SSRI Pharmacology Quiz

Pharmacokinetics of Selective Serotonin Reuptake Inhibitors (SSRIs)

• Half-lives vary significantly among SSRIs.
  • Fluoxetine (Prozac): 4-6 days (active metabolite 7-9 days)
  • Sertraline (Zoloft): 26 hours (less active metabolite 3-5 days)
  • Citalopram (Celexa): 35 hours
  • Escitalopram (Lexapro): 27-32 hours
  • Paroxetine (Paxil): 21 hours
  • Fluvoxamine (Luvox): 15 hours
• Food may slightly enhance absorption.
• SSRIs are generally well absorbed orally.
• Peak effects usually occur within 3-8 hours.
• Different binding to plasma proteins, with sertraline, fluoxetine, and paroxetine having the highest binding, and escitalopram the lowest.
• Wide therapeutic index.
• May potentially slow or block the metabolism of other drugs; fluvoxamine has the most significant potential for interactions.

Pharmacodynamics of SSRIs

• Therapeutic effect is mediated by serotonin reuptake inhibition.
• Higher doses do not increase antidepressant efficacy but may increase side effects.
• Concurrent use with triptans or tramadol can cause serotonin syndrome.

Therapeutic Uses of SSRIs

• Depression: All except fluvoxamine are FDA-approved; trial other SSRIs before switching to non-SSRIs.
• Suicide risk: Black box warning; risk may decrease over time for adults and elderly but not consistently shown for adolescents. Some studies show SSRIs can protect against suicide by improving depressive symptoms.
• Pregnancy/Postpartum: Relapse rates are high, continuing medication is common. No increased risk for major congenital malformations (except paroxetine, which has possible risk in first trimester). Paroxetine may cause infant discontinuation syndrome, and/or increased risk of congenital disabilities, particularly heart defects. Small risk to babies from mothers taking SSRIs late in pregnancy, specifically regarding pulmonary hypertension. Minimal amounts in breast milk, no known harm.
• Elderly/Medically Ill: Safe and generally well-tolerated; paroxetine has anticholinergic activity, which can cause issues. Potential for cognitive deficits, prolonged bleeding time, and hyponatremia.
• Children: Fluoxetine has shown consistent effectiveness; sertraline effective in social anxiety.
• Anxiety Disorders: Generalized anxiety disorder, obsessive-compulsive disorder, indicated for OCD, social anxiety disorders, and panic disorder. Higher doses often needed compared to typical depression doses.

Other Indications

• Panic disorder: Paroxetine, fluoxetine, and sertraline. Fluoxetine can initially heighten anxiety. Start with low doses and increase gradually.
• Social anxiety disorder: SSRIs safer than MAOIs or benzodiazepines for this.
• Post-traumatic stress disorder (PTSD): SSRIs have broad effects on symptom clusters.
• Bulimia nervosa: Fluoxetine (60mg/day).
• Anorexia nervosa: SSRIs are part of a larger therapeutic approach.
• Premenstrual dysphoric disorder: Sertraline, paroxetine, fluoxetine, and fluvoxamine show symptom reduction.
• Premature ejaculation: Fluoxetine and sertraline.
• Paraphilias: SSRIs can reduce frequency of unconventional sexual activities, urges, or fantasies.
• Autism: Sertraline, fluvoxamine, fluoxetine, and clomipramine may be considered.

Precautions and Adverse Reactions

• Sexual dysfunction: Common to all SSRIs.
• Gastrointestinal (GI) effects: Nausea, diarrhea, anorexia, vomiting, flatulence, and dyspepsia are frequent. Sertraline and fluvoxamine produce the most intense GI symptoms. Delayed-release paroxetine has less intense GI side effects.
• Weight gain: Estimated one-third of users gain weight, possibly due to metabolic mechanisms and/or increased appetite, resistant to diet and exercise. Paroxetine associated with most rapid and pronounced gain.
• Cardiovascular effects: Can prolong the QT interval, increased risk when combined with antipsychotics. FDA guidelines for citalopram in specific patient populations (hepatic impairment, age 60+, CYP2D6 poor metabolizers, concomitant cimetidine use). Maximum dose restrictions for citalopram and precautions for patients with congenital QT syndrome. Electrolyte and blood concentration monitoring.
• Headaches: Fluoxetine more likely to cause headaches.
• Central nervous system effects: Anxiety, insomnia, sedation (potential for vivid/nightmarish dreams, emotional blunting—leading to discontinuation—yawning increase. Seizures possible, more so with maximal doses). Extrapyramidal symptoms are rare. Anticholinergic effects (dry mouth, constipation, sedation): Paroxetine has mild but dose-dependent impact.
• Hematologic effects: Potential for impaired platelet aggregation (bruising/bleeding issues). NSAID use with SSRIs raises gastric bleeding risk. Proton pump inhibitors may minimize this risk.
• Electrolyte and glucose disturbances: Acute decreases in glucose are common. Possible long-term increase in glucose levels.
• Endocrine and allergic reactions: Prolactin elevation, and possibly mammoplasia and galactorrhea; reversible upon discontinuation.

Serotonin Syndrome

• Symptoms arise from combination with MAOIs, l-tryptophan, or lithium. Symptoms progress from diarrhea and restlessness to extreme agitation, hyperreflexia, autonomic instability, myoclonus, seizures, hyperthermia, rigidity, delirium, coma, status epilepticus, and death.
• Immediate withdrawal of the causative drugs and supportive care are needed.

Overdose

• Generally, not life-threatening on its own, but potentially problematic when combined with similar medications.

Withdrawal

• Possible but generally resolves over a few weeks. Fluoxetine is associated with a lower risk.

Drug Interactions

• Many specific interactions; fluvoxamine has significant risk. Other drug interactions exist.

Dosage Guidelines

• Detailed dosage guidelines exist for each SSRI, taking into consideration various factors. Specific guidelines for initiating, titrating, and maintaining dosages.

Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• Include venlafaxine, desvenlafaxine, duloxetine, levomilnacipran, and milnacipran.
• Various indications, including depression, generalized anxiety disorder, social anxiety disorder, neuropathic pain, and others.
• Specific adverse reactions, including nausea, sexual side effects, and potential discontinuation syndrome.
• Interactions with other medications occur with CYP2D6 isoenzyme.
• Detailed dosing information for each medication.

Bupropion

• Mechanism: Norepinephrine and dopamine reuptake inhibition.
• Low risk of sexual dysfunction/sedation; possible modest weight loss. No withdrawal syndrome.
• Administration form options: immediate, sustained, and extended release.
• Therapeutic indications: Depression, smoking cessation, bipolar disorders, ADHD, and others.
• Specific adverse reactions, including headaches, insomnia, dry mouth, and tremor.
• Drug interactions: Avoid with MAOIs.
• Detailed dosage guidelines and maximum doses.

Mirtazapine

• Mechanism: Antagonism of presynaptic α2-adrenergic receptors and blockade of postsynaptic serotonin receptors; unique mechanism compared to other agents.
• Potential to reduce nausea/diarrhea; increased appetite and sedation are reported side effects.
• Therapeutic indications: Depression, insomnia, nausea associated with chemotherapy or other medical treatments.
• Specific adverse reactions, including somnolence, possible breast milk excretion, and risk of agranulocytosis.
• Interactions with CNS depressants and MAOIs.
• Dosage guidelines and maximum doses.

Nefazodone

• Mechanism: Inhibits serotonin and norepinephrine uptake.
• Potential liver function issues warrant frequent monitoring.
• Therapeutic indications: Depression, panic disorder, generalized anxiety disorder, but not OCD.
• Common side effects: Sedation, nausea, dizziness, vision problems.
• Precautions: Risk of postural hypotension and potentially severe hepatic failure. Switching from SSRIs could exacerbate withdrawal.

Trazodone

• Mechanism: Weak serotonin reuptake inhibition, potent 5-HT2A/2C antagonism.
• Therapeutic indications: Depressive disorders, insomnia, but also erectile dysfunction and agitation.
• Common side effects: Sedation, dizziness, orthostatic hypotension.
• Precautions: Potential problems with priapism. Interactions with other CNS depressants.

TCAs (Tricyclic Antidepressants)

• Mechanism: Increase serotonin and norepinephrine but also affect other receptors, potentially leading to multiple side effects; this also enables use in several indications beyond depression.
• Side effects: Anticholinergic effects (dry mouth, constipation, sedation), orthostatic hypotension, sedation, lightheadedness.
• Uses: Major Depression Disorder, Panic Disorder, Generalized Anxiety Disorder, Obsessive-Compulsive Disorder, Chronic Pain and Migraines and others,
• Specific drug-related considerations and precautions.

Monoamine Oxidase Inhibitors (MAOIs)

• Mechanism: Inhibit monoamine oxidase enzymes, increasing neurotransmitters like norepinephrine, serotonin, dopamine, and tyramine.
• Crucial concern: Tyramine-rich foods can cause hypertensive crisis.
• Uses: Depression (especially atypical depression).
• Specific drug-interactions and precautions to avoid problems.

Thyroid Hormones (as Adjuvant therapy)

• Mechanism: Influences neurotransmitter receptor genes through binding to intracellular receptors.
• Primarily for augmenting antidepressants (liiothyronine.)
• Dosage parameters and risks.
• Drug interactions, notably with warfarin and other medications.

Test your knowledge on the pharmacological aspects of SSRIs, including their metabolism, side effects, and dosage recommendations. This quiz covers key concepts related to Selective Serotonin Reuptake Inhibitors used in treating depression and anxiety. Assess your understanding of the therapeutic effects and risks associated with these medications.