Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold.

OBJECTIVE: To report two cases of interaction between fluvoxamine and mirtazapine. CASE SUMMARY: A 17-year-old boy was treated with mirtazapine 30 mg/d. The addition of fluvoxamine 100 mg/d to the regimen caused a threefold increase in the mirtazapine concentration. This interaction was associated with increased anxiety. A second patient, a 43-year-old woman, was treated with mirtazapine 15 mg/d. There was a fourfold increase in her mirtazapine concentration and simultaneous mood improvements after augmentation with fluvoxamine 50 mg/d. DISCUSSION: This is the first report of any interaction between fluvoxamine and mirtazapine. Mirtazapine is mainly metabolized by cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4. Fluvoxamine and cimetidine Inhibit the same isoenzymes, but fluvoxamine is probably the only agent that causes a clinically significant interaction. CONCLUSIONS: Adding fluvoxamine to treatment with mirtazapine may cause a significant increase in mirtazapine concentration. This interaction may necessitate adjustment of the mirtazapine dosage.     

Atypical antipsychotic-induced akathisia with depression: therapeutic role of mirtazapine

OBJECTIVE: To investigate the efficacy of mirtazapine in treating akathisia caused by risperidone and olanzapine, as well as its use in alleviating comorbid depressive disorder. CASE SUMMARIES: Five patients with diagnoses varying from schizophrenia, delusional disorder, and bipolar disorder developed akathisia while on treatment with olanzapine and risperidone. The likelihood that risperidone and olanzapine had induced akathisia in all patients was rated probable according to the Naranjo probability scale. Four of these patients were also found to be depressed. The akathisia was successfully treated with mirtazapine, and 3 of the 4 depressed patients improved with mirtazapine treatment. Use of mirtazapine did not result in any adverse effect. DISCUSSION: Mirtazapine is a potent antagonist of central alpha(2) auto- and hetero-adrenergic receptors, as well as an antagonist of 5-HT(2A/2C), 5-HT(3), and histaminergic H(1) postsynaptic receptors. The efficacy of mirtazapine in treatment of akathisia may result from its antagonist property at the H(1) receptors and its dopaminergic activity in frontal cortex. The use of mirtazapine offers advantages over other anti-akathisia drugs in its better adverse effect profile, as well as its ability to treat coexisting depression. CONCLUSIONS: Mirtazapine is efficacious in treating atypical antipsychotic-induced akathisia. It may be a good option, particularly in patients with coexisting depression.     

Pulsed Radiofrequency Ablation for Residual and Phantom Limb Pain: A Case Series

Residual limb pain (RLP) and phantom limb pain (PLP) can be debilitating and can prevent functional gains following amputation. High correlations have been reported between RLP and the stump neuromas following amputation. Many treatment methods including physical therapy, medications, and interventions, have been used with limited success. Pulsed radiofrequency ablation (PRFA) has shown promise in treating neuropathic pain because of the inhibition of evoked synaptic activity. We present 4 amputees who were treated with PRFA after failing conservative management for their RLP and PLP. All 4 patients underwent PRFA and demonstrated at least 80% relief of RLP for over 6 months. One patient reported a complete resolution of phantom sensation while another patient had significantly decreased frequency of spontaneous PLP and resolution of evoked PLP. In addition, all patients reported improved overall function including increased prosthetic tolerance and decreased oral pain medications. This case series suggests that PRFA is a viable treatment option which might be used for long‐term relief of intractable RLP and/or PLP.     

Safety and Efficacy of Percutaneous Neuromodulation Therapy in the Management of Subacute Radiating Low Back Pain

Objective: Percutaneous neuromodulation therapy (PNT) is a new minimally invasive, office‐based treatment for low back pain in which electrical stimulation is delivered to the paraspinal peripheral nerves. The purpose of this study was to determine the safety, tolerability, and clinical efficacy of PNT in a population of patients with subacute low back pain with radiation to the lower extremity. Design: Open label prospective clinical trial. Setting: Multi‐center outpatient setting. Participants: We enrolled 83 patients who had radiating low back pain for 4 weeks to 6 months with a pain intensity of at least 4 on a visual analog scale of 0–10. Interventions: Subjects were treated with PNT 1 to 2 times per week for at least 4 weeks. Based on clinical response patients were treated up to an additional 8 weeks. Main Outcome Measures: We recorded baseline visual analog scale (VAS) scores of radiating pain, low back pain, physical activity, and sleep, as well as the Oswestry Disability Questionnaire. Follow‐up assessments were performed at each session, and at 5 and 12 weeks. Patients benefiting from treatments at 12 weeks were followed‐up at 6 months. Results: Fifty‐nine patients completed the study protocol. Mean VAS scores improved as follows: leg/buttock pain decreased by 37% to 4.0 ± 2.6 from a baseline of 6.6 ± 1.7 (P < 0.001); low back pain decreased by 26% to 3.9 ± 2.4 from a baseline of 5.5 ± 2.2 (P < 0.001); activity levels improved by 38% to 3.6 ± 2.2 from a baseline of 6.0 ± 2.2 (P < 0.001); and sleep improved by 27% to 3.1 ± 2.5 from a baseline of 4.8 ± 3.0 (P < 0.001). The Oswestry Low Back Pain Disability scores improved by 24% to 32 ± 16 from a baseline of 43 ± 15 (P < 0.001). Pain relief was sustained over a 3‐month observation period. Conclusion: For many patients with subacute radiating low back pain, PNT significantly reduced pain and self‐rated disability, and improved sleep quality and activity level. PNT is safe and generally well tolerated.     

Treatment of Phantom Limb Pain by Cryoneurolysis of the Amputated Nerve

The pathophysiology of phantom limb pain (PLP) is multifactorial. It probably starts in the periphery and is amplified and modified in the central nervous system. A small group of patients with PLP were questioned as to the portion of the phantom limb affected by pain (eg, “great toe,” “thumb”). In the stump, the corresponding amputated nerve was located with a nerve stimulator. With correct placement and stimulation, the PLP could then be reproduced or exacerbated. A small dose of local anesthesia was then injected, resulting in the disappearance of the PLP. If a peripheral nerve injection gave temporary relief, our final treatment was cryoanalgesia at this location. Evaluation of 5 patients, followed for at least 2.5 years, yielded the following results: 3 patients had excellent results (100%, 95%, and 90% decrease in complaints, respectively), 1 patient had an acceptable result (40% decrease), and 1 patient had only a 20% decrease in pain. Although both central and peripheral components are likely involved in PLP, treatment of a peripheral pain locus with cryoanalgesia should be considered. We propose the identification of a peripheral etiology may help match patients to an appropriate therapy, and cryoanalgesia may result in long‐term relief of PLP.     

Treatment of Ischemic Pain in Patients Suffering from Peripheral Vasculopathy with Transdermal Buprenorphine Plus Epidural Morphine with Ropivacaine vs. Epidural Morphine with Ropivacaine

Aim:   This study compared the efficacy and safety of buprenorphine transdermal delivery system with peridural infusion of morphine and ropivacaine to peridural infusion alone for the control of ischemic pain in patients suffering from peripheral vasculopathy.
Methods:   Eighty-six patients were randomized into two groups. In the first group, a buprenorphine patch 35 µg/hour TTDS (transtec transdermal device plus ropivacaine and morphine) was applied, and a peridural infusion of ropivacaine/morphine (200 mg + 2 mg) was established. In the second group, ropivacaine and morphine analgesia was obtained using a peridural infusion and a placebo patch. The primary efficacy parameter was the visual analog scale score for pain. Secondary parameters of efficacy were the short-form McGill Pain Questionnaire scores and a score for pain interference with sleep obtained from patient diaries evaluated every week for a period of 4 weeks.
Results:   Subjects in the TTDS group reported a reduction in pain, increased sleep, and a lower incidence of side effects compared with the control group.
Conclusion:   Transdermal buprenorphine use resulted in significant pain relief with excellent patient satisfaction, which may translate into improvement in mood and quality of life.     

Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial

Aims: Prominent anxiety symptoms are related to poor clinical course and outcome in major depressive disorder (MDD). The aim of this randomised, open‐label, controlled study is to compare the efficacy and tolerability of mirtazapine in the form of orally disintegrating tablets against paroxetine in treating MDD patients with anxiety symptoms. Methods: A total of 60 MDD patients with a score above 18 on the Hamilton Anxiety Rating Scale (HARS) were randomly assigned to 8 weeks of fixed dosing treatment with mirtazapine (15–30 mg/day) and paroxetine (10–20 mg/day). Efficacy was primarily assessed with the HARS and with the 17‐item Hamilton Depression Rating Scale (HDRS) at weeks 1, 2, 4 and 8 after treatment. Tolerability was assessed from adverse events. Results: The generalised estimating equations (GEE) models showed that the rates of improvement in HDRS scores from baseline to week 8 were similar between mirtazapine and paroxetine groups. However, patients with mirtazapine exhibited earlier improvement in HARS scores at weeks 1 and 2. Week‐by‐week GEE models showed that these significant differences in improvement of HARS scores between the two treatment groups were detectable from the first evaluation after the treatment (week 1) and maintained through week 2. There was no difference in the overall frequency of adverse events experienced between the two treatment groups. The most common adverse event in the mirtazapine group was somnolence (n = 8), whereas that in the paroxetine group was gastrointestinal discomfort (n = 9). Conclusions: Mirtazapine and paroxetine were equally effective and well tolerated for the depressive symptoms in MDD patients with the high level of anxiety symptoms. Mirtazapine was, however, more effective in reducing the anxiety symptoms than paroxetine in the early weeks of treatment, suggesting that mirtazapine may have an earlier‐onset action for the anxiety symptoms in MDD patients.     

Efficacy of the NMDA-receptor antagonist memantine in patients with chronic phantom limb pain--results of a randomized double-blinded,placebo-controlled trial

Phantom limb pain (PLP) associated neuroplastic changes are partly mediated by excitatory amino acids at NMDA receptor sites. This study was undertaken to deduce if NMDA-receptor antagonists may be effective in patients with chronic PLP. Therefore a four week double-blinded, randomized placebo-controlled trial was performed to evaluate the efficacy of 30 mg memantine/day, an orally administrable NMDA receptor antagonist.Thirty-six patients, 18 per group, with a history of at least 12 months PLP and an average pain of at least 4 on the 11-point numeric rating scale (NRS) were enrolled. The patients completed a standardized questionnaire before the trial. PLP intensity and the level of eight complaints were assessed during the trial. Number needed to treat (NNT) was calculated based on the average PLP during the 3rd week (steady state). In both groups, PLP declined significantly in comparison with the baseline (verum: 5.1 (+/-2.1) to 3,8 (+/-2,3), placebo from 5.1 (+/-2.0) to 3.2 (+/-1,46) NRS) without a re-rising of the PLP during the washout period. Mean pain relief was 47% in the memantine group (10 patients reported more than 50% relief), 40% in the placebo group (6>50%): NNT were 4.5 (KI: 2.1-10.6). Analysis of covariance demonstrated a significant impact only on the prior PLP intensity, but no treatment effect. Two patients have demonstrated long-term pain relief under memantine until now (16 months). The total number of slight adverse events were comparable in both groups, but the overall number of severe events was higher in the memantine group (P<0.05). This trial failed to demonstrate a significant clinical benefit of the NMDA-receptor antagonist memantine in chronic PLP. The administration of a higher dosage is probably not tolerable.     

Self‐reported sleep duration associated with distraction analgesia,hyperemia, and secondary hyperalgesia in the heat‐capsaicin nociceptive model

Although sleep deprivation is known to heighten pain sensitivity, the mechanisms by which sleep modifies nociception are largely unknown. Few studies of sleep—pain interactions have utilized quantitative sensory testing models that implicate specific underlying physiologic mechanisms. One possibility, which is beginning to receive attention, is that differences in sleep may alter the analgesic effects of distraction. We utilized the heat‐capsaicin nociceptive model to examine whether self‐reported habitual sleep duration is associated with distraction analgesia, the degree of secondary hyperalgesia and skin flare, markers implicating both central and peripheral processes that heighten pain. Twenty‐eight healthy participants completed three experimental sessions in a randomized within subjects design. In the pain only condition, pain was induced for approximately 70‐min via application of heat and capsaicin to the dorsum of the non‐dominant hand. Verbal pain ratings were obtained at regular intervals. In the distraction condition, identical procedures were followed, but during heat‐capsaicin pain, subjects played a series of video games. The third session involved assessing performance on the video games (no capsaicin). Participants indicated their normal self‐reported habitual sleep duration over the past month. Individuals who slept less than 6.5 h/night in the month prior to the study experienced significantly less behavioral analgesia, increased skin flare and augmented secondary hyperalgesia. These findings suggest that reduced sleep time is associated with diminished analgesic benefits from distraction and/or individuals obtaining less sleep have a reduced ability to disengage from pain‐related sensations. The secondary hyperalgesia finding may implicate central involvement, whereas enhanced skin flare response suggests that sleep duration may also impact peripheral inflammatory mechanisms.     

An open-label,crossover trial of mirtazapine (15 and 30 mg) in cancer patients with pain and other distressing symptoms

We performed a pilot open-label, crossover trial of mirtazapine (15 and 30 mg at night) in advanced cancer patients with pain and other distressing symptoms. Twenty patients completed the trial and sixteen dropped out. Following a baseline assessment, patients completed a one-week observation period and were then randomized to a starting dose of either 15 mg or 30 mg of mirtazapine given at bedtime. After three weeks, subjects were switched to the alternate dose and followed by an additional three-week period, completing the treatment. The average age of the completers was 60.2 years and consisted of 7 women and 13 men. The majority were Caucasian (n = 18, 90%) and married (n = 18, 90%). The drop-out group did not significantly differ from the completers based on age, gender, race, marital status, or tumor type. We examined the impact of mirtazapine therapy on patients' levels of depression, pain intensity, appetite, insomnia, weight, and overall quality of life. A series of repeated measures ANOVAs were conducted to compare the completers' status at Weeks 1, 4, and 7 compared to baseline and to examine the interaction with starting dose and baseline observations. Scores on the Zung self-rating Depression Scale (F = 8.20, P < 0.05) and the Functional Assessment of Cancer Therapy - General Measure (F = 5.73, P < 0.05) were significantly improved at study end (Week 7) and were not dependent on mirtazapine dosage. Patients' weights were significantly higher at both Week 4 and Week 7, independent of dosage. Trend level differences were found on Memorial Pain Assessment Card items for pain, pain relief, and mood and on numeric rating scales measuring nausea, anxiety, insomnia, and appetite. This open-label pilot study suggests that mirtazapine may be effective for improving multiple symptoms, depression and quality of life in patients with advanced cancer. A controlled trial of this drug would be valuable.     

Cannabis use for chronic non-cancer pain: results of a prospective survey

There has been a surge in interest in medicinal cannabis in Canada. We conducted a questionnaire survey to determine the current prevalence of medicinal cannabis use among patients with chronic non-cancer pain, to estimate the dose size and frequency of cannabis use, and to describe the main symptoms for which relief was being sought. Over a 6-week period in mid-2001, 209 chronic non-cancer pain patients were recruited in an anonymous cross-sectional survey. Seventy-two (35%) subjects reported ever having used cannabis. Thirty-two (15%) subjects reported having used cannabis for pain relief (pain users), and 20 (10%) subjects were currently using cannabis for pain relief. Thirty-eight subjects denied using cannabis for pain relief (recreational users). Compared to never users, pain users were significantly younger (P=0.001) and were more likely to be tobacco users (P=0.0001). The largest group of patients using cannabis had pain caused by trauma and/or surgery (51%), and the site of pain was predominantly neck/upper body and myofascial (68% and 65%, respectively). The median duration of pain was similar in both pain users and recreational users (8 vs. 7 years; P=0.7). There was a wide range of amounts and frequency of cannabis use. Of the 32 subjects who used cannabis for pain, 17 (53%) used four puffs or less at each dosing interval, eight (25%) smoked a whole cannabis cigarette (joint) and four (12%) smoked more than one joint. Seven (22%) of these subjects used cannabis more than once daily, five (16%) used it daily, eight (25%) used it weekly and nine (28%) used it rarely. Pain, sleep and mood were most frequently reported as improving with cannabis use, and 'high' and dry mouth were the most commonly reported side effects. We conclude that cannabis use is prevalent among the chronic non-cancer pain population, for a wide range of symptoms, with considerable variability in the amounts used. Discussions between patients and health care providers concerning cannabis use may facilitate education and follow up, and would allow side effects and potential interactions with other medications to be monitored. Clinical trials of cannabis for chronic non-cancer pain are warranted.     

Pharmacokinetics of mirtazapine: enantioselective effects of the CYP2D6 ultra rapid metabolizer genotype and correlation with adverse effects

Enantiomerically pure drugs and genotyping are promising approaches to achieve optimization in antidepressant therapy. Mirtazapine is a mixed noradrenergic serotoninergic antidepressant used as a racemate. We analyzed pharmacokinetics of its enantiomers in relation to CYP2D6 genotype and in relation to its adverse effects. Mirtazapine was enantioselectively absorbed from the gut with a rate constant of 0.2 min-1 for S+, but 0.08 min-1 for R- mirtazapine. Kinetics of R- mirtazapine was only marginally dependent on CYP2D6 genotype, but total clearance of the S+ enantiomer were 1.3, 2.3, and 3.4 L min-1 in poor, extensive, and ultrarapid metabolizers of CYP2D6 substrates with apparent substantial first-pass metabolism in rapid and ultrarapid metabolizers. Mirtazapine effects on heart rate and blood pressure correlated much more strongly with R- then with S+ concentrations, whereas sedation correlated similarly with both enantiomers. At least concerning some adverse effects, it might be worthwhile to study further mirtazapine enantiospecifically.     

Self-reported sleep quality and quality of life for individuals with chronic pain conditions

OBJECTIVE: To determine the sleep quality and quality of life for individuals with degenerative spinal disease or failed back surgery syndrome. DESIGN: Cross-sectional survey design utilizing standardized instruments. Data were analyzed with use of hierarchical stepwise multiple regression analyses. PATIENTS: One hundred sixty-seven individuals with degenerative spinal disease or postlaminectomy syndrome who presented to a tertiary care outpatient patient pain center. OUTCOME MEASURES: The Center for Epidemiological Studies Depression Index measured depressive symptomatology. A modified Pittsburgh Sleep Quality Index (PSQI) measured sleep quality. The arithmetic average of least and usual VAS ratings of pain measured everyday pain. A visual analog scale rating of highest pain during the past 2 weeks measured highest pain. The Epworth Sleepiness Scale measured daytime sleepiness. The Medical Outcome Study-Short Form-Health Survey (SF-36) measured the mental health and general health components of quality of life. RESULTS: Higher overall sleep quality and lower sleep latency primarily were related to higher ratings of physical functioning and shorter duration of pain. Ratings of the highest pain, but not everyday pain, were independent predictors of overall sleep quality and sleep latency. Daytime sleepiness was associated with younger age and depressed mood. Pain was not associated independently with daytime sleepiness. The quality of life related to mental functioning was associated positively with depressed mood and with the interaction of pain and depressed mood. None of the variables in the model (i.e., pain intensity, sleep quality, depression, and demographic variables) predicted quality of life related to overall general health. CONCLUSIONS: These data suggest that physical functioning, duration of pain, and age may be more important than pain intensity and depressed mood in contributing to decreased overall sleep quality and sleep latency. The contribution of physical functioning was particularly strong and should be included in subsequent studies of sleep, pain, and mood. The SF-36 should be compared to pain-specific quality-of-life measures to further evaluate the usefulness of this instrument with outpatients with chronic nonmalignant pain conditions.     

Sustained sleep restriction reduces emotional and physical well-being

BACKGROUND: Chronic insufficient sleep is a common finding in many pain-related and other medical diseases and is frequently experienced in the general population. Prolonged curtailment of nocturnal sleep has been studied for its adverse effect on cognitive functioning and subjective tiredness, but relatively little is known about its effect on mood and physical symptoms. OBJECTIVE: In order to test whether sleep restriction to 50% of the habitual time over 12 days affects diurnal and day-to-day variation of subjective ratings of mood and physical symptoms, 108 adjectives and statements were self-rated using visual analog scales every 2h during the waking period. DESIGN: Randomized, 16-day controlled in-laboratory study. SETTING: General Clinical Research Center (GCRC). PARTICIPANTS: Forty healthy subjects aged 21-40 years (14 females, 26 males). INTERVENTION: Subjects were randomized to either 4h of sleep per night (11 pm-3 am, N=22) or 8h of sleep per night (11 pm-7 am, N=18) for 12 consecutive days. Main Outcome Measure: Changes in the factor-derived variables optimism-sociability, tiredness-fatigue, anger-aggression, bodily discomfort, and items constituting bodily discomfort were compared between groups. RESULTS: Optimism-sociability progressively declined over consecutive days of sleep restriction by 15%. Bodily discomfort showed a slight, but significant interindividual increase of 3% across days of sleep restriction due to significant increases of generalized body pain, back pain, and stomach pain. Optimism-sociability and tiredness-fatigue showed diurnal variations with a quadratic function period within each day in both conditions. CONCLUSION: The data suggest that chronic insufficient sleep may contribute to the onset and amplification of pain and affect health by compromising optimistic outlook and psychosocial functioning.     

Das 8 %ige Capsaicin-Pflaster bei Phantomschmerz

Background

Post amputation pain presents a challenge for pain physicians and is often detrimental to the patient’s quality of life.

Patients and methods

A prospective 12-week non-interventional study (NIS) was conducted in Germany to obtain data on the effectiveness and safety of capsaicin 8?% cutaneous patches from real life use in patients with peripheral neuropathic pain. For the first time in a subgroup of amputees data on post amputation pain were collected. This article presents the results for patients who suffered from phantom limb pain (PLP), stump pain (SP) and combined phantom limb/stump pain (PLP/SP).

Results

The analyses included 21 patients with post amputation pain (PLP: n?=?10, SP: n?=?4, PLP/SP: n?=?7). The mean duration of pain (± standard deviation) was 12.8?±?13.0 years for PLP, 23.1?±?29.9 years for SP and 11.0?±?15.8 years for PLP/SP. A single treatment with capsaicin 8?% cutaneous patches significantly reduced the average pain intensity over the observational period of 12 weeks. The mean numeric pain rating scale (NPRS) baseline score changed by ??2.4 for PLP with a standard error of the mean (SEM) of 0.4 (median: ??2.9, Q1: ??3.5, Q3: ??1.0), ??1.7 for SP (SEM: 0.8, median: ??1.1, Q1: ??2.9, Q3: ??0.5) and ??1.5 for PLP/SP (SEM: 0.6, median: ??2.0, Q1: ??2.3, Q3: 0) during weeks 1–12. The 30 % responder rates (i.e. ≥?30?% reduction in pain, day 7/14 to week 12) were 70.0?% (PLP), 50.0?% (SP) and 28.6?% (PLP/SP). PLP and PLP/SP patients in particular, benefited from improvements in pain attacks, sleep duration and sleep quality and one patient (PLP/SP) reported an adverse drug reaction (increase of pain). Physicians rated the tolerability of the patch as very good or good in 90.5?% of patients. A poor tolerability was stated for none of the 21 amputees. Of the patients 80 % for PLP and 50?% for both SP and PLP/SP expressed the wish to receive retreatment with capsaicin 8?% patches.

Conclusion

Capsaicin 8?% cutaneous patches seem to be effective and safe for the treatment of post amputation pain, notably in patients suffering from phantom limb pain.     

A Randomized,Prospective Study of Efficacy and Safety of Oral Tramadol in the Management of Post‐Herpetic Neuralgia in Patients from North India

Objective: To evaluate the safety and efficacy of oral tramadol therapy (50 to 200 mg/day) in the treatment for post‐herpetic neuralgia (PHN). Methods: The study was a prospective, single‐blind, non‐responder vs. responder, randomized trial conducted in 100 outpatients of PHN after oral administration of tramadol for 4 weeks. Those patients who had achieved 50% or greater pain relief after 14 days of oral tramadol treatment were categorized as responders and those reporting < 50% pain relief were categorized as non‐responders. Rescue analgesia was provided by the topical application of a cream consisting of the combination of 3.33% doxepin and 0.05% capsaicin to the affected areas of PHN patients of both groups for at least 14 days, along with tramadol therapy. The rescue analgesia was extended to 4 weeks in patients of the non‐responder group. The primary endpoints were measured using a Numerical Rating Scale (NRS) at rest and with movement. Secondary endpoints included additional pain ratings such as global perceived effect (GPE), Neuropathic Pain Symptom Inventory scores (NPSI), daily sleep interference score (DSIS), Quality of life (QOL) as per WHO QOL‐BREF Questionnaire scores, patient and clinician ratings of global improvement. The 2 groups were compared on the basis of pain intensity scores, encompassing primary as well as secondary endpoints, and QOL after 28 days of the treatment regimen. Results: Pain intensity scores measured by NRS (at resting and with movement), NPSI, and DSIS were consistently reduced (P < 0.001) over 28 days at varying intervals in both the groups, but the magnitude of reduction was higher in responders than non‐responders. A concomitant improvement (P < 0.001) was observed in GPE on days 3, 14, and 28 as compared to the respective baseline scores in both the groups. Although the WHO QOL‐BREF scores showed significant (P < 0.001) improvement in QOL of PHN patients at days 14 and 28 in both the groups, the magnitude of improvement was higher in responders as compared to non‐responders. Significant improvement in pain intensity scores and QOL in non‐responders is mainly attributed to the use of rescue analgesia for 28 days rather than recommended tramadol therapy. Conclusions: Treatment with tramadol 50 to 200 mg per day was associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side‐effect profile, and improved QOL in PHN patients from North India. Further categorization of PHN patients may be helpful so that additional or alternative therapy may be prescribed to non‐responders.     

Which variables are associated with pain intensity and treatment response in advanced cancer patients?— Implications for a future classification system for cancer pain

Background: This study is part of a research program to reach consensus on an international cancer pain classification system. A confirmative and explorative approach was applied to investigate which of the variables identified in the literature, by experts and patients that are associated with pain. Methods: Data from an international, multicentre, cross‐sectional study of cancer patients treated with opioids were investigated. Dependent variables were: average pain, worst pain, and pain relief (11‐point Numerical Rating Scales). Forty‐six independent variables were chosen based upon previous studies. Bivariate analyses identified independent variables associated with at least one of the dependent ones; 21 were included in multivariate linear regression analyses. Results: Two thousand two hundred and seventy‐eight patients were investigated; 52% males, mean age 62 years, mean Karnofsky Performance Status 59%, mean daily opioid oral equivalent dose 341 mg. Fifty‐eight percent had breakthrough pain. Mean pain scores were: average pain 3.5, worst pain 5.3 and pain relief 74%. Variables most strongly associated with these three dependent variables were: breakthrough pain, psychological distress, sleep, and opioid dose. Conclusions: Breakthrough pain and psychological distress were confirmed as key variables of a future classification system. Candidate variables were: sleep, opioid dose, pain mechanism, use of non‐opioids, pain localisation, cancer diagnosis, location of metastases, and addiction.     

Effectiveness of a selected bedding system on quality of sleep, low back pain, shoulder pain, and spine stiffness

OBJECTIVE: To determine whether clinical and statistically significant changes in back pain, shoulder pain, spine stiffness, and quality of sleep may be documented after use of a prescribed bedding system. DESIGN: Quasi-experimental field study of single group pretest-posttest design with subjects serving as their own controls. SETTING: Two chiropractic clinics and the Oklahoma State University Program of Health and Human Performance. SUBJECTS: Convenience sample of 22 subjects (women, n = 13; men, n = 9) between the ages of 25 and 75 years with documented disturbed sleep, shoulder pain, low back pain, and spine stiffness of a chronic nature. OUTCOME MEASURES: Pretest and posttest 28-day Visual Analog Scales for pain, spine stiffness, and quality of sleep. MAIN RESULTS: The experimental bedding system reduced back pain by 57.21% (P =.000001), reduced shoulder pain by 60.83% (P =.000005), reduced back stiffness by 59.12% (P =.000004), and improved quality of sleep by 60.73% (P =.000001). CONCLUSIONS: Results suggest that subjects obtain significant improvement in shoulder and back pain, back stiffness, and quality of sleep after 28 days of prescribed bedding system use as compared with 28 days of personal bedding use. Female subjects and those with lower body weight were more likely to significantly improve than heavier and more obese subjects.     

Mirtazapine for treatment of depression and comorbidities in Alzheimer disease

BACKGROUND: Depression in patients with Alzheimer disease is a treatable cause of functional decline, caregiver burden, and mortality. It is often associated with severe weight loss, insomnia, and anxiety. These symptoms independently and collaboratively further worsen the prognosis of these vulnerable patients. An antidepressant medication with good adverse effect profile and salutary effects on these comorbid symptoms may be of significant therapeutic value in these patients. OBJECTIVE: To describe the role of mirtazapine in the treatment of depressed Alzheimer patients with comorbid weight loss, insomnia, and anxiety. CASE SUMMARY: Three patients with dementia and depression complicated by weight loss, insomnia, and anxiety were treated with mirtazapine at an outpatient memory loss clinic of a university hospital. DISCUSSION: Despite the persistence of memory loss, the patients experienced a prompt and sustained response to mirtazapine. There was a complete remission of poor appetite, weight loss, sleep disturbances, and anxiety. Other depression symptoms, including sad mood, anhedonia, and energy level, were also substantially improved. CONCLUSIONS: The clinical response of our patients underscores the usefulness of mirtazapine in the treatment of the comorbid symptoms of weight loss, insomnia, and anxiety. The effectiveness of mirtazapine in depressed Alzheimer patents may be a reflection of its enhancement of brain serotonergic and noradrenergic neurotransmission. The usefulness of mirtazapine in depressed Alzheimer patients merits further study in a large randomized, controlled, clinically comparative trial.