Effects of Pentazocine Versus Lorazepam on Manic Symptoms

• Sponsor: Mclean Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00431184
• Collaborator: Stanley Medical Research Institute (Other)
• Enrollment: 19
• Location: 1
• Arms: 2
• Duration (Months): 49.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Schizoaffective Disorder; Manic Disorder; Mania; Manic State	Drug: Pentazocine; Drug: Lorazepam	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Pentazocine Versus Lorazepam on Manic Symptoms
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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 Names: Talwin Nx ; Drug: Lorazepam; see arms description; Other Names: 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 Names: Talwin Nx ; Drug: Lorazepam; see arms description; Other Names: Ativan

Outcome Measures

Primary Outcome Measures

1. Mania Acute Rating Scale (MACS) [On Day 1 and Day 2, at the time of administration of intervention and 5 hours following administration of intervention]

   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

1. Young Mania Rating Scale (YMRS) [at the time of administration of intervention and 5 hours following administration of intervention]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• McLean hospital website, with links to research.

Publications

• 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.
• 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.
• 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
• Other Study ID Numbers: 2006-P-002344
• First Posted: Feb 5, 2007
• Last Update Posted: Mar 6, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Beth L. Murphy MD, PhD, Principal Investigator, Mclean Hospital: bipolar disorder; bipolar mania; schizoaffective disorder; schizoaffective mania; mania; kappa opiates; opiates
• Additional relevant MeSH terms: Mania; Disease; Bipolar Disorder; Psychotic Disorders; Pentazocine; Lorazepam

Study Results

Participant Flow

Arm/Group Title	Pentazocine Then Lorazepam	Lorazepam Then Pentazocine
Arm/Group Description	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.	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.
Period Title: 1st Intervention (Day 1)
STARTED	10	9
COMPLETED	10	9
NOT COMPLETED	0	0
Period Title: 1st Intervention (Day 1)
STARTED	10	9
COMPLETED	10	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Pentazocine Then Lorazepam	Lorazepam Then Pentazocine	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	10	9	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	9 100%	19 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	6 60%	6 66.7%	12 63.2%
Male	4 40%	3 33.3%	7 36.8%

Outcome Measures

1. Primary Outcome

Title	Mania Acute Rating Scale (MACS)
Description	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.
Time Frame	On Day 1 and Day 2, at the time of administration of intervention and 5 hours following administration of intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pentazocine	Lorazepam
Arm/Group Description	Subjects received 50mg of pentazocine	Subjects received 0.25mg of Lorazepam followed by a second dose of 0.25mg two hours later
Measure Participants	19	19
Mean (95% Confidence Interval) [units on a scale]	3.9	6.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pentazocine, Lorazepam
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Young Mania Rating Scale (YMRS)
Description	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.
Time Frame	at the time of administration of intervention and 5 hours following administration of intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pentazocine	Lorazepam
Arm/Group Description	The results below represent the mean change in YMRS scores for all 19 subjects following administration of Pentazocine.	The results below represent the mean change in YMRS scores for all 19 subjects following administration of Lorazepam.
Measure Participants	19	19
Mean (95% Confidence Interval) [units on a scale]	23.0	22.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pentazocine, Lorazepam
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Data was collected over two contiguous days.
Arm/Group Title	Pentazocine		Lorazepam
Arm/Group Description	All subjects receive 50mg of pentazocine followed by a second dose of 50mg two hours later on either Day 1 or Day 2.		All subjects receive 0.25mg of Lorazepam followed by a second dose of 0.25mg two hours later on either Day 1 or Day 2.
All Cause Mortality
	Pentazocine		Lorazepam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pentazocine		Lorazepam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Pentazocine		Lorazepam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.