What are the best medications for treating tiredness and low energy?

Best Medications for Tiredness and Low Energy

For general tiredness and low energy in otherwise healthy individuals, there are no medications that can be routinely recommended, as the evidence does not support pharmacologic treatment as first-line therapy. 1 Instead, structured physical exercise and addressing underlying causes should be prioritized before considering any medication. 1

Initial Assessment: Identify Treatable Causes First

Before considering medications, you must systematically rule out and treat reversible causes of fatigue:

• Screen for anemia with a complete blood count, as this is a common and treatable cause of fatigue 1, 2
• Check thyroid function (TSH, free T4), as hypothyroidism frequently presents with fatigue and low energy 1, 2
• Assess for depression and anxiety using validated screening tools, as these are among the most common causes of persistent fatigue (18.5% of cases) 3
• Evaluate electrolyte disturbances (sodium, potassium, calcium, magnesium) through a comprehensive metabolic panel, as imbalances are often reversible with supplementation 1, 2
• Review all current medications including over-the-counter drugs, as combinations of narcotics, antidepressants, antiemetics, and antihistamines commonly contribute to excessive drowsiness 1, 2
• Screen for sleep disorders, including sleep apnea, as these are among the most common causes of persistent fatigue 3

First-Line Treatment: Non-Pharmacologic Interventions

Exercise is the single most effective intervention for fatigue, with stronger evidence than any medication. 1

• Prescribe moderate-intensity aerobic exercise (walking, running, swimming, cycling) 2-3 times weekly for 30-60 minutes 1
• Start with low intensity (10-15 minutes of walking) if significantly deconditioned, then gradually increase 2, 4
• Combine endurance exercises with resistance training using light weights for optimal benefit 2

Pharmacologic Options: Limited Evidence and Specific Contexts Only

What Does NOT Work (Do Not Use)

The following medications have been studied and shown to be ineffective for fatigue:

• Modafinil and armodafinil are NOT recommended for general fatigue, as multiple trials failed to show benefit 1, 5
• Antidepressants (including paroxetine) are NOT recommended for fatigue unless depression is present 1
• Donepezil (acetylcholinesterase inhibitor) is NOT recommended, as it showed no benefit over placebo 1
• L-carnitine supplementation is NOT effective, even in patients with baseline L-carnitine deficiency 1
• Coenzyme Q10 is NOT effective for fatigue 1
• Melatonin is NOT effective for fatigue 1
• Eszopiclone (sleep medication) is NOT effective for fatigue 1

Psychostimulants: Controversial and Generally Not Recommended

Methylphenidate and other psychostimulants (dexmethylphenidate, dexamphetamine) cannot be routinely recommended because most trials failed to show intended effects on primary outcome measures. 1

• There is no consensus among expert panels regarding psychostimulants 1
• If considered at all, methylphenidate 5 mg twice daily (at breakfast and lunch) may be tried in thoroughly selected patients only, with usefulness and safety evaluated after a very short time period 1, 4
• Avoid late-day dosing to prevent insomnia 4
• This approach should be reserved for specific contexts like medication-induced fatigue (e.g., aripiprazole) rather than general tiredness 4

Corticosteroids: Only for Advanced Cancer Patients

Short-term corticosteroids may be considered ONLY in patients with metastatic cancer and severe fatigue, not for general tiredness in healthy individuals. 1

• Dexamethasone 4 mg twice daily for 14 days showed significant improvement in fatigue (P=0.008) in advanced cancer patients 1, 2
• Methylprednisolone 16 mg twice daily for 7 days demonstrated a 17-point improvement on quality of life questionnaires (P=0.003) in advanced cancer 1, 2
• Long-term use must be avoided due to significant toxicity 1, 2
• Restrict use to terminally ill patients, those with concomitant anorexia, or patients with pain related to brain or bone metastases 2

Wisconsin Ginseng: Possible Benefit but Needs Confirmation

• Wisconsin ginseng 2000 mg daily for 8 weeks showed statistically significant improvement in fatigue at 8 weeks in a randomized trial of 364 cancer patients 1
• Further studies are needed before definite recommendations can be made 1
• Ginseng appears to be safe, but evidence is limited to cancer-related fatigue 1

Practical Algorithm for General Tiredness

1. Rule out and treat underlying causes (anemia, thyroid dysfunction, depression, sleep disorders, medication effects) 1, 2, 3
2. Implement exercise program as first-line treatment (strongest evidence) 1, 2
3. Optimize sleep hygiene and address psychosocial stressors 2, 3
4. Consider cognitive behavioral therapy if fatigue persists despite addressing medical causes 1, 2
5. Avoid routine use of medications for general fatigue, as evidence does not support their efficacy 1

Critical Pitfalls to Avoid

• Do not prescribe psychostimulants routinely for general fatigue, as evidence shows lack of efficacy in most patients 1
• Do not use corticosteroids outside the context of advanced cancer due to significant toxicity 1, 2
• Do not skip exercise interventions in favor of medications, as exercise has the strongest evidence base 1
• Do not assume fatigue is benign without screening for serious underlying conditions like cancer (0.6% of cases), though this is rare 3
• Do not order extensive laboratory testing beyond basic screening (CBC, metabolic panel, TSH) unless additional symptoms are present, as results affect management in only 5% of patients 6, 3