Pharmacology Flashcards: Antidepressants, SSRIs, SNRIs, MAOIs, Tricyclics

Selective serotonin reuptake inhibitors, or SSRIs, block the reuptake of serotonin in the synaptic cleft, increasing serotonin availability in the brain. Common SSRIs include fluoxetine, sertraline, paroxetine, citalopram, and escitalopram. They are first-line for depression because they are effective, well-tolerated, and have a relatively safe side effect profile compared to older antidepressants. Common side effects include nausea, headache, sexual dysfunction, insomnia, and weight changes. Full therapeutic effect takes four to six weeks.

Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonin activity in the nervous system. It presents with a triad of mental status changes like agitation and confusion, autonomic instability including fever, tachycardia, and diaphoresis, and neuromuscular hyperactivity such as tremor, clonus, and hyperreflexia. It most commonly occurs when two or more serotonergic medications are combined, such as an SSRI with a monoamine oxidase inhibitor, tramadol, or the herbal supplement St. John's wort.

Serotonin-norepinephrine reuptake inhibitors, or SNRIs, block the reuptake of both serotonin and norepinephrine, whereas SSRIs block only serotonin reuptake. Common SNRIs include venlafaxine, duloxetine, and desvenlafaxine. The dual mechanism makes SNRIs effective for depression with prominent fatigue and pain symptoms. Duloxetine is also approved for diabetic neuropathy, fibromyalgia, and chronic musculoskeletal pain. Side effects are similar to SSRIs but can include elevated blood pressure at higher doses due to norepinephrine effects.

Monoamine oxidase inhibitors, or MAOIs, like phenelzine and tranylcypromine are effective antidepressants that block the enzyme monoamine oxidase, increasing levels of serotonin, norepinephrine, and dopamine. They are rarely prescribed because they require strict dietary restrictions. Patients must avoid foods high in tyramine, including aged cheeses, cured meats, fermented foods, soy sauce, and draft beer.

Tricyclic antidepressants, or TCAs, such as amitriptyline, nortriptyline, and imipramine block the reuptake of serotonin and norepinephrine while also affecting histamine, acetylcholine, and alpha-adrenergic receptors. This broad receptor activity causes significant side effects including sedation, dry mouth, constipation, urinary retention, blurred vision, orthostatic hypotension, and weight gain. TCAs are high risk because they have a narrow therapeutic index and are lethal in overdose, causing cardiac arrhythmias and seizures.

The FDA black box warning for antidepressants states that these medications may increase the risk of suicidal thinking and behavior in children, adolescents, and young adults under age 25 during the initial weeks of treatment. This warning applies to all antidepressant classes including SSRIs, SNRIs, TCAs, and MAOIs. Patients starting antidepressants or changing doses should be closely monitored, especially during the first four weeks.

Discontinuation syndrome occurs when antidepressants are stopped abruptly or tapered too quickly, causing flu-like symptoms, insomnia, nausea, dizziness, sensory disturbances described as "brain zaps," irritability, and anxiety. It is most common with short-acting SSRIs like paroxetine and SNRIs like venlafaxine because their blood levels drop rapidly. Fluoxetine rarely causes discontinuation syndrome because its active metabolite has a very long half-life of four to six days. The syndrome is not addiction but a physiological adjustment to reduced serotonin activity.

Bupropion is an atypical antidepressant that inhibits the reuptake of norepinephrine and dopamine but has no effect on serotonin. It is unique among antidepressants because it does not cause sexual dysfunction or weight gain, and actually tends to produce mild weight loss. Bupropion is also approved for smoking cessation under the brand name Zyban and for seasonal affective disorder. It lowers the seizure threshold and is contraindicated in patients with seizure disorders, eating disorders, or those undergoing abrupt alcohol or benzodiazepine withdrawal.

Most antidepressants take four to six weeks to reach full therapeutic effect, although some improvement in sleep, appetite, and energy may occur within one to two weeks. This delay occurs because the therapeutic benefit requires downstream changes in receptor sensitivity and neuroplasticity, not just acute increases in neurotransmitter levels. Patients must be counseled about this timeline to prevent premature discontinuation. If no improvement occurs after six to eight weeks at an adequate dose, the clinician may increase the dose, switch medications, or add an augmenting agent.

Anticholinergic side effects from tricyclic antidepressants are remembered by the phrase "blind as a bat, dry as a bone, red as a beet, mad as a hatter, hot as a hare." Specifically they include blurred vision from ciliary muscle paralysis, dry mouth from reduced salivation, constipation from decreased gut motility, urinary retention from bladder muscle relaxation, tachycardia, confusion, and flushing. These effects are most pronounced in elderly patients who are more susceptible to anticholinergic toxicity, including falls and delirium. ---