Anxiolytic drugs off-label: types, risks and safety

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There are several off-label drugs that a doctor can prescribe for anxiety, including beta blockers or anti-seizure drugs.

Propranolol (Inderal)

Propranolol belongs to a class of drugs called beta blockers. These drugs are approved to treat heart disease and high blood pressure. They block the effects of the stress hormones epinephrine and norepinephrine.

Propranolol is commonly prescribed off-label for anxiety. Many people, such as students, lecturers, and performers, take it to reduce symptoms of physical anxiety before a test or before going on stage.

Propranolol can reduce the following anxiety symptoms:

  • tremor
  • Rapid pulse
  • dry mouth
  • nausea
  • dizziness
  • sweaty hands

Research suggests that propranolol may be just as effective as benzodiazepines (such as Xanax) for panic in the short-term treatment of panic disorder.

Benzodiazepines are a class of drugs approved by the FDA for the treatment of anxiety. They work by increasing the neurotransmitter gamma-aminobutyric acid (GABA) in the brain, which has a relaxing and sedating effect.

Propranolol may be a good alternative to benzodiazepines, as many doctors are less inclined to prescribe them due to the higher risk of addiction and withdrawal.

Side effects of propranolol can include:

  • fatigue and weariness
  • cold fingers or toes
  • dizziness
  • sleep problems or nightmares

Pregabalin (Lyrica)

Pregabalin is an anti-epileptic drug approved to treat partial seizures by slowing down impulses in the brain. It can also treat nerve pain by changing chemicals in the brain that send pain signals through the nervous system.

Pregabalin is also prescribed off-label as an anxiolytic. Experts believe that pregabalin reduces anxiety by reducing the release of excitatory neurotransmitters, like glutamate.

Research suggests that pregabalin may be effective in reducing symptoms of generalized anxiety disorder (GAD). TAG involves excessive, persistent and inappropriate worrying that is not related to specific circumstances.

The side effects of pregabalin can include:

  • dizziness
  • dry mouth
  • swelling
  • Blurred vision
  • weight gain
  • abnormal thinking
  • drowsiness or drowsiness

More serious side effects include swelling of the throat or head and hypersensitivity reactions, such as hives or difficulty breathing.

Gabapentin (Neurontine)

Gabapentin is another anti-epileptic drug approved for partial seizures and nerve pain.

It is frequently used off-label to treat anxiety disorders and post-traumatic stress, because it improves the transmission of GABA.

A 2015 review several studies have found evidence that gabapentin can treat symptoms of social anxiety disorder and post-traumatic stress disorder (PTSD).

Gabapentin also reduced participants’ anxiety before surgery and reduced symptoms in some people with panic disorder.

Additionally, there is some evidence that gabapentin may work with fluoxetine (Prozac) to reduce symptoms of obsessive-compulsive disorder (OCD). However, the positive effects of adding gabapentin to fluoxetine treatment seemed to stop working by week four.

Some states have recently classified gabapentin as a controlled substance. This is due to its potential for abuse, as it increases the effects of opioids and may contribute to overdose.

Common side effects of gabapentin can include:

  • fatigue or weakness
  • dizziness
  • headache
  • drowsiness
  • tremor
  • Blurred vision

Memantine (Namenda)

Memantine belongs to a class of drugs called NMDA receptor antagonists. This drug is currently approved for the treatment of Alzheimer’s disease, but there is growing interest in its potential use for OCD.

If you have OCD, you may also experience anxiety, although OCD is not officially considered an anxiety disorder by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).

Memantine appears to work by altering the activity of glutamate, a neurotransmitter that is increasingly believed to play a role in OCD.

In a small 2013 study12 people with OCD were enrolled in a 12-week memantine trial. Of the 12 participants, 8 showed a clear benefit, with a reduction of 25% or more on an OCD symptom scale.

No side effects were observed in the study, but more participation is needed for a better understanding of the effectiveness of the drug.

Side effects of memantine can include:

  • tired
  • dizziness
  • headache
  • body or joint pain
  • nausea or vomiting
  • gastrointestinal problems, including diarrhea or constipation
  • weight gain

Quetiapine (Seroquel)

Quetiapine is an atypical antipsychotic drug that doctors prescribe to treat:

This medicine carries a risk of serious side effects. Doctors tend to only prescribe it off-label if you have severe treatment-resistant anxiety or treatment-resistant depression.

Studies suggest that quetiapine may be an effective treatment for GAD, but it tends to have poor tolerance, which is the degree to which people can cope with the side effects of the drug.

Side effects of quetiapine can include:

  • tired
  • dizziness
  • nausea and vomiting
  • mood swings
  • constipation
  • dry mouth

The most serious symptoms include uncontrolled muscle movements, high blood sugar, and difficulty speaking or swallowing.

Valproate

Valproate and its many forms are drugs primarily prescribed to treat epilepsy, migraine, and bipolar disorder. Here are some of its shapes:

  • valproic acid
  • sodium valproate
  • semi-sodium valproate

It increases GABA in the brain.

In a small study 2020, 26 of 36 men with GAD responded to valproate with at least a 50% reduction in symptoms. The most common side effects were dizziness and nausea.

Side effects of valproate can include:

  • nausea or vomiting
  • drowsiness
  • dizziness
  • weakness
  • hair loss

Serious side effects include:

  • bleeding
  • low blood platelet count
  • suicidal thoughts
  • encephalopathy, a change in the function or structure of the brain
  • low body temperature

Valproate is not considered safe to take during pregnancy.

Baclofen (Lioresal)

Baclofen is in a class of drugs called skeletal muscle relaxers. Doctors usually prescribe these medications for pain, muscle stiffness, and spasms associated with multiple sclerosis (MS) and spinal cord injury.

Baclofen activates GABA receptors, causing a feeling of calm.

Doctors may prescribe it off-label for anxiety, especially anxiety related to alcohol withdrawal. A 2014 study found that baclofen was effective in reducing anxiety in people addicted to alcohol.

Side effects of baclofen can include:

  • drowsiness
  • muscular weakness
  • dizziness
  • confusion
  • nausea

Risperidone (Risperdal)

Risperidone is an atypical antipsychotic drug commonly used to treat:

  • schizophrenia
  • manic episodes of bipolar disorder or mixed episodes
  • irritability in autism

Risperidone can rebalance the levels of the neurotransmitters dopamine and serotonin, which can improve mood, thinking and behavior.

Doctors sometimes prescribe off-label risperidone for severe anxiety that is resistant to treatment. It has been used to treat GAD, and a growing body of evidence suggests that it may help treat OCD as well.

A 2011 study found that risperidone was effective in treating OCD, but unwanted side effects were common.

Side effects of risperidone can include:

  • commotion
  • dizziness
  • nausea
  • drowsiness
  • anxiety
  • weight gain

Serious side effects can include extrapyramidal symptoms, which are drug-induced movement disorders. These may include:

  • akathisia, a feeling of restlessness and inability to sit still
  • dystonia, involuntary muscle contractions


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