Depression

Disease State Overview

Depression is a condition characterized by low mood, a lack of positive thoughts, and a loss of interest in previously pleasurable activities that lasts longer than two weeks.

Treatment of depression is based on four phases as outlined below. Treatment goals include achieving remission of depression symptoms and restoring normal functioning and quality of life. Once remission is achieved, goals of treatment include prevention of relapse, optimization of treatment modalities, and minimization of adverse effects.

Depression Treatment Phases

Risk of Condition

If left untreated, depression may cause serious, long-lasting symptoms and often disrupts a person’s ability to perform routine tasks. Untreated depression can increase a patient’s risk of developing other chronic health conditions and can also increase risk of death by suicide.

Medication

Role of Medication

The American College of Physicians recommends patient start on either pharmacologic therapy or cognitive behavioral therapy. Choice of therapy should be based on multiple factors including depression severity, depression features, medication side effect profile, medication tolerability, history of prior medication treatment, insurance coverage, patient preference, patient’s age, comorbid conditions, and concurrent medications.

Pharmacologic and non-pharmacologic treatment options as recommended by the American Psychiatric Association (APA) are outlined below. Medications should be titrated to maximally tolerated dose prior to switching or augmenting therapy.

Pharmacologic Management of Major Depressive Disorder - Therapy

Drug Class: Selective serotonin reuptake inhibitor (SSRI)
- Medications:
  - citalopram
  - escitalopram
  - fluoxetine
  - paroxetine
  - sertraline
  - fluvoxamine+
- Side Effects:
  - CNS: insomnia, headache
  - GI: nausea/vomiting, weight gain, dry mouth
  - Other: hyponatremia/SIADH, sexual dysfunction, bleeding risk, QT prolongation*

*increased risk with citalopram doses > 40mg

Drug Class: Selective serotonin-norepinephrine reuptake inhibitor (SNRI)
- Medications:
  - desvenlafaxine
  - duloxetine
  - levomilnacipran (Fetzima)
  - milnacipran
  - venlafaxine
- Side Effects:
  - CNS: insomnia, headache
  - GI: nausea/vomiting, weight gain, dry mouth
  - Cardiac: hypertension, tachycardia/palpitations
  - Other: hyponatremia/SIADH, sexual dysfunction
Drug Class: Alpha-2 antagonist (Other classifications: Tetracyclic (TeTCA), Norepinephrine-serotonin modulator, Noradrenergic and specific serotonergic (NaSSAs))
- Medications:
  - mirtazapine
- Side Effects:
  - CNS: sedation
  - GI: nausea, vomiting, constipation, weight gain
  - Cardiac: increased cholesterol
  - Other: dry mouth
Drug Class: Dopamine norepinephrine reuptake inhibitor (DNRIs)
- Medications:
  - bupropion
- Side Effects:
  - CNS: insomnia, activation/anxiety, headache
  - GI: nausea, weight loss, dry mouth
  - Cardiac: hypertension, tachyarrhythmia,
  - Other: seizures, diaphoresis
Drug Class: Tricyclic antidepressants (TCAs)
- Medications:
  - Secondary Amine
    - amoxapine
    - desipramine
    - nortriptyline
    - protriptyline
- - Tertiary Amine
    - amitriptyline
    - clomipramine+
    - doxepin
    - imipramine
    - trimipramine
- Side Effects:
  - CNS: sedation*
  - GI: weight gain
  - Anticholinergic: dry mouth, urinary retention, dry mouth, constipation, cognitive impairment
  - Cardiac: QTc prolongation, arrhythmias, orthostatic hypotension*
  - Other: sexual dysfunction, seizures
    
    *less with secondary amine vs. tertiary amine TCAs
Drug Class: Tetracyclic antidepressant (TeTCAs)
- Medications:
  - maprotiline
- Side Effects:
  - CNS: sedation
  - GI: weight gain
  - Anticholinergic: dry mouth, urinary retention, dry mouth, constipation, cognitive impairment
  - Other: blurred vision/visual disturbance
Drug Class: Serotonin Modulators (Selective Serotonin Reuptake Inhibitor/5-HT1A Receptor Partial Agonist)
- Medications:
  - vilazodone
- Side Effects:
  - CNS: insomnia
  - GI: nausea, vomiting, diarrhea
  - Other: sexual dysfunction*
    
    *potentially less than other agents
Drug Class: Serotonin Modulators (Selective Serotonin Reuptake Inhibitor/Serotonin 5-HT1A Receptor Agonist/Serotonin 5-HT3 Receptor Antagonist)
- Medications:
  - vortioxetine
- Side Effects:
  - CNS: insomnia
  - GI: nausea, vomiting diarrhea
  - Other: sexual dysfunction*
    
    *potentially less than other agents
Drug Class: Serotonin Modulators (Serotonin Reuptake Inhibitor/Antagonist)
- Medications:
  - trazodone
  - nefazodone
- Side Effects:
  - CNS: sedation
  - GI: nausea
  - Cardiac: orthostatic hypotension
  - Other: priapism*
    
    *rare but serious; trazodone only
Drug Class: Monoamine oxidase inhibitor (MAOIs)
- Medications:
  - isocarboxazide
  - phenelzine
  - selegiline
  - traylcypromine
- Side Effects:
  - CNS: insomnia, hypersomnia
  - GI: weight gain
  - Anticholinergic: dry mouth
  - Cardiac: orthostatic hypotension, decreased heart rate,
    peripheral edema, hypertensive crisis
  - Other: sexual dysfunction
  - Note: MAOIs generally restricted to patients who do not respond to other therapies

+ FDA indicated for OCD only

Non-pharmacological Therapy

Psychotherapy - Transcranial magnetic stimulation (TMS)]
Electroconvulsive therapy (ECT) - Light therapy

Adherence

Medication adherence is an essential component of treating depression because full response to pharmacotherapy typically occurs within the first 4–8 weeks of initial treatment. Discuss barriers to adherence and provide appropriate solutions. You may use the DRAW tool located in the Worksheets & Forms category of this Knowledge Base.

Educate the patient about the risks associated with sudden discontinuation of antidepressants. Symptoms may include changes in mood, irritability, anxiety, insomnia, headache, GI upset, or electric shock sensation.

Administration

Most antidepressants may be taken at any time of day. If the medication makes the patient feel stimulated or drowsy, they may need to change the time of day they take the medication.

Monitoring

Frequent follow-up should be scheduled with the patient’s prescriber to monitor response to treatment, adherence to the treatment plan, and suicide risk. Close observation and communication with the prescriber should be recommended to both the patient and their family.

The Patient Health Questionnaire (PHQ-9) is a common tool used to monitor both the severity of depression and response to treatment. Monitoring should also include screening for other mental disorders or chronic conditions.

Lifestyle Education

Lifestyle modifications can positively impact depression management. Points to discuss with patients may include the following:

Advise patient to follow a healthy diet

Encourage patient to be physical activity as physical activity has been shown to have significant benefits for mental health

Recommend limited alcohol consumption because alcohol is a depressant itself
Educate the patient about the importance of sleep hygiene because poor sleep has a strong, negative impact on mood

Additional Points

Patients with depression should be counseled on the following points related to pharmacologic treatment:

All antidepressants carry a black box warning of increased risk of suicidality in children, adolescents, and young adults ≤ 24 years of age. Advise patients who have thoughts about hurting themselves to go to the emergency room, contact their provider or call the National Suicide Prevention Hotline at 1-800-273-8255 or visit www.suicidepreventionlifeline.org.

Some medication side effects may resolve within the first few weeks of treatment initiation, so it is important to continue therapy if side effects are tolerable.
The signs and symptoms of serotonin syndrome include mental status change, autonomic hyperactivity, and neuromuscular abnormalities. Patients should seek immediate medical attention should they occur.

Resources

American Psychological Association (APA). Practice Guideline for the Treatment of Patients with Major Depressive Disorder (3rd edition). May 2011. American Psychiatric Association.
https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf
American Psychological Association (APA). Treating Major Depressive Disorder: A Quick Reference Guide.
https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd-guide.pdf
Chapman DP, Perry GS, Strine TW. The vital link between chronic disease and depressive disorders. Prev Chronic Dis [serial online] 2005;2(1).
https://pubmed.ncbi.nlm.nih.gov/15670467/
Qaseem A et al. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients with Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians. Annals of Internal Medicine.
https://www.acpjournals.org/doi/10.7326/M15-2570
Trangle M, Gursky J, Haight R, Hardwig J, Hinnenkamp T, Kessler D, Mack N, Myszkowski M. Institute for Clinical Systems Improvement. Adult Depression in Primary Care.
https://www.icsi.org/wp-content/uploads/2019/01/Depr.pdf