Effect of Combined Morphine and Duloxetine on Chronic Pain

Phase 4

Completed

Brief Summary: A double-blind, randomized, and placebo-controlled clinical study examining whether duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), could enhance opioid analgesia and reduce overall opioid use. Positive outcomes will help improve the overall effectiveness of clinical opioid therapy and reduce unnecessary opioid dose escalation.

Detailed Description: Subjects will participate in a 10-week study consisting of three phases: Phase I is the dose titration period of 4 weeks, Phase II is the dose maintenance period of 4 weeks, and Phase III is the dose taper period of 2 weeks. Seven office visits (Initial visit/baseline, weeks 1, 3, 5, 7, 9, and end of week 10) and four follow up phone calls (weeks 2, 4, 6, and 10) will be used to collect data. Since this is a prospective study, we will be able to first determine baseline QST and VAS pain score, followed by assessing their longitudinal changes at each office visit. To assess OIH, QST will be performed at each office visit before subject takes the next dose of the study drugs. We will also measure plasma morphine concentration during the titration and maintenance phase to help validate morphine intake.

Recruitment & Eligibility

Inclusion Criteria

Subject is 18-70 years old.
Subject has chronic neck or back pain for at least 3 months.
Subject has a VAS ≥ 5.
Has not taken duloxetine in the last 3 months.
Has not taken an opioid in the last 3 months, but has taken one in the past without sufficient pain control OR has never taken opioids but has failed at 3 (or more) non-opioid treatments.

Exclusion Criteria

Subject has major psychiatric disorders requiring recent hospitalization (within 3 months) such as major depression, bipolar disorder, schizophrenia, anxiety disorder, or psychotic disorder.
Subject is using illicit drugs detected by urine toxicology/drug screen.
Subject is pregnant or lactating/breast feeding.
Subject is allergic to morphine or duloxetine.
Subject is on an antidepressant including serotonin-norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitor (SSRI), tricyclic antidepressant.
Subject has a history of suicidal attempts or current suicidal ideation.
Subject takes monoamine oxidase inhibitors, antipsychotics, triptan drugs such as sumatriptan, lithium, linezolid, tramadol (Ultram), St. John's Wort, central nervous system (CNS) stimulants such as amphetamine, methylphenidate, methamphetamine, phentermine, diethylpropion, sibutramine, cocaine, or thioridazine.
Subject has uncontrolled narrow-angle glaucoma.
Subject has sensory deficits on arms or Raynaud's Syndrome.
Subject has a pending litigation related to chronic pain condition.
Subject is on methadone or suboxone treatment for addiction.

Arm && Interventions

Group	Intervention	Description
Morphine, Placebo Duloxetine	Placebo	Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and placebo duloxetine capsules.
Placebo Morphine, Duloxetine	Placebo	Subjects will take placebo morphine capsules and 60 mg of duloxetine capsules.
Morphine, Duloxetine	Duloxetine	Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and 60 mg of duloxetine capsules.
Morphine, Duloxetine	Morphine	Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and 60 mg of duloxetine capsules.
Morphine, Placebo Duloxetine	Morphine	Subjects will take a maximum dose of 60 mg/day of extended release morphine capsules and placebo duloxetine capsules.
Placebo Morphine, Duloxetine	Duloxetine	Subjects will take placebo morphine capsules and 60 mg of duloxetine capsules.

Primary Outcome Measures

Name	Time	Method
Overall Opioid Dose (Morphine-equivalent Dose in mg)	10 weeks	The investigators will compare overall opioid dose (in morphine-equivalent dose in mg) between the morphine/duloxetine group and the morphine/placebo group and compare rescue dose among all three groups. The higher overall opioid dose, the more consumption of opioid.
Visual Analog Scale (VAS)	10 weeks	To examine changes in pain intensity measured on a Visual Analog Scale with units on a scale ranging from 0 cm-10 cm (0 cm being lowest and 10 cm being the higher the score, where values closer to 10 cm reflect more pain) and to determine total versus rescue opioid use after each treatment.

Secondary Outcome Measures