyroidism, chronic fatigue syndrome, etc.), and is not better explained by other psychotic disorders.
4. Physical examination (P/E) is usually normal but dexamethasone suppression test or thyrotropin-releasing hormone test is abnormal.
Differential diagnosis
Dysthymia (with milder symptoms lasting more than 2 years); normal grief; drug abuse; drug effects; hypothyroidism; Parkinson disease; dementia; postpartum depression/Blues/psychosis.
Postpartum Blues (“Baby Blues”):
Mild depression sometimes occurs immediately after birth and lasts up to 2 weeks. Mother may have sadness, mood lability, and tearfulness, but cares about the baby. It’s self-limited and no treatment is necessary.
Postpartum depression:
Typical depressed symptoms usually occur within 1-3 months after birth (mostly the 2nd baby) and symptoms may continue more than 1 month. Patient usually has depressed mood, excessive anxiety, sleep disturbances, and weight changes. The mother may have negative thoughts of hurting the baby. Treat the patient with antidepressants.
Postpartum psychosis:
Severe depression and psychosis may occur 2-3 weeks after the first birth and may continue. Patient usually has depression and delusion, and may have thoughts of hurting the baby. Treat with anti-depressants and mood stabilizers or antipsychotics.
Normal grief:
Also known as Bereavement, it usually begins after the death of a loved one, presenting with feelings of sadness, tearfulness, worrying about the deceased, irritability, disturbed sleep, and poor concentration. It typically lasts < 6 months and only needs supportive care (psychotherapy).
Treatment
In principle, combined pharmacotherapy and psychotherapy are the most effective therapies.
1. Cognitive psychotherapy is the initial treatment, which will help change the patient’s distorted thoughts about self, future, and the world, and help the patient deal with conflicts, stress, sense of loss, etc. Combined with an SSRI, it will be the most effective treatment. Patient must first be protected from suicide.
2. Pharmacotherapy—requires 3-4 weeks for initial effects and 6 months for maintenance.
(1) SSRIs (Selective serotonin reuptake inhibitor, increasing serotonin):
They are the 1st line medications for both depression and anxiety disorder. With low toxicity but more sexual S/E, CNS and GI toxicity; avoid use with MAOIs (Serotonin syndrome: fever, CVS collapse), avoid TCAs. Fluoxetine—most commonly used; sertraline—safe with CVD; paroxetine—good with compulsive and panic disorder; newer and stronger: citalopram and escitalopram. Escitalopram and sertraline provide the best combination of efficacy and acceptability.
(2) TCAs (Tricyclic antidepressants, increasing 5-HT and NE):
They are the 2nd line drugs for depression, anxiety, chronic pain (amitriptyline), and enuresis (imipramine). Among them, nortriptyline has sedation while desipramine has not. This group of drugs has low cost but significant adverse effects—Cardiac arrhythmias, anticholinergic effects, orthostatic hypotension, sexual dysfunction, and seizures.
(3) MAOIs (Monoamine oxidase inhibitor, increasing NE):
Phenelzine and tranylcypromine are used mostly. It’s the best treatment for atypical depression with brief psychosis, phobia, hypersomnolence, or hyperphagia. It requires dietary restrictions (avoid cheese, red wine, and anti-cough agents) to avoid serious “hypertensive crisis”. Other S/E: Sexual dysfunction, orthostatic hypotension, weight gain, and sleep disorder.
(4) Heterocyclics: 2nd and 3rd-generation antidepressants with varied actions, better for atypical depression.
Bupropion—increasing both DA and NE; best for depression with ADHD, alcohol/smoking cessation, or confusion; with risk of seizure but least adverse effects on sexual function.
Trazodone—inhibiting 5-HT reuptake, good choice for depression with sleep disorder; S/E: It may cause priapism.
(5) Both short-term and maintenance treatment with esketamine are beneficial for treatment-resistant depression.
3. ECT (Electroconvulsive therapy):
It is indicated in patients with serious suicidal ideas or adverse effects of medication. It’s also safe in the first trimester pregnancy. Adverse effects include headaches, transient memory loss, and posterior shoulder dislocation (rare).
Persistent Depressive Disorder—Dysthymia
Definition and diagnosis: A chronic disorder characterized by a depressed mood lasting most of the time during the day and most of the days in a week but milder than major depression for more than 2 years (In DSM-4, it is “Chronic major depression”).
Risk factors: More common in females with low social-economic status (SES). Most patients have other psychiatric disorders such as anxiety, substance abuse or borderline personality disorder.
Treatment
1. Long-term individual insight-oriented psychotherapy: Effective in helping patient overcome long-term despair sense and childhood conflicts.
2. Antidepressant therapy: If the above therapy fails, a small dose of SSRIs can be started.
Differential diagnosis: Same as for major depression.
Atypical Depression
It is characterized by reverse vegetative changes such as increased sleep, appetite, and weight. Depressed mood tends to be worse in the evening. Patient complains of “feeling heavy.” Atypical depression is more common in females and in individuals with bipolar I, bipolar II disorder, major depressive disorder, and “seasonal affective disorder”. Depressive episodes in bipolar disorder tend to have atypical features, as does depression with seasonal patterns.
Treatment
Lifestyle modification plus medications are helpful. A SSRI (with less S/E) can be initially used. If it’s not effective, a MAOI is chosen.
Seasonal Pattern Specifier for Mood Disorders
Formerly known as seasonal affective disorder (SAD) or seasonal depression, it is characterized by seasonal, recurrent major depressive disorder that occurs at a specific time of the year (mostly during autumn and winter) and fully remits otherwise. Lethargy and increased weight and sleep may be present. In DSM-5, it is no longer classified as a unique mood disorder, but a “Seasonal Pattern Specifier”.
Treatment
Phototherapy and an antidepressive (bupropion) are helpful.
This is a potentially life-threatening condition occurring during therapeutic use of SSRIs, usually with inadvertent interactions between medications or abused substances with serotonic nature.
Common manifestations
1. Cognitive effects: agitation, confusion, hallucinations, and hypomania.
2. Automatic effects: sweating, hyperthermia, tachycardia, shivering, nausea, and diarrhea.
3. Somatic effects: tremors, myoclonus, etc.
Treatment
1. Stop the SSRIs. 2. Symptomatic treatment of fever, tachycardia, hypertension, diarrhea, etc. 3. Use serotonin antagonist—cyproheptadine if it is severe.
Bipolar and Related Disorders
Definition: Bipolar disorder is a mood disorder characterized by episodes of mania, hypomania, and major depression causing significant functional impairment. The onset age is about 30. Prevalence is 1-4% for both males and females. The subtypes include bipolar I and bipolar II.
Subtypes
1. Bipolar I: More than one manic episode or mixed depressive-manic episode.
2. Bipolar II: More than one major depressive and one hypomanic episode. This type does not meet the criteria for full manic or mixed depressive-manic episodes.
3. Other subtypes may include (1) Rapid cycling type: more than four episodes (major depressive, manic, mixed, or hypomanic episode) in 1 year; (2) Cyclothymic type: chronic and less severe, with alternating periods of hypomania and moderate depression for more than 2 years.
Etiology
Unknown. It’s more prevalent among high-income and low-education population and has a strong genetic component. It may coexist with anxiety, alcohol dependence, and substance abuse. Suicide mortality is up to 10%.
Essentials of diagnosis
1. Patient usually has persistently elevated, expansive mood lasting longer than 1 week—increased self-esteem or grandiosity, sexual activity, and distractibility; excessive goal-directed activities and talkativeness (pressured speech); decreased need for sleep; flight of ideas; psychomotor agitation.
2. P/E results are mostly normal. Diagnosis is made based on the above symptoms and by excluding other relevant disorders and drug effects (e.g., using an antidepressant may trigger manic episode).
Differential diagnosis
Schizophrenia, personality disorders, hyperthyroidism, and drug effects.
Treatment
1. Acute mania: Hospitalize the patient who is usually a risk to self and others. Most patients are initially treated with valproate or lithium +/- an antipsychotic as the first-line therapy. Mood stabilizer lithium is also used for maintenance. It takes 2-4 weeks to be fully effective and is tapered off in 1 year. Carbamazepine or lamotrigine is used as the second-line drug. Antipsychotics (haloperidol) are used in severe psychic or refractory agitation due to shorter onset of action.
2. Bipolar depression: Mood stabilizers should be used first to avoid inducing mania; antidepressants SSRIs may be added but not alone. ECT is only indicated in refractory cases.
3. Combined psychotherapy is helpful.
Summary: Main Indications and Adverse Effects (S/E) of Mood Stabilizers
Valproic acid
Indications: Acute mania and bipolar I disorder (first-line); convulsion. S/E: GI toxicity, tremor, sedation, alopecia, and weight gain; rarely, pancreatitis, hepatotoxicity, thrombocytopenia, agranulocytosis.
Indications: Acute mania (first-line and maintenance therapy); bipolar disorder (prophylaxis). S/E: Thirst, polyuria, diabetes insipidus, hypothyroidism, GI, teratogenicity, tremor, ataxia, delirium, seizure. Avoid use if renal function is impaired.
Indications: 2nd-line for bipolar disorder; convulsion; peripheral neuralgia. S/E: Skin rash, cardiac atrium-ventricle block, leukopenia; rarely, aplastic anemia or Stevens-Johnson syndrome.
Lamotrigine Indications: 2nd-line for bipolar disorder; convulsion; peripheral neuralgia. S/E: Blurred vision, GI, Stevens-Johnson syndrome.
Cyclothymic Disorder
Definition and diagnosis: It’s a chronic disorder characterized by many periods of depressed mood and hypomanic mood for more than 2 years. It’s considered a milder form of bipolar II disorder.
Risk factors: More frequent in females and in association with bipolar disorder, borderline personality disorder, substance abuse, and marriage problems.
Treatment
1. Antimanic drugs (lithium, valproic acid, or carbamazepine) are usually the drugs of choice.
2. Psychotherapy can help patient gain insight into their illness and how to cope with it.
Differential diagnosis
Substance abuse, bipolar disorder, and personality disorder.
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