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Research · Medication

Opioid pain relievers

Single doses relieved pain after surgery. In chronic pain, pooled trials found about 0.7 points of 10 less pain than placebo, and a 12-month trial found no gain over non-opioid drugs. Labels carry boxed warnings for addiction, overdose and fatal breathing depression. A label-cited study found 1% to 6% newly met addiction criteria within 12 months.

Add to Bio HackChecked 2026-11-13
Status
Prescription controlled substances in the US. Oxycodone and hydrocodone are Schedule II and tramadol is Schedule IV. FDA-approved for pain severe enough to require an opioid when other treatments are inadequate. The labels carry FDA boxed warnings for addiction, abuse and misuse, life-threatening breathing depression, accidental ingestion, use with benzodiazepines and newborn withdrawal.
Also called
hydrocodone, Norco, Vicodin, Lortab, Hysingla ER, oxycodone, OxyContin, Roxicodone, Percocet, Endocet, tramadol, Ultram, Ultracet, ConZip, hydrocodone with acetaminophen, oxycodone with acetaminophen, tramadol with acetaminophen, opioid analgesics, narcotic pain relievers
Taken for
severe acute pain, pain after surgery, injury pain, cancer pain, chronic back pain, osteoarthritis pain, nerve pain, migraine, premature ejaculation

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help6

Reported risks15

What people take it for, and what was found

Shown to help6

Moderate

Acute pain after surgery

Shown to relieve pain after surgery in single doses, with about 3 adults given oxycodone 10 mg plus acetaminophen for one extra with half pain relief.

The numbers and sources
Effect
For at least 50% pain relief after surgery, the number needed to treat against placebo was 4.6 (95% CI 2.9 to 11) for oxycodone 15 mg alone and 2.7 (2.4 to 3.1) for oxycodone 10 mg plus paracetamol 650 mg, with a dose response for the combination. Relief lasted 10 hours at that combination dose and 4 hours at half of it. Adverse events were more frequent than on placebo [1]. In individual patient data from 18 single-dose trials, tramadol 50, 100 and 150 mg had numbers needed to treat of 7.1 (4.6 to 18), 4.8 (3.4 to 8.2) and 2.4 (2.0 to 3.1) in pain after surgery, with more adverse events at higher doses [2].
Population
2,641 adults in 20 studies of oxycodone [1]; 3,453 patients with moderate or severe pain after surgery or dental extraction in 18 trials of tramadol [2].
Sources
[1], [2]
Caveats
Single doses followed for hours. The evidence here is for oxycodone and tramadol.
Strong

Chronic pain not caused by cancer

Shown to lower chronic non-cancer pain by about 0.7 points on a 10-point scale against placebo, with no advantage found over non-opioid drugs.

The numbers and sources
Effect
Across 96 trials, opioids lowered pain against placebo by 0.69 cm on a 10 cm scale (95% CI 0.56 to 0.82) and improved physical function by 2.04 points on a 100-point scale (95% CI 1.41 to 2.68). The modeled share reaching a minimally important pain difference was 11.9 percentage points higher. Pain relief was similar to that with NSAIDs (difference -0.60 cm, 95% CI -1.54 to 0.34) and tricyclic antidepressants (-0.13 cm, 95% CI -0.99 to 0.74) [6]. A federal evidence review of 115 trials also found small short-term benefits against placebo in pain, function and sleep, smaller at 3 to 6 months than at 1 to 3 months, and no difference from non-opioid drugs. It found no trial that evaluated intermediate or long-term benefits against placebo [7]. Over 12 months in veterans with chronic back pain or hip or knee osteoarthritis pain, pain-related function did not differ between opioid and non-opioid treatment (3.4 against 3.3), and pain intensity was lower in the non-opioid group (4.0 against 3.5) [8].
Population
26,169 participants in 96 trials, median age 58 [6]; 115 randomized trials and 40 observational studies [7]; 240 veterans randomized to opioid or non-opioid treatment strategies [8].
Sources
[6], [7], [8]
Caveats
Most placebo-controlled trials were short. The 12-month trial was pragmatic, with only the outcome assessment masked [8].
Strong

Knee and hip osteoarthritis pain

Shown to lower knee and hip osteoarthritis pain by small amounts against placebo, about 0.7 points of 10 for oxycodone-type opioids and 4% for tramadol.

The numbers and sources
Effect
In 22 trials, 10 of them of oral oxycodone, opioids lowered pain by 0.7 cm on a 10 cm scale against placebo (SMD -0.28, 95% CI -0.35 to -0.20), a number needed to treat of 10, and improved function by 0.6 units on a 0 to 10 scale. Effects were larger in trials of 4 weeks or less. Dropouts over adverse events were 6.4% against 1.7% [9]. In 22 trials of tramadol, pain improved 4% more than on placebo (95% CI 3% to 5%), and 15 of 100 against 10 of 100 improved by 20%. Physical function improved 4% more (95% CI 2% to 6%). The authors judged neither an important benefit [10].
Population
8,275 people with knee or hip osteoarthritis in 22 trials [9]; 22 trials with 3,871 participants randomized to tramadol alone or with acetaminophen and 2,625 to placebo or an active control, mean duration 2 months [10].
Sources
[9], [10]
Caveats
Most tramadol trials were funded by industry, and 10 of 22 had incomplete outcome data [10]. The first review found signs of small-study bias [9].
ModerateVery common

Nerve pain

Shown to give at least half pain relief to 53% on tramadol against 30% on placebo in small nerve pain trials the reviewers rated low quality.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In 3 studies, 53% on tramadol and 30% on placebo had at least 50% pain relief (RR 2.2, 95% CI 1.02 to 4.6), a number needed to treat of 4.4. Any adverse event was reported by 58% against 34%, and 16% against 3% withdrew over adverse events [11]. In 3 studies in painful diabetic neuropathy, at least moderate benefit was reported by 44% on modified-release oxycodone and 27% on placebo (number needed to treat 5.7). Any adverse event was reported by 86% against 63% [12].
Population
438 adults with neuropathic pain for at least 3 months in 6 studies of tramadol lasting 4 to 6 weeks [11]; 687 adults in 5 studies of oxycodone, 637 with painful diabetic neuropathy and 50 with postherpetic neuralgia [12].
Sources
[11], [12]
Caveats
The reviewers rated the tramadol evidence low quality and the oxycodone evidence very low quality, citing small studies, short duration and risk of bias. No oxycodone study reported at least 50% pain relief [12].
Limited

Acute migraine

One trial found tramadol with acetaminophen relieved migraine pain at 2 hours in 55.8% against 33.8% on placebo, without easing nausea.

The numbers and sources
Effect
Treatment response at 2 hours was 55.8% on tramadol with acetaminophen and 33.8% on placebo, and 22.1% against 9.3% were pain free. At 24 hours 52.7% against 37.9% were pain free. Sensitivity to light and sound was less frequent at 2 hours. Migraine-related nausea did not differ (38.5% against 29.4%) [14].
Population
305 adults with migraine, 154 on tramadol with acetaminophen and 151 on placebo [14].
Sources
[14]
Caveats
One trial of a single attack, of the tramadol and acetaminophen combination only. See the risk block on headache frequency below.
LimitedStudied in men

Premature ejaculation

Limited evidence: four tramadol trials in men found longer time to ejaculation than placebo, with high heterogeneity and more side effects.

The numbers and sources
Effect
Pooling 4 placebo-controlled trials, tramadol lengthened intravaginal ejaculatory latency time over 8 to 12 weeks (p = 0.0007), with high heterogeneity (I² 74%). Erectile dysfunction, constipation, nausea, headache, sleepiness, dry mouth, dizziness, itching and vomiting were more frequent than on placebo or behavioral therapy [15].
Population
721 men with premature ejaculation in the 4 pooled trials, from 8 trials reviewed [15].
Sources
[15]
Caveats
Most trials were of unclear quality. Doses and durations varied, and none assessed addiction. Not an FDA-approved use [16].

Not shown to help2

Moderate

Acute low back, neck and limb pain

Not shown to relieve acute low back, neck or limb pain more than placebo or non-opioid pain relievers in three randomized trials.

The numbers and sources
Effect
In adults with acute low back or neck pain, pain at 6 weeks was 2.78 on a 10-point scale on oxycodone with naloxone and 2.25 on placebo (adjusted difference 0.53, 95% CI -0.00 to 1.07). Constipation was reported by 7.5% and 3.5% [3]. In emergency department patients with acute low back pain who were all given naproxen, adding oxycodone with acetaminophen did not improve function at 1 week more than adding placebo (difference 1.3 points on a 24-point scale, 98.3% CI -1.5 to 4.1) [4]. In emergency department patients with acute arm or leg pain, pain fell at 2 hours by 4.3 points of 10 on ibuprofen plus acetaminophen, 4.4 on oxycodone plus acetaminophen, 3.5 on hydrocodone plus acetaminophen and 3.9 on codeine plus acetaminophen, with no significant difference [5].
Population
347 adults with 12 weeks or less of low back or neck pain, treated for up to 6 weeks [3]; 323 adults with acute low back pain, 108 of them assigned oxycodone with acetaminophen [4]; 416 adults aged 21 to 64 with moderate to severe acute extremity pain [5].
Sources
[3], [4], [5]
Caveats
The limb pain trial gave one dose and did not assess adverse events [5]. The back and neck pain trial used oxycodone combined with naloxone [3].
Moderate

Cancer pain, compared with morphine

Not shown to differ from morphine in the share of people with cancer pain relieved, with less constipation on controlled-release oxycodone.

The numbers and sources
Effect
Across 13 studies, the share with complete or significant pain relief did not differ between controlled-release oxycodone and controlled-release morphine (RR 1.02, 95% CI 0.95 to 1.10). Pain intensity was slightly lower on morphine (SMD 0.14, 95% CI 0.01 to 0.27), equal to 0.27 points on a 0 to 10 scale. Constipation was less frequent on oxycodone (RR 0.75, 95% CI 0.66 to 0.86). Controlled-release and immediate-release oxycodone did not differ in pain intensity [13].
Population
4,485 participants with cancer pain in 42 studies [13].
Sources
[13]
Caveats
No placebo-controlled comparison. The reviewers rated the certainty low or very low [13].

Doses studied

The single-dose trials after surgery used oxycodone 15 mg alone, oxycodone 5 or 10 mg with paracetamol 325 or 650 mg, and tramadol 50 to 150 mg [1][2]. The emergency department limb pain trial gave one dose of oxycodone 5 mg or hydrocodone 5 mg with acetaminophen [5]. The acute back and neck pain trial used up to 20 mg of oxycodone a day for up to 6 weeks [3]. The osteoarthritis trials of tramadol used 37.5 to 400 mg a day, and the nerve pain trials started at about 100 mg a day and rose to as much as 400 mg [10][11].

The cohort studies of overdose grouped people by average daily dose in morphine equivalents, comparing 1 to 20 mg a day with 50 to 99 mg and with 100 mg or more [17][18]. Hydrocodone combination tablets contain 5, 7.5 or 10 mg of hydrocodone with 325 mg of acetaminophen [19].

Risks

Reported risks15

StrongVery common

Constipation, nausea, drowsiness and other common effects

Shown to raise side effects, with any adverse event in 22% against 15% on placebo in osteoarthritis trials and vomiting in 5.9% against 2.3%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
An overview of 14 Cochrane reviews found opioids raised the risk of any adverse event against placebo (RR 1.42, 95% CI 1.22 to 1.66) and of a serious adverse event (RR 2.75, 95% CI 2.06 to 3.67), with constipation, dizziness, drowsiness, fatigue, hot flushes, sweating, nausea, itching and vomiting each more frequent [22]. In osteoarthritis trials, any adverse event was reported by 22% on opioids and 15% on control (RR 1.49, 95% CI 1.35 to 1.63) [9]. In chronic pain trials that excluded people with adverse events during a run-in, vomiting occurred in 5.9% against 2.3% [6]. In tramadol trials in chronic pain, the label reports constipation in 24% within 7 days and 46% within 90 days, nausea in 24% and 40%, and dizziness in 26% and 33% [16].
Population
18,679 participants in 61 studies lasting 2 weeks to 13 months [22]; 8,275 people in 22 osteoarthritis trials [9]; 26,169 participants in 96 trials [6]; 427 people in tramadol trials [16].
Sources
[22], [9], [6], [16]
Caveats
The tramadol label figures have no placebo comparison. None of the Cochrane reviews reported addiction, hormone effects, breathing depression or sleep apnea [22].
ModerateVery common

Low testosterone and adrenal hormones

Linked to lower testosterone in men who use opioids regularly, with hypogonadism in 63% of male long-term users across 15 studies.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In 17 studies, mean testosterone was lower in men using opioids than in controls (mean difference -164.78, 95% CI -245.47 to -84.08, reported in the abstract without a unit). Testosterone in women was not affected [23]. Across 15 studies of long-term users, 99.5% of them male, hypogonadism was present in 63% (95% CI 55% to 70%). Low cortisol was present in 15% (95% CI 6% to 28%) across 5 studies, and raised prolactin was found in 5 of 7 studies [24]. The oxycodone label states that cases of androgen deficiency have occurred with extended use and that adrenal insufficiency has been reported, more often after more than a month of use [20].
Population
800 opioid users and 1,969 controls in 17 studies, 10 cross-sectional and 7 cohort [23]; 18,428 people in 52 studies, most with chronic pain or on maintenance treatment for opioid addiction [24].
Sources
[23], [24], [20]
Caveats
Observational, with high heterogeneity. Methadone and morphine were the opioids most often studied, not hydrocodone, oxycodone or tramadol [24].
ModerateCommon

Addiction and misuse

Linked to addiction in about 1% to 6% of people within 12 months of starting long-term opioid treatment, in a study cited on the label.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The oxycodone label describes a prospective cohort study of people starting long-term Schedule II opioid treatment between 2017 and 2021. Over 12 months, about 1% to 6% across two cohorts newly met criteria for addiction, measured as moderate to severe opioid use disorder, and about 9% and 22% newly met criteria for prescription opioid abuse and misuse [20]. A systematic review of 38 studies in chronic pain found rates of problematic use ranging from under 1% to 81%. Misuse averaged 21% to 29% and addiction 8% to 12% [21].
Population
Two cohorts of 978 and 1,244 people starting long-term opioid treatment [20]; 38 studies of people with chronic pain on opioids [21].
Sources
[20], [21]
Caveats
Observational. The label notes the estimates may not apply to people with shorter or longer exposure [20]. Definitions and methods varied widely across the reviewed studies [21]. The band here is taken from the label's 1% to 6%.
ModerateCommon

Overdose

Linked to overdose that rises with daily dose, with a 5-year rate of about 1.5% to 4% among new long-term users in a label-cited study.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The oxycodone label describes a cohort of 220,249 people with new long-term use of Schedule II opioids from 2006 to 2016. The 5-year cumulative incidence of opioid-involved overdose or overdose death ranged from about 1.5% to 4% across study sites, and about 17% of first overdoses were fatal. Higher baseline dose was the strongest predictor [20]. In people prescribed opioids for chronic non-cancer pain, the annual overdose rate was 0.2% at 1 to 20 mg of morphine equivalents a day, 0.7% at 50 to 99 mg (HR 3.7, 95% CI 1.5 to 9.5) and 1.8% at 100 mg or more (HR 8.9, 95% CI 4.0 to 19.7) [17]. Among veterans, fatal overdose occurred in an estimated 0.04% of those treated, and a maximum dose of 100 mg a day or more carried hazard ratios of 7.18 in chronic pain and 6.64 in acute pain against under 20 mg [18].
Population
220,249 new long-term users [20]; 9,940 people given 3 or more opioid prescriptions within 90 days [17]; 750 overdose deaths and a sample of 154,684 veterans treated with opioids [18].
Sources
[20], [17], [18]
Caveats
Observational. About 80% of the label-cited cohort was lost to follow-up, and its exclusion criteria may have selected people at lower risk [20]. People on higher doses may differ in ways the studies could not measure [17].
LimitedCommon

Continued use after surgery

Linked to new persistent opioid use after surgery in about 6% of adults who had not been using opioids, against 0.4% of non-surgical controls.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Among adults not using opioids before surgery, new persistent opioid use followed 5.9% to 6.5% of minor and major procedures, against 0.4% in a control group that had no surgery. Tobacco use, alcohol and substance use disorders, mood disorders, anxiety and pain conditions before surgery were each associated with higher odds [25].
Population
36,177 US adults with insurance claims for surgery, 80.3% of them minor procedures [25].
Sources
[25]
Caveats
Observational. The study cannot show why opioid use continued.
ModerateCommon

Withdrawal on stopping

Shown to cause withdrawal symptoms, in 2.4% against 0.9% on placebo in osteoarthritis trials. The label warns against stopping abruptly in physically dependent people.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In 3 osteoarthritis trials, withdrawal symptoms occurred in 2.4% on opioids and 0.9% on control (OR 2.76, 95% CI 2.02 to 3.77) [9]. The oxycodone label states that tolerance and physical dependence can develop during opioid therapy, and that rapid reduction or abrupt discontinuation in physically dependent people has resulted in serious withdrawal symptoms, uncontrolled pain and suicide [20].
Population
People with knee or hip osteoarthritis in 3 trials [9]; people physically dependent on opioids, as described in the label [20].
Sources
[9], [20]
Caveats
The trials lasted weeks to months, shorter than much real-world use.
LimitedHow often is not known

Boxed warning: addiction, overdose and breathing depression

FDA states these drugs expose users to addiction, abuse and misuse that can lead to overdose and death, and can cause fatal breathing depression.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warning on oxycodone tablets states that the drug exposes patients and other users to the risks of opioid addiction, abuse and misuse, which can lead to overdose and death. It states that serious, life-threatening or fatal respiratory depression may occur, especially when starting or after a dose increase, and that accidental ingestion of even one dose, especially by children, can result in a fatal overdose. It also covers use with benzodiazepines or other central nervous system depressants, neonatal opioid withdrawal syndrome and interactions with CYP3A4 inhibitors [20]. The hydrocodone and acetaminophen label carries the same warnings and adds liver toxicity from acetaminophen [19]. The tramadol label adds that life-threatening respiratory depression and death have occurred in children given tramadol, and lists children under 12 as a contraindication [16].
Population
People taking oxycodone, hydrocodone or tramadol, as described in the labels [20][19][16].
Sources
[20], [19], [16]
Caveats
A boxed warning states a risk and gives no rate. Rates from studies are in the blocks below.
ModerateHow often is not known

Fractures

Linked to fractures, with a pooled relative risk of 1.88 across 8 cohort studies.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Across 8 cohort studies, opioid use was associated with fracture (RR 1.88, 95% CI 1.51 to 2.34) [26]. A federal evidence review also found opioids associated with fractures, falls, heart attack, overdose and death from any cause in observational studies, with a dose response for all but fractures and falls [7].
Population
8 cohort studies, 6 rated high quality [26]; 40 observational studies [7].
Sources
[26], [7]
Caveats
Observational. People prescribed opioids differ from those who are not in ways that also affect falls and fractures.
LimitedHow often is not known

Tramadol: seizures and serotonin syndrome

The label warns that tramadol has caused seizures and serotonin syndrome within its usual dose range, more so with antidepressants and other serotonergic drugs.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The tramadol label states that seizures have been reported within the usual dosage range and that the risk rises above it. It lists SSRI and tricyclic antidepressants, cyclobenzaprine, other opioids, MAO inhibitors and neuroleptics as raising seizure risk. It states that cases of serotonin syndrome have been reported, particularly with SSRIs, SNRIs, tricyclic antidepressants, triptans, cyclobenzaprine and MAO inhibitors, and that tramadol is not to be used with an MAO inhibitor or within 14 days of one [16].
Population
People taking tramadol, as described in the label [16].
Sources
[16]
Caveats
The label gives no rate for either.
LimitedHow often is not known

Tramadol: low blood sugar and low sodium

Linked to hospital admission for low blood sugar and for low blood sodium in the first 30 days of tramadol, compared with codeine.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against codeine, tramadol was associated with hospitalization for hypoglycemia (OR 1.52, 95% CI 1.09 to 2.10), more so in the first 30 days (OR 2.61, 95% CI 1.61 to 4.23). The rate in the cohort was 0.7 per 1,000 a year [27]. Hospitalization for hyponatremia in the first 30 days occurred at 4.6 per 10,000 person-months on tramadol and 1.9 on codeine (adjusted HR 2.05, 95% CI 1.08 to 3.86) [28]. The tramadol label states that hyponatremia, with serum sodium below 135 mmol/L and in many cases below 120, has been reported, mostly in women over 65 and within the first week, and that hypoglycemia has been reported, mostly in people with risk factors such as diabetes [16].
Population
334,034 UK adults starting tramadol or codeine for non-cancer pain, with 1,105 hypoglycemia admissions [27]; 332,880 UK adults starting tramadol or codeine [28].
Sources
[27], [28], [16]
Caveats
Observational. Both events were infrequent in absolute terms.
ModerateHow often is not known

With benzodiazepines, gabapentin and other sedating drugs

Linked to about twice the odds of an overdose visit when opioids were taken with benzodiazepines, and to more opioid-related deaths with gabapentin.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Among opioid users, concurrent benzodiazepine use was associated with an emergency room visit or admission for opioid overdose (adjusted OR 2.14, 95% CI 2.05 to 2.24) [29]. Among opioid users in Ontario, gabapentin in the prior 120 days was associated with opioid-related death (adjusted OR 1.49, 95% CI 1.18 to 1.88). Concurrent NSAID use was not (adjusted OR 1.14, 95% CI 0.98 to 1.32) [30]. Concurrent skeletal muscle relaxants were associated with opioid overdose (combined HR 1.21, 95% CI 1.00 to 1.48), more with baclofen (1.83, 95% CI 1.11 to 3.04) [31]. The boxed warning states that use with benzodiazepines or other central nervous system depressants, including alcohol, may result in profound sedation, respiratory depression, coma and death [20].
Population
315,428 privately insured US adults who filled an opioid prescription [29]; 1,256 opioid-related deaths and 4,619 matched controls [30]; incident and prevalent opioid user cohorts [31].
Sources
[29], [30], [31], [20]
Caveats
Observational. None of the studies gives the share of people on a combination who overdosed.
LimitedHow often is not known

With drugs that change how the liver clears opioids

The label warns that CYP3A4 inhibitors, including some antibiotics and antifungals, can raise oxycodone and hydrocodone levels and cause fatal breathing depression.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warnings state that CYP3A4 inhibitors may raise oxycodone or hydrocodone concentrations and cause potentially fatal respiratory depression, and that stopping a CYP3A4 inducer may do the same. The oxycodone label names macrolide antibiotics such as erythromycin, azole antifungals such as ketoconazole and protease inhibitors such as ritonavir as inhibitors, and rifampin, carbamazepine and phenytoin as inducers [20][19]. The tramadol label also names the CYP2D6 inhibitors quinidine, fluoxetine, paroxetine and bupropion as changing tramadol and its active metabolite [16].
Population
People taking these drugs together, as described in the labels [20][19][16].
Sources
[20], [19], [16]
Caveats
The labels give no rate.
LimitedHow often is not known

Tramadol compared with NSAIDs: deaths

Linked to more deaths within a year than naproxen in adults with osteoarthritis starting tramadol, 23.5 against 13.8 per 1,000 person-years.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In matched cohorts of adults with osteoarthritis, deaths in the first year were 23.5 per 1,000 person-years on tramadol and 13.8 on naproxen (HR 1.71, 95% CI 1.41 to 2.07). Mortality was also higher than with diclofenac (HR 1.88), celecoxib (HR 1.70) and etoricoxib (HR 2.04), and did not differ from codeine (HR 0.94, 95% CI 0.83 to 1.05) [32].
Population
88,902 adults with osteoarthritis, mean age 70.1, 61.2% women, after propensity score matching [32].
Sources
[32]
Caveats
Observational. People given tramadol in place of an NSAID may have been sicker in ways matching did not capture.
LimitedHow often is not known

Headaches becoming more frequent

Linked to about twice the odds of episodic migraine becoming chronic within a year in people using opioid-containing medicines for headaches.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Of 8,219 people with episodic migraine, 2.5% had developed chronic migraine a year later. Against people using acetaminophen, those using medicines containing opiates had higher odds of that change (OR 1.98, 95% CI 1.4 to 2.2). Triptan use was not associated with it (OR 1.25, 95% CI 0.9 to 1.7) [33].
Population
8,219 adults with episodic migraine in 2005, followed to 2006 [33].
Sources
[33]
Caveats
Observational. People with worsening headaches may be more likely to be given opioids.
LimitedStudied in pregnancyHow often is not known

Use in pregnancy: withdrawal in the newborn

FDA states that extended use in pregnancy can cause neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The boxed warning states that use of opioids for an extended period during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated and needs management by neonatology experts [20][16].
Population
Pregnant women using opioids for an extended period, and their newborns, as described in the labels [20][16].
Sources
[20], [16]
Caveats
The labels give no rate.

Claims tested and not found

  1. That opioids control chronic back or arthritis pain better than non-opioid drugs. Over 12 months in 240 veterans, pain-related function did not differ (3.4 against 3.3), pain intensity was lower in the non-opioid group (3.5 against 4.0) and medication-related symptoms were more frequent in the opioid group [8].
  2. That an opioid speeds recovery from a new episode of low back or neck pain. In 347 adults, pain at 6 weeks was 2.78 on oxycodone with naloxone and 2.25 on placebo [3].
  3. That an opioid combination relieves an acute limb injury better than ibuprofen with acetaminophen. In 416 emergency department patients, pain fell 4.3 points on ibuprofen plus acetaminophen and 3.5 to 4.4 points on three opioid combinations, with no significant difference [5].
  4. That adding oxycodone to naproxen improves acute low back pain. Function at 1 week improved 11.1 points with oxycodone and acetaminophen added and 9.8 points with placebo added (difference 1.3, 98.3% CI -1.5 to 4.1) [4].

Related

NSAIDs

Sources

  1. Gaskell H, Derry S, Moore RA, McQuay HJ. Single dose oral oxycodone and oxycodone plus paracetamol (acetaminophen) for acute postoperative pain in adults. Cochrane Database of Systematic Reviews. 2009. https://doi.org/10.1002/14651858.CD002763.pub2
  2. Moore RA, McQuay HJ. Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Pain. 1997. https://doi.org/10.1016/S0304-3959(96)03291-5
  3. Jones CMP, Day RO, Koes BW, et al. Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial. The Lancet. 2023. https://doi.org/10.1016/S0140-6736(23)00404-X
  4. Friedman BW, Dym AA, Davitt M, et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015. https://doi.org/10.1001/jama.2015.13043
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