Effects of Pentazocine Versus Lorazepam on Manic Symptoms

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
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 :	January 2007
Actual Primary Completion Date :	March 2011
Actual Study Completion Date :	March 2011

Arms and Interventions

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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 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

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. 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 ]
   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) [ Time Frame: 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

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

McLean hospital website, with links to research. 

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
First Posted:	February 5, 2007
Results First Posted:	August 21, 2014
Last Update Posted:	August 21, 2014
Last Verified:	August 2014

Keywords provided by Beth L. Murphy MD, PhD, Mclean Hospital:

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

Additional relevant MeSH terms:

Disease; Bipolar Disorder; Psychotic Disorders; Pathologic Processes; Bipolar and Related Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Lorazepam; Pentazocine; Anticonvulsants; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents	Hypnotics and Sedatives; Central Nervous System Depressants; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Analgesics, Opioid; Narcotics; Analgesics; Sensory System Agents; Adjuvants, Anesthesia; Narcotic Antagonists