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A comprehensive overview of key information related to three commonly prescribed antidepressants: sertraline, duloxetine, and paroxetine. It covers major adverse reactions, drug interactions, lab tests, neurotransmitter mechanisms, and pregnancy risks associated with each medication. The document also includes a brief discussion of common side effects and important considerations for patient care.
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Sertraline Major Adverse Reactions - ANS ✓-Rare seizures
•Rare activation of mania, depression, or suicidal ideation •Rare worsening of coexisting seizure disorders Duloxetine Major Drug Interactions - ANS ✓CYP2D6 inhibitors (duloxetine, paroxetine, fluoxetine, bupropion) cimetidine, and valproic acid can increase drug concentration •Concomitant use of potent CYP1A2 inhibitors (fluvoxamine, cimetidine, quinolone antimicrobials [eg, ciprofloxacin, enoxacin]) should be avoided •Serotonin release by platelets is important for maintaining hemostasis. Combined use of SSRIs or SNRIs (such as duloxetine) and NSAIDs, and/or drugs that affect anticoagulation has been associated with an increased risk of bleeding •CYP2D6 and 1A2 enzyme inducers, such as rifamycin, nicotine, phenobarbital, can lower levels •May cause serotonin syndrome when used within 14 days of MAO inhibitors •May increase risk of cardiotoxicity and arrhythmia when used with tricyclic antidepressants vccccccccccccc Duloxetine lab tests - ANS ✓check blood pressure at baseline and when increasing dose *Not recommended for patients with severe renal function impairment (creatinine clearance less than 30mL/min) or end-stage renal disease *Not recommended for patients with hepatic function impairment Duloxetine neurotransmitters and moa - ANS ✓-Blocks serotonin and noradrenergic reuptake pumps, increasing their levels within hours, but antidepressant effects take weeks. ------Effect is more likely related to adaptive changes in serotonin and norepinephrine receptors systems •Weakly blocks dopamine reuptake pump (dopamine transporter) Duloxetine pregnancy risk - ANS ✓-Category C. =Generally not recommended for the treatment of headache or neuropathic pain during pregnancy. Neonates exposed to duloxetine or other SNRIs or SSRIs late in the third trimester have developed complications necessitating extended hospitalizations, respiratory
support, and tube feeding. Respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying consistent with a toxic effect of the drug or drug discontinuation syndrome have been reported Paroxetine (Paxil) Major Side effects SSRI Commonly Prescribed for Major depressive disorder (paroxetine and paroxetine CR) Obsessive-compulsive disorder (OCD) Panic disorder (paroxetine and paroxetine CR) Social anxiety disorder (social phobia) (paroxetine and paroxetine CR) Posttraumatic stress disorder (PTSD) Generalized anxiety disorder (GAD) Premenstrual dysphoric disorder (PMDD) (paroxetine CR) Vasomotor symptoms (Brisdelle) Some patients may experience relief of insomnia or anxiety early after initiation of treatment - ANS ✓Withdrawal effects can be more common or more severe with paroxetine than with some other SSRIs
Hepatic Impairment: Lower dose [initial 10 mg/day (12.5 mg CR), maximum 40 mg/day (50 mg/day CR)] Cardiac Impairment Preliminary research suggests that paroxetine is safe in cardiovascular patients Treating depression with SSRIs in patients with acute angina or following myocardial infarction may reduce cardiac events and improve survival as well as mood Paroxetine pregnancy risks - ANS ✓Not generally recommended for use during pregnancy, especially during first trimester Epidemiological data have shown an increased risk of cardiovascular malformations (primarily ventricular and atrial septal defects) in infants born to women who took paroxetine during the first trimester (absolute risk is small) Unless the benefits of paroxetine to the mother justify continuing treatment, consider discontinuing paroxetine or switching to another antidepressant Paroxetine use late in pregnancy may be associated with higher risk of neonatal complications, including respiratory distress At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child For many patients this may mean continuing treatment during pregnancy SSRI use beyond the 20th week of pregnancy may be associated with increased risk of pulmonary hypertension in newborns, although this is not proven Exposure to SSRIs late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include
respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying Paroxetine neurotransmitters and moa - ANS ✓-Boosts neurotransmitter serotonin
Via CYP450 3A4 inhibition, fluvoxamine could theoretically in Fluvoxamine lab tests - ANS ✓None for healthy individuals Renal Impairment Consider lower initial dose Hepatic Impairment Lower dose or give less frequently, perhaps by half; use slower titration Cardiac Impairment Preliminary research suggests that fluvoxamine is safe in these patients Treating depression with SSRIs in patients with acute angina or following myocardial infarction may reduce cardiac events and improve survival as well as mood Fluvoxamine neurotransmitters and moa - ANS ✓Boosts neurotransmitter serotonin Blocks serotonin reuptake pump (serotonin transporter) Desensitizes serotonin receptors, especially serotonin 1A receptors Presumably increases serotonergic neurotransmission Fluvoxamine also binds at sigma 1 receptors Fluvoxamine pregnancy risks - ANS ✓Controlled studies have not been conducted in pregnant women Not generally recommended for use during pregnancy, especially during first trimester Nonetheless, continuous treatment during pregnancy may be necessary and has not been proven to be harmful to the fetus At delivery there may be more bleeding in the mother and transient irritability or sedation in the newborn Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment
(recurrence of depression, maternal health, infant bonding) to the mother and child For many patients this may mean continuing treatment during pregnancy Exposure to SSRIs early in pregnancy may be associated with increased risk of septal heart defects (absolute risk is small) SSRI use beyond the 20th week of pregnancy may be associated with increased risk of pulmonary hypertension in newborns, although this is not proven Exposure to SSRIs late in pregnancy may be associated with increased risk of gestational hypertension and preeclampsia Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying Venlafaxine (Effexor) Major Side Effects SNRI Commonly Prescribed for (FDA approved in bold) •Depression •Generalized anxiety disorder •Panic disorder •Social phobia - ANS ✓Constipation, dry mouth, sweating, blurry vision, loss of appetite, nausea, weight loss or gain, hypertension, headache, asthenia, dizziness, tremor, dream disorder, insomnia, somnolence, abnormal ejaculation, impotence, orgasm disorder, sweating, itching, sedation, nervousness, restlessness Venlaxafine Major Adverse Reactions - ANS ✓•Serotonin syndrome •Rare hepatitis •Rare activation of mania or suicidal ideation •Rare worsening of coexisting seizure disorders
hyperreflexia, tremor, jitteriness, irritability, and constant crying consistent with a toxic effect of the drug or drug discontinuation syndrome have been reported Venlafaxine neurotransmitters and moa - ANS ✓-Blocks serotonin and norepinephrine reuptake pumps, increasing their levels within hours, but antidepressant effects take weeks. Effect is more likely related to adaptive changes in serotonin and norepinephrine receptor systems over time •Weakly blocks dopamine reuptake pump (dopamine transporter) Agomelatine (Valdoxan) NRI Major Side Effects - ANS ✓-Nausea and dizziness are most common
Agomelatine lab tests - ANS ✓Liver function tests before initiation of treatment and then at 3 weeks, 6 weeks, 12 weeks, 24 weeks, and thereafter when clinically indicated When increasing the dose, liver function tests should be performed at the same frequency as when initiating treatment Liver function tests should be repeated within 48 hours in any patient who develops raised transaminases Renal Impairment Drug should be used with caution Hepatic Impairment Contraindicated Cardiac Impairment Dose adjustment not necessary Agomelatine pregnancy risk - ANS ✓Not generally recommended for use during pregnancy, especially during first trimester Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child For many patients this may mean continuing treatment during pregnancy Agomelatine neurotransmitters and moa - ANS ✓Actions at both melatonergic and 5HT2C receptors may be synergistic and increase norepinephrine and dopamine neurotransmission in the prefrontal cortex; may resynchronize circadian rhythms that are disturbed in depression No influence on extracellular levels of serotonin
Hepatic Impairment Lower initial dose, perhaps give less frequently Patient should be monitored closely In severe hepatic cirrhosis, bupropion XL should be administered at no more than 150 mg every other day Cardiac Impairment Limited available data Evidence of rise in supine blood pressure Use with caution Bupropion neurotransmitters and moa - ANS ✓-Boosts neurotransmitters norepinephrine/noradrenaline and dopamine