4.1 Antidepressants

Antidepressants are the most frequently prescribed medication class in psychiatric-mental health nursing, and safe practice requires knowing not just what each drug treats but the exact timeline of benefit, the warnings that must be taught at every visit, and the interactions that can turn a helpful medication into a medical emergency. The PMH-BC exam tests all three domains — indication, expected timeline, and safety monitoring — often within a single scenario item.

Selective Serotonin Reuptake Inhibitors (SSRIs) and SNRIs

SSRIs (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine) block presynaptic reuptake of serotonin, increasing serotonin availability in the synapse. SNRIs (venlafaxine, duloxetine, desvenlafaxine, levomilnacipran) block reuptake of both serotonin and norepinephrine. Both classes are first-line for major depressive disorder and most anxiety disorders because they are safer in overdose than older agents.

Key patient-teaching points:

• Onset: Some symptom relief (sleep, appetite, energy) may appear within 1-2 weeks, but full antidepressant effect requires 4-6 weeks at an adequate dose. Nurses must counsel patients not to stop the medication early because "it isn't working yet."
• Black-box warning: All antidepressants carry an FDA black-box warning for increased suicidal thinking and behavior in children, adolescents, and young adults under age 25, particularly during the first 1-2 months of treatment or after any dose change. Close monitoring and safety planning are essential during this window.
• Common adverse effects: GI upset, sexual dysfunction (decreased libido, anorgasmia — a leading cause of nonadherence), insomnia or sedation depending on the agent, and initial jitteriness or anxiety.
• Dose-dependent effects: Venlafaxine can raise blood pressure at higher doses, so periodic BP checks are warranted; duloxetine requires caution in significant hepatic impairment or heavy alcohol use because of rare hepatotoxicity reports.
• Discontinuation syndrome: Abruptly stopping an SSRI/SNRI — especially short-half-life agents such as paroxetine or venlafaxine — can produce a withdrawal-like syndrome remembered by the mnemonic FINISH: Flu-like symptoms, Insomnia, Nausea, Imbalance/dizziness, Sensory disturbances ("brain zaps," paresthesia), Hyperarousal (anxiety, irritability). Fluoxetine's long half-life makes it the least likely to cause this syndrome. Prevention is a gradual taper, never an abrupt stop.
• Serotonin syndrome risk: Combining an SSRI/SNRI with another serotonergic drug — an MAOI, triptan, tramadol, linezolid, or St. John's Wort — can precipitate serotonin syndrome (see Section 4.5). Switching from fluoxetine to an MAOI requires an extended washout (about 5 weeks) because of fluoxetine's long-acting active metabolite; other SSRIs typically need about 2 weeks.

Tricyclic Antidepressants (TCAs)

Amitriptyline, nortriptyline, imipramine, desipramine, and clomipramine block serotonin and norepinephrine reuptake but also block muscarinic, histaminic, and alpha-1-adrenergic receptors, producing anticholinergic effects (dry mouth, blurred vision, urinary retention, constipation, tachycardia), sedation, and orthostatic hypotension.

The defining patient-safety concern is cardiotoxicity in overdose. TCAs have a narrow therapeutic index and a quinidine-like effect on cardiac sodium channels; overdose can cause widened QRS, ventricular arrhythmias, and death — a relatively small excess quantity can be lethal. Nurses should limit the quantity dispensed to patients with suicidal ideation, obtain a baseline ECG (especially in older adults or those with cardiac history), and teach patients to avoid combining TCAs with other CNS depressants or anticholinergic agents.

Monoamine Oxidase Inhibitors (MAOIs)

Phenelzine, tranylcypromine, and isocarboxazid inhibit monoamine oxidase, the enzyme that breaks down serotonin, norepinephrine, dopamine, and dietary tyramine. Because tyramine is no longer metabolized normally, ingesting tyramine-rich foods while on an MAOI can trigger a hypertensive crisis — severe headache, markedly elevated blood pressure, tachycardia or bradycardia, and risk of stroke.

Foods to avoid (low-tyramine diet): aged cheeses, cured or processed meats, fermented foods (sauerkraut, soy sauce), tap/draft beer, and red wine. Patients need this teaching in writing, and it must continue for about two weeks after the MAOI is discontinued.

MAOIs also cannot be combined with SSRIs, SNRIs, TCAs, meperidine, dextromethorphan, or sympathomimetic decongestants — each combination risks serotonin syndrome or a hypertensive crisis. A full washout period (at least 2 weeks, longer for fluoxetine) is required before starting or stopping an MAOI relative to another serotonergic drug.

Other Antidepressants

• Bupropion (norepinephrine-dopamine reuptake inhibitor): lowers the seizure threshold (contraindicated in seizure disorders and eating disorders with purging behavior), does not cause sexual dysfunction, and may cause insomnia or anxiety — a useful option for patients whose sexual side effects from an SSRI/SNRI threaten adherence.
• Mirtazapine: an alpha-2 antagonist that increases sedation and appetite — useful for depressed patients with insomnia and weight loss.
• Trazodone: sedating; often used off-label at low doses for insomnia; carries a rare but serious risk of priapism.

Clinical Application

A patient started on sertraline two weeks ago who reports "it isn't helping" needs education, not an early switch — full effect is still 2-4 weeks away. A patient who abruptly stops paroxetine and reports dizziness, nausea, and "electric shock" sensations is experiencing discontinuation syndrome, not a relapse of depression. Recognizing these timelines prevents unnecessary medication changes and keeps patients safe during vulnerable transition periods.