Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
Condition: Hyperactive Delirium; Mixed Delirium
MeSH terms: Delirium; Hyperkinesis; Psychomotor Agitation
Intervention: Valproic Acid; Placebo; Haloperidol
Intervention description: 1.
Start:
VPA PO/NGT 500 mg BID
2.
If need to increase in 24 or more hours:
VPA 500 mg PO/NGT q am, 1000 mg PO/NGT QHS
3.
If need to increase in 24 or more hours:
VPA 500 mg PO/NGT q am, 1500 mg PO/NGT QHS
4.If need to increase in 24 or more hours:
VPA 500 mg PO/NGT Q am, 2000 mg PO/NGT QHS; Placebo 500 mg matched to VPA BID PO/NGT; Both arms (intervention VPA and placebo) will receive flexible as needed haloperidol: Rescue: HAL IV 2-5 mg Q4hr PRN
Intervention MeSH terms: Valproic Acid; Haloperidol; Haloperidol decanoate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hyperactive delirium; Mixed delirium; Anti-psychotic; Haldol; Valproic Acid

Summary:

      Delirium is the most often encountered psychiatric diagnosis in the general hospital, with
      incidence up to 85% in the intensive care unit (ICU) setting and with significant
      consequences on patients' morbidity and mortality. Currently, although not FDA approved,
      antipsychotics are often considered the first-line pharmacological treatment. However, there
      can be limitations to their use, including side effects or lack of efficacy. Valproic acid
      (VPA) is one of the alternatives at times used in such patients which from limited case
      series data appears to be helpful and tolerated. VPA can provide relief from agitation that
      poses a threat to the safety and recovery of the patient. Moreover, mechanistically it
      addresses the neurochemical and cellular abnormalities inherent in delirium (it has
      NMDA-antagonist, anti-dopaminergic, GABAergic,anti-inflammatory, anti-apoptotic, and histone
      deacetylase inhibitor properties, among others). The purpose of this study is to evaluate the
      efficacy and tolerability of the VPA in the first known to us randomized controlled trial.
    

Eligibility criteria:

        Inclusion Criteria:

          -  patients 18 years of age and older

          -  admitted to surgical ICU

          -  diagnosed with hyperactive or mixed delirium

        Exclusion Criteria:

          -  hypoactive delirium

          -  primary team does not think patient is appropriate to participate

          -  no oral access (PO or NGT)

          -  non-English speaking

          -  contraindication to study medications

          -  pregnant women or woman of child-bearing age not on documented contraception

          -  QTc = or greater than 480

          -  hepatic dysfunction

          -  decreased platelets or platelet dysfunction

          -  bleeding disorder, current major bleeding

          -  history of NMS, epilepsy, or PD

          -  diagnosis of schizophrenia, bipolar disorder or schizoaffective disorder

          -  on warfarin or carbapenems

          -  delirium due to alcohol withdrawal

          -  treated with antipsychotics for more than 48 hours prior to study enrollment.