This review evaluates the use of antidepressants in older patients for the treatment of nonspecific chronic lower back pain (LBP), emphasizing age-related physiological changes and common degenerative conditions in this age group. We conducted a comprehensive search targeting studies on antidepressant use in older patients with LBP. Selective serotonin reuptake inhibitors, while effective for mood regulation, show limited benefits for LBP. Serotonin-norepinephrine reuptake inhibitors, particularly duloxetine, demonstrate potential in managing LBP, though further research is needed to confirm these findings. Tricyclic antidepressants have shown potential for pain relief, with limited evidence for LBP, but have a substantial side effect profile, including cardiotoxicity, weight gain, and severe anticholinergic effects. The evidence for trazodone in the treatment of LBP is limited. When prescribing new medications for older adults, it is crucial to carefully consider the patient's overall health, potential drug interactions, and sensitivity to side effects, ensuring that the benefits of treatment outweigh the risks. This review underscores the need for further research to understand the long-term effects and benefits of antidepressants in older patients with LBP, aiming to balance pain relief, mood stabilization, and minimized side effects.

This study investigated the tolerability and preliminary efficacy of duloxetine as an alternative nonopioid therapeutic option for the prevention of persistent musculoskeletal pain (MSP) among adults presenting to the emergency department with acute MSP after trauma or injury. In this randomized, double-blind, placebo-controlled study, eligible participants (n = 78) were randomized to 2 weeks of a daily dose of one of the following: placebo (n = 27), 30 mg duloxetine (n = 24), or 60 mg duloxetine (n = 27). Tolerability, the primary outcome, was measured by dropout rate and adverse effects. Secondary outcomes assessed drug efficacy as measured by (1) the proportion of participants with moderate to severe pain (numerical rating scale ≥ 4) at 6 weeks (pain persistence); and (2) average pain by group over the six-week study period. We also explored treatment effects by type of trauma (motor vehicle collision [MVC] vs non-MVC). In both intervention groups, duloxetine was well tolerated and there were no serious adverse events. There was a statistically significant difference in pain over time for the 60 mg vs placebo group ( P = 0.03) but not for the 30 mg vs placebo group ( P = 0.51). In both types of analyses, the size of the effect of duloxetine was larger in MVC vs non-MVC injury. Consistent with the role of stress systems in the development of chronic pain after traumatic stress, our data indicate duloxetine may be a treatment option for reducing the transition from acute to persistent MSP. Larger randomized controlled trials are needed to confirm these promising results.

Denmark has a high consumption of prescribed opioids, and many citizens with chronic non-cancer pain (CNCP). Therefore, we aimed to characterize and assess epidemiological risk factors associated with long-term non-cancer opioid use among Danish citizens.

We conducted a longitudinal, retrospective, observational, register-based study using nationwide databases containing essential medical, healthcare, and socio-economic information. Statistical analysis, including backward stepwise logistic regression analysis, was used to explain long-term opioid use by individuals filling at least one prescription for an opioid product N02AA01-N02AX06 during 01/01/2004-31/12/2017, follow-up until the end of 2018.

The analyzed cohort contained N=1,683,713 non-cancer opioid users, of which 979,666 were classified with CNCP diagnosis using ICD-10 codes. Long-term opioid use was predicted by a mean of 1,583.30 and a median of 300 oral morphine equivalent mg (OMEQ) per day during the first year, together with divorced, age group 40-53 years, retirement, receiving social welfare or unemployment ≥6 months. In addition, living in Northern Jutland, co-medications such as beta-blockers, anti-diabetics, anti-rheumatics, and minor surgery ≤90 days before inclusion. Protective variables were an education level of secondary school or higher, children living at home, household income of middle or highest tertile, opioid doses in either the 2nd or 3rd quartile OMEQ, male, the oldest age group, living in the Capital Region or Zealand, co-medication lipid-lowering, one comorbidity, heart failure, surgeries ≤90 days before the index: lips/teeth/jaw/mouth/throat, heart/vessels, elbow/forearm, hip/thigh, knee/lower leg/ankle/foot.

Long-term opioid users differ epidemiologically from those using opioids for a shorter period. The study findings are essential for future recommendations revision in Denmark and comparable countries.

We estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. We also consider the effect of the perceived abuse potential of the medication on these variables.

This study uses the Citeline database to compute the probabilities of success, duration, and survivorship of pain medication development programs between January 1, 2000, and June 30, 2020, conditioned on the phase, type of pain (nociceptive vs. neuropathic), and the abuse potential of the medication.

The overall probability of successful development of all pain medications from phase 1 to approval is 10.4% (standard error (SE) of 1.5%). Medications to treat nociceptive and neuropathic pain have a probability of successful development of 13.1% (SE: 2.3%) and 7.1% (SE: 1.9%), respectively. The probability of successful development of medications with high abuse potential and low abuse potential are 27.8% (SE: 4.6%) and 4.7% (SE: 1.2%), respectively. The most common period for attrition is between phase 3 and approval.

Our data suggest that the unique attributes of pain medications, such as their abuse potential and intended pathology, can influence the probability of successful development and duration of development.

Chronic musculoskeletal pain affects a substantial portion of adults visiting the emergency department (ED). Current treatment is limited in scope and does not effectively reduce musculoskeletal pain in patients. The study will evaluate the use of duloxetine, a serotonin-norepinephrine reuptake inhibitor Food and Drug Administration approved for the treatment of chronic pain, as a promising option in its prevention. The proposed study may present a well-tolerated and effective non-opioid treatment for patients with acute musculoskeletal pain that may also be effective in preventing the transition to persistent or chronic musculoskeletal pain.

The primary outcome of this study will be to assess the tolerability and preliminary effectiveness of duloxetine in patients with acute musculoskeletal pain. The study will take place at two EDs in Rhode Island, USA. The study will involve randomisation to one of three arms: duloxetine 30 mg, duloxetine 60 mg or placebo. Tolerability will be assessed by comparing the proportion of participants that report an adverse event and that drop-out across the three study arms. Effectiveness will be determined by self-reported pain over 6 weeks of follow-up. Specifically, we will compare the proportion of participants with persistent pain (ongoing pain at 6-week follow-up), across the three study arms. 60 adults (aged 18-59) presenting to the ED with acute axial musculoskeletal pain within 7 days of onset are expected to be enrolled in the proposed study.

Ethics approval was obtained by the Institutional Review Board (IRB). These results will be published in a peer reviewed scientific journal and presented at one or more scientific conferences.

NCT03315533.

Back pain treatments are costly and frequently involve use of procedures that may have minimal benefit on improving patients' functional status. Two recent studies evaluated adverse outcomes (mortality and major medical complications) following receipt of spinal surgery but neither examined whether such treatments affected functional ability. Using a sample composed of Medicare patients with persistent back pain, we examined whether functional ability improved after treatment, comparing patients treated with back surgery or spinal injections to nonrecipients. We analyzed four binary variables that measure whether the ability to perform routine tasks improved. We used instrumental variables analysis to address the nonrandom selection of treatment received due to unobservable confounding. Contrary to the observational results, the instrumental variable estimates suggest that receipt of either back surgery or spinal injections does not improve back patients' functional ability. Failure to account for selection into treatment can lead to overestimating the benefits of specific treatments.

The paradoxical development of chronic abdominal pain is an underrecognized side effect of opioid use. Narcotic bowel syndrome (NBS), occurring in a small proportion of chronic opioid users, consists of chronic or intermittent abdominal pain, which often increases in severity despite continued or escalating dosages of opioids prescribed to relieve pain.

A PubMed search was conducted using terms such as "narcotic bowel syndrome" and "opioid hyperalgesia" through January 2014.

Abdominal pain is the defining symptom of NBS and is thought to be mediated by central nervous system dysfunction; it should be distinguished from the peripheral side effects of opioids, such as nausea, bloating, intermittent vomiting, abdominal distension, and constipation. This latter cluster of symptoms is called opioid bowel dysfunction, although it may co-occur with NBS. Hypothesized mechanisms of the central effects of opioids on nociception in NBS include spinal cord inflammation and dysfunction in opioid receptor activity and related neuroanatomical substrates. With continued use, ∼6% of patients taking narcotics chronically will develop NBS, with profound consequences in terms of daily function. The primary management paradigm for NBS is a structured opioid withdrawal program accompanied by centrally acting adjunctive therapy comprising antidepressants, benzodiazepines, and clonidine to target pain, anxiety, and depression, and prevent withdrawal effects, in addition to peripherally acting agents such as laxatives (e.g., osmotic laxatives and chloride channel activators) to control transient constipation. Such structured withdrawal programs have been prospectively evaluated in small clinical trials and have met with considerable success in the short term.

Because rates of NBS are likely to rise, integrated intensive pharmacotherapy and psychosocial interventions are needed to help patients with NBS go off and stay off opioids. These programs will likely also reduce comorbid psychopathology and lead to adequate pain control and improved quality of life.

Pain-related depression of behavior and mood is a key therapeutic target in the treatment of pain. Clinical evidence suggests a role for decreased dopamine (DA) signaling in pain-related depression of behavior and mood. Similarly, in rats, intraperitoneal injection of dilute lactic acid (IP acid) serves as a chemical noxious stimulus to produce analgesic-reversible decreases in both (1) extracellular DA levels in nucleus accumbens (NAc) and (2) intracranial self-stimulation (ICSS), an operant behavior reliant on NAc DA. Intraperitonial acid-induced depression of ICSS is blocked by DA transporter (DAT) inhibitors, but clinical viability of selective DAT inhibitors as analgesics is limited by abuse potential. Drugs that produce combined inhibition of both DA and serotonin transporters may retain efficacy to block pain-related behavioral depression with reduced abuse liability. Amitifadine is a "triple uptake inhibitor" that inhibits DAT with approximately 5- to 10-fold weaker potency than it inhibits serotonin and norepinephrine transporters. This study compared amitifadine effects on IP acid-induced depression of NAc DA and ICSS and IP acid-stimulated stretching in male Sprague-Dawley rats. Amitifadine blocked IP acid-induced depression of both NAc DA and ICSS and IP acid-stimulated stretching. In the absence of the noxious stimulus, amitifadine increased NAc levels of both DA and serotonin, and behaviorally, amitifadine produced significant but weak abuse-related ICSS facilitation. Moreover, amitifadine was more potent to block IP acid-induced depression of ICSS than to facilitate control ICSS. These results support consideration of amitifadine and related monoamine uptake inhibitors as candidate analgesics for treatment of pain-related behavioral depression.

Veterans have high rates of chronic pain and long-term opioid therapy (LTOT). Understanding predictors of discontinuation from LTOT will clarify the risks for prolonged opioid use and dependence among this population. All veterans with at least 90 days of opioid use within a 180-day period were identified using national Veteran's Health Affairs (VHA) data between 2009 and 2011. Discontinuation was defined as 6 months with no opioid prescriptions. We used Cox proportional hazards analysis to determine clinical and demographic correlates for discontinuation. A total of 550,616 veterans met criteria for LTOT. The sample was primarily male (93%) and white (74%), with a mean age of 57.8 years. The median daily morphine equivalent dose was 26 mg, and 7% received high-dose (>100mg MED) therapy. At 1 year after initiation, 7.5% (n=41,197) of the LTOT sample had discontinued opioids. Among those who discontinued (20%, n=108,601), the median time to discontinuation was 317 days. Factors significantly associated with discontinuation included both younger and older age, lower average dosage, and having received less than 90 days of opioids in the previous year. Although tobacco use disorders decreased the likelihood of discontinuation, co-morbid mental illness and substance use disorders increased the likelihood of discontinuation. LTOT is common in the VHA system and is marked by extended duration of use at relatively low daily doses with few discontinuation events. Opioid discontinuation is more likely in veterans with mental health and substance use disorders. Further research is needed to delineate causes and consequences of opioid discontinuation.

Prescription opioid use for chronic non-cancer pain has reached epidemic levels in the USA. With this increased use is the recognition of serious opioid-related gastrointestinal complications such as narcotic bowel syndrome (NBS) and opioid-induced constipation (OIC). NBS consists of a paradoxical worsening of abdominal pain with escalating doses of opioids and is likely mediated by the central nervous system. Therapy requires an intensive multidisciplinary approach to detoxification. OIC is the most common gastrointestinal side effect of opioids. Several novel therapeutics are available to treat OIC that fails to respond to laxative therapy. This review will summarize recent findings on the pathophysiology and treatment approaches to NBS and OIC with a focus on controversies about diagnosis and intervention.