There are tons of anxiety treatments on the market today. From supplements to holistic approaches to benzodiazepine, there’s an option for almost every lifestyle and preference. However, it’s important to note that not every treatment works for every person. While it’s easy to find tons of blogs and articles promoting yoga’s effectiveness on anxiety, it’s much more difficult to find substantive clinical backing for their claims.

The same can be said for some pharmaceutical treatments, too. One such potential drug that’s been making rounds in recent years is Depakote for anxiety management. Depakote is the brand name for valproic acid, also known as divalproex sodium or valproate. But is it safe and effective as an anxiety treatment?

That’s what we aim to find out. In this article, we’re going to look at:

  • What Depakote is
  • Risks of taking Depakote
  • Using Depakote for anxiety
  • Studies on the effectiveness of Depakote

What is Depakote?

According to the FDA, Depakote is an anticonvulsant (antiepileptic) drug approved to: 1 2

  • Manage seizure disorders, such as complex partial, simple, and complex absence seizures
  • Mitigate manic episodes associated with bipolar disorder
  • Prevent the onset of migraine headaches

It’s also important to note that the above are only the approved uses for Depakote. Doctors also use Depakote to treat a number of other disorders “off-label,” such as: 2 3

  • Neuropathy (nerve damage)
  • Neuralgia (nerve pain)
  • Conditions of traumatic brain injuries
  • Anxiety disorders (often comorbid with mood disorders)

How Does Depakote Work?

Depakote for anxiety : How does it work?

The FDA asserts that Depakote begins to work once your gastrointestinal tract breaks it down to its component molecule, valproate. However, the exact mechanism by which Depakote functions after that point is as yet unknown. Current research suggests that it may increase concentrations of GABA in your brain. GABA, or gamma-aminobutyric acid, is a neurotransmitter that activates a GABA receptor. This protein is responsible for creating calming effects in your brain – and it’s by this mechanism the FDA believes Depakote reduces seizure, mood, migraine activity. 4

Risks of Depakote

No medication comes without the risk of adverse side effects. Many of the side effects of Depakote are fairly mild and may include: 1 2

  • Abdominal pain
  • Bowel concerns
  • Dizziness
  • Nausea and vomiting
  • Sleepwalking
  • Tinnitus
  • Weight fluctuations

However, Depakote has been known to cause more serious issues in some users, especially at higher doses. As a result, the FDA has issued a black box warning for the drug to alert users to its most dangerous side effects. Some of these complications may include: 1

  • Liver disease
  • Bleeding disorders
  • Hypothermia
  • Toxicity
  • Pancreatitis
  • Suicidal thoughts or actions

Additionally, Depakote is known to cause fetal and birth defects, such as decreased IQ and neurodevelopmental disorders. Your doctor should discuss these risks and others, as well as your medical history, before starting you on Depakote. 1 2

Using Depakote for Anxiety

Depokate for anxiety

We’ve already touched on the fact that Depakote is thought to work on the GABA receptors in your brain to calm seizures, migraines, and mood instabilities. However, we’re here to talk about anxiety. So, let’s take a look at the link between anxiety and GABA, as well. 

GABA and Your Brain

GABA is a naturally occurring amino acid that acts as a neurotransmitter. (A neurotransmitter is a chemical that passes messages through your brain via neurons, proteins, and synapses, or the spaces between your neurons). In the case of GABA, this amino acid is an inhibitory neurotransmitter, which means it blocks your brain from sending these messages between neurons. In turn, this reduces nervous system activity, particularly in your brain. 4

When GABA enters a GABA receptor, it halts your brain’s reuptake process, which increases the amount of GABA in your brain. It’s this mechanism that scientists believe reduces seizure and migraine activity in the brain. However, your GABA receptors are responsible for more than that – they’re also linked to feelings of stress, fear, and anxiety. 4

Studies show that individuals with anxiety, panic and mood disorders, ADHD, and epilepsy often have lower levels of GABA in their brains. Without this neurotransmitter, the brain cannot activate enough GABA receptors to keep calm and happy. Thus, by increasing the amount of GABA – such as with Depakote – individuals can address the problem at its source to calm down frantic, misfiring, or anxious brains. 4

Studies on Depakote for

There are regrettably, few studies on Depakote for anxiety management. Typically, anxiety is an afterthought or complicating factor – these studies often focus on seizure or mood disorders directly, with anxiety listed as a comorbid condition. However, there is enough early clinical data to peek at Depakote’s potential efficacy as an anxiety treatment. 

Study 1: Effects of Depakote on Bipolar Disorder & Anxiety


This review extrapolated data from fourteen treatment studies of bipolar individuals with comorbid anxiety disorders. The authors of this study looked at 59 years of scientific literature ranging from 1950 to August of 2009 via multiple databases. While the authors concluded that most studies focused on treating anxiety disorders during manic episodes, there was still enough evidence to support theories that:

  • Divalproex sodium reduces panic disorder in bipolar individuals
  • Divalproex sodium shows promise as an anxiolytic when combined with quetiapine or olanzapine
  • Valproate (which Depakote breaks down to in the digestive tract) has potential as an anti-anxiety medication

From this data, the authors also concluded that anxiety symptoms improve as a result of treating the underlying mood disorder. Additionally, they stated that “divalproex may be the mood stabilizer of choice” for individuals with both bipolar and anxiety disorders.

Study 2: Depakote for Comorbid Panic & Mood Disorders


This 8-week, open-trial outpatient study worked with individuals with comorbid panic and mood disorders. To be eligible, participants had to have failed to respond to standard anti-panic meds, as well as a cognitive behavioral treatment program. In total, 10 patients received divalproex sodium at “flexible doses” up to 90ug/mL and answered questionnaires on their panic attacks, depression, anxiety, mood swings, and sense of well-being. In all ten patients, researchers found:

  • Significant improvement in depression, anxiety, and mood instability
  • Clinically significant improvement in panic attacks
  • Statistically significant improvement in “quality of life” measures

At the end of the study, researchers concluded that Depakote for anxiety was a viable treatment if the individual also suffered from mood instability. However, they acknowledged that further double-blind studies would be needed to verify their findings. 

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