Clinical trial NCT01760785: Valproate for Mood Swings and Alcohol Use Following Head Injury
Official title: A Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Traumatic Brain Injury (TBI)
Alcoholism
Keywords: Veterans
Traumatic Brain Injury(TBI)
Alcoholism
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2013-01-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Successful treatment of traumatic brain injury (TBI)-induced mood lability may reduce or eliminate drinking behaviors in persons with alcohol abuse/dependence (AA/D) and affective lability following TBI. Observed clinically, the symptoms of poorly regulated affective expression of AA/D+TBI patients who reach alcohol abstinence do not appear to be those of an idiopathic mood or anxiety disorder. These symptoms do not present the severity or the same natural courses as do Major Depressive Disorder, Bipolar Illness, or Anxiety Disorder, for example. Instead, both symptoms and course appear more characteristic of the sustained affect lability often observed following TBI. This observation suggests that TBI survivors represent a patient group for whom treatment of neuropsychiatric symptoms following TBI may alleviate both TBI-related affect lability and also heavy ethanol use by treating the condition that is contextually related to excessive alcohol use.

Based on this concept of consequently treating AA/D through the management of post-TBI affective lability, this study was conducted observing the efficacy of divalproex sodium on the severity of affective lability and AA/D in persons suffering from a moderate TBI. Divalproex sodium has been shown to ameliorate mood disorders, even in those with substance abuse problems. This drug has also shown positive results as an alternate medication to benzodiazapines in the treatment of alcohol withdrawal, significantly reducing the progression of withdrawal symptoms in patients.

Detailed description: Despite the body's natural healing during the first year after a head injury, many veterans who have suffered even mild brain injuries find themselves easily upset or fearful as they go about their daily lives. While these reactions to the world around them were easily managed before the head injury, they now occur with little or no interruption and are exceedingly difficult to manage. Such reactions include a sense of always being upset or fearful that often makes it difficult to get along with family members, friends, coworkers, and employers. This may lead to broken marriages, unemployment, and even homelessness.

Some people with head injuries try to manage their unmanageable moods by drinking alcohol because it can create a sense of calm. However, alcohol's actions are short in duration. Most find that they have to drink more and more for a similar calming effect, and they soon become dependent on alcohol. This makes working and being part of their families even more difficult.

To treat the unmanageable mood, we tried a medicine called valproate, one that eases mood problems in people without head injury. We gave valproate to head injured persons with mood problems in a "non-blinded" study where both the doctor and the patient knew that the medicine was valproate and both were optimistic that it would work. In a small sample of eighteen people, 85% found mood relief and most of those either stopped drinking alcohol or drank much less than before. However, this might have been because both the doctor and patient were hopeful that the medication would make the patient feel better or because the medicine actually worked.

The only way to know for sure if the medicine works is to perform a study in which people receive either valproate or a sugar pill while neither they nor their doctor know which one they are taking. This is called a double blind study, as proposed here, and will involve nearly three times as many head injured persons as the first study.

If it is successful, the new study will show that valproate treatment helps head injured people manage their moods and allows them to return to families, friends, and work. It will also show that they drink alcohol less or not at all, improving their health even further. Then doctors will know that they can use this medicine for large numbers of people who suffer from head injury and help them to lead normal lives. If the outcome of the study shows that the medicine works well, doctors can then use this medicine to treat people with head injury immediately after the study results are published.

Eligibility criteria: Inclusion Criteria:

* Veteran
* history of closed-head traumatic brain injury (TBI) at least one year prior to enrollment
* symptoms of affective lability such as mood swings, irritability, frustration and anxiety
* currently using alcohol

Exclusion Criteria:

* history of Axis I bipolar disorder or anxiety disorder prior to the TBI
* skull opened either surgically or traumatically
* history of stroke
* current diagnosis or past history of major psychosis as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)
* active liver disease
* evidence of the alcohol amnesic syndrome
* history of seizure disorder other than those caused by ethanol withdrawal
* any type of dementia
* current suicidal/homicidal ideations
* symptomatic thiamine, folate or Vitamin B-12 deficiency
* HIV positive
* any medical conditions that would constitute contraindications to treatment with divalproex sodium

Primary outcomes:
measure: Severity of Affective Lability Based on Shortened Agitated Behavior Scale
timeFrame: Weeks 2 through 8
Secondary outcomes:
measure: Frequency of Alcohol Use
timeFrame: Weeks 1-10
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Veteran's Affairs Medical Center
state: Colorado
Study officials:
affiliation: Denver Veteran's Affairs Medical Center
name: Thomas P Beresford, MD
role: PRINCIPAL_INVESTIGATOR
References: