MDD Pharmacotherapy

CORE | What are the goals of the acute phase of MDD treatment?

Achieve remission, prevent suicide, and improve functioning and quality of life.

CORE | What are the goals of the continuation phase of MDD treatment?

Prevent relapse after remission, eliminate unresolved symptoms, prevent suicide, and restore psychosocial/occupational function.

CORE | What are the goals of the maintenance phase of MDD treatment?

Prevent a new depressive episode (recurrence), prevent suicide, and enable lasting functional recovery.

CORE | What is “response” in MDD treatment?

Approximately a 50% reduction in depressive symptoms.

CORE | What is “remission” in MDD treatment?

Removal or near-removal of symptoms so criteria for a major depressive episode are no longer met; the lecture describes it as return toward normalcy.

CORE | What is relapse?

Return of the same depressive episode after improvement/remission, typically during the vulnerable continuation period.

CORE | What is recurrence?

A new depressive episode after recovery, generally associated with the maintenance phase.

CORE | What are the three MDD treatment phases?

Acute, continuation, and maintenance.

CORE | What psychotherapies are listed as nonpharmacologic MDD treatments?

Behavioral therapy, interpersonal psychotherapy, group therapy, CBT, and mindfulness-based cognitive therapy.

CORE | What brain-stimulation treatments are listed for depression?

ECT, vagus nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation.

CORE | What is antidepressant monotherapy?

Use of one antidepressant.

CORE | What is adjunctive/augmentation therapy in MDD?

Use of an antidepressant together with an agent not conventionally used as first-line monotherapy in MDD.

CORE | What is combination antidepressant therapy?

Use of two antidepressants, each approved as monotherapy for MDD.

CORE | What should be checked before declaring a first antidepressant inadequate?

Confirm the dose has been optimized and sufficient treatment time has passed.

CORE | What are the main second-line strategies after inadequate antidepressant response?

Switch antidepressants, augment with a non-antidepressant, or combine with another antidepressant.

CORE | When switching antidepressants, must the new drug be from a different class?

No. The new antidepressant may be from the same or a different class; washout or cross-titration may be needed.

DETAIL | Give an example of a serotonergic combination strategy from the lecture.

Sertraline plus a subtherapeutic dose of trazodone.

DETAIL | Give an example of a serotonergic/noradrenergic combination strategy from the lecture.

Citalopram plus bupropion.

CORE | What does the lecture suggest for mild MDD?

Recommendations vary from watchful waiting to psychotherapy and/or antidepressants; the lecture associates mild MDD with PHQ-9 <10.

CORE | What are first-line options for moderate MDD?

Antidepressant monotherapy, psychotherapy, or their combination; the lecture associates moderate MDD with PHQ-9 >10.

CORE | What are first-line options for severe MDD?

Combination antidepressant + psychotherapy or ECT.

CORE | How should severe MDD with psychotic features be treated according to the lecture?

An antidepressant plus an antipsychotic is suggested as first-line treatment.

CORE | What pharmacotherapy classes are preferred first-line in the lecture summary?

An SSRI or another newer agent such as an SNRI or SARI; avoid TCAs and MAOIs as routine first-line choices.

CORE | When should a patient first be reassessed after starting an antidepressant?

About 2–4 weeks.

CORE | When should treatment change be considered for inadequate response?

Around 4–8 weeks, considering augmentation, combination, or switching.

CORE | How long should continuation treatment last according to the guideline summary?

At least 4–6 months; later clinical pearls describe a continuation phase of about 9 months.

CORE | How long may maintenance therapy be needed in patients who require it?

At least 2–3 years according to the guideline summary.

CORE | What factors should guide antidepressant selection?

Side-effect profile, patient or family response history, possible drug interactions, comorbidities, cost, and sometimes target symptoms such as pain, fatigue, insomnia, or anxiety.

DETAIL | What proportion of patients achieve remission with the first antidepressant tried?

Less than one-third, according to the lecture.

CORE | Which non-MAOI antidepressants are highlighted as having higher drug-interaction risk?

Fluoxetine, fluvoxamine, and paroxetine.

CORE | Which antidepressants are highlighted as having lower drug-interaction risk?

Citalopram, escitalopram, venlafaxine, desvenlafaxine, and mirtazapine.

CORE | What dosing principle is emphasized for elderly and young patients?

Start low and go slow.

CASE | Depression with comorbid anxiety: which common first-line class is attractive?

An SSRI; SNRIs are also listed as useful when anxiety is comorbid.

CASE | Depression with cardiovascular disease: which SSRI is specifically highlighted?

Sertraline.

CASE | Depression with pain, fibromyalgia, or neuropathy: which class is attractive?

An SNRI, especially duloxetine in the lecture.

CASE | Depression with insomnia and low body weight: which drug is attractive?

Mirtazapine.

CASE | Depression with concern for sexual dysfunction: which drugs are highlighted as options?

Bupropion, mirtazapine, vilazodone, or vortioxetine depending on the patient.

CASE | Depression with obesity/weight concern: which agent is attractive and which SSRI is cautioned?

Bupropion is attractive; paroxetine is cautioned in overweight/obese patients.

CASE | Depression with seizure disorder: which antidepressant is clearly contraindicated/cautioned?

Bupropion; the lecture also cautions with some SSRIs/SNRIs such as escitalopram and venlafaxine/desvenlafaxine.

CASE | Depression with hypertension: which antidepressant categories require caution?

SNRIs and bupropion.

CASE | Depression with daytime drowsiness or obesity: what issue makes mirtazapine less attractive?

Mirtazapine can cause drowsiness and weight gain.

CASE | Depression with anxiety/insomnia: why might bupropion be less attractive?

Bupropion can be activating and may worsen anxiety or insomnia.

CASE | A patient taking anticoagulants needs an antidepressant. What SSRI-related caution is emphasized?

SSRIs can increase bleeding risk, so use caution and monitor.

CORE | What is the basic mechanism of SSRIs?

Selective inhibition of serotonin reuptake, increasing serotonin availability in the synapse.

CORE | What are common SSRI adverse effects?

GI effects, fatigue, agitation, insomnia, sexual dysfunction, weight gain, headache, increased bleeding risk, and rarely serotonin syndrome.

DRUG | Citalopram: usual initial and dose range in the lecture?

Initial 20 mg/day; range 20–40 mg/day.

DRUG | What is the major citalopram dose-related safety concern?

QT prolongation; doses above 40 mg/day are not recommended, and the lecture notes a 20 mg/day maximum in elderly patients.

DRUG | Escitalopram: usual initial and dose range in the lecture?

Initial 10 mg/day; range 10–20 mg/day.

DRUG | What is an important escitalopram safety concern in the lecture?

Dose-dependent QT prolongation.

DRUG | Fluoxetine: usual initial and dose range in the lecture?

Initial 20 mg/day; range 20–60 mg/day, with a listed maximum of 80 mg/day.

DRUG | What makes fluoxetine distinctive pharmacokinetically?

Very long half-life/slow elimination; the lecture describes it as “self-tapering” and notes no cross-taper is required in some switching contexts.

DRUG | Which SSRI is described as the most stimulating?

Fluoxetine.

DRUG | Paroxetine: what adverse-effect pattern is highlighted?

More drowsiness/dry mouth and a higher incidence of anticholinergic effects; dosing adjustments are needed in renal/hepatic impairment.

DRUG | Sertraline: usual initial and dose range in the lecture?

Initial 50 mg/day; range 50–200 mg/day.

DRUG | What hepatic dosing point is noted for sertraline?

Reduce the dose by 50% in mild hepatic impairment.

DRUG | Fluvoxamine: usual initial and dose range in the lecture?

Initial 50 mg/day; range 50–300 mg/day, with doses above 100 mg/day generally divided.

CORE | What is the basic mechanism of SNRIs?

Inhibition of serotonin and norepinephrine reuptake.

CORE | How do SNRI adverse effects differ from SSRI adverse effects?

They share serotonergic effects but add noradrenergic effects such as increased heart rate, pupil dilation, dry mouth, sweating, insomnia, constipation, and possible BP elevation.

DRUG | Desvenlafaxine: standard dose highlighted in the lecture?

50 mg/day; higher doses were studied but adverse effects increase with no clear added benefit beyond 50 mg in the slide.

DRUG | What major cautions are listed for desvenlafaxine?

Hypertension risk, decreased seizure threshold, and renal-dose adjustment.

DRUG | Duloxetine: usual initial and dose range in the lecture?

Initial 30 mg/day; range 30–90 mg/day; the slide lists a maximum of 120 mg/day divided.

DRUG | What comorbidity makes duloxetine especially useful?

Chronic neuropathic pain; the selection table also highlights pain related to depression, fibromyalgia, and neuropathy.

DRUG | Venlafaxine XR: usual initial and dose range in the MDD lecture?

Initial 37.5–75 mg/day; range 75–375 mg/day.

DRUG | What major cautions are listed for venlafaxine?

Hypertension, decreased seizure threshold, renal/hepatic dose adjustment, and caution with glaucoma/ocular pressure.

DRUG | Levomilnacipran: what cardiovascular adverse effects are emphasized?

Increased heart rate and blood pressure, including tachycardia.

CORE | Why are TCAs generally not first-line?

Poor tolerability, substantial anticholinergic/cardiovascular effects, and high toxicity in overdose.

CORE | What are typical TCA adverse effects?

Profound sedation, weight gain, anticholinergic effects, cognitive impairment, orthostatic hypotension, tachycardia/arrhythmia/QT prolongation, sexual dysfunction, dizziness, and other CNS effects.

CORE | What makes TCA overdose especially dangerous?

Risk of coma/seizure and potentially fatal cardiac arrhythmia/arrest.

DRUG | Amitriptyline: what major clinical characteristics are emphasized?

Highly anticholinergic/sedating, can cause weight gain, orthostasis, tachycardia and cognitive issues; QT/cardiac cautions; often used at low dose for sleep.

DRUG | Desipramine: how does it differ from many TCAs?

It is less sedating and has fewer anticholinergic effects.

DRUG | Doxepin: what nondepression uses are highlighted?

Chronic hives/itching and low-dose use for insomnia; it is sedating and can increase appetite/weight.

DRUG | Protriptyline: what is unusual about its sedation profile?

It tends to be energizing rather than sedating and may be used for narcolepsy.

DRUG | Clomipramine: what important cautions are listed?

Anticholinergic effects and contraindication/caution with seizure disorder and recent MI; use in MDD is off-label in the slide.

CORE | What is bupropion’s main pharmacologic class?

Norepinephrine/dopamine reuptake inhibitor (NDRI).

DRUG | What are common clinical advantages of bupropion?

Lower risk of sexual dysfunction, little drowsiness/weight gain, and usefulness in smoking cessation.

DRUG | What are key bupropion adverse effects/cautions?

Insomnia, agitation, headache, hypertension risk, and dose-related seizure risk; avoid in seizure disorders and eating disorders such as bulimia/anorexia.

DRUG | What is the maximum bupropion dose listed in the lecture?

450 mg/day.

DRUG | What are the key trazodone clinical features?

Highly sedating, commonly used for insomnia at subtherapeutic doses, orthostasis, and rare priapism; it has little anticholinergic effect compared with TCAs.

DRUG | What serious toxicity is emphasized for nefazodone?

Severe hepatic damage.

DRUG | What administration point is emphasized for vilazodone?

Take with food to ensure bioavailability; it requires a complex titration.

DRUG | What common adverse effects are noted for vortioxetine?

GI effects and sexual dysfunction; the lecture describes it as generally well tolerated.

DRUG | What are the major mirtazapine effects useful for patient selection?

Sedation/sleep induction and increased appetite; adverse effects include weight gain, drowsiness, and constipation.

DRUG | What is the key treatment-setting requirement for intranasal esketamine (Spravato)?

REMS-controlled administration in a healthcare setting with direct monitoring for 2 hours after dosing.

DRUG | What boxed-warning-type risks are emphasized for esketamine?

Sedation, dissociation, misuse, and suicidal thoughts/behaviors; it is intended with a traditional antidepressant in the lecture.

DRUG | What is brexanolone (Zulresso) used for?

Postpartum depression; it is given by a 60-hour continuous infusion with REMS monitoring for excessive sedation/sudden loss of consciousness and hypoxia.

DRUG | What is zuranolone (Zurzuvae) used for in the lecture?

Postpartum depression; a 14-day oral course, usually taken in the evening with a fat-containing meal.

DRUG | What is gepirone ER (Exxua) pharmacologically related to?

Buspirone; it has greater activity at the 5-HT1A receptor.

DRUG | What major safety issues are listed for gepirone ER?

QT prolongation, serotonin syndrome, and activation of mania/hypomania; screen for bipolar history/risk.

DRUG | What pathways does dextromethorphan/bupropion (Auvelity) modulate?

Both glutamatergic and monoaminergic pathways; the exact MDD mechanism is described as unclear.

DRUG | What major contraindications/cautions are listed for Auvelity?

Seizure disorder, current/prior bulimia or anorexia, abrupt withdrawal from alcohol/benzodiazepines/barbiturates/antiepileptics, and MAOI use within the relevant 14-day window.

CORE | What is the major dietary danger with MAOIs?

Potentially fatal hypertensive crisis after eating tyramine-rich foods.

CORE | What is the major serotonergic danger of combining an MAOI with an SSRI or other serotonergic drug?

Potentially fatal serotonin syndrome.

CORE | What common MAOI adverse effects are listed?

Insomnia, sedation, orthostatic hypotension, sexual dysfunction, weight gain, and myoclonic jerking.

DRUG | What MAOIs are listed in the MDD pharmacotherapy lecture?

Phenelzine, transdermal selegiline, and tranylcypromine.

CORE | What is the initiation phase duration in the antidepressant clinical pearls?

0–2 weeks.

CORE | When are any antidepressant benefits usually first seen?

About 2–4 weeks.

CORE | What symptom reduction is desired by the first 2–4 week follow-up?

About 25–30% reduction in PHQ-9/symptoms.

CORE | When does the lecture expect antidepressant therapy to become fully effective?

About 6–8 weeks.

CORE | By when should a ~50% response ideally occur?

By about week 8.

CORE | By when should remission ideally occur?

By about 12 weeks (3 months).