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Depression
Suma P. Chand; Hasan Arif.

Author Information and Affiliations

Last Update: April 8, 2023.

Continuing Education Activity

Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest. The
American Psychiatric Association’s Diagnostic Statistical Manual of Mental Disorders, Fifth
Edition (DSM-5) classifies the depressive disorders into Disruptive mood dysregulation disorder;
Major depressive disorder; Persistent depressive disorder (dysthymia); Premenstrual dysphoric
disorder; and Depressive disorder due to another medical condition. The common features of all
the depressive disorders are sadness, emptiness, or irritable mood, accompanied by somatic and
cognitive changes that significantly affect the individual’s capacity to function. This activity
reviews the evaluation and management of depression and the role of interprofessional team
members in collaborating to provide well-coordinated care and enhance patient outcomes.

Objectives:

Review the risk factors for depression.

Describe DSM V criteria for the diagnosis of depression.

Summarize the treatment of depression.

Outline the evaluation and management of depression and the role of interprofessional
team members in collaborating to provide well-coordinated care and enhance patient
outcomes.

Earn FREE continuing education credits (CME/CE) on this topic.

Introduction
Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest.[1]
[2] The American Psychiatric Association’s Diagnostic Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5) classifies the depressive disorders into:

1. Disruptive mood dysregulation disorder

2. Major depressive disorder

3. Persistent depressive disorder (dysthymia)

4. Premenstrual dysphoric disorder

5. Depressive disorder due to another medical condition

The common features of all the depressive disorders are sadness, emptiness, or irritable mood,
accompanied by somatic and cognitive changes that significantly affect the individual’s capacity
to function.[3]
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Because of false perceptions, nearly 60% of people with depression do not seek medical help.
Many feel that the stigma of a mental health disorder is not acceptable in society and may hinder
both personal and professional life. There is good evidence indicating that most antidepressants
do work but the individual response to treatment may vary. 

Etiology
The etiology of major depressive disorder is multifactorial with both genetic and environmental
factors playing a role. First-degree relatives of depressed individuals are about 3 times as likely
to develop depression as the general population; however, depression can occur in people
without family histories of depression.[4][5]

Some evidence suggests that genetic factors play a lesser role in late-onset depression than in
early-onset depression. There are potential biological risk factors that have been identified for
depression in the elderly. Neurodegenerative diseases (especially Alzheimer disease and
Parkinson disease), stroke, multiple sclerosis, seizure disorders, cancer, macular degeneration,
and chronic pain have been associated with higher rates of depression. Life events and hassles
operate as triggers for the development of depression. Traumatic events such as the death or loss
of a loved one, lack or reduced social support, caregiver burden, financial problems,
interpersonal difficulties, and conflicts are examples of stressors that can trigger depression.

Epidemiology
Twelve-month prevalence of major depressive disorder is approximately 7%, with marked
differences by age group.  The prevalence in 18- to 29-year-old individuals is threefold higher
than the prevalence in individuals aged 60 years or older. Females experience 1.5- to 3-fold
higher rates than males beginning in early adolescence.  In the US, depression affects nearly 17
million adults but these numbers are gross underestimates as many have not even come to
medical attention.

Pathophysiology
The underlying pathophysiology of major depressive disorder has not been clearly defined.
Current evidence points to a complex interaction between neurotransmitter availability and
receptor regulation and sensitivity underlying the affective symptoms.

Clinical and preclinical trials suggest a disturbance in central nervous system serotonin (5-HT)
activity as an important factor. Other neurotransmitters implicated include norepinephrine (NE),
dopamine (DA), glutamate, and brain-derived neurotrophic factor (BDNF).

The role of CNS 5-HT activity in the pathophysiology of major depressive disorder is suggested
by the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs). Research findings
imply a role for neuronal receptor regulation, intracellular signaling, and gene expression over
time, in addition to enhanced neurotransmitter availability.

Seasonal affective disorder is a form of major depressive disorder that typically arises during the
fall and winter and resolves during the spring and summer. Studies suggest that seasonal
affective disorder is also mediated by alterations in CNS levels of 5-HT and appears to be
triggered by alterations in circadian rhythm and sunlight exposure.

Vascular lesions may contribute to depression by disrupting the neural networks involved in
emotion regulation—in particular, frontostriatal pathways that link the dorsolateral prefrontal

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cortex, orbitofrontal cortex, anterior cingulate, and dorsal cingulate. Other components of limbic
circuitry, in particular, the hippocampus and amygdala, have been implicated in depression.

History and Physical

The investigation into depressive symptoms begins with inquiries of the neurovegetative
symptoms which include changes in sleeping patterns, appetite, and energy levels. Positive
responses should elicit further questioning focused on evaluating for the presence of the
symptoms which are diagnostic of major depression. These are the 9 symptoms listed in the
DSM-5. Five must be present to make the diagnosis (one of the symptoms should be depressed
mood or loss of interest or pleasure):

1. Sleep disturbance

2. Interest/pleasure reduction

3. Guilt feelings or thoughts of worthlessness

4. Energy changes/fatigue

5. Concentration/attention impairment

6. Appetite/weight changes

7. Psychomotor disturbances

8. Suicidal thoughts

9. Depressed mood

All patients with depression should be evaluated for suicidal risk. Any suicide risk must be given
prompt attention which could include hospitalization or close and frequent monitoring.

Other areas of investigation include:

1. Past medical history and family medical history, and current medications

2. Social history with a focus on stressors and the use of drugs and alcohol

3. History and physical examination to rule out organic causes of depression. Depressive
symptoms and their severity are also evaluated with the help of questionnaires such as the
Beck's Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), and Zung Self
Rating Depression Scale

Evaluation
The diagnosis of depression is based on history and physical findings. No diagnostic laboratory
tests are available to diagnose major depressive disorder. Laboratory studies are, however, useful
to exclude medical illnesses that may present as major depressive disorder. [6][7][8]These
laboratory studies might include the following:

Complete blood cell (CBC) count

Thyroid-stimulating hormone (TSH)

Vitamin B-12

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Rapid plasma reagin (RPR)

HIV test

Electrolytes, including calcium, phosphate, and magnesium levels

Blood urea nitrogen (BUN) and creatinine

Liver function tests (LFTs)

Blood alcohol level

Blood and urine toxicology screen

Arterial blood gas (ABG)

Dexamethasone suppression test (Cushing disease, but also positive in depression)

Cosyntropin (ACTH) stimulation test (Addison disease)  

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain
should be considered if organic brain syndrome or hypopituitarism is included in the
differential diagnosis

Treatment / Management
Medication alone and brief psychotherapy (cognitive-behavioral therapy, interpersonal therapy)
alone can relieve depressive symptoms. Combination therapy has also been associated with
significantly higher rates of improvement in depressive symptoms; increased quality of life; and
better treatment compliance. There is also empirical support for the ability of CBT to prevent
relapse.[9][10]

Electroconvulsive therapy is useful for patients who are not responding well to medications or
are suicidal.[11][1]

Medications

1. Selective serotonin reuptake inhibitors (SSRIs)

2. Serotonin/norepinephrine reuptake inhibitors (SNRIs)     

3. Atypical antidepressants

4. Serotonin-Dopamine Activity Modulators (SDAMs)     

5. Tricyclic antidepressants (TCAs)

6. Monoamine oxidase inhibitors (MAOIs)  

7. Selective serotonin reuptake inhibitors (SSRIs): SSRIs have the advantage of ease of
dosing and low toxicity in overdose. They are also the first-line medications for late-onset
depression.

8. SSRIs include: Citalopram, escitalopram, fluoxetine,  fluvoxamine, paroxetine, sertraline,

vilazodone, vortioxetine

9. Serotonin/norepinephrine reuptake inhibitors (SNRIs): SNRIs, which include venlafaxine,

desvenlafaxine, duloxetine, and levomilnacipran can be used as first-line agents,

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particularly in patients with significant fatigue or pain syndromes associated with the
episode of depression. SNRIs also have an important role as second-line agents in patients
who have not responded to SSRIs. 

10. Atypical antidepressants: Atypical antidepressants include bupropion, mirtazapine,

nefazodone, and trazodone. They have all been found to be effective in monotherapy in
major depressive disorder and may be used in combination therapy for more difficult to
treat depression.

11. Serotonin-Dopamine Activity Modulators (SDAMs): SDAMs include brexpiprazole and

aripiprazole. SDAMs act as a partial agonist at 5-HT1A and dopamine D2 receptors at
similar potency, and as an antagonist at 5-HT2A and noradrenaline alp Brexpiprazole is
indicated as adjunctive therapy for major depressive disorder (MDD).

12. Tricyclic antidepressants (TCAS): TCAs include the

following: Amitriptyline, clomipramine, desipramine, doxepin, imipramine,
nortriptyline, protriptyline, trimipramine. TCAs have a long record of efficacy in the
treatment of depression. They are used less commonly because of their side-effect profile
and their considerable toxicity in overdose.

13. Monoamine oxidase inhibitors (MAOIs): MAOIs include isocarboxazid, phenelzine,

selegiline, and tranylcypromine. These agents are widely effective in a broad range of
affective and anxiety disorders. Because of the risk of hypertensive crisis, patients on these
medications must follow a low-tyramine diet. Other adverse effects can include insomnia,
anxiety, orthostasis, weight gain, and sexual dysfunction.

Electroconvulsive Therapy (ECT)

ECT is a highly effective treatment for depression. Onset of action may be more rapid than that
of drug treatments, with benefit often seen within 1 week of commencing treatment. A course of
ECT (usually up to 12 sessions) is the treatment of choice for patients who do not respond to
drug therapy, are psychotic, or are suicidal or dangerous to themselves. Thus, the indications for
the use of ECT include the following:

1. Need for a rapid antidepressant response  Failure of drug therapies   

2. History of a good response to ECT     

3. Patient preference     

4. High risk of suicide

5. High risk of medical morbidity and mortality

Although advances in brief anesthesia and neuromuscular paralysis have improved the safety and
tolerability of ECT, this modality poses numerous risks, including those associated with general
anesthesia, postictal confusion, and, more rarely, short-term memory difficulties.  

Psychotherapy

Cognitive Behavior Therapy and Interpersonal Therapy are evidence-based psychotherapies that
have been found to be effective in the treatment of depression.

Cognitive-behavioral therapy (CBT)

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CBT is a structured, and didactic form of therapy that focuses on helping individuals identify and
modify maladaptive thinking and behavior patterns (16 to 20 sessions). It is based on the premise
that patients who are depressed exhibit the “cognitive triad” of depression, which includes a
negative view of themselves, the world, and the future. Patients with depression also exhibit
cognitive distortions that help to maintain their negative beliefs. CBT for depression typically
includes behavioral strategies (i.e., activity scheduling), as well as cognitive restructuring to
change negative automatic thoughts and addressing maladaptive schemas.

There is evidence supporting the use of CBT with individuals of all ages. It is also considered
being efficacious for the prevention of relapse. It is particularly valuable for elderly patients, who
may be more prone to problems or side effects with medications.  

Mindfulness-based cognitive therapy (MBCT) was designed to reduce relapse among individuals

who have been successfully treated for an episode of recurrent major depressive disorder. The
primary treatment component is mindfulness training. MBCT specifically focuses on ruminative
thought processes as being a risk factor for relapse. Research indicates that MBCT is effective in
reducing the risk of relapse in patients with recurrent depression, especially in those with the
most severe residual symptoms. Interpersonal therapy (IPT)

Interpersonal Therapy (IPT)

Interpersonal therapy (IPT) is a time-limited (typically 16 sessions) treatment for major

depressive disorder. IPT draws from attachment theory and emphasize the role of interpersonal
relationships, focusing on current interpersonal difficulties. Specific areas of emphasis include
grief, interpersonal disputes, role transitions, and interpersonal deficits.

Differential Diagnosis

Adjustment disorders

Anaemia

Chronic Fatigue syndrome

Dissociative disorders

Illness anxiety disorders

Hypoglycemia

Hypopituitarism

Schizoaffective disorders

Schizophrenia

Somatic symptom disorders

Prognosis
Major depression has very high morbidity and mortality contributing to high rates of suicide.
Even though effective drug treatment is available, nearly 50% may not initially respond.
Complete remission is not common but at least 40% achieve partial remission in 12 months.

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However, relapses are common and many patients require a variety of treatments to control the
symptoms. The quality of life of most patients with depression is poor.

Depression accounts for nearly 40,000 cases of suicide each year in the US. The highest rate of
suicides is in older men.

Enhancing Healthcare Team Outcomes

Depression is a very common disorder encountered by the nurse practitioner, primary care
provider, psychiatrist, and mental health worker, coordinating as an interprofessional healthcare
team. The disorder has extremely high morbidity including the risk of suicide. All healthcare
workers should be knowledgeable about this disorder and refer the patient to a psychiatrist if
there is a risk of self-harm.

Education plays an important role in the successful treatment of major depressive disorder. This
would include the education of the family and the patient. Lack of accurate information and
misperceptions of the illness as a personal weakness or failings leads to painful stigmatization
and avoidance of the diagnosis by many of those affected. Patients should know the rationale
behind the choice of treatment, potential adverse effects, and expected results.

The involvement of the pharmacist in the treatment plan can enhance medication compliance and
referral for psychotherapy. The pharmacist can also check that dosing is appropriate, that there
are no significant interactions, and counsel on adverse effects. Engaging family members can be
a critical component of a treatment plan. Family members are helpful informants, can ensure
medication compliance, be a big source of social support and can encourage patients to change
behaviors that perpetuate depression (e.g., inactivity).

Patients with moderate to severe depression should also be seen by a social worker or case
management nurse to ensure that they have a support system and finances for treatment. If there
is a concern, the person managing the case should present the issues to the interprofessional team
so that a plan can be developed to get the patient the care they need.  Overall, depression is
managed by an interprofessional team dedicated to the management of mental health disorders.
Open communication between all the members of the interprofessional team is the key to
lowering the morbidity of the disorder. [Leve 5]

Outcomes

The outcomes for patients with depression are guarded. There is no cure and the condition has
frequent relapses and remissions, leading to a poor quality of life.[3][12][13]

Review Questions

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Disclosure: Suma Chand declares no relevant financial relationships with ineligible companies.

Disclosure: Hasan Arif declares no relevant financial relationships with ineligible companies.

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