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DIAGNOSIS

HISTORY

DSM-5 requires all of the following criteria for MDD:

Criterion A: ≥5 of the following symptoms present nearly every day during the same 2-week period, with at least 1 of the 5 being either depressed mood or loss of interest or pleasure:

–Depressed mood most of the day by subjective report or observation from other people

–Diminished interest or pleasure in all activities most of the day by subjective report or observation from other people

–Decreased or increased appetite or significant weight loss without dieting or weight gain

–Insomnia or hypersomnia

–Fatigue or energy loss

–Restlessness, irritability, or withdrawal observable by others

–Worthlessness, excessive/inappropriate guilty feelings

–Diminished thinking/concentration, poor memory, indecisiveness

–Recurrent thoughts of death, suicidal ideations, or suicide attempt or a specific plan for committing suicide

Criterion B: Symptoms cause significant social, occupational, or functional distress or impairment.

Criterion C: symptoms not attributable to substance effects or other medical conditions

Geriatric Considerations

Difficult to diagnose due to medical comorbidity

Can present with memory difficulties as chief complaint; treatment reverses memory difficulty.

Can be the initial presentation of irreversible dementia

Geriatric Depression Scale (GDS 15) improves rate of diagnosis in primary care setting (2,3)[A].

Pediatric Considerations

Can present as irritable or angry rather than sad or dejected

Failure to make expected weight gains can substitute weight loss symptom above.

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Asudden and remarkable drop in grades can indicate difficulty concentrating.

Can present with separation anxiety

PHYSICALEXAM

Complete physical with focus on endocrine, cardiac, neurologic, and psychiatric (affect, attention, cognition, memory); look for evidence of contributing medical or neurologic disorder.

DIFFERENTIALDIAGNOSIS

Psychiatric: depressed phase of bipolar disorder—inquire if prior mania, family or personal history of bipolar disorder, prior agitation, or excitement with antidepressant medication. If positive, monitor carefully for mood elevation or destabilization, adjustment disorder, and bereavement.

Neurologic or degenerative CNS diseases, dementias

Medical comorbidity: adrenal disease, thyroid disorders, diabetes, metabolic abnormalities (hypercalcemia), liver/renal failure, malignancy, chronic fatigue syndrome, fibromyalgia, lupus

Nutritional: pernicious anemia, pellagra

Medications/substances: abuse, side effects, overdose, intoxication, dependence, withdrawal

DIAGNOSTIC TESTS & INTERPRETATION

Aclinical diagnosis made by eliciting personal, family, social, and psychosocial factors

The Patient Health Questionnaire-9 (PHQ-9) is a brief screening test valid for diagnosis of MDD in primary care settings (3)[A].

Other validated standard rating scales include the following: Beck Depression Inventory, Zung, GDS 15, and so forth. Rating scales are also useful to track response to treatment over time (3)[A].

Rule out hypothyroidism, anemia, and metabolic disorders with TSH, CBC, and comprehensive metabolic panel (CMP).

Order urine drug screen if symptoms suggest intoxication.

TREATMENT

American Psychiatric Association (APA) 2010 guidelines recommend phasic approach: acute phase (first 3 months), continuation phase (4 to 9 months), and maintenance (9 months until discontinuation) (4)[A].

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Acute phase

–Full evaluation, including risk to self and others, with selection of appropriate treatment setting (hospitalization for those at risk of harm to self or others or so incapacitated as to be unable to take care of themselves and/or who have no support system to assist with treatment)

–Goal should be symptom remission, with intervention based on clinical picture, including patient’s preference, availability of services.

–For mild to moderate depression, psychotherapies (individual, interpersonal, or cognitive-behavioral therapy [CBT]) and/or medication are recommended.

–For refractory/severe depression, medication is indicated.

–For patients not responding to medication alone, CBT should be added.

–Continue to increase dosage q3–4wk until symptoms in remission. Full medication effect is complete in 4 to 6 weeks. Augmentation with second medication may be necessary.

–See within 2 to 4 weeks of starting medication and q2wk until improvement and then monthly to monitor medication changes.

–≥6 visits recommended for monitoring (younger patients, those at high suicide risk, see within 1st week, and follow frequently)

Continuation/maintenance phase

–Regular visits to monitor for signs of relapse, q3–6mo if stable; depression rating scales should be used.

–Once remission achieved, dosage should be continued for at least 6 to 9 months to reduce relapse; CBT is also effective in reducing relapse (visits typically q2wk).

–If/when drug discontinuation is considered, medications should be tapered gradually (weeks to months).

ISSUES FOR REFERRAL

Refer immediately for active suicidal ideation, severe self-neglect, and significant risk of self-harm.

Failed response to medication, suspected bipolar or personality disorder.

MEDICATION

Effectiveness of medications is comparable between/within classes; selection should be based on provider familiarity and patient characteristics/preferences (5)[A].

Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants

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(TCAs) are effective, but TCAs are second line due to side effects and lethality in overdose. Tolerability is much poorer than newer antidepressants. First-line SSRIs* (starting dose; usual dose)

–Fluoxetine (Prozac): 20 mg/day; 20 to 60 mg/day; FDA-approved for teens

–Sertraline (Zoloft): 50 mg/day; 50 to 200 mg/day

–Paroxetine (Paxil): 10 mg/day; 20 to 50 mg/day

–Paroxetine CR (Paxil CR): 12.5 mg/day; 25.0 to 62.5 mg/day

–Citalopram (Celexa): 20 mg/day; 20 to 40 mg/day (higher doses not advised; ECG monitoring for doses >40 mg/day due to increased risk of QTc prolongation)

–Escitalopram (Lexapro): 10 mg/day; 10 to 20 mg/day

–Precautions: Abrupt discontinuation may result in withdrawal symptoms (i.e., dizziness, nausea, headache, paresthesia).

–Fluoxetine, paroxetine may raise serum levels of other drugs; escitalopram, sertraline have minimal to no drug interactions.

–Common side effects: sexual dysfunction (20%), nausea, GI upset, dizziness, insomnia, headache; typically resolve in the 1st week

–Less common side effects: drowsiness, weight gain, emotional blunting, dry mouth

–*Lower starting doses for elderly, adolescents, those with comorbid conditions, panic disorder, significant anxiety, or hepatic conditions

–Paroxetine is Category D for pregnancy with increased risk of

teratogenicity in 1st trimester. Others (starting dose; usual dose)

–Venlafaxine (Effexor, Effexor XR): 37.5 mg/day; 300 mg/day

–Bupropion XL(Wellbutrin XL): 150 mg/day; 300 to 450 mg/day (precautions: powers seizure threshold at doses >450 mg/day)

–Duloxetine (Cymbalta): 30 mg/day; 60 to 120 mg/day

–Desvenlafaxine (Pristiq): 50 to 100 mg/day

–Vilazodone: (Viibryd) start 10 mg/day; usual target 40 mg/day

–Vortioxetine: (Trintellix) start 5 mg/day; target dose 20 mg/day

–Levomilnacipran: (Fetzima) start 20 mg/day; target dose 40 to 120 mg/day

Second Line

TCAs (starting dose; usual dose)

–Amitriptyline (Elavil): 25 to 50 mg/day; 100 to 300 mg/day

–Nortriptyline (Pamelor): 25 mg/day; 50 to 150 mg/day

–Doxepin (Sinequan): 25 to 50 mg/day; 100 to 300 mg/day

–Imipramine (Tofranil, Tofranil-PM): 25 to 50 mg/day; 100 to 300 mg/day

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–Desipramine (Norpramin): 25 to 50 mg/day; 100 to 300 mg/day

–Precautions: advanced age, glaucoma, benign prostate hyperplasia, hyperthyroidism, cardiovascular disease, liver disease, monoamine oxidase inhibitor (MAOI) treatment, potential for fatal overdose, arrhythmia, worsening glycemic control, SSRIs recommended for patients with diabetes (4)[A]

–Common side effects: dry mouth, blurred vision, constipation, urinary retention, tachycardia, confusion/delirium; elderly particularly susceptible

α2-Antagonists (sedating, appetite stimulant) (starting dose; usual dose)

– Mirtazapine (Remeron): 15 mg/day; 15 to 45 mg/day Atypical antipsychotics

–Adjunctive treatment: aripiprazole or quetiapine

–Treatment-resistant depression (TRD): olanzapine

–Significant side effects: dyslipidemia, hypertriglyceridemia, glucose dysregulation, diabetes mellitus, hyperprolactinemia, tardive dyskinesia, neuroleptic malignant syndrome, QTc prolongation (6)[A]

–Recommended for depression with psychotic features; consult with psychiatrist and consider carefully before starting (4)[A].

Significant potential interactions

–TCAs: amphetamines, barbiturates, clonidine, epinephrine, ethanol, norepinephrine

–All antidepressants: Allow 14-day washout period before starting MAOIs.

–MAOIs: not recommended in primary care. Significant drug and food interactions limit use.

ALERT

Black box warning: increased risk of suicidality in children, adolescents, and young adults up to age 25 years who are treated with antidepressants. Although this has not been extended to adults, suicide risk assessments are warranted for all patients.

Serotonin syndrome—a rare but potentially lethal complication from rapid increase in dose or new addition of medication with serotonergic effects

Caution with personal or family history of bipolar disorder: Antidepressants can precipitate mania.

Pregnancy Considerations

SSRIs: fluoxetine, sertraline, and bupropion considered safe in pregnancy (paroxetine, Category D; other SSRIs, Category C)

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ADDITIONALTHERAPIES

CBT

–CBT is a type of psychotherapy that focuses on how persons perceive a situation and helping them to change their unhelpful thinking and behavior, which leads to enduring improvement in their mood and functioning. It is more focused on the present, more limited in duration, and more problemsolving oriented.

Electroconvulsive therapy (ECT) for refractory cases

Repetitive transcranial magnetic stimulation (rTMS) may be helpful for TRD (6)[A].

COMPLEMENTARY& ALTERNATIVE MEDICINE

Used in mild depression but not regulated by FDAnor recommended by APA

Hypericum perforatum (St. John’s wort): multiple drug interactions; not safe in pregnancy

Data do not support S-adenosyl-l-methionine (SAMe) or acupuncture.

ONGOING CARE

PATIENT EDUCATION

Depression is a common medical illness, not a character defect.

Emphasize the need for long-term treatment and follow-up, which includes lifestyle changes.

Exercise, good sleep hygiene, nutrition, and decreased use of tobacco and alcohol are recommended.

PROGNOSIS

70% show significant improvement.

Of patients with a single depressive episode, 50% will relapse over their lifetime.

COMPLICATIONS

Suicide

Substance misuse Weight gain

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REFERENCES

1.Flint J, Kendler KS. The genetics of major depression. Neuron. 2014;81(3):484–503.

2.Mitchell AJ, Bird V, Rizzo M, et al. Diagnostic validity and added value of the Geriatric Depression Scale for depression in primary care: a meta-analysis of GDS30 and GDS15. J Affect Disord. 2010;125(1–3):10–17.

3.Deneke DE, Schultz H, Fluent TE. Screening for depression in the primary care population. Prim Care. 2014;41(2):399–420.

4.American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. http://www.psychiatryonline.com/pracGuide/pracGuideTopic_7.aspx. Accessed September 21, 2016.

5.Arroll B, Elley CR, Fishman T, et al. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev. 2009; (3):CD007954.

6.McIntyre RS, Filteau MJ, Martin L, et al. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014;156:1–7.

SEE ALSO

Algorithms: Depressed Mood Associated with Medical Illness; Depressive

Episode, Major

CODES

ICD10

F32.9 Major depressive disorder, single episode, unspecified

F33.9 Major depressive disorder, recurrent, unspecified F34.1 Dysthymic disorder

CLINICALPEARLS

Therapeutic alliance is important to treatment success.

Given the high recurrence rates, long-term treatment is often necessary.

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DEPRESSION, ADOLESCENT

Joseph B. Gladwell, MD Stephen J. Knox, MD

BASICS

DESCRIPTION

DSM-5 depressive disorders include disruptive mood dysregulations disorder (DMDD), major depressive disorder (MDD), persistent depressive disorder, premenstrual dysphoric disorder, substance/ medication-induced depressive disorder, and other nonspecific depression. This chapter focuses on MDD.

MDD is a primary mood disorder characterized by sadness and/or irritable mood with impairment of functioning; abnormal psychological development; and a loss of self-worth, energy, and interest in typically pleasurable activities.

DMDD is characterized by having severe, recurrent outbursts along with persistent irritability and anger.

Persistent depressive disorder is characterized by a depressed mood for most days lasting at least 1 year in a child/adolescent.

Adolescents with depression are likely to suffer broad functional impairment across social, academic, family, and occupational domains, along with a high incidence of relapse and a high risk for substance abuse and other psychiatric comorbidity.

EPIDEMIOLOGY

Incidence

During adolescence, the cumulative probability of depression ranges from 5% to 20% (1).

Prevalence

MDD: 2–11% of adolescents; twice as common in females

DMDD: 2–5%; more prominent in males

ETIOLOGYAND PATHOPHYSIOLOGY

Unclear; low levels of neurotransmitters (serotonin, norepinephrine) may produce symptoms; decreased functioning of the dopamine system also contributes.

External factors may affect neurotransmitters independently.

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Hormonal changes during puberty likely contribute as well.

Genetics

Offspring of parents with depression have 3 to 4 times increased rates of depression compared with offspring of parents without mood disorder (1).

Family studies indicate that anxiety in childhood tends to precede adolescent depression (1).

RISK FACTORS

Increased 3 to 6 times if first-degree relative has a major affective disorder; 3 to 4 times in offspring of parents with depression

Prior depressive episodes

History of low self-esteem, anxiety disorders, attention deficit hyperactivity disorder (ADHD), and/or learning disabilities

Increased screen time

Female gender

Low socioeconomic status

General stressors: adverse life events, difficulties with peers, loss of a loved one, academic difficulties, abuse, chronic illness, and tobacco abuse

GENERALPREVENTION

Insufficient evidence for universal depression prevention programs (psychological and social)

Some evidence indicates that child and adolescent mental health can be improved by successfully treating maternal depression (1)[A].

Agency for Healthcare Research and Quality (AHRQ) recommends the screening of adolescents (12 to 18 years of age) for MDD when systems are in place to ensure accurate diagnosis, appropriate treatment, and follow-up.

COMMONLYASSOCIATED CONDITIONS

2/3 of adolescents with depression have at least one comorbid psychiatric disorder.

20% meet the criteria for generalized anxiety disorder.

Also associated with behavioral disorders, substance abuse, eating disorders

DIAGNOSIS

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HISTORY

Adolescents may present with medically unexplained somatic complaints (fatigue, irritability, headache).

Based on DSM-5 criteria, ≥5 of the following symptoms have been present during the same 2-week period and represent a change from previous functioning: At least one of the symptoms is either depressed mood or loss of interest or pleasure:

–Criterion A

Depressed mood most of the day either subjective report or observation by others (feelings of sadness, emptiness, hopelessness; in children, can be irritability)

Markedly diminished interest or pleasure in all activities most of the day

Significant weight loss when not dieting or weight gain (>5% body weight in 1 month)

Insomnia or hypersomnia

Psychomotor agitation or retardation nearly every day

Fatigue or loss of energy

Feelings of worthlessness or excessive or inappropriate feelings of guilt nearly every day

Diminished ability to think or concentrate, or indecisiveness, nearly every day

Recurrent thoughts of death, recurrent suicidal ideation, or attempt

–Criterion B. Symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

–Criterion C. Episode is not attributable to substances’effects or other medical conditions.

–Criterion D. Episode is not better explained by a schizoaffective, schizophreniform, or delusional disorder.

–Criterion E. There has never been a manic or hypomanic episode.

PHYSICALEXAM

Psychomotor retardation/agitation may be present.

Clinicians should carefully assess patients for signs of self-injury (such as wrist lacerations) or abuse.

DIFFERENTIALDIAGNOSIS

Normal bereavement Substance-induced mood disorder

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