What is causing my fatigue and increased appetite after changing from quazepam (a benzodiazepine) to clonazepam (a benzodiazepine) and adding melatonin?

Medication-Induced Fatigue and Increased Appetite

Your early evening fatigue at 6 PM is most likely caused by the combination of clonazepam's long half-life (30-40 hours) accumulating in your system over two days, compounded by adding 3 mg melatonin, which commonly causes morning sleepiness that can persist into the evening, especially when combined with benzodiazepines.

Primary Culprit: Clonazepam Accumulation

Clonazepam is the dominant factor in your fatigue due to its pharmacokinetic properties:

• Clonazepam has an elimination half-life of 30-40 hours, meaning it accumulates significantly over the first several days of use 1
• After only two days on 25 mg (which appears to be an unusually high dose—typical dosing is 0.25-2.0 mg), you haven't reached steady-state yet, but drug levels are building rapidly 1
• Somnolence is the most common adverse effect, occurring in 37% of patients versus 10% on placebo 2
• Morning sedation is specifically documented as a common side effect that can persist throughout the day 1, 3

Contributing Factor: Melatonin Addition

The 3 mg melatonin you added yesterday is compounding your fatigue:

• Melatonin side effects include morning sleepiness and morning headache 1
• When combined with clonazepam, these sedative effects are additive 1
• The timing of your first melatonin dose (yesterday) coincides with when you first noticed the 6 PM fatigue 1

Dose Reduction Effect: Minimal Impact

Your reduction from 0.5 mg to 0.25 mg clonazepam last night is unlikely to be causing your symptoms because:

• Given clonazepam's 30-40 hour half-life, a single-night dose reduction would not yet produce noticeable effects 1
• Withdrawal symptoms from benzodiazepines typically include anxiety, insomnia, and restlessness—not increased fatigue 2
• You would need several days at the lower dose before experiencing any change in sedation levels 3

Increased Appetite Explanation

Increased appetite is not a commonly reported side effect of either clonazepam or melatonin in the clinical literature provided 2. However:

• Appetite changes can occur with benzodiazepines as part of general CNS depression 2
• The fatigue itself may be altering your eating patterns or perception of hunger
• This symptom warrants monitoring but is less concerning than the excessive sedation

Critical Safety Concerns

Your clonazepam dose appears problematic:

• You mentioned "25 mg clonazepam"—if this is accurate, this is 12-50 times higher than typical therapeutic doses (0.25-2.0 mg) 1
• If you meant 2.5 mg, this is still at the high end and associated with increased risk of confusion, falls, and cognitive impairment 1
• Clonazepam is listed on the American Geriatrics Society Beers Criteria as potentially inappropriate in older adults due to somnolence, ataxia, and cognitive impairment 1, 4

Immediate Recommendations

Contact your prescribing physician immediately to:

1. Clarify your actual clonazepam dose (25 mg would be dangerous; even 2.5 mg is high) 1
2. Consider discontinuing or significantly reducing clonazepam given the excessive sedation 3
3. Temporarily stop melatonin to isolate which medication is causing the most sedation 1
4. Screen for sleep apnea, as clonazepam at 0.5-1.0 mg can worsen or cause sleep apnea, which would compound fatigue 1, 4

Alternative Approach

If you require treatment for a sleep disorder:

• Melatonin monotherapy (3-12 mg) has fewer side effects than clonazepam and may be preferable 1
• Melatonin causes less daytime sedation and has a better safety profile 1, 3
• If both medications are needed, start with the lowest effective doses and titrate slowly 1