Clinical trial NCT00431184: Effects of Pentazocine Versus Lorazepam on Manic Symptoms
Official title: Effects of Pentazocine Versus Lorazepam on Manic Symptoms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bipolar Disorder
Schizoaffective Disorder
Manic Disorder
Mania
Manic State
Keywords: bipolar disorder
bipolar mania
schizoaffective disorder
schizoaffective mania
mania
kappa opiates
opiates
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2007-02-05
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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).

Eligibility 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

Primary outcomes:
measure: Mania Acute Rating Scale (MACS)
timeFrame: On Day 1 and Day 2, at the time of administration of intervention and 5 hours following administration of intervention
Secondary outcomes:
measure: Young Mania Rating Scale (YMRS)
timeFrame: at the time of administration of intervention and 5 hours following administration of intervention
Other outcomes:
Locations:
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
Study officials:
affiliation: Mclean Hospital
name: Beth L Murphy, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1016/s0306-4522(03)00397-x.
citation: 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. doi: 10.1124/jpet.105.092304. Epub 2005 Oct 13.
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. doi: 10.1124/jpet.102.046433.
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. doi: 10.1007/s00213-003-1680-y. Epub 2004 Jan 16.