Critical Summaries of Innovations in Palliative Care Pharmacotherapy

ABSTRACT

Timely and important studies are reviewed and commentaries provided by leading palliative care clinicians. Symptoms, interventions, and treatment-related adverse events addressed in this issue are: the effect of sorafenib on sarcopenia; defining, classifying, and assessing cancer breakthrough pain; treatment of opioid-dependent human immunodeficiency virus (HIV) patients (clinic-based versus referred treatment); the predictors and course of depression in metastatic cancer patients; and the effectiveness of treatment agreements and urine analysis for reducing opioid misuse in outpatients with chronic noncancer pain.     

FLUOXETINE ALTERS MU OPIOID RECEPTOR EXPRESSION IN OBESE ZUCKER RAT EXTRAHYPOTHALAMIC REGIONS

The aim of this article was to describe the effects of chronic fluoxetine on mu opioid receptor expression in obese Zucker rat extrahypothalamic regions. Male obese Zucker (fa/fa) rats were administered with fluoxetine (10 mg/kg; i.p.) daily for two weeks. Brain regional immunostaining for mu opioid receptor was carried out. An increase in the numbers of neural cells immunostained for mu opioid receptor in caudatus-putamen, dentate gyrus, lateral septum, amygdala, and frontal, parietal, and piriform cortices was observed. Increased mu opioid receptor expression in the central amygdaloid nuclei suggests a decreased opioidergic tone at this level that could be involved in fluoxetine anorectic action.     

A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

Background:

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT).

Methods:

Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect.

Results:

After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different.

Conclusions:

We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT.     

The use of opioids for treatment of cancer pain

Introduction: Pain is commonly experienced by patients with cancer, particularly those with advanced disease. Alleviating pain is an important goal of cancer treatment. Opioids are the cornerstone of the analgesic treatment.

Areas covered: Pharmacology, characteristics, and use of opioids in clinical practice are presented.

Expert opinion: Although the use of opioids is largely accepted as a fundamental step for controlling cancer pain, existing data supporting this statement are poor. All opioids provide analgesia and are effective in controlling cancer pain. New drugs have been developed and experience is accumulating among clinicians. Despite these drugs having different pharmacokinetic and chemical properties, there is no proof that one opioid is better than another one. Thus, the optimum benefit depends on the experience of the users. Clinicians should weight evidence, clinical experience, patient preferences, and treatment costs when choosing the optimal treatment for an individual patient with cancer pain. New opioids with specific receptor activities are under investigation.     

Prolonged-release oxycodone/naloxone in opioid-naïve patients – subgroup analysis of a prospective observational study

Objective: Prolonged-release oxycodone/naloxone (OXN PR) showed improved gastrointestinal tolerability and equivalent analgesic efficacy compared to oxycodone alone in patients with non-cancer pain or cancer pain. This is the first dataset to demonstrate its effectiveness and safety compared to other strong opioids in opioid-naïve patients.

Methods: This is a subgroup analysis of a 4- to 6-week multicenter, observational study. A total of 162 opioid-naïve patients with moderate-to-severe pain of varying etiologies received either OXN PR or other strong opioids (control group). Documented parameters include pain relief (numeric rating scale), bowel function (Bowel Function Index [BFI]), pain-related functional impairment (Brief Pain Inventory Short Form), quality of life (QoL; EuroQol EQ-5D-3L) and a global therapy assessment.

Results: OXN group patients experienced a substantial clinically important reduction in mean pain intensity of 51.4%, compared to a 28.6% reduction in control patients. Although the BFI remained in the reference range in both groups, there was a difference between BFI changes during treatment in favor of OXN PR. The superior effectiveness of OXN PR was paralleled by greater improvements of pain interference and QoL and fewer adverse drug reactions compared to other strong opioids.

Conclusion: The favorable outcomes under real-life conditions suggest that OXN PR provides a valuable option for treatment of moderate-to-severe pain without using weak opioids first.