Effects of Pentazocine on Manic Symptoms

Study Description

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Brief Summary:

The opiate neurotransmitter system is thought to be involved in many abnormal mood states. Some researchers have suggested that changes in this system may trigger the switch to/from manic and depressive states in bipolar disorder. One problem with most of the currently available opiate medications is that they can produce addiction/dependence. A particular kind of opiate medication known as kappa-opiates may be able to produce changes in this system with much less risk of addiction. This study looks at Talwin (a combination of pentazocine and naloxone), a medication which affects the kappa and mu opiate systems. The study will examine whether two doses of Talwin affect manic symptoms in people who have been admitted to the hospital. This study will give more information about the involvement of the opiate system in bipolar disorder, and give important information for use in developing new treatments.

Condition or disease	Intervention/treatment	Phase
Bipolar Disorder	Drug: Talwin Nx	Phase 2

Detailed Description:

Opiates have a long history of treating mood disorders. Some researchers have suggested that changes in this system may trigger the switch to/from manic and depressive states in bipolar disorder. The clinical use of opiate medications has been limited by their abuse/dependence potential. Studies of opiate receptor subtypes have raised the possibility that medications targeting the kappa/dynorphin system could be used to target mood symptoms with reduced/limited addiction potential. Rodent studies at Mclean indicate that kappa-agonists have pro-depressant effects and kappa-antagonists have anti-depressant effects. In addition, antimanic/antipsychotic medications regulate the activity of dynorphin cells. This study is a pilot open-label investigation using Talwin, a combination of pentazocine and naloxone. Pentazocine is a kappa agonist and mixed mu agonist. Two doses of Talwin will be given to acutely manic inpatients in a cumulative-dosing strategy. Measurements of manic symptoms will be conducted before, during, and after administration. This study will determine whether pentazocine has an immediate or sustained impact on acute mania symptoms.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Inpatient Clinical Trial Examining the Effects of Pentazocine on Manic Symptoms
Study Start Date :	September 2005
Actual Primary Completion Date :	August 2008
Actual Study Completion Date :	December 2008

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Pentazocine/Talwin; Talwin NX	Drug: Talwin Nx; Talwin NX 50mg po twice; Other Name: Pentazocine

Outcome Measures

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Primary Outcome Measures :

1. Mania Symptoms Using MACS [ Time Frame: hourly for 6 hours after first dose of pentazocine; hour 0 is the baseline score and also when first dose of pentazocine was administered ]
   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.

Secondary Outcome Measures :

1. YMRS Scores [ Time Frame: Each morning of the three-day study ]
   Assessment of current mania symptoms using YMRS. All questions have a 0 (absent)-4(most severe) range for describing mania symptoms. The mean YMRS scores were reported, with the total ranging from 0-44. 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Young Mania Rating Scale (YMRS) greater than 14
• Inpatient

Exclusion Criteria:

• History of opiate abuse/dependence
• Recent history of substance abuse
• Pregnancy
• Unstable medical issues
• Use of opiate medications for pain management

Contacts and Locations

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

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 of Results:

Cohen BM, Murphy B. The effects of pentazocine, a kappa agonist, in patients with mania. Int J Neuropsychopharmacol. 2008 Mar;11(2):243-7. Epub 2007 Sep 26.

Other 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:	NCT00125931 History of Changes
Other Study ID Numbers:	2005P-001260
First Posted:	August 2, 2005
Results First Posted:	September 4, 2014
Last Update Posted:	September 4, 2014
Last Verified:	August 2014

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

bipolar disorder; mania; manic state; opiate; kappa

Additional relevant MeSH terms:

Bipolar Disorder; Bipolar and Related Disorders; Mental Disorders; Pentazocine; Analgesics, Opioid; Narcotics; Central Nervous System Depressants	Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adjuvants, Anesthesia; Narcotic Antagonists