Bipolar Disorder
Conditions
Keywords
bipolar disorder, mania, manic state, opiate, kappa
Brief summary
The opiate neurotransmitter system is thought to be involved in many abnormal mood states. Some researchers have suggested that changes in this system may trigger the switch to/from manic and depressive states in bipolar disorder. One problem with most of the currently available opiate medications is that they can produce addiction/dependence. A particular kind of opiate medication known as kappa-opiates may be able to produce changes in this system with much less risk of addiction. This study looks at Talwin (a combination of pentazocine and naloxone), a medication which affects the kappa and mu opiate systems. The study will examine whether two doses of Talwin affect manic symptoms in people who have been admitted to the hospital. This study will give more information about the involvement of the opiate system in bipolar disorder, and give important information for use in developing new treatments.
Detailed description
Opiates have a long history of treating mood disorders. Some researchers have suggested that changes in this system may trigger the switch to/from manic and depressive states in bipolar disorder. The clinical use of opiate medications has been limited by their abuse/dependence potential. Studies of opiate receptor subtypes have raised the possibility that medications targeting the kappa/dynorphin system could be used to target mood symptoms with reduced/limited addiction potential. Rodent studies at Mclean indicate that kappa-agonists have pro-depressant effects and kappa-antagonists have anti-depressant effects. In addition, antimanic/antipsychotic medications regulate the activity of dynorphin cells. This study is a pilot open-label investigation using Talwin, a combination of pentazocine and naloxone. Pentazocine is a kappa agonist and mixed mu agonist. Two doses of Talwin will be given to acutely manic inpatients in a cumulative-dosing strategy. Measurements of manic symptoms will be conducted before, during, and after administration. This study will determine whether pentazocine has an immediate or sustained impact on acute mania symptoms.
Interventions
DRUGTalwin Nx
Talwin NX 50mg po twice
Sponsors
Stanley Medical Research Institute
Mclean Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Young Mania Rating Scale (YMRS) greater than 14 * Inpatient
Exclusion criteria
* History of opiate abuse/dependence * Recent history of substance abuse * Pregnancy * Unstable medical issues * Use of opiate medications for pain management
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mania Symptoms Using MACS | hourly for 6 hours after first dose of pentazocine; hour 0 is the baseline score and also when first dose of pentazocine was administered | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| YMRS Scores | Each morning of the three-day study | Assessment of current mania symptoms using YMRS. All questions have a 0 (absent)-4(most severe) range for describing mania symptoms. The mean YMRS scores were reported, with the total ranging from 0-44. 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. |
Participant flow
Recruitment details
Subjects were 18-60 year old male and female individuals who were currently hospitalized.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Open label treatment with pentazocine | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Open Label |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Mania Symptoms Using 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.
Time frame: hourly for 6 hours after first dose of pentazocine; hour 0 is the baseline score and also when first dose of pentazocine was administered
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Group | Mania Symptoms Using MACS | Hour 2 | 18.6 units on a scale | Full Range 8.9 |
| Open Label Group | Mania Symptoms Using MACS | Hour 3 | 11.0 units on a scale | Full Range 6.9 |
Comparison: comparison of mean scores at hour 2 vs 3p-value: 0.01ANOVA
Secondary
YMRS Scores
Assessment of current mania symptoms using YMRS. All questions have a 0 (absent)-4(most severe) range for describing mania symptoms. The mean YMRS scores were reported, with the total ranging from 0-44. 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.
Time frame: Each morning of the three-day study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Group | YMRS Scores | pre-treatment day | 23.6 units on a scale | Standard Deviation 8.9 |
| Open Label Group | YMRS Scores | treatment day | 22.0 units on a scale | Standard Deviation 6.9 |
| Open Label Group | YMRS Scores | post-treatment day | 12.7 units on a scale | Standard Deviation 8.4 |
Comparison: comparison of mean score on treatment vs post-treatment daysp-value: 0.01t-test, 1 sided
Comparison: comparison of mean scores at pre-treatment vs treatment daysp-value: 0.4t-test, 1 sided