Ch. 7 Phsychopharm: Depression- Mod 2

What is the modern neurobiologic understanding of depression?

Depression is not simply a serotonin deficiency

Which neurotransmitters are implicated in depression?

Serotonin (5-HT), norepinephrine (NE), dopamine (DA), glutamate, GABA, acetylcholine, histamine, and neuropeptides.

What role does BDNF play in depression?

BDNF promotes neuroplasticity

What is the HPA axis?

The hypothalamic-pituitary-adrenal axis

What is the primary goal of antidepressant therapy?

Achieve remission with functional recovery and prevent relapse or recurrence.

What is response to treatment?

≥50% reduction in depressive symptoms.

What is remission?

Near absence of depressive symptoms with restoration of functioning.

What is relapse?

Return of symptoms before full recovery from the current episode.

What is recurrence?

Development of a new depressive episode after recovery.

What is first-line treatment for mild depression?

Psychotherapy (especially CBT or IPT), antidepressants if indicated.

What is first-line treatment for moderate to severe depression?

Antidepressant medication often combined with psychotherapy.

How long should antidepressants be continued after remission?

At least 6–12 months after the first episode

How do SSRIs work?

Block serotonin reuptake transporter (SERT), increasing serotonin availability.

Examples of SSRIs?

Fluoxetine, sertraline, escitalopram, citalopram, paroxetine, fluvoxamine.

Common SSRI adverse effects?

GI upset, headache, insomnia, sexual dysfunction, weight changes, emotional blunting.

Black box warning for SSRIs?

Increased suicidal thoughts/behaviors in children, adolescents, and young adults ≤24 years.

Which SSRI has the longest half-life?

Fluoxetine.

Which SSRI has the highest risk of withdrawal symptoms?

Paroxetine.

Which SSRI is associated with QT prolongation?

Citalopram.

How do SNRIs work?

Inhibit reuptake of serotonin and norepinephrine.

Examples of SNRIs?

Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran.

What adverse effect is common with SNRIs?

Dose-dependent hypertension (especially venlafaxine), sweating, nausea.

Which SNRI is useful for neuropathic pain?

Duloxetine.

How do TCAs work?

Block serotonin and norepinephrine reuptake

Examples of TCAs?

Amitriptyline, nortriptyline, imipramine, desipramine, clomipramine.

Major adverse effects of TCAs?

Anticholinergic effects, orthostatic hypotension, sedation, cardiac conduction abnormalities.

Why are TCAs dangerous in overdose?

Potentially fatal arrhythmias and seizures.

How do MAOIs work?

Irreversibly inhibit monoamine oxidase, increasing serotonin, norepinephrine, and dopamine.

Examples of MAOIs?

Phenelzine, tranylcypromine, isocarboxazid.

Major MAOI dietary restriction?

Avoid tyramine-containing foods to prevent hypertensive crisis.

What is serotonin syndrome?

Potentially life-threatening excess serotonergic activity causing autonomic instability, neuromuscular abnormalities, and altered mental status.

Symptoms of serotonin syndrome?

Agitation, hyperreflexia, clonus, diaphoresis, fever, diarrhea.

How is serotonin syndrome treated?

Stop serotonergic agents, supportive care, benzodiazepines, cyproheptadine if severe.

How does bupropion work?

Norepinephrine-dopamine reuptake inhibitor (NDRI).

Advantages of bupropion?

Minimal sexual dysfunction, weight neutral, smoking cessation aid.

Major contraindication for bupropion?

Seizure disorders and eating disorders.

How does mirtazapine work?

Alpha-2 antagonist increasing NE and serotonin release

Advantages of mirtazapine?

Improves appetite, promotes sleep, minimal sexual dysfunction.

Common adverse effects of mirtazapine?

Sedation and weight gain.

How does trazodone work?

Serotonin antagonist and reuptake inhibitor (SARI).

Common use of trazodone?

Low-dose treatment of insomnia.

Serious adverse effect of trazodone?

Priapism.

How does vortioxetine work?

Serotonin modulator affecting multiple serotonin receptors and inhibiting serotonin reuptake.

Potential benefit of vortioxetine?

Improvement in cognitive symptoms of depression.

How does vilazodone work?

SSRI plus partial 5-HT1A agonist.

What is treatment-resistant depression (TRD)?

Failure of at least two adequate antidepressant trials.

Augmentation strategies for TRD?

Lithium, atypical antipsychotics, thyroid hormone, psychotherapy, ECT, TMS, ketamine/esketamine.

Which atypical antipsychotics are FDA-approved for augmentation in depression?

Aripiprazole, brexpiprazole, quetiapine XR.

Mechanism of ketamine/esketamine?

NMDA receptor antagonists producing rapid antidepressant effects.

Monitoring requirements for esketamine?

REMS program with observation for sedation, dissociation, and blood pressure changes.

When is ECT indicated?

Severe depression with suicidality, psychosis, catatonia, or treatment resistance.

Most common ECT adverse effect?

Transient memory impairment.

What is TMS?

Transcranial magnetic stimulation

Which antidepressants are safest in pregnancy?

SSRIs (especially sertraline) are commonly preferred when benefits outweigh risks.

Which antidepressant should generally be avoided in pregnancy?

Paroxetine due to congenital cardiac defect concerns.

Preferred antidepressant during breastfeeding?

Sertraline.

Depression treatment considerations in older adults?

Start low, go slow

What antidepressant has the greatest anticholinergic burden?

Paroxetine among SSRIs

How long before antidepressants show clinical benefit?

Typically 2–6 weeks.

What should patients be told before antidepressants begin working?

Early side effects may occur before mood improves

When should suicide risk be monitored most closely?

At initiation, after dose changes, and in young patients.

What laboratory tests may be indicated before treatment?

TSH, CBC, CMP, vitamin B12, folate, vitamin D when clinically indicated.

Why screen for bipolar disorder before prescribing antidepressants?

Antidepressants may precipitate mania or rapid cycling.

Which screening tool is commonly used for depression?

PHQ-9.

Which screening tool helps identify bipolar disorder?

Mood Disorder Questionnaire (MDQ).

What is the modern neurobiologic understanding of depression?

Depression is not simply a serotonin deficiency

Which neurotransmitters are implicated in depression?

Serotonin (5-HT), norepinephrine (NE), dopamine (DA), glutamate, GABA, histamine, acetylcholine, and brain-derived neurotrophic factor (BDNF)-mediated neuroplasticity.

What role does BDNF play in depression?

BDNF promotes neuroplasticity

What is the HPA axis?

The hypothalamic-pituitary-adrenal axis

What is the primary goal of antidepressant therapy?

Achieve remission with functional recovery and ultimately sustained recovery while preventing relapse and recurrence.

Define antidepressant response.

A ≥50% reduction in depressive symptoms.

Define remission.

Minimal or no depressive symptoms with functional recovery

Define recovery.

Sustained remission with prevention of relapse or recurrence.

What occurs during the acute phase of depression treatment?

Lasts approximately 6–12 weeks and aims to achieve symptom remission.

What occurs during the continuation phase?

Lasts approximately 4–9 months and aims to prevent relapse after remission.

What occurs during the maintenance phase?

Lasts ≥1–2 years or indefinitely to prevent recurrence in high-risk patients.

Which patients benefit most from maintenance antidepressant therapy?

Patients with history of recurrent depression, severe episodes, persistent distress, or suicide risk.

What is the mechanism of action of SSRIs?

Selectively block the serotonin transporter (SERT) to increase synaptic serotonin levels.

What is SERT?

The serotonin transporter responsible for reuptake of serotonin into the presynaptic neuron.

What happens after chronic SSRI administration?

Desensitization of presynaptic 5-HT1A autoreceptors occurs, restoring serotonin release and downstream neuroplasticity.

Why do SSRIs require several weeks before improving depression?

Autoreceptor desensitization and neuroplastic changes take weeks despite immediate neurotransmitter elevation.

When do monoamine neurotransmitter levels increase after starting SSRIs?

Hours to days after initiation.

When is clinical improvement expected after initiating an SSRI?

Typically within 2–4 weeks

Why is delayed antidepressant response a favorite ANCC concept?

It highlights the difference between immediate neurochemical actions and long-term neuroplastic adaptation.

What does SSRI stand for?

Selective Serotonin Reuptake Inhibitor

What does SNRI stand for?

Serotonin-Norepinephrine Reuptake Inhibitor

What does NDRI stand for?

Norepinephrine-Dopamine Reuptake Inhibitor

What does NaSSA stand for?

Noradrenergic and Specific Serotonergic Antidepressant

What does SARI stand for?

Serotonin Antagonist and Reuptake Inhibitor

Which medications are classified as SSRIs?

Fluoxetine, Sertraline, Paroxetine, Citalopram, Escitalopram, Fluvoxamine.

Which medications are classified as SNRIs?

Venlafaxine, Desvenlafaxine, Duloxetine, Levomilnacipran.

Which medication is the primary NDRI?

Bupropion

Which medication is the primary NaSSA?

Mirtazapine

Which medication is the primary SARI?

Trazodone

Which medications are common tricyclic antidepressants (TCAs)?

Amitriptyline, Nortriptyline, Imipramine, Desipramine, Clomipramine, Doxepin.

Which medication is a classic MAOI?

Phenelzine, Tranylcypromine, Isocarboxazid, Selegiline.

What is the mechanism of action of SSRIs?

Selectively inhibit SERT, increasing synaptic serotonin.

What is the mechanism of action of SNRIs?

Inhibit both SERT and NET (norepinephrine transporter), increasing serotonin and norepinephrine.

What is the mechanism of action of NDRIs?

Inhibit DAT (dopamine transporter) and NET, increasing dopamine and norepinephrine without direct serotonin effects.

What is the mechanism of action of NaSSAs?

Antagonize presynaptic alpha-2 autoreceptors/heteroreceptors, increasing release of norepinephrine and serotonin, while blocking 5-HT2 and 5-HT3 receptors.