Bipolar, Mania, Bipolar, Mixed State
Conditions
Keywords
treatment of bipolar, mania, double-blind, placebo-controlled study, drug intervention, add-on study, prazosin, alpha-1 adrenergic antagonist
Brief summary
Mania has been considered to be, in part, a hyperadrenergic state. One focus of treatment of mania involves directly targeting this hyperexcitable state by reducing arousal with antiadrenergic agents. This can be achieved by decreasing norepinephrine release by stimulating presynaptic inhibitory receptors. Prazosin, FDA approved for the treatment of high blood pressure works in part by blocking postsynaptic alpha-adrenergic receptors. Prazosin has been found to be clinically useful for the treatment of Post Traumatic Stress Disorder. It is reasonable, therefore, to anticipate that prazosin might be helpful in the treatment of mania.
Interventions
DRUGAddition of prazosin to usual care (add-on study)
Prazosin and placebo will be gradually titrated over 10 days to a final dose of 10 mg/day, given in divided doses (three times a day). During this time subjects will be monitored for adverse effects to prazosin and manic symptoms will be monitored. Vital signs will be monitored three times a day throughout the study. If a subject receiving prazosin or placebo develops distressing adverse effects, the dose will be decreased to the next lower dose.If there is a greater than 15 mg mercury postural fall in systolic bBP, dosing will be held at the previous day's dose.Subjects who do not tolerate prazosin or placebo will be discharged from the study.
DRUGPlacebo
Prazosin and placebo will be gradually titrated over 10 days to a final dose of 10 mg/day, given in divided doses (three times a day). During this time subjects will be monitored for adverse effects to prazosin and manic symptoms will be monitored. Vital signs will be monitored three times a day throughout the study. If a subject receiving prazosin or placebo develops distressing adverse effects, the dose will be decreased to the next lower dose.If there is a greater than 15 mg mercury postural fall in systolic bBP, dosing will be held at the previous day's dose.Subjects who do not tolerate prazosin or placebo will be discharged from the study.
Sponsors
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-60 * Primary diagnosis of bipolar disorder with severe mania or mixed episode * YMRS score of \> 20 * Documented medical evaluation without acute or serious medical illness * Negative pregnancy test * Healthy functioning liver
Exclusion criteria
* Lack of capacity to provide informed consent * Involuntary commitment * Low blood pressure * History of adverse reaction or allergy to prazosin or other quinazolines * Informed consent not given or retracted during study * History of narcolepsy * Unstable or acute medical illness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Young Mania Rating Scale (YMRS) | 10 days |
Secondary
| Measure | Time frame |
|---|---|
| Mania Acute Changes Scale (MACS) | 10 days |
Outcome results
None listed