Daniel G
Prescribing for Older Adults: Major Depressive Disorder (MDD) in Older Adults
FDA-Approved Drug
Sertraline, a selective serotonin reuptake inhibitor (SSRI), is an FDA-approved first-line option for MDD in older adults. Research shows that sertraline has the best safety profile for potential drug–drug interaction with older adults’ medications compared to tricyclics and monoamine oxidase inhibitors (MAOIs) and is well tolerated when started low and titrated slowly (Jaros et al., 2024).
Off-Label Drug
For treatment-resistant cases or severe/refractory depression, the off-label use of repeated intravenous ketamine infusion (or clinic-administered ketamine protocols) a rapid-acting antidepressant strategy can be used. While, evidence for older adults is limited, early studies and pilot data suggest potential benefits with attention to cardiovascular, cognitive, and urinary risks (Srifuengfung et al., 2023).
Non-Pharmacological Intervention
Problem-Solving Therapy (PST) for late life depression, including home-based or case-management and PST adaptations, has demonstrated consistent randomized controlled trial evidence for reduction of depressive symptoms and improvement of functioning in older adults, even those with executive dysfunction and limited access to services (Shang et al., 2023).
Risk Assessment to Inform Treatment Decisions
In older adult populations, a structured risk assessment is necessary before any pharmacological treatment is begun. The risk assessment should include, first, comorbidity & organ function screening, which should review cardiac history, blood pressure control, orthostatic hypotension, renal and hepatic function, and urinary symptoms. (Older adults have decreased renal/hepatic clearance and higher sensitivity to adverse effects) (Malhi et al., 2023). Second, medication reconciliation and drug-drug interactions should be done since, older adults are frequently on multiple agents (polypharmacy). Third, baseline cognition, orthostasis, and fall risk (antidepressants and rapid-acting agents can affect balance, blood pressure, or cognition) should also be assessed. Fourth, for ketamine, pre-treatment cardiovascular assessment should be done given transient hypertension and tachycardia reported with ketamine infusions. Finally, suicide risk assessment should be carried out and urgent referral or higher level of care if imminent risk (Malhi et al., 2023).
Risks and Benefits
Sertraline
Benefits: It is well-studied in older adults; generally favorable tolerability; lower anticholinergic and cardiotoxic effects than TCAs; effective for depressive symptoms and anxiety comorbidity (Jaros et al., 2024).
Risks: It can lead to gastrointestinal upset, hyponatremia (SIADH) particularly in the elderly, increased bleeding risk with concomitant anticoagulants/NSAIDs, possible sexual side effects, and potential for drug–drug interactions (Jaros et al., 2024).
IV Ketamine
Benefits: Compared with treatment resistant depression, many experience quicker antidepressant effects (hours to days) as well as reduction in suicidal ideation especially when other methods slow down. There is credible and increasing supportive literature on its use for older adults under close supervision (Srifuengfung et al., 2023).
Risks: Transient hypertension and tachycardia during dosing, dissociative and perceptual disturbances, potential cognitive effects, urinary adverse effects with repeated exposure, potential for misuse/abuse, and incomplete long-term safety data in geriatric populations (Srifuengfung et al., 2023).
Clinical Practice Guidelines and Justification
Primary care and psychiatric guidance commonly recommend SSRIs such as sertraline or escitalopram as first-line agents in older adults because of tolerability and evidence base; sources supporting these recommendations include AAFP reviews and geriatric psychiatry reviews (Jaros et al., 2024). This justifies selecting sertraline as a first-line pharmacologic option. IV racemic ketamine remains an off-label option and is supported by growing but still limited evidence in older adults; specialty consultation, risk-benefit discussion, and facility-level monitoring protocols are recommended before use (Srifuengfung et al., 2023).
KELLY E L
Bipolar Disorder in Pregnancy
FDA-Approved Pharmacotherapy
Lamotrigine is an FDA-approved mood stabilizer commonly used for maintenance treatment in bipolar disorder and is considered one of the safest options during pregnancy (Jin, 2022). Lamotrigine is particularly effective for those patients with a higher prevalence of depressive episodes, and is effective during pregnancy and postpartum to prevent relapse of symptoms (Hasser et al., 2024).
Off-Label Pharmacotherapy
A medication that may be used off-label in bipolar disorder is sertraline. It has been established to be largely safe to use in pregnancy (Singh & Deep, 2022). It is particularly used in bipolar depression, when mood stabilizers are contraindicated or poorly tolerated.
Nonpharmacologic Intervention
Nonpharmacologic interventions that can be used during pregnancy for bipolar disorder include cognitive behavioral therapy (CBT), interpersonal and social rhythm therapy, and light therapy (Bhat, n.d).
Risk Assessment
To inform treatment decisions for a pregnant patient with bipolar disorder, it is recommended to use a comprehensive perinatal psychiatric risk assessment that includes suicide risk, risk of relapse, and medication teratogenicity. The Edinburgh Postnatal Depression Scale (EPDS) screens for perinatal depression but also flags bipolar symptoms when scores are high and atypical (Bradley et al., 2025). The recommendation is to utilize this tool at the initial prenatal visit, third trimester, and postpartum. Additional tools include the C-SSRS to assess suicidal ideation and behavior, and should be used for any patient with mood instability during pregnancy (Bhat, n.d). To guide medication decisions during pregnancy or lactation, providers must weigh the risks of untreated psychiatric illness against potential harms like birth defects and neurodevelopmental issues. While each case is unique, experts generally agree that continuing medication often offers greater benefits, especially for patients with a history of severe illness.
Risks and Benefits of Lamotrigine
Lamotrigine is generally considered safe for use during pregnancy in patients with bipolar disorder, particularly when used as monotherapy, and has not been associated
with a significant increase in major congenital malformations (The Organization of Teratology Information Specialists, 2025). However, its clearance increases during pregnancy, which may reduce serum levels and heighten relapse risk, making therapeutic drug monitoring essential (Nonacs, 2021). While early concerns about neural tube defects existed, more recent data suggest minimal teratogenic risk when lamotrigine is used alone.
Risks and Benefits of Sertraline
Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly prescribed during pregnancy due to its relatively low teratogenic risk. A large population-based study found no significant association between sertraline use in early pregnancy and major birth defects, supporting its safety when used as monotherapy (Anderson et al., 2020). Although SSRIs may be linked to neonatal adaptation syndrome, characterized by transient symptoms such as jitteriness or respiratory distress, these effects are typically mild and self-limiting.
Clinical Practice Guidelines
There are clinical practice guidelines for bipolar disorder by the Veterans’ Administration (VA). In regards to sertraline, recommendation number 14 states that there is insufficient evidence for or against using sertraline, but the research results indicate little to no effectiveness, and a risk of switching to mania (Department of Veterans Affairs, 2023). The VA suggests against lamotrigine as monotherapy for the prevention of recurrence of mania, but recommends it for the prevention of recurrence of bipolar depressive episodes (2023). These recommendations are not specific to pregnancy, but it does list specific recommendations specific to pregnancy that include valproate, carbamazepine, and topiramate in women of childbearing potential, and continuing lithium low-dose in women who are or may become pregnant (Department of Veterans Affairs, 2023).
Respond to at least two of your colleagues on 2 different days who selected different disorders. Propose an alternative on-label, off-label, or nonpharmacological treatment for the disorders. Justify your suggestions with at least two references to the literature.
