Tramadol Side Effects

Primary Adverse Effects

Tramadol commonly causes vomiting, dizziness, and weakness—producing more adverse effects than hydrocodone and codeine in comparative studies. 1

The most frequently reported side effects include:

Nausea and vomiting - occurs early in treatment and is one of the most common adverse effects 1, 2, 3
Dizziness and drowsiness - can impair mental and physical abilities required for driving or operating machinery 2, 3, 4
Constipation - though less severe than with traditional opioids 3, 4
Sweating - reported commonly in clinical use 3, 4
Dry mouth - frequent complaint among users 4, 5
Sedation - particularly problematic in elderly patients 4, 5
Weakness - documented in comparative cancer pain studies 1

Tramadol lowers seizure threshold, requiring dose reduction in high-risk patients. 1, 6, 7

Maximum daily dose should not exceed 400 mg for immediate-release formulations (300 mg for extended-release) to reduce seizure risk 1, 8
Lower doses are mandatory for adults ≥75 years (maximum 300 mg/day) 1
Patients with hepatic or renal dysfunction require dose reduction to prevent seizures 1
Seizures occur through inhibition of nitric oxide, serotonin reuptake, and inhibitory effects on GABA receptors 9

Tramadol causes cognitive impairment including memory problems and increased delirium risk, especially in elderly patients. 6, 2

Altered mental status should raise high suspicion for adverse drug reaction in patients receiving tramadol 2
Long-term use is associated with neurological disorders including potential links to Alzheimer's disease and Parkinson's disease 9
Elderly patients are particularly vulnerable to cognitive side effects 6

Tramadol must be avoided in patients taking SSRIs or tricyclic antidepressants due to severe serotonin syndrome risk. 1, 6, 7

Tramadol affects serotonin metabolism through reuptake inhibition, potentially leading to serotonin toxicity 10, 8, 7
Concomitant use with MAO inhibitors is contraindicated—use with great caution only if absolutely necessary 2
Serotonin syndrome presents with agitation, confusion, hyperthermia, hyperreflexia, and autonomic instability 7
Treatment requires immediate discontinuation of tramadol, benzodiazepine administration, and cyproheptadine in moderate to severe cases 7

Tramadol causes CNS depression that is dangerously potentiated by alcohol and other CNS depressants. 2

Excessive doses alone or combined with CNS depressants (including alcohol) are a cause of drug-related deaths 2
Prescribe with caution when patients require concomitant sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS depressants 2
Respiratory depression can occur, though less severe than traditional opioids 2, 3, 5

Tramadol has mu-opioid agonist activity and carries risk for misuse, abuse, and physical dependence. 2

Drug-seeking behavior is common in addicts and abusers, including emergency visits near office closing, refusal of appropriate examination, repeated "loss" of prescriptions, and "doctor shopping" 2
Physical dependence manifests as withdrawal symptoms upon abrupt discontinuation 2
Withdrawal symptoms include anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, and rarely hallucinations 2
Taper tramadol gradually at discontinuation to avoid withdrawal symptoms 2

Unlike NSAIDs, tramadol does not aggravate hypertension or congestive heart failure 3
Does not cause peptic ulcer disease, making it potentially safer in elderly populations 3
Elevates lipid peroxidation and free radicals with extensive intake, leading to neurotoxicity 9

Maximum 50 mg every 12 hours in patients with hepatic or renal dysfunction 1, 8, 6
Altered metabolism increases risk of adverse effects 8

Never exceed 400 mg/day (or 300 mg/day in elderly)—higher doses only increase adverse effects without improving analgesia 10
Never combine with SSRIs, tricyclic antidepressants, or MAO inhibitors without extreme caution due to serotonin syndrome risk 1, 6, 2
Never use in patients with seizure history without careful risk-benefit assessment 6, 7
Never abruptly discontinue—taper gradually to prevent withdrawal syndrome 2
Never ignore altered mental status—maintain high suspicion for tramadol-related adverse reaction 2