What are the risks of long-term tramadol (opioid analgesic) prescription for a patient?

Downsides of Long-Term Tramadol Prescription

Long-term tramadol prescription carries significant risks including physical dependence, tolerance, withdrawal syndromes, seizures, and diminishing efficacy beyond 3 months, with no evidence supporting safety or effectiveness beyond 1 year. 1

Evidence-Based Duration Limitations

The most critical downside is prescribing beyond the evidence base:

• No randomized controlled trial evidence exists for tramadol use beyond 1 year, representing a fundamental knowledge gap about long-term safety and efficacy 1
• Clinical trials demonstrate only "very modest" beneficial effects for long-term (3 months to 1 year) management of non-cancer pain 1
• Systematic reviews show that less pain relief occurs during longer trials, suggesting diminishing returns with extended use 1
• Most acute pain studies lasted fewer than 3 weeks, establishing this as the evidence-based timeframe for acute conditions 1

Physical Dependence and Withdrawal

Long-term use inevitably leads to physical dependence:

• Tolerance and withdrawal are more likely to occur the longer a patient is on continuous therapy with tramadol 2
• Withdrawal symptoms include anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations 2
• Less frequently reported symptoms include panic attacks, severe anxiety, and paresthesias 2
• Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation or upon administration of an antagonist 2

Seizure Risk

Tramadol carries a unique seizure risk that increases with duration:

• Seizures have been reported in patients receiving tramadol within the recommended dosage range 2
• Spontaneous post-marketing reports indicate that seizure risk is increased with doses above the recommended range 2
• Risk of convulsions increases in patients with epilepsy, history of seizures, head trauma, metabolic disorders, alcohol and drug withdrawal, or CNS infections 2
• Concomitant use with SSRIs, SNRIs, tricyclic antidepressants, MAO inhibitors, neuroleptics, or other seizure-threshold lowering drugs significantly increases seizure risk 2

Abuse and Addiction Potential

Despite being marketed as having "low abuse potential," long-term use carries real risks:

• Tramadol has mu-opioid agonist activity and can be abused and subject to criminal diversion 2
• All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use carries risk of addiction even under appropriate medical use 2
• Drug-seeking behavior is common in addicts and drug abusers, including emergency calls near end of office hours, refusal to undergo appropriate examination, repeated "loss" of prescriptions, and "doctor shopping" 2
• Tramadol-related deaths have occurred in patients with previous histories of emotional disturbances, suicidal ideation, or histories of misuse of tranquilizers, alcohol, and other CNS-active drugs 2

Respiratory Depression

While less severe than traditional opioids, respiratory depression remains a concern:

• When large doses are administered with anesthetic medications or alcohol, respiratory depression may result 2
• The respiratory depressant effects include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, which may be markedly exaggerated in patients with increased intracranial pressure or head injury 2

Drug Interactions and Serotonin Syndrome

Long-term prescribing increases cumulative exposure to potentially life-threatening interactions:

• Development of potentially life-threatening serotonin syndrome may occur with concomitant use of SSRIs, SNRIs, TCAs, MAOIs, and triptans 2
• Serotonin syndrome may include mental-status changes (agitation, hallucinations, coma), autonomic instability (tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (hyperreflexia, incoordination), and gastrointestinal symptoms 2
• Tramadol should be used with great caution in patients taking MAO inhibitors, as animal studies have shown increased deaths with combined administration 2

High Adverse Event Burden

The cumulative burden of side effects over time is substantial:

• 85% incidence of adverse events occurs in patients on opioids, necessitating ongoing evaluation of whether benefits justify continued use 1
• Common adverse effects include dizziness, nausea, sedation, dry mouth, and sweating 2
• In comparative studies, tramadol produced more adverse effects including vomiting, dizziness, and weakness than hydrocodone and codeine 3
• Tramadol may impair mental and physical abilities required for potentially hazardous tasks such as driving or operating machinery 2

CNS Depression and Cognitive Impairment

Long-term use compounds central nervous system effects:

• Tramadol should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers, or sedative hypnotics 2
• Tramadol increases the risk of CNS and respiratory depression in these patients 2
• Tramadol may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression 2

Specific Vulnerable Populations

Certain patients face amplified risks with long-term use:

• Lower doses are recommended for patients over 75 years or with hepatic/renal impairment to reduce seizure risk 1
• For elderly patients and those with renal or hepatic dysfunction, lower doses should be used due to risk of drug accumulation 4
• Tramadol should not be prescribed for patients who are suicidal or addiction-prone 2

Clinical Positioning Context

Guidelines consistently position tramadol as a time-limited option:

• The American College of Rheumatology recommends using the lowest possible doses for the shortest possible length of time, given high risk of toxicity and dependence with prolonged opioid therapy 1
• Tramadol should be considered only as second- or third-line agent when first-line therapies (acetaminophen, NSAIDs) have failed 3, 1
• The American College of Rheumatology conditionally recommends tramadol only when patients have contraindications to NSAIDs, find other therapies ineffective, or have no available surgical options 1

Critical Prescribing Pitfall

Do not assume efficacy beyond 3 months based on short-term response: evidence quality diminishes substantially for longer durations, and prescribing beyond 1 year represents prescribing outside the evidence base requiring exceptional clinical justification 1