Effects of Pentazocine Versus Lorazepam or Placebo on Manic Symptoms

Condition(s) targeted: Bipolar Disorder; Schizoaffective Disorder; Manic Disorder; Mania; Manic State

Intervention: pentazocine (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Mclean Hospital

Official(s) and/or principal investigator(s):
Beth L Murphy, MD/PhD, Principal Investigator, Affiliation: Mclean Hospital

Overall contact:
Sue B, Phone: 617-855-3184

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.

Official title: Effects of Pentazocine Versus Lorazepam or Placebo on Manic Symptoms

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Efficacy Study

Primary outcome: Mania Acute Rating Scale

Secondary outcome: Young Mania Rating Scale

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, placebo, and 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 a placebo control at one site, and with an active control (ativan)at the second site.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Sue B, Phone: 617-855-3184

McLean Hospital, Belmont, Massachusetts 02478, United States; Recruiting
Jin K, Phone: 617-855-2540
Beth L Murphy, MD/PhD, Principal Investigator
Bruce Cohen, MD, PhD, Sub-Investigator

Jersey Shore Psychiatric Associates, Neptune, New Jersey 07753, United States; Recruiting
Peter Harris, MD, PhD

McLean hospital website, with links to research.

Related 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, Beguin 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.

Starting date: January 2007
Ending date: July 2010
Last updated: June 4, 2009