Clinical trial NCT01200069: IV Ibuprofen for Post-Electroconvulsive Therapy Myalgia
Official title: Intravenous Ibuprofen/Caldolor for Post-Electroconvulsive Therapy Myalgia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Depression, Myalgia
Keywords: depression,myalgia
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2010-09-13
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Post-procedure myalgia (muscle ache) is a well-known and common complication of Electro-convulsive Treatment (ECT). Myalgias are a serious concern of patients and occur in approximately 50% of these cases. The pain is usually described as muscle soreness, similar to that resulting from strenuous exercise. The myalgias typically begin shortly after the procedure, lasting approximately 2-7 days in total. A recent study reported that 89% of patients considered prevention significant and would be willing to pay a median of $33 out of pocket to avoid this side effect. In addition to patient discomfort, myalgias can have a further financial burden if these patients are unable to return to work or resume previous daily activities in the days following the procedure. An agent that could treat and possibly even prevent these myalgias has the potential to be very beneficial to these patients. IV ibuprofen (trade name Caldolor) is a novel therapeutic modality approved by the US Food and Drug Administration (FDA) in June 2009 for the treatment of mild to moderate pain, as an adjunct to opioid analgesics, and for the reduction of fever.

Detailed description: IV ibuprofen (trade name Caldolor) is a novel therapeutic modality approved by the US Food and Drug Administration (FDA) in June 2009 for the treatment of mild to moderate pain, as an adjunct to opioid analgesics, and for the reduction of fever. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID), which produces its effect through inhibition of the enzyme cyclooxygenase (COX). There are at least 2 variations of cyclooxygenase (COX-1 and COX-2) and ibuprofen non-selectively inhibits both, thus decreasing prostaglandin synthesis. This action gives ibuprofen its analgesic, anti-pyretic, and anti-inflammatory properties. NSAIDs have an established history of efficacy in the treatment of both acute and chronic somatic pain. Caldolor, being an intravenous formulation, offers a distinct advantage in patients who either are unable to take medications orally or are fasting preoperatively.

Post-procedure myalgia is a well-known and common complication of ECT. Although the exact etiology is unknown, the myalgias are believed to result from a combination of succinylcholine administration and the seizure activity induced by the ECT procedure itself. Succinylcholine-induced postoperative myalgias are a well-known phenomenon, initially described in the early 1950's. The exact pathogenesis is unknown, with muscle damage from succinylcholine-induced fasciculations or calcium-mediated phospholipase A2 activation and prostaglandin production being proposed as possible etiologies. The latter mechanism provides the rationale for using NSAID therapy. However, succinylcholine is unlikely to be the only factor involved in the development of myalgias following ECT, as a recent study showed that dose adjustments to succinylcholine did not affect rates of myalgia in these patients. Furthermore, seizures can also cause direct muscle injury and there have been reports of muscle pain after ECT both with and without succinylcholine.

A thorough literature search using Medline, Ovid, and scholar.google failed to find any research articles evaluating pretreatment therapy for myalgias in post-ECT patients. The current practice for the treatment of myalgias following ECT has been extrapolated from research on succinylcholine-induced myalgia in post-surgical patients. Previous studies have shown at least partial efficacy with pretreatment of nondepolarizing neuromuscular blocking agents, benzodiazepines, sodium channel blockers (predominantly lidocaine), and nonsteroidal anti-inflammatory drugs. The nature of the ECT procedure itself makes several of these modalities undesirable. Both Lidocaine and benzodiazepines can alter the seizure threshold and the short duration of the procedure possibly increases the risks associated with longer acting nondepolarizing muscle relaxants (ie. blurred vision, diplopia, difficulty breathing and swallowing). Therefore, the options for pretreatment are limited. In addition, a recent meta-analysis of randomized trials determined NSAIDs to cumulatively have the best efficacy of any pretreatment therapy in the prevention of post-procedural myalgias. Due to its intravenous formulation, some practitioners have administered ketorolac to ECT patients before the procedure. However, despite a proven efficacy in myalgia prevention shown by NSAIDs as a class, a study specifically examining the use of ketorolac in this regard failed to show any benefit. The use of Ibuprofen has yet to be examined.

Myalgias are a serious concern of patients and occur in approximately 50% of these cases. The pain is usually described as muscle soreness, similar to that resulting from strenuous exercise. The myalgias typically begin shortly after the procedure, lasting approximately 2-7 days in total. A recent study reported that 89% of patients considered prevention significant and would be willing to pay a median of $33 out of pocket to avoid this side effect. In addition to patient discomfort, myalgias can have a further financial burden if these patients are unable to return to work or resume previous daily activities in the days following the procedure. An agent that could treat and possibly even prevent these myalgias has the potential to be very beneficial to these patients.

Experimental Plan:

The study will be a prospective, randomized, double-blinded placebo-controlled clinical trial. The subject population will consist of patients undergoing first time electroconvulsive therapy, ranging in age from 18 to 80 years. Subjects will be given a Mini-Mental State Examination at the time of their presentation for ECT to assess their cognitive ability. If the patient consents and fits the inclusion criteria, patients will be randomized to one treatment modality, which they will receive for the first three treatment sessions. The subject and the person collecting the data will both be blinded as to what treatment modality the subject belongs to. The patients will be divided into two groups, Group 1 and Group 2. Group 1 will be treated with IV ibuprofen 800mg/8ml given over 30 minutes, prior to induction for ECT; while Group 2 will receive an identically appearing placebo dose, also administered IV, over that same time period. Both groups will receive a standardized anesthetic consisting of methohexital at 1 mg/kg IV for induction and succinylcholine 1 mg/kg IV for muscle paralysis. Other medications (eg. anticholinergic or antihypertensive drugs) will be administered at the discretion of the anesthesiologist. ECT will be administered by the psychiatrist in order to achieve a seizure with a motor component of \> 15 second duration. Patients will be transported to the recovery room for post-anesthesia care. Rescue analgesics (Tylenol 500mg PO, Tylenol with codeine 300/30mg PO, Fentanyl 25 mcg IV) will be available to any patient with complaints of myalgia or headache pain of VAS \>4.

Measurement Tools:

Severity of myalgias will be assessed based on a self-reported assessment utilizing a numerical rating scale (NRS). The scale will be rated as 0 meaning no pain at all and 10 meaning that pain is so severe as to interfere with daily activities.

Questionnaire:

Do you have any muscle aches or pain right now? If yes, how would you rate that muscle ache/pain on a scale of 0 to 10, with 0 being no pain and 10 being pain that is the worst imaginable?

Example:

0 = No pain 1-3 = Mild Pain (nagging, annoying, little interference with everyday activities) 4-6 = Moderate Pain (interferes significantly with everyday activities) 7-10 = Severe Pain (unable to perform everyday activities) Have you had to take any medications to treat your muscle aches? If yes, what medication did you take? How many pills? What was the strength of the medication? Do you have a headache right now? If yes, how would you rate that headache on a scale of 0 to 10, with 0 being no pain and 10 being pain that is the worst imaginable?

Measurements:

Each patient will have a self-reported numerical pain score assessed at baseline before therapy, 1 hour post-ECT, 6 hours post-ECT, 24 hours post-ECT, and finally at 48 hours post-ECT. The 6, 24 and 48 hour post-ECT assessments will be conducted via a telephone conversation. The use of rescue analgesics during recovery will also be documented as well as time from the end of procedure to discharge. The presence of headache will also be documented in each patient.

Eligibility criteria: Inclusion Criteria:

* Capable of providing informed consent
* American Society Anesthesiologists (ASA) rating I-III
* Subjects age 18-80 capable of providing consent.
* Subjects undergoing electroconvulsive therapy using succinylcholine as the sole neuromuscular blocking agent.
* Subjects who have scored ≥23 on the Mini-Mental State Examination.

Exclusion Criteria:

* Subjects who have had a recent thrombotic event, myocardial infarction or stroke or episode of Congestive Heart Failure (CHF) within less than 3 months.
* Subjects who have had a recent cardiovascular surgery within the last 3 months.
* Subjects with active Gastrointestinal bleeding
* Subjects who have asthma, itching or allergic type reaction following aspirin or other NSAID administration
* Subjects with a known hypersensitivity to ibuprofen
* Subjects with heart failure, bleeding disorders or kidney failure
* Subjects taking aspirin, Angiotensin converting enzyme (ACE) inhibitors, or anticoagulants within one month.
* Subjects with any devices used to treat pain (intrathecal pumps, spinal cord stimulators etc)
* Subjects with a history of fibromyalgia or chronic myositis
* Subjects who are pregnant
* Subjects who do not have a phone
* Subjects who have had previous ECT
* Subjects receiving toradol (Ketorolac)
* Subjects with reported renal disease within less than 3 months.
* Subjects who have had previous electroconvulsive therapy within the last 3 months

Primary outcomes:
measure: Subject Self Reported Numerical Rating of Incidence and Severity of Post-Electroconvulsive Therapy Myalgias After Treatment 1
timeFrame: Treatment day 1 at 1hour, 6 hour, 24 hours, 48 hours
measure: Myalgia Reported on Treatment Day 2
timeFrame: 1 hour, 6 hours, 24 hours & 48 hours following procedure
measure: Myalgia Reported After Treatment #3
timeFrame: 1 hour, 6 hour, 24 hour, 48 hour after 3rd ECT treatment
Secondary outcomes:
measure: Subject Self Reported Numerical Rating of Incidence and Severity of Post Electroconvulsive Therapy Headache After Treatment Day 1
timeFrame: 1 hour, 6 hours, 24 hours & 48 hours following procedure
measure: Incidence and Severity of Headache After ECT Treatment 2
timeFrame: 1 hour, 6 hour, 24 hour and 48 hours
measure: Incidence of Headache & Severity Headache After ECT Treatment #3
timeFrame: 1 hour after treatment, 6 hours, 24 hours and 48 hours
Other outcomes:
Locations:
city: Newark
country: United States
facility: University Hospital
state: New Jersey
Study officials:
affiliation: UMDNJ-NJMS
name: Vasanti Tilak, MD
role: PRINCIPAL_INVESTIGATOR
References: