What are the most effective and safe drugs for clinical practice?

Best Drugs for Clinical Practice

The most effective approach to selecting drugs for clinical practice is to create a personal formulary of 1-2 rigorously selected medications for each commonly encountered clinical condition, prioritizing drugs with proven efficacy in large randomized controlled trials, favorable safety profiles, and established clinical experience. 1

Framework for Drug Selection

Primary Selection Criteria

Efficacy should be evaluated through large, methodologically sound clinical trials that measure meaningful clinical outcomes (such as mortality, morbidity, and quality of life) rather than surrogate markers alone. 1, 2 The most objective efficacy data comes from randomized, double-blind trials with adequate sample sizes and patient-relevant endpoints.

Safety assessment must include three critical components:

• Adverse drug effect profiles documented in clinical trials and post-marketing surveillance 1
• Drug-drug interaction potential, particularly with commonly co-prescribed medications 3
• Extent of clinical experience with the medication in real-world practice 4, 1

Published adverse event rates in controlled trials often underestimate real-world rates, as trial participants are typically healthier with fewer comorbidities than patients seen in routine practice. 4

Disease-Specific Recommendations

For Type 2 Diabetes: Metformin is the drug of choice for initial pharmacologic therapy in most patients, as it demonstrates superior efficacy in reducing glycemic levels without weight gain, reduces LDL cholesterol and triglycerides, and is associated with lower all-cause and cardiovascular mortality compared to sulfonylureas. 4 When metformin monotherapy fails to control hyperglycemia, add a second agent (generic sulfonylureas are the most cost-effective option, though they carry higher hypoglycemia risk). 4

For Primary Open-Angle Glaucoma: Prostaglandin analogs are the most effective drug class for lowering intraocular pressure and should be considered as initial medical therapy. 4 Specifically, bimatoprost demonstrated the highest ranking for IOP reduction in network meta-analyses. 4

For Moderate-to-Severe Ulcerative Colitis: High-efficacy medications include vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, and guselkumab, with upadacitinib showing large desirable effects (>20% absolute benefit) compared to other biologics. 4 Moderate-efficacy options include golimumab, ustekinumab, tofacitinib, and mirikizumab, while adalimumab has lower relative efficacy. 4

For Alzheimer Disease: Donepezil at 5-10 mg daily improves cognition and global function assessment in patients with mild to moderate disease, though effects are small and primarily demonstrated in short-term studies (≤6 months). 4 Prostaglandin analogs remain the highest-ranking class through 2009 data. 4

For Hypertension: Five drug classes meet requirements for effective blood pressure lowering with proven cardiovascular morbidity and mortality reduction: diuretics, beta-blockers, ACE inhibitors, calcium-channel blockers, and angiotensin II antagonists. 4 Most patients require combination therapy with 2-3 drugs to achieve blood pressure goals (<140/90 mmHg for most patients; <130/80 mmHg for high-risk patients and those with diabetes). 4

For Acute Mania: Antipsychotics (olanzapine 10-15 mg daily, risperidone 2-3 mg daily, or aripiprazole 15 mg daily) are first-line treatments, with or without adjunctive benzodiazepines for severe agitation. 5 Benzodiazepines should never be used as monotherapy as they do not treat underlying manic psychosis. 5

For Opioid Withdrawal: Buprenorphine is more effective than clonidine or lofexidine for managing withdrawal severity, treatment duration, and completion rates (number needed to treat = 4). 4 Buprenorphine and methadone appear equally effective, though data are limited. 4

Critical Implementation Considerations

Avoid common prescribing pitfalls:

• Do not use drugs with no proven efficacy that provoke severe adverse effects, even in serious situations where no effective treatment exists 6
• Recognize that 74 drugs identified in systematic review (2010-2015) are more harmful than beneficial in all authorized indications 6
• Be aware that drug-drug interactions may be underestimated; for example, macrolide antibiotics (clarithromycin, erythromycin) inhibit CYP3A4 and dramatically increase statin levels, risking rhabdomyolysis, particularly in elderly patients, females, those with renal insufficiency, or on higher statin doses 3

Patient-specific risk factors requiring dose adjustment or drug avoidance:

• Advanced age (>80 years), small body frame, and multisystem disease increase adverse event risk 3
• Renal or hepatic impairment may contraindicate certain medications (e.g., metformin contraindicated with impaired kidney function) 4
• Polypharmacy increases interaction risk and requires careful medication reconciliation 3

Monitoring requirements vary by drug class:

• Statins with concurrent macrolides: assess for muscle symptoms before starting therapy, obtain baseline CK in high-risk patients, and discontinue if CK exceeds 10× upper limit of normal 3
• Antihypertensives: monitor blood pressure response and titrate gradually to avoid excessive reduction 4
• Diabetes medications: monitor HbA1c every 3 months during titration, with individualized targets (generally <7% for most patients) 4

Practical Application Strategy

Build your personal formulary systematically:

1. Identify the 20-30 most common clinical conditions in your practice
2. Select 1-2 drugs per condition based on highest-quality evidence from peer-reviewed randomized controlled trials 1
3. Prioritize drugs with established efficacy for patient-relevant outcomes (mortality, morbidity, quality of life) over surrogate markers 1, 2
4. Consider cost only when comparing drugs of similar efficacy and safety 1
5. Update selections when new high-quality evidence emerges, though recognize that keeping guidelines current is challenging 7

Use clinical practice guidelines appropriately: Guidelines should frame decision-making but recognize their limitations—many clinical situations lack guideline coverage, guidelines may conflict with each other, and some are too complex for practical application. 7 When guidelines diverge, prioritize those from prestigious societies with transparent methodology and recent publication dates.