Depression – Causes, Symptoms, Diagnosis, Treatment and Ongoing care



Depression is a primary mood disorder characterized by a depressed mood and/or decreased interest in things that used to give pleasure (anhedonia) during the same 2-week period, and representing a change from previous functioning:

  • Synonym(s): Unipolar affective disorder
  • System(s) affected: Nervous



Affects >78 million in the US


  • 15% lifetime risk of having major depressive disorder (MDD)
  • 4th most common reason to visit a physician

Risk Factors

  • Female > Male (2:1)
  • Predominant age: 1st onset usually in late 20s (earlier in women than men)
  • Elderly (≥65)
  • History of behavioral disorders
  • Presence of chronic disease(s)
  • Recent myocardial infarction/stroke
  • Peptic ulcer disease
  • Strong family history (depression, bipolar, suicide, alcoholism, other substance abuse)
  • Domestic abuse or violence
  • Substance abuse and dependence
  • Losses and stressors
  • Single, divorced, or unhappily married


Multiple gene loci place a person at increased risk when faced with environmental stressors.


  • Changes in receptor–neurotransmitter relationship in the limbic system:
    • Serotonin and norepinephrine are the primary neurotransmitters involved; dopamine, acetylcholine, and γ-aminobutyric acid have also been involved.
  • As action potential is passed on, the neurotransmitter is:
    • Reabsorbed into the neuron, where it is either destroyed by an enzyme or actively removed by a reuptake pump and stored until needed or
    • Destroyed by monoamine oxidase in the mitochondria
  • Symptoms related to decreased levels of norepinephrine (dullness and lethargy) and serotonin (irritability, hostility, and suicidal ideation)


  • Impaired synthesis of neurotransmitters
  • Increased metabolism of neurotransmitters
  • Environmental factors and learned behavior may affect neurotransmitters and/or have an independent influence on depression.

Commonly Associated Conditions

  • Manic depression (bipolar disorder)
  • Cyclothymic and grief reactions
  • Anxiety disorders
  • Schizophrenia/schizoaffective disorders
  • Psychophysiologic disorders
  • Physical disorders
  • Substance abuse

Selective serotonin reuptake inhibitor, Major depressive disorder, Tricyclic antidepressant, Imipramine, Fluoxetine, Mental health, unipolar affective disorder, serotonin and norepinephrine, depressed mood, suicidal ideation, neurotransmitters,



  • Depressed mood most of the day, nearly every day
  • Anhedonia
  • Depression is probable when at least 4 of the following exist in addition to depressed mood or anhedonia:
    • Appetite: Significant weight gain or loss when not dieting (change of >5% of body weight in 1 month)
    • Sleep disturbance: Insomnia or hypersomnia nearly every day
    • Fatigue: Out of proportion to the amount of energy expended
    • Psychomotor retardation or agitation: Restlessness, irritability, or withdrawal
    • Poor self-image: Worthlessness, excessive or inappropriate guilt
    • Concentration: Diminished thinking or concentration, poor memory, indecisiveness
    • Suicidal ideation: Recurrent thoughts of death; sometimes, as patients begin to recover, they gain enough energy to think about and sometimes attempt suicide.

Geriatric Considerations

  • Can present with pseudodementia
  • More common in elderly and difficult to precisely diagnose due to medical comorbidities (highest rates of depression are associated with stroke, coronary artery disease, cancer, Parkinson disease, and Alzheimer disease)

Pediatric Considerations

Depression occurs in children and can present with somatic complaints, irritability (versus depressed mood), and social withdrawal.

Physical Exam

Vital signs and complete physical exam with special attention paid to:

  • Thyroid
  • Cardiac exam, listening for arrhythmias
  • Mental status, including affect

Diagnostic Tests & Interpretation


Initial lab tests

Labs may not be necessary, but are sometimes used to rule out other diagnoses:

  • Thyroid-stimulating hormone
  • Complete blood count
  • Chem 7, including blood sugar
  • Calcium
  • Liver function tests

Follow-Up & Special Considerations

Electrocardiogram to rule out arrhythmia


Initial approach

Electroencephalogram, computed tomography, or magnetic resonance imaging of brain to rule out organic brain disease if suspected

Diagnostic Procedures/Surgery

  • Depression is primarily a clinical diagnosis made by eliciting personal, family, social, and psychosocial factors.
  • Validated standard rating scales can assist:
    • Clinical Global Impressions Scale
    • Montgomery-Asberg Depression Rating Scale
    • Hamilton Rating Scale for Depression
    • Beck Depression Inventory

Differential Diagnosis

  • Dysthymic disorder
  • Bipolar disorder
  • Organic brain diseases
  • Endocrine/thyroid disorders, diabetes
  • Metabolic abnormalities (hypercalcemia)
  • Adrenal disease (Cushing)
  • Liver/renal failure
  • Malignancy
  • Chronic fatigue syndrome
  • Lupus
  • Nutritional: Pernicious anemia, pellagra
  • Medications: Abuse, side effects, overdose
  • Substances: Abuse, dependence, withdrawal



First Line

  • Selective serotonin reuptake inhibitors (SSRIs):
    • Fluoxetine (Prozac): 20–80 mg/d
    • Sertraline (Zoloft): 50–200 mg/d
    • Paroxetine (Paxil): 10–50 mg/d
    • Paroxetine CR (Paxil CR): 12.5–62.5 mg/d
    • Citalopram (Celexa): 20–60 mg/d
    • Escitalopram (Lexapro): 10–20 mg/d
  • Others:
    • Venlafaxine (Effexor): 75–375 mg/d (divided doses)
    • Venlafaxine XR(Effexor XR): 75–225 mg/d
    • Bupropion (Wellbutrin): 100–450 mg/d (divided doses, t.i.d.)
    • Bupropion SR (Wellbutrin SR): 100–450 mg/d (divided doses, b.i.d.)
    • Bupropion XL (Wellbutrin XL): 150–300 mg/d
    • Duloxetine (Cymbalta): 30–60 mg/d

Second Line

  • Tricyclic antidepressants (TCAs) with sedating properties condensed list:
    • Amitriptyline (Elavil): 50–150 mg/QHS, max 300
    • Nortriptyline (Pamelor): 75–150 mg QHS
    • Doxepin (Prudoxin, Zonalon): 75–150 mg QHS
  • TCAs with activating properties condensed list:
    • Imipramine (Tofranil, Tofranil-PM): 150–200 mg QHS
    • Desipramine (Norpramin): 150–300 mg/d
  • α2-antagonists (sedating):
    • Mirtazapine (Remeron): 15–45 mg QHS
  • SSRI/antagonists:
    • Trazodone: 150 mg/d (divided doses), maximum 600 mg/d (divided doses)
  • Precautions:
    • Bupropion: Increased risk of seizures
    • TCAs: Advanced age, glaucoma, benign prostate hypertrophy, hyperthyroidism, cardiovascular disease, liver disease, urinary retention, MAOI treatment, potential for fatal overdose
    • SSRIs: Abrupt discontinuation may result in withdrawal symptoms (i.e., dizziness), may raise serum levels of other drugs
  • Significant potential interactions:
    • TCAs: Amphetamines, barbiturates, clonidine, epinephrine, ethanol, norepinephrine, MAOIs: Allow 14-day washout period before starting MAOIs, propoxyphene
    • SSRIs and MAOIs: 14-day washout before instituting therapy
    • Venlafaxine may cause fatal serotonin syndrome
    • MAOIs: Significant drug and food interactions limit use, but can be useful in refractory cases.


Black-box warning: Increased risk of suicidality in children, adolescents, and young adults up to age 25 treated with SSRI antidepressant medications. Although this has not been extended to adults, suicide risk assessments are warranted for all patients.

Geriatric Considerations

Reduce dosage of medications (1/2 usual starting dose); may need to treat longer than younger adults.

Pediatric Considerations

Support's development and hosting

Reduce dosage of medications in adolescents; also see Alert.

Pregnancy Considerations

SSRIs: If possible, taper and discontinue. (Paroxetine is Category D; the rest of SSRIs are Category C.)

Additional Treatment

General Measures

Psychotherapeutic interventions act synergistically with pharmacologic therapy.

Additional Therapies

Electroconvulsive therapy for refractory cases

Complementary and Alternative Medicine

Use in mild depression; evidence is inconsistent:

  • Hypericum perforatum (St. John’s wort) (1)[A]: Be aware of multiple drug interactions.
  • SAM-e (S-adenosyl methionine): 400–1,600 mg/d (2)[A]

In-Patient Considerations

Admission Criteria

Inpatient care is indicated for severely depressed, psychotic, or suicidal patients.

Discharge Criteria

Depressive symptoms improving, no longer suicidal

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

  • See within 2 weeks after starting medication.
  • During follow-up, evaluate the side effects, dosage, and effectiveness of the medication.
  • Follow up every 2 weeks until improvement.
  • Follow up every 3 months thereafter.
  • Explain treatment must continue for at least 6 months to 2 years; longer with family history, severe depression, and in the very young.

Patient Education

  • Depression is a medical illness, not a character defect.
  • Stress need for long-term treatment and follow-up, which includes lifestyle changes.
  • 30 minutes of moderate-intensity exercise, 3–5 days per week for healthy adults (3)[A]


  • 70% significant improvement
  • It has been shown that of patients with a single depressive episode, 50% develop a recurrent episode.


  • Suicide
  • Lower quality-of-life


1. Keller MB. Issues in treatment-resistant depression. J Clin Psychiatry.2005;66(Suppl 8):5–12.

2. Institute for Clinical Systems Improvement. Major Depression in Adults in Primary Care. Bloomington, MN: Institute for Clinical Systems Improvement; 2006.

3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR. 4th ed. [text revision]. Washington, DC: American Psychiatric Publishing, 2000.

Additional Reading

Adams SM, Miller KE, Zylstra RG. Pharmacologic management of adult depression. Am Fam Physician. 2008;77:785–92.

Fochtmann LJ, et al. Guideline Watch: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 2nd ed. Accessed June 1, 2008 at:

Halfin A. Depression: the benefits of early and appropriate treatment. Am J Manag Care. 2007;13:S92–7.

Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).JAMA. 2003;289:3095–105.

Kocsis JH, et al. Prevention of recurrent episodes of depression with venlafaxine ER in a 1-year maintenance phase from the PREVENT Study. J Clin Psychiatry. 2007;68:1012–23.

Kornstein SG, Bose A, Li D, et al. Escitalopram maintenance treatment for prevention of recurrent depression: a randomized, placebo-controlled trial. J Clin Psychiatry. 2006;67:1767–75.

Maurer D, Colt R. An evidence-based approach to the management of depression. Prim Care. 2006;33:923–41.

Roose SP, Sackeim HA, Krishnan KR, et al. Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial. Am J Psychiatry. 2004;161:2050–9.

Skultety KM, Rodriguez RL. Treating geriatric depression in primary care. Curr Psychiatry Rep. 2008;10:44–50.

Thase ME. Treatment of severe depression. J Clin Psychiatry. 2000;61(Suppl 1):17–25.

See Also (Topic, Algorithm, Electronic Media Element)

Algorithms: Depressive Episode, Major; Depressed Mood Resulting from Medical Illness



  • 296.20 Major depressive affective disorder, single episode, unspecified degree
  • 296.30 Major depressive affective disorder, recurrent episode, unspecified degree
  • 311 Depressive disorder, not elsewhere classified


  • 35489007 Depressive disorder (disorder)
  • 36923009 Major depression, single episode (disorder)
  • 66344007 Recurrent major depression (disorder)

Clinical Pearls

  • The relationship (therapeutic alliance) between the patient and health care provider is important to the success of treatment.
  • Depression management has 2 main goals:
    • Remission: Absence of depressive symptoms with return to full functioning
    • Recovery: No longer meets MDD criteria for at least 8 weeks
  • Given the high recurrence rates, long-term treatment is often necessary.

About the author

Many tips are based on recent research, while others were known in ancient times. But they have all been proven to be effective. So keep this website close at hand and make the advice it offers a part of your daily life.