Clinical Care Guideline: Major Depressive Disorder (MDD)

MDD is defined by the experience of depressed mood or anhedonia (a loss of interest or pleasure) persisting nearly all day, every day for at least two weeks, which distinguishes it from an occasional sad mood or lack of interest that lasts for a few hours or days.(1) Based on the severity of symptoms, functional impairment, and level of patient distress, MDD can be characterized as mild, moderate, or severe. In the United States, more than 20% of adults experience MDD in their lifetime.(2)

This care guideline offers a brief summary of the evidence-based, best practices for the effective treatment of major depressive disorder in adults.

Diagnostic considerations for MDD in Adults

Is your client experiencing five or more of the following, most days?

  • Depressed mood
  • Loss of interest or pleasure in all, or almost all, things they previously enjoyed (anhedonia)
  • Loss of appetite
  • Difficulty falling or staying asleep, or alternatively excessive sleep
  • Loss of energy
  • Feeling worthless
  • Feeling guilty
  • Trouble concentrating
  • Suicidal ideation

Have the above symptoms negatively impacted the client’s ability to function in important areas of life, such as in relationships, at work, at school or complete activities of daily living (such as hygiene, keeping up with responsibilities, etc)?

It’s important to note, the above symptoms and experiences may also be attributable to an alternative disorder (such as persistent depressive disorder or bipolar disorder), a neurological cause or due to the direct physiologic effects of a substance. As a result, a clinical best practice is to engage in a differential diagnostic assessment prior to determining if MDD is the clinically indicated diagnosis. 

For complete diagnostic criteria, consult the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.). American Psychiatric Association. (2022).

noun-lightbulb-1262995.png When documenting care, be sure to include the specific symptoms of MDD experienced by the client. This ensures your note reflects alignment with the diagnosis and demonstrates medical necessity for the service.

Symptom Screening and Monitoring

The PHQ-9 (Patient Health Questionnaire - 9 item) is a brief validated, client self-report screening tool used to assess the frequency and severity of depressive symptoms. Routine use of this measure is foundational to providing effective care for individuals who experience depression, as it supports accurate diagnoses, identification of treatment plan goals based on symptom severity, and can guide effective clinical interventions. You can learn more about the PHQ-9 and strategies for incorporating Measurement Informed Care (MIC) into your practice here.

Evidence-Based Approaches to Treatment 

The American Psychological Association (APA) recommends several evidence-based psychotherapy interventions for the treatment of MDD in adults. For clients who experience moderate to severe depressive symptoms, the use of second-generation antidepressants (SSRIs, SNRIs, or NDRIs) in addition to psychotherapy has demonstrated efficacy.(4)


Therapists are encouraged to become familiar with each of the different evidence-based approaches, as well as engage in shared decision-making with the client to determine which intervention is right for each clinical situation.

  • Cognitive-behavioral therapy (CBT) is the most studied psychotherapy for depression and has the largest weight of evidence for its efficacy.
  • Interpersonal psychotherapy (IPT) 
  • Problem-solving therapy (PST)

Meta-analyses that compare the effectiveness of CBT, IPT, and PST indicate no large differences in effectiveness between these treatments.


Second-generation antidepressants include SSRIs, SNRIs, and NDRIs, and are recommended as “first-line” medications for use in the treatment of depression. These medications regulate the neurotransmitters serotonin, norepinephrine, and dopamine, which are involved in brain functions related to mood and behavior. Some examples of evidence-based effective medications include:

  • Sertraline (Zoloft)
  • Escitalopram (Lexapro)
  • Duloxetine (Cymbalta)
  • Venlafaxine-XR (Effexor)

Antidepressant selection should be individualized based on clinical factors, including symptom profile, comorbidity, tolerability profile, previous response, potential drug-drug interactions, patient preference, and cost. No FDA-approved antidepressant has been clearly shown to be superior to another.

Benzodiazepines (such as diazepam and clonazepam) are generally not recommended for the treatment of depression due to their high potential for dependence as well as their limited long-term effectiveness.

When should I refer my client for psychiatric medication management? 

Clients with moderate to severe depression may benefit from discussing the use of medication (in conjunction with continued therapy) with a Psych NP or Psychiatrist to maximize treatment response and symptom reduction. The use of medications is also often clinically indicated for the management of MDD with symptoms of psychosis. This step by step guide walks you through how to easily refer your client for a psychiatric medication management evaluation at Rula. 

noun-lightbulb-1262995.png As a reminder, it is beyond the scope of a psychotherapist to suggest specific medications, groups of medications, specific supplements, or advise on the frequency of taking or stopping medications. These discussions must only be carried out by a medical provider.

Assessing Risk and Higher Level of Care Needs

The risk of suicide in individuals with major depression is about 20 times that of the general population.(5) Research has shown that feelings of hopelessness, worthlessness, delusionally depressive thoughts, anxiety, and sleep disturbances, directly and indirectly contribute to an increase in risk of suicide attempts. 

Particularly for clients who respond affirmatively to thoughts of suicide or self-harm on the PHQ-9 (Question #9) or any item on the C-SSRS (Columbia Suicide Severity Rating Scale) Screener, it is imperative that therapists engage in (and document) thorough risk assessment, completion of a safety plan and referral for additional services (such as IOP, PHP, Group therapy) if clinically indicated. 

noun-lightbulb-1262995.png Rula’s team of care coordinators is available to support your client in accessing these additional clinical services outside of Rula. Click here to learn more about how to easily refer your client for a Higher Level of Care (HLOC).

Cultural Considerations

The expression of depressive symptoms is often influenced by cultural contexts, including perceptions of illness and symptoms (including their causes), social pressures and stigma, gender and racial identification, what life experiences are considered typical in a particular cultural environment as well as how one is expected to respond or cope with those stimuli. In some cultures, depressive symptoms might not  be expressed in words at all, but in the form of physical symptoms, such as headaches, backaches or stomach discomfort. Some clients may feel thor symptoms are better explained through a lens of religious or spiritual beliefs and values.(7) As a result, it is important to always consider the social and cultural contexts of a client's treatment needs as part of the diagnostic process.

“When a mental health professional understands the role that culture plays in the diagnosis of a condition and incorporates cultural needs and differences into a person’s care, it significantly improves outcomes.”(8)

Disclaimer: MDD in Children and Adolescents

This care guide focuses on best practice guidelines for treating Adults with MDD, however, major depressive disorder is one of the most common psychiatric disorders of childhood and adolescence, but because of symptom variation from the adult criteria, it is often unrecognized and untreated.(6) For information on providing effective care for children and adolescents with MDD, check out the below resources:

Downloadable Digital Guide

Click HERE for a downloadable digital copy of this guide. 


  1. Anxiety & Depression Association of America.
  2. American College of Physicians.
  3. American Psychological Association.
  4. American Psychological Association.
  5. American Academy of Suicidology.
  6. Mental Health Clinician.
  7. Anxiety and Depression Association of America
  8. National Alliance on Mental Illness (NAMI). (n.d.). Identity and Cultural Dimensions.

Was this article helpful?

0 out of 0 found this helpful