Effects of Pentazocine Versus Lorazepam on Manic Symptoms - Full Text View

Purpose

Pilot data indicates that pentazocine decreases manic symptoms in hospitalized individuals. To follow up these initial findings, we plan to conduct a larger, more rigorous, double-blind study. We will examine whether pentazocine, an agent with kappa-opiate activity, decreases manic symptoms.

Condition	Intervention	Phase
Bipolar Disorder Schizoaffective Disorder Manic Disorder Mania Manic State	Drug: Pentazocine Drug: Lorazepam	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effects of Pentazocine Versus Lorazepam on Manic Symptoms

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Pentazocine Lorazepam Pentazocine lactate Pentazocine hydrochloride Talwin Nx

U.S. FDA Resources

Further study details as provided by Mclean Hospital:

Primary Outcome Measures:

Mania Acute Rating Scale (MACS) [ Time Frame: On Day 1 and Day 2, at the time of administration of intervention and 5 hours following administration of intervention ] [ Designated as safety issue: No ]
Assessment of current mania symptoms using Mania Acute Change Scale (MACS). All 20 questions on the scale have a 0 (absent)-4(most severe) range for describing mania symptoms. The mean MACS score totals were reported, with the total ranging from 0-80. A higher total score indicates a greater number of symptoms and higher symptom intensity, while a smaller score indicates a lesser number of symptoms and higher lower intensity. The change in MACS scores from baseline and those following treatment administration were averaged. The number below represents the average mean change.

Secondary Outcome Measures:

Young Mania Rating Scale (YMRS) [ Time Frame: at the time of administration of intervention and 5 hours following administration of intervention ] [ Designated as safety issue: No ]
The YMRS is used to assess manic symptoms. There are 11 questions which ask the patient to rate the severity of symptoms. Scores range from 0 to a maximum of 60. All questions are rated based on severity, with a higher score signifying increased severity. Questions 1-4, 7, and 10 are rated on a 0-4 scale. Questions 5, 6, 8, and 9 are rated on a 0-8 scale.


Enrollment:	19
Study Start Date:	January 2007
Study Completion Date:	March 2011
Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Pentazocine then Lorazepam In the first leg of the study, pentazocine will be given to subjects randomly assigned to this group. On Day 1, subjects will receive 50mg of pentazocine followed by a second dose of 50mg two hours later. On Day 2, subjects in this group will be given 0.25mg of Lorazepam followed by a second dose of 0.25mg two hours later.	Drug: Pentazocine see arms description Other Name: Talwin Nx Drug: Lorazepam see arms description Other Name: Ativan
Active Comparator: Lorazepam then Pentazocine In the first leg of the study, lorazepam will be given to subjects randomly assigned to this group. On Day 3, subjects in this group will be given 0.25mg of Lorazepam followed by a second dose of 0.25mg two hours later. On Day 2, subjects will receive 50mg of pentazocine followed by a second dose of 50mg two hours later.	Drug: Pentazocine see arms description Other Name: Talwin Nx Drug: Lorazepam see arms description Other Name: Ativan

Detailed Description:

Dysregulation of the opioid system may underlie the pathophysiology of mood disorders, such as bipolar disorder. Drugs that modulate the opioid system might be effective treatments for bipolar disorder. The profile and actions of the kappa-opioid system make drugs that target this system particularly promising as a treatment modality, with relatively low risk of addictive properties. Pentazocine is an approved drug for pain relief with a good side effect profile. It is predominantly a kappa opioid agonist with weaker side effects at mu opioid receptors, at which it is an antagonist. Data from our open-label pilot study of pentazocine had promising results. We will follow up on these findings with a double-blind, active-control study of individuals with bipolar disorder or schizoaffective disorder who are currently hospitalized with acute mania. The antimanic effects of pentazocine will be compared with an active control (ativan).

Eligibility


Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

bipolar or schizoaffective disorder
currently manic
no acute medical issues
no substance withdrawal

Exclusion Criteria:

unable to give informed consent
using opiates for pain management
history of head injury, dementia, or mental retardation
seizure disorder
glaucoma
unstable cardiac condition or arrhythmia
moderate-severe pulmonary disease
pregnancy

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00431184

Locations


United States, Massachusetts
McLean Hospital
Belmont, Massachusetts, United States, 02478

Sponsors and Collaborators

Mclean Hospital

Stanley Medical Research Institute

Investigators


Principal Investigator:	Beth L Murphy, MD/PhD	Mclean Hospital

More Information

Additional Information:

McLean hospital website, with links to research. This link exits the ClinicalTrials.gov site

Publications:

Ma J, Ye N, Lange N, Cohen BM. Dynorphinergic GABA neurons are a target of both typical and atypical antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus and thalamic central medial nucleus. Neuroscience. 2003;121(4):991-8.

Carlezon WA Jr, Béguin C, DiNieri JA, Baumann MH, Richards MR, Todtenkopf MS, Rothman RB, Ma Z, Lee DY, Cohen BM. Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. J Pharmacol Exp Ther. 2006 Jan;316(1):440-7. Epub 2005 Oct 13.

Mague SD, Pliakas AM, Todtenkopf MS, Tomasiewicz HC, Zhang Y, Stevens WC Jr, Jones RM, Portoghese PS, Carlezon WA Jr. Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. J Pharmacol Exp Ther. 2003 Apr;305(1):323-30.

Todtenkopf MS, Marcus JF, Portoghese PS, Carlezon WA Jr. Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats. Psychopharmacology (Berl). 2004 Apr;172(4):463-70. Epub 2004 Jan 16.


Responsible Party:	Beth L. Murphy MD, PhD, Principal Investigator, Mclean Hospital
ClinicalTrials.gov Identifier:	NCT00431184 History of Changes
Other Study ID Numbers:	2006-P-002344
Study First Received:	February 1, 2007
Results First Received:	June 19, 2014
Last Updated:	August 5, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by Mclean Hospital:


bipolar disorder bipolar mania schizoaffective disorder schizoaffective mania	mania kappa opiates opiates

Additional relevant MeSH terms:


Bipolar Disorder Disease Psychotic Disorders Affective Disorders, Psychotic Mental Disorders Mood Disorders Pathologic Processes Schizophrenia and Disorders with Psychotic Features Lorazepam Pentazocine Adjuvants, Anesthesia Analgesics Analgesics, Opioid Anti-Anxiety Agents Anticonvulsants	Antiemetics Autonomic Agents Central Nervous System Agents Central Nervous System Depressants GABA Agents GABA Modulators Gastrointestinal Agents Hypnotics and Sedatives Molecular Mechanisms of Pharmacological Action Narcotic Antagonists Narcotics Neurotransmitter Agents Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 27, 2015