Effects of Pentazocine on Manic Symptoms

Bipolar Disorder Clinical Trial

Official title:

Inpatient Clinical Trial Examining the Effects of Pentazocine on Manic Symptoms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00125931
• Other study ID #: 2005P-001260
• Status: Completed
• Phase: Phase 2
• First received: August 1, 2005
• Last updated: August 25, 2014
• Start date: September 2005
• Est. completion date: December 2008

Study information

• Verified date: August 2014
• Source: Mclean Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Talwin Nx
Talwin NX 50mg po twice

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Mclean Hospital	Stanley Medical Research Institute

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mania Symptoms Using MACS	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.	hourly for 6 hours after first dose of pentazocine; hour 0 is the baseline score and also when first dose of pentazocine was administered	No
Secondary	YMRS Scores	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.	Each morning of the three-day study	No

External Links

•   McLean hospital website, with links to research.