Bipolar Disorder, Mania, Manic Disorder, Manic State, Schizoaffective Disorder
Conditions
Keywords
bipolar disorder, bipolar mania, schizoaffective disorder, schizoaffective mania, mania, kappa opiates, opiates
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).
Interventions
DRUGPentazocine
see arms description
DRUGLorazepam
see arms description
Sponsors
Stanley Medical Research Institute
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mania Acute Rating Scale (MACS) | On Day 1 and Day 2, at the time of administration of intervention and 5 hours following administration of intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Young Mania Rating Scale (YMRS) | at the time of administration of intervention and 5 hours following administration of intervention | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pentazocine Then Lorazepam 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. | 10 |
| Lorazepam Then Pentazocine 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. | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Pentazocine Then Lorazepam | Lorazepam Then Pentazocine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
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.
Time frame: On Day 1 and Day 2, at the time of administration of intervention and 5 hours following administration of intervention
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pentazocine | Mania Acute Rating Scale (MACS) | 3.9 units on a scale |
| Lorazepam | Mania Acute Rating Scale (MACS) | 6.4 units on a scale |
p-value: 0.22Mixed Models Analysis
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.
Time frame: at the time of administration of intervention and 5 hours following administration of intervention
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pentazocine | Young Mania Rating Scale (YMRS) | 23.0 units on a scale |
| Lorazepam | Young Mania Rating Scale (YMRS) | 22.6 units on a scale |
p-value: 0.83Mixed Models Analysis