Depression: DSM-5-TR Diagnosis, the 9 Symptoms, Assessment Questions and Medication for Each Symptom

Introduction

Depression is one of the most common and disabling mental health conditions worldwide. Accurate diagnosis matters because depression can look like other conditions, such as bipolar disorder, thyroid disease, anemia or substance use, and because treatment works best when it targets the patient’s actual symptoms. Clinicians use the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) to make a standardized diagnosis (American Psychiatric Association [APA], 2022). They then use a careful interview and screening tools to assess each symptom.

Use of the DSM-5-TR in diagnosing depression

DSM-5-TR criteria for major depressive disorder (MDD)

Most symptoms must be present most of the day, nearly every day. The DSM-5-TR also advises careful clinical judgment when depressive symptoms follow a significant loss, such as bereavement, to distinguish normal grief from a major depressive episode.

Specifiers

After diagnosis, the clinician describes the episode with specifiers that guide treatment:

• Course: single episode or recurrent; in partial or full remission.
• Severity: mild, moderate or severe.
• Features: with anxious distress, mixed features, melancholic features, atypical features, psychotic features, catatonia, peripartum onset or seasonal pattern.

Using the DSM-5-TR in practice

1. Screen with a validated tool such as the PHQ-2 or PHQ-9 (Kroenke et al., 2001). The PHQ-9 maps directly onto the nine DSM symptoms and also tracks severity: 5, 10, 15 and 20 mark mild, moderate, moderately severe and severe.
2. Interview to confirm each symptom, its duration and its impact.
3. Rule out medical causes (thyroid function, CBC, metabolic panel, B12/folate as indicated), substances and medications.
4. Screen for bipolar disorder by asking about any history of elevated mood, decreased need for sleep or risky behavior.
5. Assess suicide risk at every visit, for example with the Columbia Suicide Severity Rating Scale (Posner et al., 2011).
6. Record the diagnosis with specifiers and set a baseline score to measure response.

The nine specific symptoms of depression

Assessment questions and medication options for each symptom

The questions below are open, non-judgmental and written in plain language. For each symptom, ask about frequency (“How many days in the past 2 weeks?”), duration and impact on daily life.

The medication options reflect a symptom-based approach: first-line antidepressants (SSRIs, SNRIs, bupropion, mirtazapine) treat the overall depressive syndrome, and the choice of agent, or of add-on treatment, can be matched to the patient’s most troublesome symptoms (Stahl, 2021). Psychotherapy, such as CBT, is effective for every symptom and is recommended alongside or instead of medication for many patients (Department of Veterans Affairs & Department of Defense [VA/DoD], 2022).

1. Depressed mood

Assessment questions:

• “How would you describe your mood over the past 2 weeks?”
• “Have you been feeling sad, down, empty or hopeless? How much of the day, and how many days?”
• “Have you been more irritable or tearful than usual?” (Irritability may be the main sign in children and adolescents.)

Medication options: first-line SSRIs (sertraline, escitalopram, fluoxetine) or SNRIs (venlafaxine, duloxetine, desvenlafaxine). Alternatives include bupropion, mirtazapine and vortioxetine. Most antidepressants have broadly similar overall efficacy (Cipriani et al., 2018), so choice depends on side effects, other symptoms, interactions and patient preference.

2. Loss of interest or pleasure (anhedonia)

Assessment questions:

• “What do you usually enjoy doing? Do you still enjoy those things?”
• “Have you stopped doing hobbies or seeing people you used to enjoy?”
• “When something good happens, are you able to feel pleasure?”

Medication options: anhedonia is linked to reduced dopamine and norepinephrine activity in reward circuits. Consider bupropion (an NE/DA reuptake inhibitor), vortioxetine or an SNRI. Adjunctive aripiprazole or brexpiprazole can be added for inadequate response. Some patients on SSRIs report “emotional blunting,” which may need a change of agent.

3. Appetite or weight change

Assessment questions:

• “Has your appetite changed? Are you eating more or less than usual?”
• “Have you lost or gained weight without trying? About how much, and over what time?”
• “Are you craving particular foods, such as sweets or carbohydrates?”

Medication options:

• Poor appetite and weight loss: mirtazapine, which increases appetite and promotes weight gain.
• Increased appetite and weight gain (common with atypical features): bupropion, which is weight-neutral or associated with weight loss. Fluoxetine or sertraline are relatively weight-neutral options. Avoid mirtazapine and paroxetine, which are more likely to cause weight gain.

4. Sleep disturbance (insomnia or hypersomnia)

Assessment questions:

• “How have you been sleeping? Do you have trouble falling asleep, staying asleep, or waking too early?”
• “Are you sleeping much more than usual, or finding it hard to get out of bed?”
• “Do you feel rested when you wake up?”

Medication options:

• Insomnia: a sedating antidepressant such as mirtazapine, or low-dose trazodone at bedtime as an add-on (off-label as a hypnotic). Give activating antidepressants in the morning. Cognitive behavioral therapy for insomnia (CBT-I) is first-line for persistent insomnia. Benzodiazepines and Z-drugs, if used at all, should be short-term and used cautiously.
• Hypersomnia: more activating agents such as bupropion or fluoxetine, given in the morning. Specialists sometimes add modafinil off-label.

5. Psychomotor agitation or retardation

Assessment questions:

• “Have you felt restless, fidgety or unable to sit still?”
• “Have you or others noticed that you are moving, speaking or thinking more slowly than usual?”
• Also observe: pacing, hand-wringing, slowed speech, long pauses before answering. The DSM requires changes that are observable by others.

Medication options:

• Agitation: a sedating agent such as mirtazapine, or an adjunctive atypical antipsychotic such as quetiapine XR. Assess carefully for mixed features or bipolarity, because antidepressant monotherapy may worsen agitation in these patients.
• Retardation: activating agents such as bupropion or an SNRI. Severe retardation, especially with poor oral intake, catatonia or psychosis, may need ECT.

6. Fatigue or loss of energy

Assessment questions:

• “How is your energy level? Do you feel tired even without exertion?”
• “Are everyday tasks, like showering or cooking, harder to do than before?”

Medication options: fatigue is linked to reduced NE and DA activity. Consider bupropion or an SNRI (duloxetine, venlafaxine, desvenlafaxine). Rule out and treat medical causes such as hypothyroidism, anemia and sleep apnea, and review medications that cause sedation.

7. Feelings of worthlessness or excessive guilt

Assessment questions:

• “How have you been feeling about yourself lately?”
• “Do you feel like a failure, or that you have let others down?”
• “Do you blame yourself for things that are not really your fault?” (Explore for delusional guilt, which suggests psychotic features.)

Medication options: no single drug specifically targets guilt. It usually improves with effective SSRI or SNRI treatment of the overall episode. Psychotherapy, especially CBT that targets negative self-beliefs, is particularly helpful. If guilt is delusional (psychotic depression), combine an antidepressant with an antipsychotic, or consider ECT.

8. Diminished ability to think, concentrate or make decisions

Assessment questions:

• “Have you had trouble concentrating, for example reading, watching TV or following conversations?”
• “Is it harder to make decisions, even small ones?”
• “Has your work or school performance changed?”

Medication options: vortioxetine has evidence for improving cognitive function in MDD (McIntyre et al., 2014). Bupropion and SNRIs may also help through NE and DA effects. Avoid or minimize drugs that impair cognition, such as anticholinergic tricyclics and benzodiazepines, especially in older adults.

9. Recurrent thoughts of death, suicidal ideation or suicide attempt

Assessment questions (ask directly; asking does not increase risk):

• “Have you felt that life isn’t worth living, or wished you could go to sleep and not wake up?”
• “Have you had thoughts of killing yourself?”
• “Have you thought about how you might do it? Do you have a plan or access to means, such as firearms or medications?”
• “Have you ever tried to end your life? Have you done anything recently to prepare?”
• “What has kept you safe so far?” (protective factors)

Management and medication options: safety comes first. Assess the level of risk, create a safety plan, restrict access to lethal means, involve supports, and arrange urgent or emergency care when risk is high. Medication considerations:

• Esketamine nasal spray, given with an oral antidepressant, is FDA-approved for depressive symptoms in adults with MDD with acute suicidal ideation or behavior. It is given under supervision in certified settings.
• Lithium has evidence of reducing suicide risk in mood disorders.
• ECT is rapidly effective for severe, suicidal or psychotic depression.
• Prescribe limited quantities of medication when overdose risk is a concern.
• Monitor closely after starting antidepressants. They carry an FDA boxed warning for increased suicidal thoughts and behaviors in children, adolescents and young adults under 25.

In the United States, the 988 Suicide & Crisis Lifeline (call or text 988) provides 24/7 support. Elsewhere, use local emergency and crisis services.

Summary table

Conclusion

The DSM-5-TR provides a standard framework for diagnosing major depressive disorder: at least five of nine symptoms over 2 weeks, including depressed mood or anhedonia, with functional impairment, after ruling out medical causes, substances and bipolar disorder. A skilled, empathetic interview with clear questions for each symptom, supported by tools such as the PHQ-9, confirms the diagnosis and shows which symptoms matter most to the patient. Matching treatment to those symptoms, combining medication with psychotherapy, and continually assessing suicide risk leads to more personalized care and better outcomes. For the neurobiology behind these choices, see our article on mood disorders and the norepinephrine and GABA networks.

References

American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.). https://doi.org/10.1176/appi.books.9780890425787

Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., Egger, M., Takeshima, N., Hayasaka, Y., Imai, H., Shinohara, K., Tajika, A., Ioannidis, J. P. A., & Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. The Lancet, 391(10128), 1357–1366.

Department of Veterans Affairs & Department of Defense. (2022). VA/DoD clinical practice guideline for the management of major depressive disorder (Version 4.0).

Kroenke, K., Spitzer, R. L., & Williams, J. B. W. (2001). The PHQ-9: Validity of a brief depression severity measure. Journal of General Internal Medicine, 16(9), 606–613.

McIntyre, R. S., Lophaven, S., & Olsen, C. K. (2014). A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. International Journal of Neuropsychopharmacology, 17(10), 1557–1567.

Posner, K., Brown, G. K., Stanley, B., Brent, D. A., Yershova, K. V., Oquendo, M. A., Currier, G. W., Melvin, G. A., Greenhill, L., Shen, S., & Mann, J. J. (2011). The Columbia–Suicide Severity Rating Scale: Initial validity and internal consistency findings from three multisite studies with adolescents and adults. American Journal of Psychiatry, 168(12), 1266–1277.

Stahl, S. M. (2021). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (5th ed.). Cambridge University Press.