Methadone Withdrawal: Clinical Presentation and Timeline
Methadone withdrawal presents with a constellation of autonomic, gastrointestinal, and neuropsychiatric symptoms that typically begin 24-30 hours after the last dose—significantly later than short-acting opioids—and can persist for weeks due to methadone's long half-life of 19-41 hours. 1, 2
Physical Symptoms
The acute withdrawal syndrome includes:
- Autonomic symptoms: Excessive perspiration, lacrimation (tearing), rhinorrhea (runny nose), fever, chilliness alternating with flushing, dilated pupils, tachycardia, and hypertension 2, 3
- Gastrointestinal symptoms: Nausea, vomiting, diarrhea, abdominal cramps, intestinal spasms, anorexia, and weight loss 2
- Musculoskeletal symptoms: Body aches, tremors, involuntary twitching and kicking movements, and muscular aching 2, 3
- Respiratory symptoms: Sneezing and yawning 2
- Dermatologic symptoms: Goose-flesh (piloerection) 2
Neuropsychiatric Symptoms
The psychological component is substantial and often the most treatment-resistant:
- Mood disturbances: Anxiety, restlessness, irritability, depression, and dysphoria 2, 3
- Sleep disturbances: Insomnia that can be severe and persistent 3
- Cognitive symptoms: Weakness and general malaise 2
Notably, anxiety, restlessness, insomnia, and muscular aching are the most resistant to pharmacological treatment and persist even with adjunctive medications like clonidine. 3
Timeline and Duration
- Onset: Withdrawal symptoms typically begin 24-30 hours after the last methadone dose, considerably later than heroin (12 hours) due to methadone's long half-life 1, 2
- Peak: Symptoms generally peak within 72 hours but can take up to 5-7 days to reach maximum intensity in patients on higher doses 1
- Duration: Unlike short-acting opioids where acute withdrawal resolves in 5-7 days, methadone withdrawal can produce protracted symptoms lasting weeks 1, 4
Clinical Assessment
Use the Clinical Opiate Withdrawal Scale (COWS) to objectively quantify withdrawal severity, with a score >8 indicating moderate-to-severe withdrawal. 1 This validated tool measures:
- Resting pulse rate
- Sweating
- Restlessness
- Pupil size
- Bone or joint aches
- Runny nose or tearing
- GI upset
- Tremor
- Yawning
- Anxiety or irritability
- Gooseflesh skin
Important Clinical Caveats
The severity and duration of methadone withdrawal are dose-dependent and duration-dependent. Patients on higher doses (>80-100 mg daily) or longer treatment durations will experience more severe and prolonged withdrawal 1, 4.
Abrupt discontinuation produces significantly worse outcomes than gradual tapering. Research demonstrates that withdrawal at approximately 3% of the initial dose per week produces better retention and less severe symptoms compared to rapid withdrawal at 10% per week 4. However, even with optimal tapering, relapse rates remain high, as detoxification alone does not address the chronic relapsing nature of opioid use disorder 5.
During the induction phase when transitioning from heroin to methadone, patients may exhibit withdrawal symptoms from heroin that should be differentiated from methadone-induced side effects. 2