Impact of the World Health Organization Pain Treatment Guidelines and the European Medicines Agency Safety Recommendations on Nonsteroidal Anti-Inflammatory Drug Use in Lithuania: An Observational Study.

Background and objective: Irrational use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the main cause of adverse effects-associated hospitalizations among all medication groups leading to extremely increased costs for health care. Pharmacoepidemiological studies can partly reveal such issues and encourage further decisions. Therefore, the aim of our study was to evaluate the utilization of non-opioid analgesics (ATC classification N02B and M01A) in Lithuania, and to compare it with that of other Baltic and Scandinavian countries in terms of compliance to the WHO pain treatment guidelines and the EMA safety recommendations on NSAID use. Materials and methods: The dispensing data were obtained from the sales analysis software provider in the Baltic countries (SoftDent, Ltd., Kaunas, Lithuania); State Medicine Control Agencies of Lithuania, Latvia, and Estonia; Norwegian Prescription Database; Swedish Database for Medicines; and Danish Prescription Database. Data included the utilization of both prescription and over-the-counter drugs. Utilization was expressed in defined daily doses (DDD)/1000 inhabitants/day. Results: During the 11-year period, the utilization of drugs belonging to the N02B and M01A groups increased by 22.8%, from 58.37 in 2005 to 71.68 DDD/1000 inhabitants/day in 2016 in Lithuania. Contrary to the WHO guidelines on pain management, all Baltic countries were more likely to use NSAIDs than other analgesics and antipyretics: in 2015, the drugs of the M01A group were used 6.04, 5.79, and 6.11 times more than those of N02B in Lithuania, Estonia, and Latvia, respectively, whereas the Scandinavian countries preferred the N02B to the M01A group: in Denmark and Sweden, the utilization of other analgesics and antipyretics was 2.33 and 1.24, respectively, times higher than that of NSAIDs. In Norway, the use of both groups was similar. In the Scandinavian countries, paracetamol was the analgesic of first choice, whereas, in Lithuania, it took only the third place. The most popular drug in Lithuania was diclofenac, and its utilization accounted for 30.04% of all non-opioid analgesics in 2016. Although the European Medicines Agency (EMA) restricted the use of certain NSAIDs, i.e., cyclooxygenase-2 (COX-2) inhibitors, nimesulide, and diclofenac, their use consistently increased by 15.91, 2.83, and 1.41 times, respectively, showing incompliance with the international guidelines. Conclusions: Neither the EMA safety policy on NSAID use nor the WHO pain treatment guidelines had a sufficient impact on the rational use of NSAIDs in Lithuania. The use of NSAIDs restricted by the EMA (diclofenac, COX-2 inhibitors, nimesulide, and piroxicam) remains high or even increases, while the utilization of safer alternatives (paracetamol and naproxen) remains relatively low as compared with the Scandinavian countries. Incompliance with international guidelines may result in increased morbidity, mortality and higher costs for health care.

Barriers to cancer pain management in Danish and Lithuanian patients treated in pain and palliative care units.

The prevalence of cancer-related pain is high despite available guidelines for the effective assessment and management of that pain. Barriers to the use of opioid analgesics partially cause undertreatment of cancer pain. The aim of this study was to compare pain management outcomes and patient-related barriers to cancer pain management in patient samples from Denmark and Lithuania. Thirty-three Danish and 30 Lithuanian patients responded to, respectively, Danish and Lithuanian versions of the Brief Pain Inventory pain scale, the Barriers Questionnaire II, the Hospital Anxiety and Depression Scale, the Specific Questionnaire On Pain Communication, and the Medication Adherence Report Scale. Emotional distress and patient attitudes toward opioid analgesics in cancer patient samples from both countries explained pain management outcomes in the multivariate regression models. Pain relief and pain medication adherence were better in Denmark, and the country of origin significantly explained the difference in the regression models for these outcomes. In conclusion, interventions in emotional distress and patient attitudes toward opioid analgesics may result in better pain management outcomes generally, whereas poor adherence to pain medication and poor pain relief appear to be more country-specific problems.

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain.

Neuropathic pain is a debilitating condition characterized by abnormal signaling within the nervous system, resulting in persistent and often intense sensations of pain. It can arise from various causes, including traumatic nerve injury, neuropathy, and certain diseases. We present an overview of current and emerging pharmacotherapies for neuropathic pain, focusing on novel drug targets and potential therapeutic agents. Current pharmacotherapies, including tricyclic antidepressants, gabapentinoids, and serotonin norepinephrine re-uptake inhibitors, are discussed, as are emerging treatments, such as ambroxol, cannabidiol, and N-acetyl-L-cysteine. Additionally, the article highlights the need for further research in this field to identify new targets and develop more effective and targeted therapies for neuropathic pain management.

Associations between chronic pain and depressive symptoms in patients with trigeminal neuralgia.

UNLABELLED: Trigeminal neuralgia (TN) is a rare neuropathic disorder with an excruciating facial pain. The unpredictable pain attacks may result in anxiety and depression. The aim of this study was to determine and to evaluate the level of chronic facial pain and its association with the appearance of anxiety and depression. MATERIALS AND METHODS: A total of 30 patients with TN and chronic facial pain (group A, 25 women and 5 men; mean age, 64.2±3.2 years) and 30 with atypical facial pain (group B, 26 women and 4 men; mean age, 64.8±1.9 years) were examined. A standardized diagnostic protocol was applied to all of them, which consisted of the following: 1) demographic data and estimation of overall pain on a visual analog scale; and 2) evaluation of emotional status using the Sheehan Disability Scale, Covi's Anxiety Scale, and Beck Depression Inventory. RESULTS: The intensity of facial pain was much higher in the group A than the group B (89.7±2.5 versus 44.0±2.9, P<0.0001). Besides, the group A reported increased scores on the disability and anxiety symptom scales (17.4±1.3 and 9.7±0.3 vs. 6.4±0.7 and 3.6±0.1, respectively, P<0.0001). Severe (46.7%) or moderate (30%) levels of depression were documented in the majority of patients in the group A, while the group B did not show depressive symptoms (P<0.0001). CONCLUSIONS: Patients with TN and chronic facial pain had a significantly higher level of pain perception, and they presented the higher level for anxiety and depression than those with atypical facial pain. A multidisciplinary approach is needed for the additional assessment of emotional status of patients in order to improve the efficacy of treatment and patients' quality of life.

Importance of pain evaluation for more accurate diagnosis of painful diabetic polyneuropathy.

UNLABELLED: Pain is a common problem in diabetic neuropathy, but relatively little has been published regarding the extent to which it needs to be addressed in clinical practice. OBJECTIVE: To assess neuropathic pain profile and its association with quantitative sensory testing in painful diabetic polyneuropathy. MATERIAL AND METHODS: Altogether, 61 consecutive diabetic inpatients with symmetric neuropathic complaints were enrolled. Clinical neurological examination and quantitative sensory testing (QST) were performed. Patients were interviewed using the Neuropathic Pain Scale (NPS) and filled in the McGill Pain Questionnaire (MPQ). RESULTS: Of all patients, 49 (80.3%) had clinical diabetic polyneuropathy. Only 17 of these patients complained of lower extremity pain on an initial interview, while 27 marked it in the MPQ. The intensity of deep and superficial pain did not differ, but patients rated deep pain as more unpleasant than superficial (6.27±2.37 vs. 4.30±1.42 on the NPS, P=0.034). Superficial pain NPS items tended to correlate with QST results, while deep pain items did not. Only female gender (OR=7.87) and lower glycosylated hemoglobin level (OR=0.65) were predictive of pain in case of diabetic neuropathy. CONCLUSIONS: Standard pain questionnaires were useful in identifying pain sufferers. At the same intensity, deep neuropathic pain was more unpleasant than superficial. Pain manifestation was associated with female gender and lower level of glycosylated hemoglobin.

Barriers to pain management among Lithuanian cancer patients.

OBJECTIVES: The objectives of this study are (1) to describe Lithuanian cancer patients' barriers to pain management as well as pain management outcomes, (2) to check the reliability and validity of the questionnaires used in Lithuanian for the first time, and (3) to formulate patient-centered recommendations for better cancer pain management. METHODS: Thirty patients from the Pain Clinic of Kaunas University of Medicine Hospital responded to the Lithuanian versions of: (1) Brief Pain Inventory pain scale, (2) Barriers Questionnaire-II, (3) Hospital Anxiety and Depression Scale, (4) Modified version of the Perceived Involvement in Care Scale, and (5) Medication Adherence Report Scale. RESULTS: The translated questionnaires had fear internal consistency reliability and construct validity. Reported average (standard deviation [SD]) pain intensity among Lithuanian cancer patients was 3.9 (1.30) on a scale 0-10. The mean (SD) scores of anxiety and depression among the surveyed patients were 8.7 (4.86) and 7.5 (5.05) on a scale 0-21, respectively. The percentage of the patients, who reported stopping taking pain medicine because of its side effects, was 33.3%. The biggest patients' concerns were about physiological consequences and harmful effects of opioid use. The average (SD) level of perceived communication among Lithuanian patients was 3.1 (0.95) on a scale 0-5, whereas the average level (SD) of self-reported adherence to pain medication among Lithuanians was 13.0 (3.65) on a scale 4-20. CONCLUSIONS: The authors believe, that to improve cancer pain management in Lithuania (1) more attention should be paid to psychological status of patients, (2) patients should be more educated about the need and consequences of opioid use for cancer pain, and (3) adherence to pain management regimens should be improved.