Effects of Pentazocine Versus Lorazepam on Manic Symptoms

Bipolar Disorder Clinical Trial

Official title:

Effects of Pentazocine Versus Lorazepam on Manic Symptoms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00431184
• Other study ID #: 2006-P-002344
• Status: Completed
• Phase: Phase 2
• Start date: January 2007
• Est. completion date: March 2011

Study information

• Verified date: February 2019
• Source: Mclean Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder
• Disease
• Mania
• Manic Disorder
• Manic State
• Psychotic Disorders
• Schizoaffective Disorder

Intervention

Drug:
• Pentazocine
see arms description
• Lorazepam
see arms description

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Mclean Hospital	Stanley Medical Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (4)

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

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 Acute Rating Scale (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. The change in MACS scores from baseline and those following treatment administration were averaged. The number below represents the average mean change.	On Day 1 and Day 2, at the time of administration of intervention and 5 hours following administration of intervention
Secondary	Young Mania Rating Scale (YMRS)	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.	at the time of administration of intervention and 5 hours following administration of intervention

External Links

•   McLean hospital website, with links to research.