SSRIs are generally well-tolerated. Common class adverse effects include constipation, diarrhea, dry mouth, headache, nausea, sleep disturbances, and weight change (Chu & Wadhwa, 2022). These often abate or disappear entirely over time with continued treatment. Sexual dysfunction is also common and tends to persist throughout treatment, although this varies among individual medications. SSRIs can also induce anxiety or jitteriness, particularly at the beginning of therapy. This may be due to an initial surge in serotonin. Clinicians should begin patients with a low dose and slowly titrate the dose to help mitigate or avoid this adverse effect. SSRIs can prolong the QT interval and can cause development of Torsades de Pointes. Citalopram and escitalopram have been linked with prolonged QT interval more than other SSRIs (Chu & Wadhwa, 2022). Before prescribing an SSRI, review the patient’s medication list for other agents capable of QT-interval prolongation. An electrocardiogram (EKG) should also be considered in patients with cardiac risk factors (Chu & Wadhwa, 2022). Consider switching to another medication if EKG shows a QT interval greater than 500 milliseconds (ms), or if there is change in baseline greater than 60 ms. Use of SSRIs can result in SSRI-induced syndrome of inappropriate antidiuretic hormone (SIADH) secretion. SSRI- induced SIADH leads to hyponatremia, with symptoms ranging from mild (appetite loss, fatigue, headache, nausea and vomiting) to severe (altered mental status, coma, seizures). Geriatric patients are at higher risk for SSRI-induced SIADH and must be monitored closely (Landy et al., 2022). SSRIs can cause serotonin syndrome, a potentially life- threatening condition with symptoms ranging from mild to severe. Most cases are not caused by the use of a single serotonergic agent. Rather, it is often the addition of multiple serotonergic medications in a patient previously stable on a single serotonergic agent that leads to serotonin syndrome (Simon & Keenaghan, 2022). Symptoms of serotonin syndrome can include (Simon & Keenaghan, 2022): ● Agitation. ● Bilateral Bibinski sign. ● Diaphoresis. Because there is no confirmatory test or diagnostic for serotonin syndrome, the true incidence of the condition is unknown. Mild cases are frequently overlooked, dismissed, or missed entirely, while serious cases are often attributed to other causes. One key feature to look for: symptoms of serotonin syndrome tend to develop rapidly after exposure to the precipitating agent: 30% of patients will develop symptoms within an hour; 60% develop symptoms within 6 hours, and practically all patients develop symptoms within 24 hours. Mild cases should resolve with removal of the offending agent. Beyond discontinuing the serotonergic drug(s), care is supportive and initiated to prevent further complications. Avoid antipsychotics, as their anticholinergic properties can inhibit sweating and further worsen hyperthermia. Benzodiazepines are the best choice for initiating sedation when required. Acetaminophen and other antipyretics are ineffective in this setting, as hyperthermia in serotonin syndrome is a result of increased muscle activity (Simon & Keenaghan, 2022). ● Dilated pupils. ● Disorientation. ● Dry mucous membranes. ● Hyperthermia. ● Increased bowel sounds. ● Muscle rigidity. ● Nausea and vomiting. ● Tachycardia. ● Tremor.
Like all antidepressants, SSRIs carry a FDA boxed warning regarding the possibility of increased suicide risk in pediatrics and young adults up to age 25 years (Chu & Wadhwa, 2022). Escitalopram (Lexapro) Escitalopram is FDA-approved to treat generalized anxiety disorder. It’s also commonly used off-label to treat panic disorder and social anxiety disorder. A meta-analysis conducted by Curtiss and his colleagues in 2017 analyzing efficacy of pharmacotherapy for SAD found escitalopram to have the largest effect size for this condition among SSRIs The typical escitalopram starting dose is 10 mg once daily, and this may be increased to 20 mg after one week. Due to reduced clearance in the setting of hepatic impairment, 10 mg is the recommended maintenance dose in patients with impaired liver function. Escitalopram should be used with caution in patients with a creatinine clearance below 20 mL/min. AUC and half-life are increased by approximately 50% in geriatric patients, and it’s recommended to stick to a 10-mg dose in this population (Landy et al., 2022). Escitalopram has a terminal half-life of 27 to 32 days and needs 7 to 10 days in order for steady-state serum concentrations to take hold. When trying to switch from escitalopram to another SSRI, the dose should be reduced gradually over four weeks (Landy et al., 2022). If escitalopram is abruptly discontinued, the patient may experience withdrawal symptoms including dizziness, lethargy, and nausea. Escitalopram is metabolized by CYP2C19. Those with low CYP2C19 activity, or persons known to be poor metabolizers, are at higher risk for adverse drug reactions. Paroxetine (Paxil) Paroxetine is FDA-approved to treat generalized anxiety disorder, panic disorder, and social anxiety disorder. It may also be used off-label to treat separation anxiety (Shrestha et al., 2021). In addition to inhibiting serotonin reuptake, paroxetine has shown affinity for adrenergic (alpha and beta), dopaminergic (D2), histaminergic (H1), and muscarinic receptors. This may contribute to paroxetine’s adverse effect profile, which are dose- dependent. In addition to class adverse effects, paroxetine can also cause apathy or emotional flattening due to an indirect decrease in dopamine. Extrapyramidal symptoms, tachycardia, alopecia, and photosensitivity have also been reported (Shrestha et al., 2021). Paroxetine is available as a tablet, delayed-release tablet (Paxil CR), and liquid suspension. Dosing varies slightly between the regular release and delayed-release tablets. See Table 1. Table 1: Paroxetine Dosing for Anxiety Disorders in Adults Starting Dose Titration Maximum Dose GAD Immediate- release paroxetine 20 mg once daily 10 mg, in weekly intervals 60 mg/day Panic Disorder Immediate- release 10 mg once daily 10 mg, in weekly intervals 60 mg/day Delayed- release 12.5 mg once daily 12.5 mg, in weekly intervals 75 mg/day SAD Immediate- release 20 mg once daily 10 mg, in weekly intervals 60 mg/day Delayed- release 12.5 mg once daily 12.5 mg, in weekly intervals 37.5 mg/day
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Book Code: RPTTX2024
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