Desipramine relieves postherpetic neuralgia

Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressant agents, but its pain-relieving potential has received little study. Other antidepressant agents--notably amitriptyline--are known to ameliorate postherpetic neuralgia, but those agents are often toxic. In a randomized double-blind crossover design, we gave 26 postherpetic neuralgia patients 6 weeks of treatment with desipramine (mean dose, 167 mg/day) and placebo. Nineteen patients completed both treatments; 12 reported at least moderate relief with desipramine and two reported relief with placebo. Pain relief with desipramine was statistically significant from weeks 3 to 6. Psychiatric interview at entry into the study produced a diagnosis of depression for 4 patients; pain relief was similar in depressed and nondepressed patients and was statistically significant in the nondepressed group alone. We conclude that desipramine administration relieves postherpetic neuralgia and that pain relief is not mediated by mood elevation. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressant agents that have relieved neuropathic pain, may be involved in relief of postherpetic neuralgia.     

Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review

To determine the relative efficacy and adverse effects of antidepressants and anticonvulsants in the treatment of diabetic neuropathy and postherpetic neuralgia, published reports were identified from a variety of electronic databases, including Medline, EMBASE, the Cochrane Library and the Oxford Pain Relief Database, and from two previously published reviews. Additional studies were identified from the reference lists of retrieved reports. The relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief was calculated from available dichotomous data, as was the relative risk (RR) and number-needed-to-harm (NNH) for minor adverse effects and drug related study withdrawal. In diabetic neuropathy, 16 reports compared antidepressants with placebo (491 patient episodes) and three compared anticonvulsants with placebo (321). The NNT for at least 50% pain relief with antidepressants was 3.4 (95% confidence interval 2.6–4.7) and with anticonvulsants 2.7 (2.2–3.8). In postherpetic neuralgia, three reports compared antidepressants with placebo (145 patient episodes) and one compared anticonvulsants with placebo (225), giving an NNT with antidepressants of 2.1 (1.7–3) and with anticonvulsants 3.2 (2.4–5). There was little difference in the incidence of minor adverse effects with either antidepressants or anticonvulsants compared with placebo, with NNH (minor) values of about 3. For drug-related study withdrawal, antidepressants had an NNH (major) of 17 (11–43) compared with placebo, whereas with anticonvulsants there was no significant difference from placebo. Antidepressants and anticonvulsants had the same efficacy and incidence of minor adverse effects in these two neuropathic pain conditions. There was no evidence that selective serotonin reuptake inhibitors (SSRIs) were better than older antidepressants, and no evidence that gabapentin was better than older anticonvulsants. In these trials patients were more likely to stop taking antidepressants than anticonvulsants because of adverse effects.     

A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy

An 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy.     

Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study

To evaluate the efficacy and safety of 6 weeks of venlafaxine extended-release (ER) (75 mg and 150–225 mg) treatment in patients with painful diabetic neuropathy. This multicenter, double-blind, randomized, placebo-controlled study included 244 adult outpatients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy. Primary efficacy measures were scores on the daily 100 mm Visual Analog Pain Intensity (VAS-PI) and Pain Relief (VAS-PR) scales. Secondary efficacy measures included the Clinical Global Impressions–Severity of Illness and the Clinical Global Impressions–Improvement, Patient Global Rating of Pain Relief, and percentage of patients achieving 50% reduction in pain intensity. Baseline pain intensity was 68.7 mm (moderately severe). At week 6, the percentage reduction from baseline in VAS-PI was 27% (placebo), 32% (75 mg), and 50% (150–225 mg; P<0.001 vs placebo). Mean VAS-PR scores in the 150–225 mg group were significantly greater than placebo at week 6 (44 vs 60 mm; P<0.001). The number needed to treat (NNT) for 50% pain intensity reduction with venlafaxine ER 150–225 mg was 4.5 at week 6. Nausea and somnolence were the most common treatment-emergent adverse events. Seven patients on venlafaxine had clinically important ECG changes during treatment. Venlafaxine ER appears effective and safe in relieving pain associated with diabetic neuropathy. NNT values for higher dose venlafaxine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin.     

Treatment of neuropathic pain with venlafaxine

OBJECTIVE: To report a case of successful treatment of neuropathic pain with venlafaxine. CASE REPORT: A 39-year-old white woman presented with neuropathic back pain. The patient obtained 50% pain relief with consecutive use of amitriptyline, desipramine, and imipramine. Anticholinergic effects prompted a switch to extended-release venlafaxine 75 mg/d. Pain relief was as effective with this therapy as with the tricyclic antidepressants. The absence of adverse effects allowed the patient to discontinue all laxatives. DISCUSSION: Venlafaxine is an antidepressant that inhibits reuptake of norepinephrine and serotonin. This is the major mechanism by which tricyclic antidepressants relieve neuropathic pain. Venlafaxine does not bind to muscarinic-cholinergic, histaminic or alpha1-adrenergic receptors responsible for the common adverse effects seen with tricyclic antidepressants. CONCLUSIONS: This report describes the efficacious use of venlafaxine in the treatment of neuropathic pain. Double-blind, randomized, controlled trials are needed to explore this further.     

A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: a randomized, double-blind, cross-over clinical trial

OBJECTIVE

To compare the efficacy and safety of duloxetine and amitriptyline in painful diabetic neuropathy (PDN).

RESEARCH DESIGN AND METHODS

In this randomized, double-blind, cross-over, active-control trial, 58 patients received amitriptyline and duloxetine orally once daily at bedtime, each for 6 weeks with optional dose uptitration fortnightly. Single-blinded placebo washout was given for 2 weeks between the two treatments and a single-blinded placebo run-out phase of 4 weeks was given at the end of the treatment period. Pain relief was measured by the patient’s global assessment of efficacy, using a visual analog scale (0–100) as a primary end point, and overall improvement and adverse events were assessed as secondary outcome measures. Median pain score reductions of >50%, 25–50%, and <25% were considered good, moderate, and mild responses, respectively.

RESULTS

There was a significant improvement in pain with both treatments compared with their baseline values (P < 0.001 for both). Good, moderate, and mild pain relief was achieved in 55, 24, and 15% of patients, respectively, on amitriptyline and 59, 21, and 9% of patients, respectively, on duloxetine. There were no significant differences in various other outcome measures between the groups. Of the reported adverse events, dry mouth was significantly more common with amitriptyline than duloxetine (55 vs. 24%; P < 0.01). Although, numerically, more patients preferred duloxetine, overall this was not statistically significant (48 vs. 36%; P = 0.18).

CONCLUSIONS

Both duloxetine and amitriptyline demonstrated similar efficacy in PDN. A large, multicentric clinical trial in other populations could possibly demonstrate the superiority of either drug.The management of painful diabetic neuropathy (PDN) includes intensive glycemic control and drugs for pain relief. The American Diabetes Association recommends amitriptyline, a tricyclic antidepressant, as the first choice; however, titration to higher doses is limited by its anticholinergic adverse effects (1). The selective serotonin norepinephrine reuptake inhibitor, duloxetine, is approved by the Food and Drug Administration for the treatment of PDN. It attenuates persistent pain mechanisms, including the central sensitization and hyperexcitability of the spinal and supraspinal pain-transmitting pathways. Duloxetine has been evaluated in placebo-controlled trials for a variety of chronic pain, including PDN (2–6). It not only relieves pain but also improves functionality and quality of life in patients with PDN. An extensive search of literature did not reveal any head-to-head comparison of duloxetine with amitriptyline, an established first-line therapy for PDN (1). Thus, the current study was planned to compare the efficacy and safety of duloxetine with amitriptyline in PDN.     

Treatment response in antidepressant-na?ve postherpetic neuralgia patients: double-blind, randomized trial.

In 47 patients with postherpetic neuralgia (PHN) who had never had an adequate trial of any antidepressant, we performed a randomized, double-blind, parallel design trial comparing desipramine, amitriptyline, and fluoxetine. Patients were titrated to a maximum of 150 mg/day for desipramine and amitriptyline and 60 mg/day for fluoxetine over a 3-week period and then treated for an additional 3 weeks before tapering off study medication. A total of 38 subjects (81%) completed the entire trial. The modified intent-to-treat analysis of percent change in daily diary pain intensity scores showed no significant differences among the 3 drugs (ANOVA P = .120). Desipramine produced the greatest reduction in pain intensity (47%), followed by amitriptyline (38%) and fluoxetine (35%). Clinically meaningful pain relief (moderate or better) was significantly more likely with desipramine (12/15 patients) than with amitriptyline (9/17) or fluoxetine (5/15); chi(2)P = 0.036). The 11 subjects using opioids at study entry had smaller reductions in pain than those not using concomitant opioids. The fluoxetine group had the highest noncompletion rate (33%), with 1 subject hospitalized for hyponatremia. Although the magnitude of pain reduction and the category pain relief rating was not significantly different among the 3 drugs, the tricyclics desipramine and amitriptyline were well tolerated and provided clinically meaningful pain relief in 53% to 80% of subjects. PERSPECTIVE: Few clinical trials focus on patients who are na?ve to an entire class of medication. In this randomized blinded trial, the tricyclic antidepressants desipramine and amitriptyline were compared to the serotonin-selective antidepressant fluoxetine. All 3 drugs reduced PHN pain, with desipramine providing satisfactory relief in 80% of those treated.     

Sodium valproate for painful diabetic neuropathy: a randomized double-blind placebo-controlled study

BACKGROUND: Various drugs are effective in the management of painful diabetic neuropathy, but none is completely satisfactory. We previously found sodium valproate to be effective and safe in a short-term study. AIM: To test the effectiveness and safety of sodium valproate in the management of painful diabetic neuropathy over 3 months. DESIGN: Randomized double-blind placebo-controlled study. METHODS: Consecutive attending patients with type 2 diabetes mellitus with painful neuropathy were asked to participate in the trial: 48 agreed. Five were excluded: three with HbA(1c) > 11, one with too low a pain level and one who withdrew consent. The remaining 43 were given either drug (group A) or placebo (group B). Each patient was assessed clinically. Quantitative assessment of pain was done by McGill Pain Questionnaire, Visual Analogue Score and Present Pain Intensity, at the beginning of the study, after 1 month and after 3 months. Motor and sensory nerve conduction velocities were measured initially and after 3 months. Liver function tests and other adverse drug-related effects were assessed periodically. RESULTS: Of the 43 patients, four dropped out: one in group A and three in group B. There was significant improvement in pain score in group A, compared to group B, at 3 months (p < 0.001). Changes in electrophysiological data were not significant. The drug was well-tolerated by all patients, except one, who had raised serum AST and ALT levels after 1 month of treatment, and whose treatment was discontinued. DISCUSSION: Sodium valproate is well-tolerated, and provides significant subjective improvement in painful diabetic neuropathy.     

Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two-stage ‘enriched enrollment’ design

Because a variety of mechanisms may generate pain in neuropathic pain syndromes, conventional clinical trial methods may fail to identify some potentially useful drugs; a drug affecting just a single mechanism may work in too few patients to yield a statistically significant result for the trial. To test a previous clinical observation that approximately one-quarter of patients with painful diabetic neuropathy appear responsive to clonidine, we conducted a formal clinical trial of transdermal clonidine in painful diabetic neuropathy patients using a 2-stage enriched enrollment design. In the first stage (study I), 41 patients with painful diabetic neuropathy completed a randomized, 3-period crossover comparison of transdermal clonidine (titrated from 0.1 to 0.3 mg/day) to placebo patches. Twelve apparent responders from study I were entered into the ‘enriched enrollment’ second stage (study II), consisting of an additional 4 double-blind, randomized, 1-week treatment periods with transdermal clonidine and placebo. Study I showed that in the overall group of 41 patients, pain intensity differed little during clonidine and placebo treatment. In study II, however, the 12 apparent responders from study I had 20% less pain with clonidine than placebo (95% confidence interval (CI): 4–35% pain reduction; P = 0.015), confirming that their pain was responsive to clonidine. None of the 3 consistent clonidine responders who were tested with the -adrenergic blocker phentolamine had relief of pain, suggesting that clonidine's pain relief is not mediated by a decrease in sympathetic outflow. A post-hoc analysis of many variables suggested that patients who described their pain as sharp and shooting may have a greater likelihood of responding to clonidine. The results of this study support the hypothesis that there is a subset of patients with painful diabetic neuropathy who benefit from systemic clonidine administration and illustrate the value of an enriched enrollment technique in analgesic trials.     

Topical amitriptyline versus lidocaine in the treatment of neuropathic pain

OBJECTIVE: Oral amitriptyline, a tricyclic antidepressant, is effective for treating neuropathic pain. We conducted a double-blind, randomized, placebo-controlled crossover study to evaluate the efficacy of topical 5% amitriptyline and 5% lidocaine in treating patients with neuropathic pain. METHODS: Thirty-five patients with postsurgical neuropathic pain, postherpetic neuralgia, or diabetic neuropathy with allodynia or hyperalgesia were assigned to receive 3 topical creams (5% amitriptyline, 5% lidocaine, or placebo) in random sequence. The primary outcome measure was change in pain intensity (baseline vs. posttreatment average pain) using a 0 to 100 mm Visual Analog Scale. Secondary outcome measures included the McGill Pain Questionnaire, requirement for rescue medication, and patient satisfaction. Primary statistical comparisons were made with paired t tests or signed-rank tests. RESULTS: A reduction in pain intensity was observed with topical lidocaine (P<0.05). No significant change in pain intensity was found with topical amitriptyline or placebo. In pairwise comparison of treatments, topical lidocaine and placebo each reduced pain more than topical amitriptyline (P<0.05). DISCUSSION: This randomized, placebo-controlled crossover study examining topical 5% amitriptyline and 5% lidocaine in the treatment of neuropathic pain showed that topical lidocaine reduced pain intensity but the clinical improvement is minimal and that topical 5% amitriptyline was not effective.     

Sodium Channel Blockade May Contribute to the Analgesic Efficacy of Antidepressants

Sodium channel blockers such as lidocaine, lamotrigine, and carbamazepine can be effective in the treatment of neuropathic pain. Though not approved for neuropathic pain indications, tricyclic antidepressants are often considered first-line treatment for conditions such as post-herpetic neuralgia and diabetic neuropathy. Several tricyclic antidepressants have been shown to block peripheral nerve sodium channels, which may contribute to their antihyperalgesic efficacy. In this study, we compared the sodium channel–blocking potency of a number of antidepressants, including tricyclic antidepressants and selective serotonin reuptake inhibitors. All compounds tested inhibited Na_V1.7 in a state- and use-dependent manner, with affinities for the inactivated state ranging from 0.24 μmol/L for amitriptyline to 11.6 μmol/L for zimelidine. The tricyclic antidepressants were more potent blockers of Na_V1.7. Moreover, IC₅₀s for block of the inactivated state for amitriptyline, nortriptyline, imipramine, desipramine, and maprotiline were in the range of therapeutic plasma concentrations for both the treatment of depression as well as neuropathic pain. By contrast, fluoxetine, paroxetine, mianserine, and zimelidine had IC₅₀s for Na_V1.7 outside their therapeutic concentration ranges and generally were not efficacious against post-herpetic neuralgia or diabetic neuropathy. These results suggest that block of peripheral nerve sodium channels may contribute to the antihyperalgesic efficacy of certain antidepressants.PerspectiveTricyclic antidepressants are often considered first-line treatment for neuropathic pain. Some tricyclic antidepressants block sodium channels, which may contribute to their antihyperalgesic efficacy. In the current study, we compared the potency of peripheral sodium channel blockade for several tricyclic antidepressants and selective serotonin reuptake inhibitors with their therapeutic efficacy.     

Lacosamide in painful diabetic peripheral neuropathy: a phase 2 double-blind placebo-controlled study

BACKGROUND: Peripheral diabetic neuropathy affects between 20% and 45% of patients with diabetes. OBJECTIVE: To ascertain the effect of lacosamide on pain associated with peripheral diabetic neuropathy. METHODS: One hundred nineteen patients with a 1 to 5-year history of pain attributed to diabetic neuropathy and a score of > or =4 on the Likert pain scale entered the multicenter, randomized, double-blind, placebo-controlled trial. Lacosamide (N=60) titrated from 100 to 400 mg/d or maximum tolerated dose and placebo (N=59) were the trial interventions. Primary efficacy criterion was change in pain score on the 11-point Likert pain scale. Secondary assessments included Short-Form McGill Pain and Short-Form-36 Quality of Life Questionnaires, sleep/activity interference, pain intensity, Patient and Clinical Global Impression of Change, and Profile of Mood. Patients receiving at least 1 dose of medication underwent safety evaluation. RESULTS: Ninety-four patients (lacosamide 46; placebo 48) completed the trial. Lacosamide had significantly (P=0.039) better pain relief versus placebo (primary outcome). Improvements were also seen in secondary outcome measures. Adverse events occurred in 52 lacosamide and 44 placebo patients. Common adverse events, occurring in > or =5% of patients, were headache (lacosamide 18%, placebo 22%), dizziness (lacosamide 15%, placebo 8%), and nausea (lacosamide 12%, placebo 7%). Five lacosamide and 3 placebo patients withdrew for adverse events. DISCUSSION: Lacosamide seems to attenuate pain in diabetic neuropathy in doses up to 400 mg/d and improves quality of life issues.     

Pathophysiology and treatment of painful diabetic neuropathy

Diabetes is the most common cause of peripheral neuropathy, and painful diabetic neuropathy (PDN) affects approximately 30% of diabetic patients with neuropathy. It is extremely distressing for the patient and poses significant management difficulties because no treatment provides total relief, and side effects of therapy are a major limiting factor for titrating therapy. Understanding the pathogenesis of diabetic neuropathy may lead to the development of new treatments to prevent nerve damage, and a better understanding of the mechanisms that modulate pain may lead to more effective relief of painful symptoms. We provide an update on the pathogenesis, diagnosis, and treatment of PDN.     

18. Painful Diabetic Polyneuropathy

In the industrialized world, polyneuropathy induced by diabetes mellitus (DM) is one of the most prevalent forms of neuropathy. Diabetic neuropathy can result from a direct toxic effect of glucose on nerve cells. Additionally, the damage of the nerve structures (central and peripheral) is accompanied by a microvascular dysfunction, which damages the vasa nervorum. More than 80% of the patients with DM‐induced polyneuropathy have a distal and symmetric presentation. The initial symptoms are: signs of diminished sensation, burning feet, which may occur particularly during the night and worsen when touched, and tingling sensation in the feet. Attacks of shooting pain may also occur. Proper control of DM is mandatory. Based on the recently published National Institute for Health and Clinical Excellence guidelines, treatment of painful diabetic neuropathy should start with duloxetine or amitriptyline if duloxetine is contraindicated. If pain relief is inadequate, monotherapy with amitriptyline or pregabalin, or combination therapy with amitriptyline and pregabalin should be considered. If pain relief is still insufficient, tramadol instead of or in combination with a second‐line agent should be considered. In patients who are unable to take oral medication, topical lidocaine can be considered for localized pain. There are currently four studies showing that spinal cord stimulation can potentially provide pain alleviation for the longer term in patients with painful diabetic polyneuropathy. Complications are mainly implant related, though infections also occur. The available evidence (2 C+) justifies spinal cord stimulation to be considered, preferably study related.     

Effects of a single oral dose of desipramine on postoperative morphine analgesia

Drugs that block norepinephrine reuptake offer promise as opioid potentiators, because norepinephrine mediates opioid analgesia but not side effects such as sedation or nausea. In a two-by-two factorial design, we randomized 62 inpatients with pain following major surgery to receive either desipramine, 50 mg by mouth, or placebo at 6 a.m. on the first day after surgery. At their first request of pain medication after 8 a.m., they were given intravenous morphine, either 0.033 mg/kg or 0.10 mg/kg. Pain relief and side effects were assessed for 4 hr; peak relief on the visual analog scale (VAS) was the primary outcome variable. Pain relief, side effect scores, and time to remedication were significantly greater with the higher dose than with the lower dose of morphine, verifying assay sensitivity, but desipramine pretreatment did not significantly enhance morphine analgesia. The mean increase in peak VAS relief score after desipramine pretreatment, relative to placebo, was 6%; the 95% confidence interval for this estimate ranged from a 21% reduction to a 34% increase in pain relief. These results differ from a previous report that 1 week of pretreatment with desipramine, 75 mg per day, potentiated postoperative morphine analgesia. We conclude that if desipramine potentiation of opioid analgesia occurs in humans, its demonstration may require higher doses or chronic treatment.     

Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial.

This was a 6-week, randomized, double-blind, multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy. Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo. The primary efficacy variable was mean pain score at the end of treatment. Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 (vs 5.6 for placebo, P = .0002) and increased the proportion of patients who had a > or =50% decrease from baseline pain (39% vs 15% for placebo, P = .002). Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and bodily pain and decreased by > or =50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing-cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. Pregabalin 150 mg/day was essentially no different from placebo. Dizziness was the most common side effect. These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy. PERSPECTIVE: Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome. This randomized controlled trial demonstrates that pregabalin, a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel, is an efficacious and safe treatment for the pain of this condition.     

A Randomized Clinical Trial of the Effectiveness of Photon Stimulation on Pain,Sensation, and Quality of Life in Patients With Diabetic Peripheral Neuropathy

ContextPeripheral neuropathy is one of the most common complications of diabetes.ObjectivesThe purpose of this study was to evaluate the effects of photon stimulation on pain intensity, pain relief, pain qualities, sensation and quality of life (QOL) in patients with painful diabetic peripheral neuropathy.MethodsIn this randomized, placebo-controlled trial, patients were assigned to receive either four photon stimulations (n = 63) or four placebo (n = 58) treatments. Pain intensity, pain relief, and pain qualities were assessed using self-report questionnaires. Sensation was evaluated using monofilament testing. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36). Multilevel regression model analyses were used to evaluate between-group differences in study outcomes.ResultsNo differences, over time, in any pain intensity scores (i.e., pain intensity immediately post-treatment, average pain, worst pain) or pain relief scores were found between the placebo and treatment groups. However, significant decreases, over time, were found in some pain quality scores, and significant improvements in sensation were found in patients who received the photon stimulation compared with placebo. In addition, patients in the treatment group reported significant improvements in SF-36 social functioning and mental health scores. Findings from a responder analysis demonstrated that no differences were found in the percentages of patients in the placebo and treatment groups who received 30% or more or 50% or more reduction in pain scores immediately post-treatment. However, significant differences were found in the distribution of the changes in pain relief scores, with most of the patients in the photon stimulation group reporting a slight (28.6%) to moderate (34.9%) improvement in pain relief from the beginning to the end of the study compared with no change in pain relief (43.1%) in the placebo group.ConclusionFour treatments with photon stimulation resulted in significant improvements in some pain qualities, sensation, and QOL outcomes in a sample of patients with a significant amount of pain and disability from their diabetes. A longer duration study is needed to further refine the photon stimulation treatment protocol in these chronically ill patients and to evaluate the sustainability of its effects.     

Injected morphine in postoperative pain: a quantitative systematic review

This systematic review of single-dose, placebo-controlled, randomized trials assessed pain relief from subcutaneous, intramuscular or intravenous morphine compared with placebo in postoperative pain. Pain relief or pain intensity difference over 4 to 6 hours was extracted and converted into the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and the number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. In 15 trials, comparing intramuscular morphine 10 mg (486 patients) with placebo (460 patients) morphine had an NNT of 2.9 (95% confidence interval 2.6-3.6). This meant that one of every three patients with moderate or severe postoperative pain treated with 10 mg intramuscular morphine had at least 50% pain relief, and would not have achieved this had they been given placebo. Minor adverse effects were more common with morphine (34%) than with placebo (23%) (relative risk 1.49 [1.09-2.04]), but drug related study withdrawal was rare (1.2% overall) and no different from placebo.     

Evidence for the use of gabapentin in the treatment of diabetic peripheral neuropathy

BACKGROUND: One of the most common peripheral nerve complications of diabetes is painful diabetic peripheral neuropathy (DPN). Although tricyclic antidepressants (TCAs) have traditionally been used to relieve the pain of this condition, gabapentin's reported efficacy in various neuropathic pain states and its favorable side-effect profile compared with other available agents have led to interest in the use of this agent for the treatment of DPN. OBJECTIVES: This paper reviews the current clinical literature on the effectiveness and tolerability of gabapentin in the treatment of DPN. It also considers whether the evidence favors gabapentin's use as an alternative or first-line agent. METHODS: A search of the English- and French-language literature for the years 1990 through 2000 was performed using MEDLINE, Current Contents/Clinical Medicine, and International Pharmaceutical Abstracts, plus the reference lists of the articles identified through this search. The search terms used were gabapentin, anticonvulsant, diabetic peripheral neuropathy, and neuropathy. Included studies were limited to trials in human subjects. RESULTS: The literature search identified several case reports and case series, as well as 3 small placebo-controlled studies (2 complete, 1 brief report) and 1 comparative trial against the TCA amitriptyline. The designs and dosing regimens differed between studies. CONCLUSIONS: Many clinicians consider gabapentin an alternative treatment option in patients with DPN who are unable to tolerate traditional agents or in whom traditional agents are contraindicated. To date, gabapentin has been well tolerated, superior to placebo, and equivalent to amitriptyline in small clinical trials of short duration. Although overall efficacy and safety profiles appear to be favorable, larger long-term studies are needed to determine the place of gabapentin in relation to other treatment options. There is currently insufficient evidence from controlled trials to support the use of gabapentin as first-line therapy for DPN.