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Bipolar disorder

Mood disorder secondary to a medical condition (thyroid, anemia, vitamin deficiency, diabetes)

Organic CNS diseases

Malignancy

Infectious mononucleosis or other viral diseases

ADHD, posttraumatic stress disorder (PTSD), eating disorders, and anxiety disorders

Sleep disorder

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

May be used to rule out other diagnoses (i.e., CBC, TSH, glucose, mono spot, and urine drug)

Follow-Up Tests & Special Considerations

None with sufficient sensitivity/specificity for diagnosis

Diagnostic Procedures/Other

Depression is primarily diagnosed after a formal interview, with supporting information from caregivers and teachers.

Standardized tests are useful as screening tools and to monitor response to treatment but should not be used as the sole basis for diagnosis:

–Beck Depression Inventory II (BDI-II): ages 13+ to 18 years (1)[A]

–Child Depression Inventory 2 (CDI2): ages 7 to 17 years

–Center for Epidemiologic Studies: Depression scale for Children (CES-D): ages 6 to 17 years

–Patient Health Questionnaire-9 (PHQ-9): ages 13 to 17 years with ideal cut point of 11 or higher (instead of 10 used for adults)

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for suicide risk in adolescents in a primary care setting.

TREATMENT

GENERALMEASURES

Active support and monitoring with short validated scales should be used in

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mild cases for 6 to 8 weeks.

Psychotherapy and/or medication should be considered if active support and monitoring do to improve symptoms (2)[A].

Treatment should include psychoeducation, supportive management, and family and school involvement (3)[C].

Initial management should include treatment planning and ensuring that the patient and family is comfortable with the plan (3)[C].

ACochrane review showed that there was no significant difference between remission rates for adolescents treated with cognitive-behavioral therapy (CBT) versus medication or combination therapy immediately postintervention (4)[A].

Amultitreatment meta-analysis showed that combined fluoxetine/CBT had higher efficacy than monotherapies, but other selective serotonin reuptake inhibitors (SSRIs), such as sertraline and escitalopram, were better tolerated (2)[A].

MEDICATION

First Line

Fluoxetine: for depression in age >8 years. Starting dose 10 mg/day; effective dose 10 to 60 mg/day. The most studied SSRI, with the most favorable effectiveness and safety data. It has the longest half-life of the SSRIs and is not generally associated with withdrawal symptoms between doses or upon discontinuation.

Escitalopram: for depression in age >12 years. Starting dose of 5 mg/day; effective dose of 10 to 20 mg/day

Citalopram: for depression in age >12 years. Starting dose of 10 mg/day; effective dose of 10 to 40 mg/day (5)[A]

Sertraline: for depression in age >12 years. Starting dose of 25 mg/day; effective dose of 50 to 200 mg/day (5)[A]

Can titrate dose every 1 to 2 weeks if no significant adverse effects emerge (headaches, GI upset, insomnia, agitation, behavior activation, suicidal thoughts) (5)[A]

SSRI black box warning to monitor for worsening condition, behavior changes, and suicidal thoughts (5)[A]

Antidepressant treatment should be continued for 6 to 12 months at full therapeutic dose after the resolution of symptoms at the same dosage (3)[C]. Given their rates of increased drug metabolism, adolescents may be at higher risk for withdrawal symptoms from SSRIs than adults; if these are present,

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twice-daily dosing may be considered (2)[A].

All other SSRIs except fluoxetine should be slowly tapered when discontinued (2)[A].

Pediatric Considerations

Tricyclic antidepressants (TCAs) have not been proven to be effective in adolescents and should not be used (2)[A].

Paroxetine (SSRI): Avoid use due to short half-life, associated withdrawal symptoms, and higher association with suicidal ideation.

ISSUES FOR REFERRAL

Collaborative care interventions between mental health and primary care have a greater improvement in depressive symptoms after 12 months (5)[B].

Primary care providers should provide initial treatment of pediatric depression. Refer to a child psychiatrist for severe, recurrent, or treatmentresistant depression or if the patient has comorbidities.

COMPLEMENTARY& ALTERNATIVE MEDICINE

Physical exercise and light therapy may have a mild to moderate effect.

There is some evidence that online therapies may be beneficial in treatment of adolescent depression.

St. John’s wort, acupuncture, S-adenosylmethionine, and 5-hydroxytryptophan have not been shown to have an effect or have inadequate studies to support use in adolescent depression.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

If severely depressed, psychotic, suicidal, or homicidal, one-on-one supervision may be needed.

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Patient Monitoring

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Systematic and regular tracking of goals and outcomes from treatment should be performed, including assessment of depressive symptoms and functioning in home, school, and peer settings (5)[A].

Diagnosis and initial treatment should be reassessed if no improvement is noted after 6 to 8 weeks of treatment (5)[A].

The goal of treatment should be sustained symptom remission and restoration of full function.

Educate patients and family members about the causes, symptoms, course and treatments of depression, risks of treatments, and risk of no treatment.

PROGNOSIS

60–90% of episodes remit within 1 year.

50–70% of remissions develop subsequent depressive episodes within 5 years.

Depression in adolescence predicts mental health disorders in adult life, psychosocial difficulties, and ill health.

Baseline symptom severity and comorbid anxiety may impact treatment response.

Parental depression at baseline significantly affects intervention effects.

COMPLICATIONS

Treatment-induced mania, aggression, or lack of improvement in symptoms

School failure/refusal

One-third of adolescents with suicidal ideation go on to make an attempt.

REFERENCES

1.Thapar A, Collishaw S, Pine DS, et al. Depression in adolescence. Lancet. 2012;379(9820):1056–1067.

2.Ma D, Zhang Z, Zhang X, et al. Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multipletreatments meta-analysis. Curr Med Res Opin. 2014;30(6):971–995.

3.Cheung AH, Kozloff N, Sacks D. Pediatric depression: an evidence-based update on treatment interventions. Curr Psychiatry Rep. 2013;15(8):381.

4.Cox GR, Callahan P, Churchill R, et al. Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents. Cochrane Database Syst Rev. 2014; (11):CD008324.

5.Reeves GM, Riddle MA. Apractical and effective primary care intervention

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for treating adolescent depression. JAMA. 2013;312(8):797–798.

ADDITIONALREADING

LeFevre ML; for U.S. Preventive Services Task Force. Screening for suicide risk in adolescents, adults, and older adults in primary care: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med.

2014;160(10):719–726.

Pooper CW. Mood disorders in youth: exercise, light therapy, and pharmacologic complementary and integrative approaches. Child Adolesc Psychiatr Clin N Am. 2013;22(3):403–441.

CODES

ICD10

F32.9 Major depressive disorder, single episode, unspecified

F33.9 Major depressive disorder, recurrent, unspecified F32.8 Other recurrent depressive disorders

CLINICALPEARLS

Adolescent depression is underdiagnosed and often presents with irritability and anhedonia.

Fluoxetine is the most studied FDA-approved for treatment of adolescent depression.

Escitalopram, citalopram, and sertraline are also FDA-approved antidepressants.

CBT combined with fluoxetine is efficacious for adolescents with major depression.

Paroxetine and TCAs should not be used to treat adolescent depression.

Referral to a child psychiatrist is appropriate for complex cases or treatmentresistant depression.

Monitor all adolescents with depression for suicidality, especially during the first month of treatment with an antidepressant.

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DEPRESSION, GERIATRIC

Fozia Akhtar Ali, MD Nneka I. Okafor, MD, MPH

BASICS

DESCRIPTION

Depression is a primary mood disorder characterized by a depressed mood and/or a markedly decreased interest or pleasure in normally enjoyable activities most of the day, almost every day for at least 2 weeks, and causing significant distress or impairment in daily functioning with at least four other symptoms of depression.

Depression is not a normal result of aging.

EPIDEMIOLOGY

Prevalence rates among the elderly vary largely depending on the specific diagnostic instruments used and their current health and/or home environment:

2–10% of community-dwelling elderly

5–10% seen in primary care clinics

10–37% of hospitalized elderly patients

12–27% of nursing home residents

ETIOLOGYAND PATHOPHYSIOLOGY

Significant gaps exist in the understanding of the underlying pathophysiology. Ongoing research has identified several possible mechanisms, including the following:

–Monoamine transmission and associated transcriptional and translational activity

Epigenetic mechanisms and resilience factors

Neurotrophins, neurogenesis, neuroimmune systems, and neuroendocrine systems

Depression appears to be a complex interaction between heritable and environmental factors.

RISK FACTORS

General

– Female sex

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–Lower socioeconomic status

–Widowed, divorced, or separated marital status

–Chronic physical health condition(s)

–History of mental health problems

–Family history of depression

–Death of a loved one

–Caregiving

–Social isolation

–Functional/cognitive impairment

–Lack/loss of social support

–Significant loss of independence

–Uncontrolled or chronic pain

–Insomnia/sleep disturbance

Prevalence of depression in medical illness

–Stroke (22–50%)

–Cancer (18–50%)

–Myocardial infarction (15–45%)

–Parkinson disease (10–39%)

–Rheumatoid arthritis (13%)

–Diabetes mellitus (5–11%)

–Alzheimer dementia (5–15%)

Suicide

–Suicide is the 11th leading cause of death in the United States for all ages.

–Elderly account for 24% of all completed suicides.

–Suicide rates are highest for males aged >85 years (rate 55/100,000).

DIAGNOSIS

HISTORY

Depressed mood most of the day, nearly every day, and/or loss of interest/pleasure in life for at least 2 weeks

Other common symptoms include the following:

–Feeling hopeless, helpless, or worthless

–Insomnia and loss of appetite/weight (alternatively, hypersomnia with increased appetite/weight in atypical depression)

–Fatigue and loss of energy

–Somatic symptoms (headaches, chronic pain)

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–Neglect of personal responsibility or care

–Psychomotor retardation or agitation

–Diminished concentration, indecisiveness

–Thoughts of death or suicide

Screening with “SIGECAPS”

–Sleep: changes in sleep habits from baseline, including excessive sleep, early waking, or inability to fall asleep

–Interest: loss of interest in previously enjoyable activities (anhedonia)

–Guilt: excessive or inappropriate guilt that may or may not focus on a specific problem or circumstance

–Energy: perceived lack of energy

–Concentration: inability to concentrate on specific tasks

–Appetite: increase/decrease in appetite

–Psychomotor: restlessness and agitation or the perception that everyday activities are too strenuous to manage

–Suicidality: desire to end life or hurt oneself, harmful thoughts directed internally, recurrent thoughts of death or thoughts of homicidality

PHYSICALEXAM

Mental status exam, thorough neurologic exam, and general physical exam to rule out other conditions

DIFFERENTIALDIAGNOSIS

Concurrent medical conditions, cognitive disorders, and medications may cause symptoms that mimic depression:

Medical conditions: hypothyroidism, vitamin B12 or folate deficiency, liver or

renal failure, cancers, stroke, sleep disorders, electrolyte imbalances, Cushing disease, chronic fatigue syndrome

Dementia and neurodegenerative disorders

Delirium

Medication-induced: interferon-α, β2-blockers, isotretinoin, benzodiazepines, glucocorticoids, levodopa, clonidine, H2 blockers, baclofen, varenicline,

metoclopramide, reserpine

Psychiatric disorders: adjustment disorder with depressed mood, grief reaction, bipolar disorder, dysthymic disorder, anxiety disorders, substance abuse–related mood disorders, psychotic disorders

DIAGNOSTIC TESTS & INTERPRETATION

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Initial Tests (lab, imaging)

Initial laboratory evaluation is done primarily to rule out potential medical factors that could be causing symptoms.

Thyroid-stimulating hormone (hypothyroidism)

CBC with differential (anemia, infection)

Vitamin B12, folic acid (deficiencies)

Urinalysis (urinary tract infection, glucosuria)

Comprehensive metabolic panel (uremia, hypoor hyperglycemia, hypoor hypernatremia, hypercalcemia, liver failure)

Urine drug screen

24-hour urine-free cortisol (Cushing disease)

Follow-Up Tests & Special Considerations

Additional testing for possible confounding medical and cognitive disorders, as warranted; may consider a sleep study for patients with decreased energy, sleep disturbances, changes in concentration, or psychomotor activity

Diagnostic Procedures/Other

Validated screening tools and rating scales:

Geriatric Depression Scale: 15or 30-point scales

Patient Health Questionnaire (PHQ-2 or PHQ-9)

Hamilton Depression Rating Scale

Beck Depression Inventory

Cornell Scale for Depression in Dementia (1)[A]

TREATMENT

Although response alone, usually interpreted as a 50% reduction in symptoms, can be clinically meaningful, the goal is to treat patients to the point of remission (i.e., essentially the absence of depressive symptoms).

GENERALMEASURES

Lifestyle modifications:

–Increase physical activity.

–Improve nutrition.

–Encourage social interactions.

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– Exercise: may be beneficial for depression in the elderly population (2)[A]

Psychotherapy: Studies do show some benefit in depressed elderly patients (3) [B]:

–Cognitive-behavioral therapy

–Problem-solving therapy

–Interpersonal therapy

–Psychodynamic psychotherapy

MEDICATION

Typically, more conservative initial dosing and titration of antidepressants in the elderly, starting with 1/2 of the usual initiation dose and increasing within 2 to 4 weeks, as tolerated

Continue titrating dose every 2 to 4 weeks, as appropriate, to reach an adequate treatment dose.

First Line

SSRIs have been found to be effective in treating depression in the elderly and are considered first line in pharmacotherapy for depression (2)[A].

No single SSRI clearly outperforms others in the class; choice of medication often reflects side effect profile or practitioner familiarity (4)[A]:

–Citalopram: Start at 10 mg/day; treatment range 10 to 20 mg/day

–Sertraline: Start at 25 to 50 mg/day; treatment range 50 to 200 mg/day

–Escitalopram: Start at 10 mg/day; treatment range 10 to 20 mg/day

–Fluoxetine: Start at 10 mg/day; treatment range 20 to 60 mg/day

–Paroxetine: Start at 10 mg/day; treatment range 20 to 40 mg/day

SSRIs should not be used concomitantly with monoamine oxidase inhibitors (MAOIs).

Common side effects—increased risk of falls, nausea, diarrhea, sexual dysfunction

Second Line

Atypical antidepressants: more effective than placebo in treatment of depression in the elderly, although additional studies are needed to better delineate patient factors that determine response:

Bupropion (sustained/twice a day and extended/once daily available): Start at 150 mg/day. Increase dose in 3 to 4 days. Treatment range 300 to 450 mg/day. Avoid in patients with elevated seizure risk, tremors, or anxiety (5)[A].

Venlafaxine (immediateand extended-release available): Start at 37.5 mg/day

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