Effects of Pentazocine Versus Lorazepam on Manic Symptoms

Study Overview
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Brief Summary
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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
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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).

Official Title
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Effects of Pentazocine Versus Lorazepam on Manic Symptoms

Conditions
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Bipolar Disorder, Schizoaffective Disorder, Manic Disorder, Mania, Manic State

Intervention / Treatment
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* Drug: Pentazocine
* Drug: Lorazepam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pentazocine then Lorazepam<br>In the first leg of the study, pentazocine will be given to subjects randomly assigned to this group. On Day 1, subjects will receive 50mg of pentazocine followed by a second dose of 50mg two hours later. On Day 2, subjects in this group will be given 0.25mg of Lorazepam followed by a second dose of 0.25mg two hours later. | Drug: Pentazocine<br>* see arms description<br>* Other names: Talwin Nx;Drug: Lorazepam<br>* see arms description<br>* Other names: Ativan;|
| Active Comparator: Lorazepam then Pentazocine<br>In the first leg of the study, lorazepam will be given to subjects randomly assigned to this group. On Day 3, subjects in this group will be given 0.25mg of Lorazepam followed by a second dose of 0.25mg two hours later. On Day 2, subjects will receive 50mg of pentazocine followed by a second dose of 50mg two hours later. | Drug: Pentazocine<br>* see arms description<br>* Other names: Talwin Nx;Drug: Lorazepam<br>* see arms description<br>* Other names: Ativan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar disorder, bipolar mania, schizoaffective disorder, schizoaffective mania, mania, kappa opiates, opiates