What is the best management approach for a 72-year-old female patient with newly diagnosed Parkinson's disease, a past medical history of prediabetes, obesity, bipolar disorder, anxiety, hypercholesterolemia, irritable bowel syndrome (IBS) symptoms, depression, arthritis, history of deep vein thrombosis (DVT) and pulmonary embolism (PE) on apixaban (Eliquis), and mild chronic kidney disease (CKD), currently taking buspirone, lorazepam, brexpiprazole (Rexulti), venlafaxine, rosuvastatin, semaglutide (Wegovy), and mirabegron?

Management of Newly Diagnosed Parkinson's Disease in a Complex 72-Year-Old Patient

For this 72-year-old patient with newly diagnosed Parkinson's disease and multiple comorbidities, initiate symptomatic treatment with carbidopa-levodopa as first-line therapy given her age and need for effective symptom control, while immediately addressing critical medication safety issues including discontinuation of lorazepam (benzodiazepine) and careful monitoring of brexpiprazole (Rexulti) for worsening parkinsonian symptoms. 1, 2

Immediate Medication Safety Concerns

High-Priority Medication Modifications

• Discontinue lorazepam immediately: Benzodiazepines significantly increase risk of delirium, falls, fractures, cognitive impairment, and dependence in older adults with Parkinson's disease 1
• Critically evaluate brexpiprazole (Rexulti): Most antipsychotics are contraindicated in Parkinson's disease due to dopamine receptor blockade that worsens parkinsonian symptoms; only quetiapine, clozapine, and pimavanserin are acceptable 1
• Discontinue ibuprofen: NSAIDs may be contributing to elevated blood pressure (135/90 mmHg) and worsening heart failure symptoms in this patient with HFrEF 3
• Avoid metoclopramide: If prescribed for gastroparesis or nausea, this medication causes extrapyramidal signs including acute dystonic reactions, drug-induced parkinsonism, akathisia, and tardive dyskinesia 1

Medication Timing Optimization

• Administer levodopa at least 30 minutes before meals to optimize absorption, and separate from iron and calcium supplements by at least 2 hours 1
• Ensure Parkinson's medications are given on time when hospitalized or in care facilities, as delayed dosing significantly worsens symptoms 4

Parkinson's Disease Treatment Initiation

First-Line Pharmacologic Therapy

Start carbidopa-levodopa as initial monotherapy for this 72-year-old patient with preserved mental function but multiple comorbidities 2, 5, 6:

• Levodopa remains the most effective agent for relief of Parkinson's symptoms 2, 6
• For patients above 65 years old, initial monotherapy with levodopa is advisable rather than dopamine agonists 5
• Sustained-release levodopa preparations are preferred as they have longer half-life and stimulate dopamine receptors more continuously 5
• Begin with low doses and titrate gradually based on symptom response and tolerability 2

Alternative Considerations

• MAO-B inhibitors (selegiline, rasagiline) have only mild symptomatic effects and may be considered as adjunctive therapy 5, 6
• Dopamine agonists are NOT recommended as initial therapy in this patient given her age >65 years, though they may delay motor complications in younger patients 5
• Amantadine can be added later if dyskinesias develop 5

Multidisciplinary Care Framework

Essential Specialist Referrals

Establish comprehensive team-based care 3, 4:

• Physical therapy: Endurance and resistance exercises slow disease progression and may improve quality of life 3
• Occupational therapy: Address activities of daily living and home safety modifications 4
• Speech and language therapy: Proactive management of dysarthria and dysphagia risk 4
• Renal dietitian: Given mild CKD (CrCl 47 mL/min) and need for protein intake optimization 3
• Pharmacist consultation: Medication review for drug interactions and CKD-appropriate dosing 3

Nutritional Monitoring

Implement regular nutritional surveillance 3:

• Monitor body weight routinely as Parkinson's patients are at 15% risk of malnutrition in community-dwelling settings 3
• Supplement vitamin D, folic acid, and vitamin B12 as needed 3
• Predictors of malnutrition include older age at diagnosis, higher levodopa doses, anxiety, depression, and living alone 3
• Maintain protein intake of 0.8 g/kg body weight/day given CKD G3a; avoid high protein intake >1.3 g/kg/day 3

Chronic Kidney Disease Management Considerations

Medication Dosing Adjustments

Review all medications for CKD-appropriate dosing with eGFR 47 mL/min 3:

• Use validated eGFR equations using serum creatinine for most drug dosing decisions 3
• For medications with narrow therapeutic range (like apixaban), consider equations combining creatinine and cystatin C 3
• Apixaban 2.5 mg twice daily is appropriate given CKD and likely meets dose-reduction criteria 3
• Monitor eGFR, electrolytes, and therapeutic medication levels regularly 3

Holistic CKD Risk Modification

Implement comprehensive CKD treatment strategy 3:

• Continue rosuvastatin for statin-based therapy 3
• Optimize blood pressure control with target <120 mmHg systolic; current BP 135/90 mmHg requires intensification 3
• Consider adding/optimizing RAS inhibitor (ACE inhibitor or ARB) given proteinuria, though losartan 25 mg is suboptimal dosing 3
• Evaluate for SGLT2 inhibitor addition given prediabetes, obesity, and CKD with proteinuria 3

Cardiovascular and Metabolic Optimization

Polypharmacy Reduction Strategy

Prioritize treatments based on mortality and morbidity reduction 3:

• Discontinue aspirin: Combined treatment with aspirin and rivaroxaban increases bleeding risk without clear benefit in atrial fibrillation 3
• Optimize heart failure therapy: Current metoprolol succinate 50 mg daily is suboptimal; titrate to target dose for HFrEF 3
• Consider sacubitril/valsartan to replace losartan for superior HFrEF outcomes 3
• Add SGLT2 inhibitor: Provides kidney protection, heart protection, glucose-lowering, and weight management benefits 3

Diabetes Management

Optimize glycemic control while addressing weight 3:

• Current HbA1c 7.5% is acceptable but could be improved 3
• Wegovy (semaglutide) 0.5 mg weekly provides weight management and may improve glycemic control 3
• Consider adding SGLT2 inhibitor for multisystem benefits (cardiac, renal, glycemic) 3
• Continue metformin 1000 mg twice daily with appropriate CKD monitoring 3

Psychiatric Medication Management

Bipolar Disorder and Anxiety Treatment

Reassess psychiatric medication regimen given Parkinson's diagnosis 1:

• Brexpiprazole (Rexulti) requires urgent evaluation: Most antipsychotics worsen parkinsonian symptoms through dopamine receptor blockade 1
• If antipsychotic is necessary for bipolar disorder, switch to quetiapine, clozapine, or pimavanserin (only acceptable options in Parkinson's) 1
• Discontinue lorazepam: Replace with non-benzodiazepine anxiolytic if needed 1
• Continue buspirone: Appropriate anxiolytic without parkinsonian worsening 1
• Continue venlafaxine: Appropriate for depression/anxiety management in Parkinson's disease 2

Physical Activity and Lifestyle Modifications

Exercise Prescription

Prescribe structured physical activity program 3:

• Recommend moderate-intensity physical activity for cumulative duration of at least 150 minutes per week 3
• Both endurance and resistance exercises slow Parkinson's disease progression and improve quality of life 3
• Physical activity should be advised as long as it does not worsen physical state 3
• Address knee, hip, and back pain with physical therapy to enable exercise participation 3

Weight Management

Target weight optimization given BMI 35 kg/m² 3:

• Continue Wegovy titration as planned for weight management 3
• Encourage plant-based diet with lower consumption of ultra-processed foods 3
• Weight management provides cardiovascular, metabolic, and mobility benefits 3

Monitoring and Follow-Up Framework

Regular Assessments Required

Establish systematic monitoring schedule 3:

• Every 3-6 months: Reassess nutritional status, body weight, vitamin levels (D, B12, folic acid), and disease progression 3
• Medication review at each visit: Assess adherence, continued indication, drug interactions, and adverse effects 3
• Monitor for motor complications: Watch for "off periods," dyskinesias, and medication-resistant tremor that may require advanced therapies 2
• Screen for non-motor symptoms: Depression (use PHQ-2), cognitive decline, sleep disorders, constipation, and autonomic dysfunction 2, 7

Point of Contact Establishment

Provide clear access to specialist services 4:

• Designate point of contact with Parkinson's specialist team for urgent questions 4
• Ensure communication pathway for medication adjustments and symptom management 4
• Coordinate care between neurology, cardiology, nephrology, and primary care 3

Critical Pitfalls to Avoid

Common Errors in Parkinson's Management

• Do not confuse drug-induced parkinsonism with disease progression: Antipsychotics and metoclopramide cause acute worsening that resolves with discontinuation 1
• Do not restrict protein intake given risk of sarcopenia and malnutrition in Parkinson's disease 3
• Do not use pethidine (meperidine) for pain management due to high delirium risk 1
• Do not delay levodopa when functional disability is present; concerns about long-term complications should not prevent appropriate symptom control 2, 5
• Do not assume all movement disorders are parkinsonian tremor: Distinguish myoclonus, akathisia, and restless legs syndrome 1

Medication Safety During Transitions

Implement safeguards during care transitions 3:

• Communicate clear plan for medication continuation after acute illness or procedures 3
• Consider planned discontinuation of metformin, losartan, and SGLT2i (if added) 48-72 hours before elective surgery 3
• Ensure documentation of restart plan to prevent unintentional harm from prolonged discontinuation 3

Prognosis and Disease Trajectory

Subtype Considerations

This patient likely has mild motor-predominant Parkinson's disease (49-53% of patients) given newly diagnosed status 2:

• Expected good response to dopaminergic medications 2
• Slower disease progression compared to diffuse malignant subtype 2
• Intermediate subtype possible given multiple comorbidities 2

Long-Term Planning

Address advance care planning proactively 3:

• Discuss future medical decision-making capacity given risk of cognitive decline 3
• Establish healthcare proxy and advance directives 3
• Consider palliative care consultation as part of comprehensive Parkinson's management 2
• Monitor for early-onset complications given multiple comorbidities and reduced life expectancy 3