Dominik Ose, DrPH, MPH

Evidence summary

Symptoms improve with PRP—but not significantly

A 2014 double-blind RCT (n = 23) explored recovery outcomes in patients with patellar tendinopathy who received either 1 injection of leukocyte-rich PRP or ultrasound-­guided dry needling.¹ Both groups also completed standardized eccentric exercises. Participants were predominantly men, ages ≥ 18 years. Symptomatic improvement was assessed using the Victorian Institute of Sport ­Assessment–Patella (VISA-P), an 8-item subjective questionnaire of functionality with a range of 0 to 100, with 100 as the maximum score for an asymptomatic individual.

At 12 weeks posttreatment, VISA-P scores improved in both groups. However, the improvement in the dry needling group was not statistically significant (5.2 points; 95% CI, –2.2 to 12.6; P = .20), while in the PRP group it was statistically significant (25.4 points; 95% CI, 10.3 to 40.6; P = .01). At ≥ 26 weeks, statistically significant improvement was observed in both treatment groups: scores improved by 33.2 points (95% CI, 24.1 to 42.4; P = .001) in the dry needling group and by 28.9 points (95% CI, 11.4 to 46.3; P = .01) in the PRP group. However, the difference between the groups’ VISA-P scores at ≥ 26 weeks was not significant (P = .66).¹

No significant differences observed for PRP vs placebo or physical therapy

A 2019 single-blind RCT (n = 57) involved patients who were treated with 1 injection of either leukocyte-rich PRP, leukocyte-poor PRP, or saline, all in combination with 6 weeks of physical therapy.² Participants were predominantly men, ages 18 to 50 years, and engaged in recreational sporting activities. There was no statistically significant difference in mean change in VISA-P score at any timepoint of the 2-year study period. P values were not reported.²

A 2010 RCT (n = 31) compared PRP (unspecified whether leukocyte-rich or -poor) in combination with physical therapy to physical therapy alone.³ Groups were matched for sex, age, and sports activity level; patients in the PRP group were required to have failed previous treatment, while control subjects must not have received any treatment for at least 2 months. Subjects were evaluated pretreatment, immediately posttreatment, and 6 months posttreatment. Clinical evaluation was aided by use of the Tegner activity score, a 1-item score that grades activity level on a scale of 0 to 10; the EuroQol-visual analog scale (EQ-VAS), which evaluates subjective rating of overall health; and pain level scores.

At 6 months posttreatment, no statistically significant differences were observed between groups in EQ-VAS and pain level scores. However, Tegner activity scores among PRP recipients showed significant percent improvement over controls at 6 months posttreatment (39% vs 20%; P = .048).³

Recommendations from others

Currently, national orthopedic and professional athletic medical associations have recommended that further research be conducted in order to make a strong statement in favor of or against PRP.^4,5

Editor’s takeaway

Existing data regarding PRP fails, again, to show consistent benefits. These small sample sizes, inconsistent comparators, and heterogeneous results limit our certainty. This lack of quality evidence does not prove a lack of effect, but it raises serious doubts.

Evidence summary

Symptoms improve with PRP—but not significantly

A 2014 double-blind RCT (n = 23) explored recovery outcomes in patients with patellar tendinopathy who received either 1 injection of leukocyte-rich PRP or ultrasound-­guided dry needling.¹ Both groups also completed standardized eccentric exercises. Participants were predominantly men, ages ≥ 18 years. Symptomatic improvement was assessed using the Victorian Institute of Sport ­Assessment–Patella (VISA-P), an 8-item subjective questionnaire of functionality with a range of 0 to 100, with 100 as the maximum score for an asymptomatic individual.

At 12 weeks posttreatment, VISA-P scores improved in both groups. However, the improvement in the dry needling group was not statistically significant (5.2 points; 95% CI, –2.2 to 12.6; P = .20), while in the PRP group it was statistically significant (25.4 points; 95% CI, 10.3 to 40.6; P = .01). At ≥ 26 weeks, statistically significant improvement was observed in both treatment groups: scores improved by 33.2 points (95% CI, 24.1 to 42.4; P = .001) in the dry needling group and by 28.9 points (95% CI, 11.4 to 46.3; P = .01) in the PRP group. However, the difference between the groups’ VISA-P scores at ≥ 26 weeks was not significant (P = .66).¹

No significant differences observed for PRP vs placebo or physical therapy

A 2019 single-blind RCT (n = 57) involved patients who were treated with 1 injection of either leukocyte-rich PRP, leukocyte-poor PRP, or saline, all in combination with 6 weeks of physical therapy.² Participants were predominantly men, ages 18 to 50 years, and engaged in recreational sporting activities. There was no statistically significant difference in mean change in VISA-P score at any timepoint of the 2-year study period. P values were not reported.²

A 2010 RCT (n = 31) compared PRP (unspecified whether leukocyte-rich or -poor) in combination with physical therapy to physical therapy alone.³ Groups were matched for sex, age, and sports activity level; patients in the PRP group were required to have failed previous treatment, while control subjects must not have received any treatment for at least 2 months. Subjects were evaluated pretreatment, immediately posttreatment, and 6 months posttreatment. Clinical evaluation was aided by use of the Tegner activity score, a 1-item score that grades activity level on a scale of 0 to 10; the EuroQol-visual analog scale (EQ-VAS), which evaluates subjective rating of overall health; and pain level scores.

At 6 months posttreatment, no statistically significant differences were observed between groups in EQ-VAS and pain level scores. However, Tegner activity scores among PRP recipients showed significant percent improvement over controls at 6 months posttreatment (39% vs 20%; P = .048).³

Recommendations from others

Currently, national orthopedic and professional athletic medical associations have recommended that further research be conducted in order to make a strong statement in favor of or against PRP.^4,5

Editor’s takeaway

Existing data regarding PRP fails, again, to show consistent benefits. These small sample sizes, inconsistent comparators, and heterogeneous results limit our certainty. This lack of quality evidence does not prove a lack of effect, but it raises serious doubts.

Evidence summary

Symptoms improve with PRP—but not significantly

A 2014 double-blind RCT (n = 23) explored recovery outcomes in patients with patellar tendinopathy who received either 1 injection of leukocyte-rich PRP or ultrasound-­guided dry needling.¹ Both groups also completed standardized eccentric exercises. Participants were predominantly men, ages ≥ 18 years. Symptomatic improvement was assessed using the Victorian Institute of Sport ­Assessment–Patella (VISA-P), an 8-item subjective questionnaire of functionality with a range of 0 to 100, with 100 as the maximum score for an asymptomatic individual.

At 12 weeks posttreatment, VISA-P scores improved in both groups. However, the improvement in the dry needling group was not statistically significant (5.2 points; 95% CI, –2.2 to 12.6; P = .20), while in the PRP group it was statistically significant (25.4 points; 95% CI, 10.3 to 40.6; P = .01). At ≥ 26 weeks, statistically significant improvement was observed in both treatment groups: scores improved by 33.2 points (95% CI, 24.1 to 42.4; P = .001) in the dry needling group and by 28.9 points (95% CI, 11.4 to 46.3; P = .01) in the PRP group. However, the difference between the groups’ VISA-P scores at ≥ 26 weeks was not significant (P = .66).¹

No significant differences observed for PRP vs placebo or physical therapy

A 2019 single-blind RCT (n = 57) involved patients who were treated with 1 injection of either leukocyte-rich PRP, leukocyte-poor PRP, or saline, all in combination with 6 weeks of physical therapy.² Participants were predominantly men, ages 18 to 50 years, and engaged in recreational sporting activities. There was no statistically significant difference in mean change in VISA-P score at any timepoint of the 2-year study period. P values were not reported.²

A 2010 RCT (n = 31) compared PRP (unspecified whether leukocyte-rich or -poor) in combination with physical therapy to physical therapy alone.³ Groups were matched for sex, age, and sports activity level; patients in the PRP group were required to have failed previous treatment, while control subjects must not have received any treatment for at least 2 months. Subjects were evaluated pretreatment, immediately posttreatment, and 6 months posttreatment. Clinical evaluation was aided by use of the Tegner activity score, a 1-item score that grades activity level on a scale of 0 to 10; the EuroQol-visual analog scale (EQ-VAS), which evaluates subjective rating of overall health; and pain level scores.

At 6 months posttreatment, no statistically significant differences were observed between groups in EQ-VAS and pain level scores. However, Tegner activity scores among PRP recipients showed significant percent improvement over controls at 6 months posttreatment (39% vs 20%; P = .048).³

Recommendations from others

Currently, national orthopedic and professional athletic medical associations have recommended that further research be conducted in order to make a strong statement in favor of or against PRP.^4,5

Editor’s takeaway

Existing data regarding PRP fails, again, to show consistent benefits. These small sample sizes, inconsistent comparators, and heterogeneous results limit our certainty. This lack of quality evidence does not prove a lack of effect, but it raises serious doubts.

EVIDENCE SUMMARY

Benzodiazepines work—but how do they compare?

A 2010 Cochrane meta-analysis of 64 RCTs and controlled clinical trials (CCTs; N = 4309) evaluated the use of benzodiazepines for treatment of AWS in adults.¹ This systematic review compared benzodiazepines

• vs placebo (10 studies)
• vs other drugs, including phenobarbital, carbamazepine, topiramate, lamotrigine, gabapentin, haloperidol, clonidine, hydroxyzine, propranolol, and baclofen (42 studies)
• to other benzodiazepines, including chlordiazepoxide, alprazolam, diazepam, and lorazepam (18 studies)
• in combination with other drugs vs other drugs alone (3 studies)
• administered on a fixed schedule vs symptom-triggered administration (3 studies).

Primary outcomes included efficacy (alcohol withdrawal seizures, alcohol withdrawal delirium, alcohol withdrawal symptoms, global improvement), safety (adverse events and severe, life-threatening adverse events), and acceptability (dropouts and dropouts due to adverse events).

Benzodiazepines performed better than placebo for seizures in 3 studies (N = 324), with a relative risk (RR) of 0.16 (95% confidence interval [CI], 0.04-0.69). Studies assessing the described outcomes between benzodiazepines and other drugs were often of small sample size and heterogeneous in ­interventions and outcomes, limiting the ability to draw clear conclusions regarding benzodiazepine superiority. Comparisons of different benzodiazepines with each other and comparisons of benzodiazepines combined with other drugs vs other drugs alone did not reach statistical significance. Data on harms of benzodiazepines were lacking.

Anticonvulsants are not better than placebo for AWS

Another 2010 Cochrane meta-analysis of 56 RCTs and CCTs (N = 4076) evaluated the use of anticonvulsants for AWS.² This systematic review compared anticonvulsants

• vs placebo (17 studies)
• vs other drugs, such as bromocriptine, piracetam, gamma-hydroxybutyric acid, trifluoperazine, clonidine, and various benzodiazepines (32 studies)
• to other anticonvulsants (10 studies)
• in combination with other drugs vs other drugs alone (6 studies)
• in combination with other drugs vs different anticonvulsants (1 study).

Primary outcomes included reductions in alcohol withdrawal seizures, adverse events, and acceptability of medication as indicated by participant dropouts.

Anticonvulsants were not superior to placebo for any outcome. Three studies (N = 260) favored carbamazepine over benzodiazepine (oxazepam or lorazepam) for 1 secondary outcome: a reduction of Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) score (maximum score of 7; mean difference [MD] = –1 [95% CI, –1.9 to –0.2]).

Continue to: Gabapentin is effective; less sedating than chlordiazepoxide

A 2013 RCT of US veterans with AWS (N = 26; 25 men; average age, 53.5 years) compared gabapentin and chlordiazepoxide.³ Endpoints were ratings on the Epworth Sleepiness Scale (ESS; maximum score = 24), Penn Alcohol Craving Scale (PACS; maximum score, 30), and CIWA-Ar.

In the early treatment period (Days 1-4), ESS and PACS scores did not differ significantly between groups. At end of treatment (Days 5-7), ESS and PACS scores were lower in gabapentin-treated patients (ESS: MD = –3.7; 95% CI, –7.2 to –0.19; P = .04; PACS: MD = –6.05; 95% CI –12.82 to 0.72; P = .08). CIWA-Ar did not differ between treatment groups.

Recommendations from others

In January 2020, the American Society of Addiction Medicine (ASAM) published a clinical practice guideline for alcohol withdrawal management. Protocols for diagnosis, assessment, level of care determination, and management are delineated.⁴

Dozens of small trials and meta-analyses confirm the benefits (sometimes marginal) of sedation to treat alcohol withdrawal.

Benzodiazepines are the first-line treatment for moderate-to-severe AWS, or when there is risk for severe AWS. In the ambulatory setting, when AWS is mild and there is no risk for worsening, AWS can be managed with supportive care or with either benzodiazepines, gabapentin, or carbamazepine as monotherapy. ASAM recommends long-­acting benzodiazepines (eg, chlordiazepoxide or diazepam) over short-acting benzodiazepines (eg, alprazolam or lorazepam), except in the elderly and those with liver or lung disease.⁵

Editor’s takeaway

Dozens of small trials and meta-analyses confirm the benefits (sometimes marginal) of sedation to treat alcohol withdrawal. Given that the evidence fails to point to the superiority of 1 agent over another, it seems reasonable to make treatment decisions based on physician and perhaps patient preference. This review does not support a change in clinical practice.

EVIDENCE SUMMARY

Benzodiazepines work—but how do they compare?

A 2010 Cochrane meta-analysis of 64 RCTs and controlled clinical trials (CCTs; N = 4309) evaluated the use of benzodiazepines for treatment of AWS in adults.¹ This systematic review compared benzodiazepines

• vs placebo (10 studies)
• vs other drugs, including phenobarbital, carbamazepine, topiramate, lamotrigine, gabapentin, haloperidol, clonidine, hydroxyzine, propranolol, and baclofen (42 studies)
• to other benzodiazepines, including chlordiazepoxide, alprazolam, diazepam, and lorazepam (18 studies)
• in combination with other drugs vs other drugs alone (3 studies)
• administered on a fixed schedule vs symptom-triggered administration (3 studies).

Primary outcomes included efficacy (alcohol withdrawal seizures, alcohol withdrawal delirium, alcohol withdrawal symptoms, global improvement), safety (adverse events and severe, life-threatening adverse events), and acceptability (dropouts and dropouts due to adverse events).

Benzodiazepines performed better than placebo for seizures in 3 studies (N = 324), with a relative risk (RR) of 0.16 (95% confidence interval [CI], 0.04-0.69). Studies assessing the described outcomes between benzodiazepines and other drugs were often of small sample size and heterogeneous in ­interventions and outcomes, limiting the ability to draw clear conclusions regarding benzodiazepine superiority. Comparisons of different benzodiazepines with each other and comparisons of benzodiazepines combined with other drugs vs other drugs alone did not reach statistical significance. Data on harms of benzodiazepines were lacking.

Anticonvulsants are not better than placebo for AWS

Another 2010 Cochrane meta-analysis of 56 RCTs and CCTs (N = 4076) evaluated the use of anticonvulsants for AWS.² This systematic review compared anticonvulsants

• vs placebo (17 studies)
• vs other drugs, such as bromocriptine, piracetam, gamma-hydroxybutyric acid, trifluoperazine, clonidine, and various benzodiazepines (32 studies)
• to other anticonvulsants (10 studies)
• in combination with other drugs vs other drugs alone (6 studies)
• in combination with other drugs vs different anticonvulsants (1 study).

Primary outcomes included reductions in alcohol withdrawal seizures, adverse events, and acceptability of medication as indicated by participant dropouts.

Anticonvulsants were not superior to placebo for any outcome. Three studies (N = 260) favored carbamazepine over benzodiazepine (oxazepam or lorazepam) for 1 secondary outcome: a reduction of Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) score (maximum score of 7; mean difference [MD] = –1 [95% CI, –1.9 to –0.2]).

Continue to: Gabapentin is effective; less sedating than chlordiazepoxide

A 2013 RCT of US veterans with AWS (N = 26; 25 men; average age, 53.5 years) compared gabapentin and chlordiazepoxide.³ Endpoints were ratings on the Epworth Sleepiness Scale (ESS; maximum score = 24), Penn Alcohol Craving Scale (PACS; maximum score, 30), and CIWA-Ar.

In the early treatment period (Days 1-4), ESS and PACS scores did not differ significantly between groups. At end of treatment (Days 5-7), ESS and PACS scores were lower in gabapentin-treated patients (ESS: MD = –3.7; 95% CI, –7.2 to –0.19; P = .04; PACS: MD = –6.05; 95% CI –12.82 to 0.72; P = .08). CIWA-Ar did not differ between treatment groups.

Recommendations from others

In January 2020, the American Society of Addiction Medicine (ASAM) published a clinical practice guideline for alcohol withdrawal management. Protocols for diagnosis, assessment, level of care determination, and management are delineated.⁴

Dozens of small trials and meta-analyses confirm the benefits (sometimes marginal) of sedation to treat alcohol withdrawal.

Benzodiazepines are the first-line treatment for moderate-to-severe AWS, or when there is risk for severe AWS. In the ambulatory setting, when AWS is mild and there is no risk for worsening, AWS can be managed with supportive care or with either benzodiazepines, gabapentin, or carbamazepine as monotherapy. ASAM recommends long-­acting benzodiazepines (eg, chlordiazepoxide or diazepam) over short-acting benzodiazepines (eg, alprazolam or lorazepam), except in the elderly and those with liver or lung disease.⁵

Editor’s takeaway

Dozens of small trials and meta-analyses confirm the benefits (sometimes marginal) of sedation to treat alcohol withdrawal. Given that the evidence fails to point to the superiority of 1 agent over another, it seems reasonable to make treatment decisions based on physician and perhaps patient preference. This review does not support a change in clinical practice.

EVIDENCE SUMMARY

Benzodiazepines work—but how do they compare?

A 2010 Cochrane meta-analysis of 64 RCTs and controlled clinical trials (CCTs; N = 4309) evaluated the use of benzodiazepines for treatment of AWS in adults.¹ This systematic review compared benzodiazepines

• vs placebo (10 studies)
• vs other drugs, including phenobarbital, carbamazepine, topiramate, lamotrigine, gabapentin, haloperidol, clonidine, hydroxyzine, propranolol, and baclofen (42 studies)
• to other benzodiazepines, including chlordiazepoxide, alprazolam, diazepam, and lorazepam (18 studies)
• in combination with other drugs vs other drugs alone (3 studies)
• administered on a fixed schedule vs symptom-triggered administration (3 studies).

Primary outcomes included efficacy (alcohol withdrawal seizures, alcohol withdrawal delirium, alcohol withdrawal symptoms, global improvement), safety (adverse events and severe, life-threatening adverse events), and acceptability (dropouts and dropouts due to adverse events).

Benzodiazepines performed better than placebo for seizures in 3 studies (N = 324), with a relative risk (RR) of 0.16 (95% confidence interval [CI], 0.04-0.69). Studies assessing the described outcomes between benzodiazepines and other drugs were often of small sample size and heterogeneous in ­interventions and outcomes, limiting the ability to draw clear conclusions regarding benzodiazepine superiority. Comparisons of different benzodiazepines with each other and comparisons of benzodiazepines combined with other drugs vs other drugs alone did not reach statistical significance. Data on harms of benzodiazepines were lacking.

Anticonvulsants are not better than placebo for AWS

Another 2010 Cochrane meta-analysis of 56 RCTs and CCTs (N = 4076) evaluated the use of anticonvulsants for AWS.² This systematic review compared anticonvulsants

• vs placebo (17 studies)
• vs other drugs, such as bromocriptine, piracetam, gamma-hydroxybutyric acid, trifluoperazine, clonidine, and various benzodiazepines (32 studies)
• to other anticonvulsants (10 studies)
• in combination with other drugs vs other drugs alone (6 studies)
• in combination with other drugs vs different anticonvulsants (1 study).

Primary outcomes included reductions in alcohol withdrawal seizures, adverse events, and acceptability of medication as indicated by participant dropouts.

Anticonvulsants were not superior to placebo for any outcome. Three studies (N = 260) favored carbamazepine over benzodiazepine (oxazepam or lorazepam) for 1 secondary outcome: a reduction of Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) score (maximum score of 7; mean difference [MD] = –1 [95% CI, –1.9 to –0.2]).

Continue to: Gabapentin is effective; less sedating than chlordiazepoxide

A 2013 RCT of US veterans with AWS (N = 26; 25 men; average age, 53.5 years) compared gabapentin and chlordiazepoxide.³ Endpoints were ratings on the Epworth Sleepiness Scale (ESS; maximum score = 24), Penn Alcohol Craving Scale (PACS; maximum score, 30), and CIWA-Ar.

In the early treatment period (Days 1-4), ESS and PACS scores did not differ significantly between groups. At end of treatment (Days 5-7), ESS and PACS scores were lower in gabapentin-treated patients (ESS: MD = –3.7; 95% CI, –7.2 to –0.19; P = .04; PACS: MD = –6.05; 95% CI –12.82 to 0.72; P = .08). CIWA-Ar did not differ between treatment groups.

Recommendations from others

In January 2020, the American Society of Addiction Medicine (ASAM) published a clinical practice guideline for alcohol withdrawal management. Protocols for diagnosis, assessment, level of care determination, and management are delineated.⁴

Dozens of small trials and meta-analyses confirm the benefits (sometimes marginal) of sedation to treat alcohol withdrawal.

Benzodiazepines are the first-line treatment for moderate-to-severe AWS, or when there is risk for severe AWS. In the ambulatory setting, when AWS is mild and there is no risk for worsening, AWS can be managed with supportive care or with either benzodiazepines, gabapentin, or carbamazepine as monotherapy. ASAM recommends long-­acting benzodiazepines (eg, chlordiazepoxide or diazepam) over short-acting benzodiazepines (eg, alprazolam or lorazepam), except in the elderly and those with liver or lung disease.⁵

Editor’s takeaway

Dozens of small trials and meta-analyses confirm the benefits (sometimes marginal) of sedation to treat alcohol withdrawal. Given that the evidence fails to point to the superiority of 1 agent over another, it seems reasonable to make treatment decisions based on physician and perhaps patient preference. This review does not support a change in clinical practice.