Major Depressive Disorder (MDD) remains one of the most common and impactful conditions seen in primary care. While many of us treat depression daily, it is valuable to periodically revisit the foundational principles of diagnosis and initial treatment to ensure we are offering the best possible care.
This article highlights key takeaways and “clinical pearls” from a recent presentation on the initial treatment of MDD. For those interested in a deeper dive, a link to the full transcript is provided at the end of this article.
Diagnosis: Beyond the Checklist
The DSM-5 criteria for a Major Depressive Episode are familiar to most: five or more symptoms present for at least two weeks, representing a change from previous functioning. One of the symptoms must be either depressed mood or loss of interest/pleasure (anhedonia).
However, beyond the checklist, pay attention to functional impairment. Is the patient calling in sick to work? Withdrawing socially? Spending excessive time in bed? These behavioral changes are often the most reliable indicators of severity.
The PHQ-9 as a Clinical Tool The PHQ-9 is not just a screener; it maps directly to DSM-5 criteria and can support your diagnosis. It is also the standard for measurement-based care to track symptoms and response to treatment over time. Initially, the total score helps stratify severity and guide treatment selection:
- 5-9 (Mild): Consider psychotherapy or behavioral activation first.
- 10-14 (Moderate): Psychotherapy, medication, or both are reasonable initial options based on patient preference.
- 15-19 (Moderately Severe) & 20+ (Severe): Combination treatment (medication + psychotherapy) is often the gold standard.
Don’t Forget the Differential Before initiating treatment, rule out common mimics:
- Medical causes: Hypothyroidism (TSH), anemia (CBC), vitamin deficiencies (B12, Folate, Vitamin D), and obstructive sleep apnea (OSA). Treating OSA can often resolve depressive symptoms entirely.
- Substance use: Alcohol and cannabis are frequent contributors.
- Bipolar Disorder: Screening for mania/hypomania is critical before starting an antidepressant. Use the Mood Disorder Questionnaire (MDQ) to reduce the likelihood of triggering a manic episode. The MDQ can be self-administered or administered with a provider. If the MDQ is negative, you can feel reassured that the likelihood of triggering a manic episode is unlikely. However, if it is positive, you will need to review the results to clarify the diagnosis as false positives are common.
Initial Treatment Selection
For mild to moderate depression, psychotherapy (CBT, Behavioral Activation) is as effective as medication and has lasting benefits. For more severe cases, or when therapy is inaccessible, pharmacotherapy is indicated.
Choosing an Antidepressant Most first-line agents (SSRIs, SNRIs, Bupropion, Mirtazapine) have comparable efficacy across the population. Therefore, selection should be driven by:
- Side Effect Profile: Leverage side effects to the patient’s advantage.
- Insomnia + Weight Loss? Consider Mirtazapine (sedating, increases appetite).
- Low Energy + Smoking + No anxiety? Consider Bupropion (activating, helps cessation, may worsen anxiety).
- Sexual Dysfunction Concern? Bupropion and mirtazapine have a lower risk than SSRIs and SNRIs
- Prior Response: If it worked before (for the patient or a family member), try it again.
- Comorbidities:
- Chronic Pain? Duloxetine (SNRI) has an FDA indication for certain kinds of pain.
- Anxiety? SSRIs are generally preferred.
Initiating and Monitoring Treatment
Start Low and Go Slow: Minimize initial side effects to improve adherence. Titrate every few weeks until you reach a therapeutic dose or see a response.
The 4-6 Week Rule: An adequate trial is typically 4-6 weeks at a therapeutic dose.
- No response? Switch to a different medication (different SSRI or different class).
- Partial response? Consider augmentation (e.g., adding Bupropion, Mirtazapine, or a second-generation antipsychotic like aripiprazole).
Duration of Treatment: For a first episode, continue treatment for 6-12 months after remission to prevent relapse. For recurrent or severe episodes, long-term maintenance may be necessary.
Clinical Pearls & FAQs
- Anxiety Spike: Warn patients that anxiety may briefly worsen when starting an antidepressant. This prevents early discontinuation.
- Sexual Side Effects: Patients rarely volunteer this information, but it is a common reason why patients stop the medication without telling their provider. Ask directly. If present, consider switching to Bupropion or adding it as an adjunct.
- Pharmacogenomics: Tests like GeneSight are not a “magic bullet” for initial selection. They help guide dosing based on metabolism but do not predict efficacy. Reserve them for treatment-resistant cases or those with unusual side effects. Most insurances will not pay for gene-drug interaction tests unless the patient has failed at least two antidepressant trials.
- Exercise as Medicine: For mild-moderate depression, exercise can be as effective as medication. Use behavioral activation (“Just walk to the mailbox today”) to help patients overcome the inertia of depression.
- Cannabis Use: Daily cannabis use can mimic or worsen depression. While we can’t force patients to quit, encouraging a “tincture of time” off the substance can clarify the diagnosis. Note that substance-induced depression often resolves without antidepressants once substance use stops.
When to Refer to Psychiatry (if/when available) or Call the UW Psychiatry Consultation Line (PCL)
Primary care is the ideal setting for uncomplicated depression. Consider referral if:
- Diagnosis is unclear (e.g., suspected bipolar or schizoaffective disorder).
- Treatment resistance (failed 2+ medication trials).
- High safety risk (active suicidal ideation, psychosis).
- Complex comorbidities (severe substance use, personality disorders).
If a referral to psychiatry is not possible, you can always call the PCL for free clinical advice about your adult patients with mental health and/or substance use conditions. Prescribing providers can call any time, 24/7, and non-prescribing providers can call Mon-Fri, 8 AM – 5 PM (excluding holidays). 877-WA-PSYCH/877-927-7924 We are here to help!
To see Dr. Duncan’s complete UW PACC presentation on this topic, click on this link: Initial Treatment of MDD
Dr. Duncan, trained in both family medicine and addiction psychiatry, practices at the intersection of mental health and primary care. He is the co-medical director for the University of Washington Psychiatry and Addiction Case Conference (UW PACC), a weekly online learning collaborative to help community providers across the state improve their psychiatric and addiction clinical skills. Dr. Duncan is one of the PCL’s core weekday faculty where his unique expertise in primary care and psychiatry is available to healthcare providers across Washington.