What is the difference between unipolar depression and major depressive disorder in terms of treatment?

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Last updated: June 26, 2025View editorial policy

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From the Guidelines

Unipolar depression and major depressive disorder (MDD) are actually the same condition, with "unipolar depression" being an older term that distinguishes it from bipolar disorder. The treatment approaches are identical since they refer to the same illness. First-line treatment typically involves selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (20-80mg daily), sertraline (50-200mg daily), or escitalopram (10-20mg daily), usually continued for at least 6-12 months after symptom resolution to prevent relapse, as recommended by the American College of Physicians 1. Alternative medications include serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine (75-225mg daily) or duloxetine (30-120mg daily), bupropion (150-450mg daily), or mirtazapine (15-45mg daily). Psychotherapy, particularly cognitive behavioral therapy (CBT) or interpersonal therapy (IPT), is equally effective for mild to moderate cases and can be used alone or in combination with medication, as supported by the evidence 1. For more severe or treatment-resistant cases, combination therapy, augmentation strategies (adding medications like aripiprazole 2-15mg daily), or treatments like electroconvulsive therapy may be necessary. These treatments work by addressing neurotransmitter imbalances and negative thought patterns that contribute to depressive symptoms. Key considerations in treatment selection include discussing treatment effects, adverse effect profiles, cost, accessibility, and patient preferences, as emphasized in the clinical practice guidelines 1.

Some key points to consider in the treatment of unipolar depression/MDD include:

  • The importance of continuing treatment for 4 to 9 months after a satisfactory response to prevent relapse, with longer durations potentially beneficial for patients with multiple episodes of depression 1.
  • Regular assessment of patient status, therapeutic response, and adverse effects of antidepressant therapy, beginning within 1 to 2 weeks of initiation of therapy 1.
  • Modification of treatment if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder 1.
  • The use of second-generation antidepressants, such as SSRIs and SNRIs, due to their similar efficacy and lower toxicity compared to first-generation antidepressants 1.

From the Research

Definition and Diagnosis

  • Unipolar depression is a type of depressive disorder characterized by a persistent feeling of sadness or loss of interest in external stimuli, which is not accompanied by manic or hypomanic episodes 2.
  • Major depressive disorder (MDD) is a broader term that encompasses unipolar depression, and is defined as a mood disorder characterized by one or more major depressive episodes in a person's lifetime 3, 4.

Treatment Options

  • For unipolar depression, treatment options include pharmacotherapy, psychotherapy, or a combination of both, with the choice of treatment depending on the severity of the depression and the patient's preferences 2.
  • For MDD, treatment options also include pharmacotherapy, psychotherapy, or a combination of both, as well as other therapies such as electroconvulsive therapy or transcranial magnetic stimulation 5, 6.
  • The combination of fluoxetine with cognitive-behavioral therapy (CBT) has been shown to be an effective treatment for adolescents with MDD, with a response rate of 71% compared to 60.6% for fluoxetine alone and 43.2% for CBT alone 6.

Treatment Recommendations

  • For mild depressive episodes, watchful waiting for 14 days may be an appropriate initial treatment, while for moderate depressive episodes, pharmacotherapy and psychotherapy are equally effective treatment options 2.
  • For severe depression, a combination of pharmacotherapy and psychotherapy is recommended, and if 4 to 6 weeks of acute therapy are insufficiently effective, lithium augmentation may be considered rather than combination antidepressant therapy or a switch to another antidepressant 2.
  • Maintenance therapy should be continued for 4 to 9 months after remission, and in cases of recurrent depression, pharmacotherapy and/or psychotherapy should be continued for at least two years 2.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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