Most Effective Treatments for Adults Compared to Placebo with Clinically Relevant Outcomes
Based on the most recent and highest quality evidence, the most effective treatments for adults with clinically relevant outcomes compared to placebo include semaglutide 2.4mg for obesity, upadacitinib for ulcerative colitis, and infliximab (especially in combination with purine analogues) for inflammatory bowel disease.
Inflammatory Bowel Disease Treatments
Infliximab for Crohn's Disease
- Infliximab is more effective than placebo for induction of clinical remission (RR=4.55,95% CI 1.53 to 13.50) and response (RR=4.09,95% CI 1.63 to 10.25) in Crohn's disease 1
- For maintenance therapy, infliximab is superior to placebo in preventing clinical relapse (56% vs 75%, RR=0.73,95% CI 0.63 to 0.84) 1
- Combination therapy with infliximab and purine analogues shows approximately 20% higher efficacy for maintenance therapy compared to monotherapy 1
Treatments for Ulcerative Colitis
- Upadacitinib demonstrates the largest desirable effect (exceeding 30% for relevant comparisons) for moderate-to-severe ulcerative colitis compared to placebo 1
- Tofacitinib and ustekinumab also show large desirable effects for ulcerative colitis treatment 1
- Methotrexate is not recommended for ulcerative colitis as studies showed no benefit over placebo (RR=1.19,95% CI 0.72 to 1.96) 1
Obesity Treatments
Pharmacotherapy for Obesity
- Semaglutide 2.4mg shows the highest efficacy with 10.76% more total body weight loss compared to placebo (high certainty evidence) 1
- Phentermine-topiramate ER demonstrates 8.45% higher total body weight loss compared to placebo (high certainty evidence) 1
- Liraglutide 3.0mg shows 4.81% lower total body weight loss compared to placebo (high certainty evidence) 1
- Naltrexone-bupropion ER shows 3.01% lower total body weight loss compared to placebo (moderate certainty evidence) 1
Depression Treatments
Comparative Efficacy for Major Depressive Disorder
- Cognitive Behavioral Therapy (CBT) demonstrates similar treatment effects to second-generation antidepressants across several outcomes (moderate certainty evidence) 1
- For second-step treatments, various pharmacologic switch strategies show similar efficacy 1
- Switching antidepressants shows similar efficacy to augmentation with buspirone or bupropion SR (moderate certainty evidence) 1
Fibromyalgia Treatments
Pharmacologic Options
- Duloxetine and milnacipran are weakly recommended for fibromyalgia (100% agreement) 1
- Cyclobenzaprine is weakly recommended (75% agreement) with patients reporting themselves as "improved" (NNT 4.8,95% CI 3.0 to 11.0) 1
- Growth hormone is strongly recommended against (94% agreement) despite showing an effect size on pain of 1.36 (0.01 to 1.34) due to safety concerns 1
- Monoamine oxidase inhibitors are weakly recommended against (81% agreement) despite moderate effect on pain (-0.54; -1.02 to -0.07) 1
- NSAIDs are weakly recommended against (100% agreement) with no evidence of improved outcomes compared to placebo 1
Cardiovascular Treatments
Amlodipine for Angina and Coronary Artery Disease
- Amlodipine 10mg increases exercise time by 12.8% (63 sec) compared to placebo in chronic stable angina 2
- In patients with documented coronary artery disease, amlodipine reduced the risk of hospitalization for angina by 42% (p=0.002) and coronary revascularization by 27% (p=0.033) compared to placebo 2
- The composite cardiovascular endpoint was reduced by 31% (p=0.003) in the amlodipine group versus placebo 2
Implementation Considerations
Treatment Selection Factors
- Treatment selection should be based on the clinical profile and specific needs of the patient 1
- Consider comorbidities, patient preferences, costs, and access to therapy when selecting treatments 1
- For inflammatory bowel disease, consider whether to use originator or biosimilar preparations within the local clinical commissioning context 1
Safety Considerations
- Treatment discontinuation due to adverse effects varies significantly between medications:
Common Pitfalls and Caveats
- Many clinical trials have methodological shortcomings such as high dropout rates or lack of blinding of outcome assessors 1
- Trials often inadequately report harms or don't report them at all, making it difficult to assess the balance between benefits and harms 1
- Most trials are explanatory rather than pragmatic, potentially compromising applicability to real-world clinical practice 1
- Publication bias may affect the available evidence, particularly for treatments with negative results 1
- Treatment effects in clinical trials represent average effects and may not apply equally to all individuals 3