Prazosin as an Antimanic Agent in Severe Mania or Mixed States

Study Overview
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Brief Summary
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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.

Official Title
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Prazosin as an Antimanic Agent in Severe Mania or Mixed Episodes: a Double-blind, Placebo-controlled Study

Conditions
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Bipolar, Mania, Bipolar, Mixed State

Intervention / Treatment
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* Drug: Addition of prazosin to usual care (add-on study)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: prazosin<br>Add prazosin to usual medications and monitor manic symptoms and for adverse effects | Drug: Addition of prazosin to usual care (add-on study)<br>* 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.<br>* Other names: Minipress;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Young Mania Rating Scale (YMRS) |  | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mania Acute Changes Scale (MACS) |  | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug intervention, prazosin, alpha-1 adrenergic antagonist, treatment of bipolar, mania, double-blind, placebo-controlled study, add-on study