27.1 Introduction

Major depression affects more than 350 million people worldwide and is the leading cause of disability worldwide [1]. Mental health-related chief complaints make up about 3 % of the patients who present for care in the emergency setting, with depression being the most common mental health-related chief complaint [2]. It is estimated that up to 10 % of patients who present to primary care providers including the emergency department (ED) have major depression, and around half of these patients are undiagnosed [3].

It is well known that depressed patients may present with psychosomatic symptoms such as lower back pain or abdominal pain, but it is also important to know that depressed patients tend to have more medical comorbidities and are more likely to require admission to the hospital. More than 50 % of patients with major depression have at least one comorbid chronic medical condition, and depressed patients are more likely to suffer complications and present to the ED for these conditions [3]. Major depression is associated with numerous comorbidities and is associated with significantly increased rates of heart disease, diabetes, and stroke and with a decreased life expectancy [3–5].

While recognition of depression in the emergency department (ED) or an ambulatory care clinic can be challenging due to the large volume of patients and high acuity of patients being seen, it is nonetheless important. Recognition of depression can save lives by prevention of suicide, improvement of quality of life for the patient and their family, as well as prevention of unnecessary health-care visits for somatic complaints related to their emotional problems [6].

27.2 Risk Factors for Depression

Lifetime prevalence of a major depressive episode is reported at around 15 % for the general population. Certain populations are known to be at an increased risk. Published risk factors for major depression include:

  • Female gender

  • Middle age (45–64 years old)

  • Multiple medical comorbidities

  • Assisted living or skilled nursing home residents

  • Widowed, divorced, or never-married individuals

  • Lesbian, gay, bisexual, or transgender sexual orientation

For emergency providers, the principal goal in identifying depression is to prevent depressed patients from harming themselves or others. The risk factors for depression and suicidality do not necessarily coincide. For example, females are more likely to be depressed, but males are more likely to succeed in committing suicide.

The following factors are known to be linked with greater risk of suicide and should be taken into consideration when deciding whether or not to admit a patient for depression/suicidality:

  • Repeated suicide attempts

    • Strongest predictive factor of suicide risk! Especially if previous attempts were planned and lethal means were used

  • Male gender

  • Widowed, divorced, or separated individuals

  • Relationship difficulties and conflicts

  • Active unemployment

  • Social isolation – lack of supportive family and friends

  • Substance abuse

  • Acute or chronic progressive illness

  • No insight into condition

  • Antisocial personality or disruptive behavior

  • History of depression (unipolar or bipolar), schizophrenia, or panic disorder

  • Family history of suicide

  • Recent disciplinary action at school or work

  • Lack of religious taboo against suicide

  • Unstable or inappropriate affect

27.3 Diagnostic Criteria

The diagnosis of depression requires a total of five of the listed criteria below, but anhedonia or depressed mood must be one of the criteria:

  • Depressed mood

  • Anhedonia

  • Significant weight change or appetite change (e.g., a change of more than 5 % of body weight in a month)

  • Insomnia or hypersomnia

  • Psychomotor agitation or retardation

  • Fatigue or loss of energy nearly every day

  • Feelings of worthlessness and excessive or inappropriate guilt nearly every day

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

  • Recurrent thoughts of death and/or suicide

The symptoms must cause significant distress or impairment and may not be due to the direct physiological effects of a substance or general medical condition [8].

An easy way to remember the symptoms described above is using the mnemonic SIG E CAPS:

  • S – sleep disturbance

  • I – interest loss (anhedonia)

  • G – guilt

  • E – energy loss

  • C – concentration decreased

  • A – appetite change

  • P – psychomotor change

  • S – suicide or death preoccupation

27.4 Differential Diagnosis

The differential diagnosis for major depression includes:

  • Infection

    • HIV encephalopathy

    • Meningitis

    • Encephalitis

    • Lyme disease

  • Substance abuse

    • Intoxication or withdrawal

  • Medication side effects:

    • Steroids, antihypertensives, and hormone therapy are common causes.

  • Trauma

  • Intracranial mass

  • CNS disorders

    • MS

    • Seizures

    • Alzheimer’s

    • Microangiopathic lesions

  • Metabolic disorders

    • Vitamin deficiencies – thiamine (B1), pyridoxine (B6), and cobalamin (B12)

  • Endocrine disorders

    • Hypothyroidism

    • Cushing

    • Hyperparathyroidism

    • Addison disease

  • Autoimmune disease

    • Systemic lupus erythematosus

  • Obstructive sleep apnea

  • Other psychiatric conditions

    • Bereavement

    • Bipolar depression

    • Schizoaffective disorder

27.5 History

Important clues from history known to increase a patient’s likelihood of committing suicide include:

  • Feelings of hopelessness, helplessness, and guilt.

  • Few or weak reasons to live.

  • Suicidal ideations that are frequent, intense, prolonged, and pervasive:

    • As opposed to ideations that are infrequent, transient, and low intensity

  • Patient with an unambiguous or continuing wish to die:

    • As opposed to patients who had no previous wish to die or no ongoing wish to die after making an attempt

  • Suicide plan is realistic.

  • Patient has access to firearms.

  • Planned suicide includes a situation where rescue is unlikely.

Depressed patients will likely present to the ED with other complaints, and many will have actual pathology, so a thorough history is essential.

27.6 Physical Exam

The diagnosis of depression is usually made with a thorough history, but physical examination of a depressed patient remains an important adjunct. A comprehensive physical exam will help in the investigation of somatic complaints and in evaluating other potentially more emergent issues that may present with the chief complaint of depression (i.e., ingestion, intoxication).

One vital aspect of the physical exam is the mental status exam which should include determination of:

  • The patient’s affect

  • Appearance

  • Orientation

  • Attention

  • Memory

  • Speech pattern

  • Level of consciousness

  • Judgment

  • Thought content

27.6.1 Red Flags of Depression

These physical exam red flags should alert you to consider more pressing diagnoses and consider medical/toxicologic explanations for a patient’s depressed feelings:

  • Abnormal vital signs

  • Disorientation

  • Clouded consciousness, comatose patients

  • Focal neurologic deficits

  • Recent memory loss, patient over 40 with no prior psychiatric disease

  • Signs of trauma

Patients with any of these findings warrant further work-up. Helpful labs for these patients may include [7]:

  • Complete blood count

  • Serum electrolytes

  • Creatinine

  • Hepatic enzymes

  • Thyroid-stimulating hormone level ± free T4

  • Ethanol

  • Urinalysis

  • Pregnancy test

  • Arterial blood gas

  • Cerebrospinal fluid examination

  • Electrocardiogram

  • Computed tomography or magnetic resonance imaging of the brain

  • Salicylate and acetaminophen levels in suicidal patients

27.7 Treatment

After properly recognizing a patient with depression in the ED or in the clinic, it can be challenging to provide proper treatment and disposition. An important first step is to stratify patients as high, moderate, or low risk for immediate harm to self and others.

High-risk patients are those who:

  • Exhibit violent behaviors

  • Exhibit agitation

  • Endorse active suicidal or homicidal intent

  • Require physical restraints

  • Present after engaging in a possibly lethal suicide attempt (i.e., gunshot wound to the head or reported ingestion)

These patients will require admission to a psychiatric facility for inpatient psychiatric therapy, but only after medical clearance.

The following important steps should also be taken for all patients who are in the high-risk category:

  • Disrobe, gown, and search the patient for potentially dangerous items.

  • Determine if the patient needs to be detained for emergency evaluation.

  • Treat medical conditions.

  • Communication with the patient should be made while keeping the exit accessible for the provider, while avoiding excessive eye contact, and while using a nonthreatening voice.

  • Enforce acceptable limits of behavior with the patient.

Any patient who is significantly agitated (shouting, cursing, threatening, physically aggressive, those attempting to elope) or who is noncompliant with the established limits may require sedation and/or restraints. There is potential for harm to the patient with either sedation or restraints, so an effort should be made to de-escalate the situation verbally. If this is not successful, parenteral administration of sedation agents may be used. Benzodiazepines and antipsychotics (first and second generation) are considered first-line agents [9, 10]. The time to onset of sedation, dosing, and special considerations for benzodiazepines and antipsychotics are summarized in the table below.

27.7.1 Parenteral Options for Acute Agitation [9]

 

Onset (min)

Initial dose (mg)

Considerations

Benzodiazepines

Diazepam

30

5–10 IV

Avoid IM because of unpredictable absorption. Useful in the setting of alcohol withdrawal

Lorazepam

2–5 IV, 15–30 IM

1–2 IM/IV

–

Midazolam

120 IV, 240–300 IM

2.5–5 IM/IV

Higher risk of respiratory depression compared with lorazepam and diazepam

Antipsychotics

Aripiprazole

60

9.75 IM

Relatively safe side effect profile

Haloperidol

1–2 IV, 30–60 IM

5 IM/IV

Risk for extrapyramidal symptoms. Higher risk of QT prolongation, particularly if given IV. IV haloperidol is an off-label route and requires careful monitoring for cardiac arrhythmias if used

Olanzapine

15–45

10 IM

Use with caution when given with benzodiazepines because of increased risk of cardiopulmonary depression

Ziprasidone

30–45

20 IM

Low risk of QT prolongation

Those patients who are stratified as low or moderate risk may not require admission for psychiatric treatment, but consultation with a psychiatrist is prudent especially for moderate-risk patients. Factors arguing for safe discharge of depressed patients include:

  • Close follow-up with psychiatric consultant

  • Good social support

    • Including someone willing to stay with the patient

  • The absence of high-risk factors mentioned in the above risk factors and history sections

27.8 Other Treatment Modalities

Lifestyle changes, psychotherapy, and pharmacotherapy are all potentially effective treatment options for patients with a major depressive episode. Performance of psychotherapy is not appropriate for providers in the emergency setting because of the limited amount of time available. Patients who desire this treatment should be referred to providers who can provide these services. While emergency providers will not perform psychotherapy, it is important for them to know this is an effective option, particularly for patients with less severe depressive symptoms.

27.8.1 Lifestyle Changes

The following lifestyle changes have been shown to be efficacious in the treatment of depression:

  • Exercise*

  • Relaxation therapy*

  • Change in diet away from calorie-rich and nutrition-poor foods

  • Improved sleep hygiene

    • Including CPAP treatment for individuals with obstructive sleep apnea

  • Decreased alcohol intake

* denotes lifestyle changes that have the best evidence of efficacy [11].

27.8.2 Pharmacotherapy

There is debate about whether patients with major depression should have pharmacologic therapy initiated in the emergency department. While over 60 % of prescriptions written for antidepressants are written by nonpsychiatrists [11], many emergency providers feel initiation of pharmacotherapy in the ED should only be carried out under the direction of a psychiatrist because of the significant risk of side effects, the long period of time before drugs become effective, and the lack of adequate follow-up.

However, there are some emergency providers who do not have access to an on-call psychiatric specialist and may want to initiate therapy in the emergency setting. When unsure about the need for initiation of pharmacotherapy, there are several decision aids which can be useful. One such aid is the PHQ-9 questionnaire which uses nine questions to come up with a score from 0 to 27 and gives the recommendation to initiate pharmacotherapy for any patient with a score equal to or greater than 15 [12].

When the decision is made to treat the patient, a second-generation antidepressant should be the first-line treatment. First-generation antidepressants (tricyclic antidepressants, monoamine oxidase inhibitors) and second-generation antidepressants (selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and atypical antidepressants) have been shown to be equally effective, but the side effect profile and overall safety relating to possible overdose make second-generation antidepressants a better option in most cases. Emergency providers should be familiar with these medications and their side effects because depressed patients may ingest these drugs during suicide attempts.

Classes of antidepressants

Class

Mechanism of action

Important side effects

Tricyclic antidepressants (TCAs) – amitriptyline, clomipramine, desipramine, doxepin, imipramine, nortriptyline, selegiline, trimipramine

Block action of norepinephrine and serotonin at neural synapses

Long QT

Has some antihistamine and antiadrenergic effects

Cardiotoxicity

Arrhythmia

Sedation

Monoamine oxidase inhibitors (MAOIs) – phenelzine, tranylcypromine

Inhibits degradation of monoamine oxidases which leads to increased levels of neurotransmitters in the neural synapses

Dietary interaction with tyramine-rich foods (aged cheese, wine) causes uncontrolled hypertension from adrenergic excess

Insomnia

Selective serotonin reuptake inhibitors (SSRIs) – citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline

Inhibits reuptake of serotonin, but not norepinephrine at the neural synapses

GI upset

Sexual dysfunction

Serotonin syndrome

Increased suicidality in young adults aging 18–24 during initial treatment (generally the first 1–2 months)

Selective norepinephrine reuptake inhibitors (SNRIs) – desvenlafaxine, duloxetine, levomilnacipran, milnacipran, sibutramine, venlafaxine

Inhibits the reuptake of norepinephrine at the neural synapses

Same as SSRIs

Increased blood pressure

Anxiety

Atypical antidepressants – bupropion, mirtazapine, nefazodone, trazodone, vilazodone, vortioxetine

Variable effects on levels of dopamine, norepinephrine, and serotonin at neural synapses

Common effects include dry mouth, constipation, and light-headedness

Trazodone – associated with priapism and arrhythmias

Mirtazapine – arrhythmia

Nefazodone – liver problems

Bupropion – lowers seizure threshold

The side effect profiles of the individual drugs vary within the classes and can be tailored by the prescriber to meet the specific needs of patients. For example, patients with insomnia may benefit from trazodone as this medication causes increased somnolence. The following table contains other examples of important side effects of antidepressants.

Antidepressants and common side effects

Side effect

Medications

Clinical pearl

Nausea and vomiting

Venlafaxine highest. Common in multiple antidepressants

Use extended-release formulation of venlafaxine to reduce nausea. Start at lower doses. Take with food

Diarrhea

Sertraline > paroxetine

Consider using in patients with constipation

Weight gain

TCAs/MAOIs, mirtazapine > paroxetine

Consider using in patients with anorexia or unintentional weight loss

Somnolence

Trazodone > mirtazapine

Use in patients with concurrent insomnia. Dose at night

Dizziness

Venlafaxine > sertraline, duloxetine

Consider bedtime dosing

Headache

Venlafaxine > bupropion, paroxetine, sertraline, escitalopram

 

Sexual dysfunction

Sertraline > venlafaxine > citalopram > paroxetine

May require dose reduction or medication switch

Bupropion and mirtazapine do not have this effect

Insomnia

Bupropion > sertraline, fluoxetine, paroxetine, venlafaxine

Take in the morning

Smoking cessation

Bupropion superior

Bupropion proven to help patients quit smoking

Escitalopram and sertraline have been shown in multiple studies to be slightly more efficacious and easier tolerated than other second-generation antidepressants making them good first choices [13]. It is important to keep in mind the antidepressant effects of the medications often take several weeks, while the side effects may begin to manifest in only a few days. Side effects are the most common reason for discontinuation of pharmacotherapy, so patients need to be counseled about the common side effects prior to administration and the need to continue taking the medications if tolerable.

Pitfalls in treating depressed patients in the ED:

  • Failure to ask about the patient’s specific plan for committing suicide

    • Some physicians concerned asking the question may increase risk of later suicide – a sentiment which has been proven to be false [2].

  • Patients who “only took a few pills” do not get a full work-up”

    • Do not believe patients when they tell you they only took a few pills or were only seeking attention – full work-ups are a necessity.

  • Double-edged sword of somatic complaints

    • Do not ignore somatic complaints (chest pain, low back pain) as many depressed patients have true pathology.

    • But do not ignore the depression, and discharge suicidal patients after medical work-up.

  • Failure to provide a sitter for depressed patients

    • Provide 1:1 sitters for all patients who may harm themselves or others during ED admission.

  • Failure to diagnose major depression in patients with terminal conditions

    • Even patients with good reason to feel depressed should receive a full psychiatric and safety evaluation.