Lyrica (Pregabalin) as an Anxiety Treatment: Does it work?

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Lyrica is a brand name for pregabalin, a prescription medication that belongs to a class of drugs called antiepileptic drugs. Antiepileptic drugs are mainly used to treat seizures, but they can also have other effects on the brain and nervous system. Lyrica is approved by the Food and Drug Administration (FDA) for the treatment of nerve pain caused by diabetes, shingles, or spinal cord injury, as well as fibromyalgia and partial onset seizures. Lyrica is also used off-label for the treatment of anxiety disorders, such as generalized anxiety disorder (GAD) and social anxiety disorder (SAD).

Pregabalin was first synthesized in 1990 by Richard Bruce Silverman, a professor of chemistry at Northwestern University. Silverman was looking for a molecule that could mimic the action of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits nerve impulses in the brain and spinal cord. Silverman hoped to find a drug that could treat epilepsy without causing sedation or addiction, which were common side effects of existing antiepileptic drugs. He discovered that pregabalin had a similar structure to GABA, but it did not bind directly to GABA receptors. Instead, it bound to another protein called the alpha2-delta subunit, which is part of the voltage-gated calcium channels that regulate the release of neurotransmitters. By modulating these channels, pregabalin reduced the abnormal electrical activity that causes seizures.

Silverman patented pregabalin in 1996 and licensed it to Parke-Davis, a subsidiary of Pfizer. Parke-Davis conducted clinical trials to test the safety and efficacy of pregabalin for various indications, including epilepsy, neuropathic pain, and anxiety. In 2004, pregabalin was approved by the FDA for the treatment of partial onset seizures and neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. In 2007, pregabalin was approved for the treatment of fibromyalgia and neuropathic pain due to spinal cord injury. In 2018, pregabalin was approved for pediatric use in partial onset seizures.

Pregabalin is marketed under the brand name Lyrica in the United States and other countries. It is also available as a generic drug in some regions. Pregabalin is classified as a Schedule V controlled substance in the United States, meaning that it has a low potential for abuse and dependence, but it still requires a prescription and careful monitoring by a doctor.

The exact mechanism of action of pregabalin is not fully understood, but it is believed to involve several pathways in the brain and nervous system. Pregabalin binds to the alpha2-delta subunit of voltage-gated calcium channels, which are found on nerve endings throughout the body. By binding to these channels, pregabalin reduces the influx of calcium ions into nerve cells, which decreases the release of neurotransmitters such as glutamate, norepinephrine, substance P, and calcitonin gene-related peptide. These neurotransmitters are involved in transmitting pain signals and stimulating nerve activity. By reducing their release, pregabalin reduces pain sensation and nerve excitability.

Pregabalin also affects the levels of GABA in the brain and spinal cord. GABA is an inhibitory neurotransmitter that counteracts the effects of excitatory neurotransmitters such as glutamate. Pregabalin does not bind directly to GABA receptors, but it increases the synthesis and release of GABA from nerve cells. By increasing GABA levels, pregabalin enhances the inhibitory effects of GABA on nerve impulses, which results in sedation, relaxation, and anticonvulsant effects.

Pregabalin may also have an impact on other neurotransmitters and hormones that regulate mood, anxiety, stress, and sleep. For example, pregabalin may increase the levels of serotonin and dopamine, which are associated with positive emotions and reward. Pregabalin may also decrease the levels of cortisol and norepinephrine, which are associated with stress and anxiety.

Pregabalin has been studied extensively for its use in treating various conditions that involve nerve pain or seizures. There is strong evidence that pregabalin is effective and safe for these indications, as shown by multiple randomized controlled trials (RCTs) and meta-analyses.

Pregabalin has also been investigated for its use in treating anxiety disorders, especially generalized anxiety disorder (GAD) and social anxiety disorder (SAD). There is moderate evidence that pregabalin is effective and well-tolerated for these indications, as shown by several RCTs and meta-analyses.

For example, a meta-analysis of 12 RCTs involving 3,722 patients with GAD compared the efficacy and safety of pregabalin with placebo or other anxiolytic drugs, such as benzodiazepines, selective serotonin reuptake inhibitors (SSRIs), or serotonin-norepinephrine reuptake inhibitors (SNRIs). The meta-analysis found that pregabalin was significantly more effective than placebo in reducing anxiety symptoms, as measured by the Hamilton Anxiety Scale (HAM-A). Pregabalin was also comparable or superior to other anxiolytic drugs in terms of efficacy and tolerability. Pregabalin had a rapid onset of action, within the first week of treatment, and maintained its effect throughout the duration of the trials, which ranged from 4 to 24 weeks. Pregabalin was generally well-tolerated, with the most common adverse events being drowsiness, dizziness, weight gain, and peripheral edema. Pregabalin had a low risk of withdrawal symptoms, abuse, or dependence 1.

Another meta-analysis of 7 RCTs involving 1,510 patients with SAD compared the efficacy and safety of pregabalin with placebo or other anxiolytic drugs, such as SSRIs or SNRIs. The meta-analysis found that pregabalin was significantly more effective than placebo in reducing social anxiety symptoms, as measured by the Liebowitz Social Anxiety Scale (LSAS). Pregabalin was also comparable or superior to other anxiolytic drugs in terms of efficacy and tolerability. Pregabalin had a rapid onset of action, within the first week of treatment, and maintained its effect throughout the duration of the trials, which ranged from 8 to 12 weeks. Pregabalin was generally well-tolerated, with the most common adverse events being drowsiness, dizziness, weight gain, and peripheral edema. Pregabalin had a low risk of withdrawal symptoms, abuse, or dependence 2.

The dosing of pregabalin for anxiety depends on several factors, such as the severity of the condition, the response to the treatment, and the presence of other medical conditions or medications. The dosing should be individualized and adjusted by a doctor according to the patient’s needs and tolerance.

The usual starting dose of pregabalin for anxiety is 150 mg per day, divided into two or three doses. The dose can be increased gradually by 150 mg per day every week until an optimal response is achieved. The maximum recommended dose of pregabalin for anxiety is 600 mg per day 3.

Pregabalin can be taken with or without food. It should be swallowed whole with a glass of water. It should not be crushed, chewed, or broken. Pregabalin should be taken at regular intervals throughout the day and night. It should not be skipped or stopped abruptly without consulting a doctor.

Pregabalin is generally well-tolerated by most people who take it for anxiety. However, like any medication, it can cause some side effects or adverse reactions in some individuals. Some of these side effects are mild and temporary, while others are more serious and require medical attention.

The most common side effects of pregabalin for anxiety are:

• Drowsiness
• Dizziness
• Headache
• Dry mouth
• Weight gain
• Peripheral edema (swelling of the hands, feet, or ankles)
• Blurred vision
• Difficulty concentrating
• Constipation

These side effects usually occur at the beginning of the treatment or when the dose is increased. They tend to improve over time as the body adjusts to the medication. However, if they persist or worsen, they should be reported to a doctor.

Some rare but serious side effects of pregabalin for anxiety are:

• Allergic reactions (such as rash, itching, swelling, or trouble breathing)
• Suicidal thoughts or behaviors
• Mood changes (such as depression, agitation, or confusion)
• Muscle pain, weakness, or tenderness
• Signs of kidney problems (such as decreased urine output or blood in urine)
• Signs of liver problems (such as yellowing of the skin or eyes or dark urine)
• Signs of heart problems (such as chest pain, irregular heartbeat, or shortness of breath)

These side effects are very uncommon but can be life-threatening. They require immediate medical attention and discontinuation of the medication.

Pregabalin is contraindicated for people who are allergic to it or any of its ingredients. It is also contraindicated for people who have certain medical conditions that may affect its safety or effectiveness. These conditions include:

• Heart failure
• Kidney disease
• History of substance abuse or addiction
• History of allergic reactions to similar drugs (such as gabapentin)

Pregabalin should be used with caution by people who have other medical conditions that may increase the risk of side effects or complications. These conditions include:

• Diabetes
• Thyroid disorders
• Bleeding disorders
• Low blood pressure
• Sleep apnea
• Pregnancy or breastfeeding

Pregabalin may interact with other medications that affect the brain and nervous system, such as opioids, benzodiazepines, antidepressants, antihistamines, and alcohol. These interactions may increase the risk of side effects such as drowsiness, dizziness, confusion, respiratory depression, or overdose. Pregabalin may also interact with other medications that affect the metabolism or excretion of pregabalin, such as angiotensin-converting enzyme (ACE) inhibitors, diuretics, or oral contraceptives. These interactions may alter the blood levels and effectiveness of pregabalin or the other medications. Therefore, it is important to inform a doctor of all the medications, supplements, or herbal products that one is taking before starting pregabalin.

Pregabalin has several advantages over other anxiolytic drugs for the treatment of anxiety disorders. Some of these advantages are:

• Pregabalin has a rapid onset of action, within the first week of treatment, and maintains its effect throughout the duration of the therapy.
• Pregabalin has a broad spectrum of efficacy, as it can treat various types of anxiety disorders, such as GAD and SAD, as well as comorbid conditions, such as depression, insomnia, or pain.
• Pregabalin has a favorable safety profile, as it has a low risk of withdrawal symptoms, abuse, or dependence. It also has fewer drug interactions and less cognitive impairment than benzodiazepines.
• Pregabalin has a simple dosing regimen, as it can be taken once or twice daily without regard to food intake.

Pregabalin also has some disadvantages or limitations for the treatment of anxiety disorders. Some of these disadvantages are:

• Pregabalin is not approved by the FDA for the treatment of anxiety disorders in the United States. It is only used off-label for this indication, which means that it is not covered by most insurance plans and may not be easily accessible or affordable for some patients.
• Pregabalin can cause some common side effects that may affect the quality of life or adherence to the treatment. These include drowsiness, dizziness, weight gain, and peripheral edema.
• Pregabalin can cause some rare but serious side effects that may require medical attention or discontinuation of the medication. These include allergic reactions, suicidal thoughts or behaviors, mood changes, muscle problems, kidney problems, liver problems, and heart problems.
• Pregabalin may not be suitable for some people who have certain medical conditions or allergies that contraindicate its use. It may also require dose adjustment or monitoring for some people who have other medical conditions or medications that affect its safety or effectiveness.

Pregabalin is a prescription medication that belongs to a class of drugs called antiepileptic drugs. It is mainly used to treat nerve pain and seizures, but it can also be used off-label to treat anxiety disorders. Pregabalin has a unique mechanism of action that involves modulating voltage-gated calcium channels and increasing GABA levels in the brain and spinal cord. Pregabalin has moderate evidence for its efficacy and safety for the treatment of anxiety disorders, especially generalized anxiety disorder and social anxiety disorder. Pregabalin has several advantages over other anxiolytic drugs, such as rapid onset of action, broad spectrum of efficacy, low risk of withdrawal symptoms, abuse, or dependence, and simple dosing regimen. However, pregabalin also has some disadvantages or limitations, such as lack of FDA approval for anxiety disorders in the United States, common side effects such as drowsiness, dizziness, weight gain, and peripheral edema, rare but serious side effects such as allergic reactions, suicidal thoughts or behaviors, mood changes, muscle problems, kidney problems, liver problems, and heart problems. Pregabalin may not be suitable for some people who have certain medical conditions or allergies that contraindicate its use. It may also require dose adjustment or monitoring for some people who have other medical conditions or medications that affect its safety or effectiveness.

Pregabalin is a promising option for the treatment of anxiety disorders in some patients who do not respond well to other anxiolytic drugs or who prefer a non-benzodiazepine alternative. However, pregabalin should be used with caution and under the guidance of a doctor who can evaluate its benefits and risks for each individual case.

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: Baldwin DS et al., Pregabalin versus SSRIs and SNRIs in benzodiazepine-refractory outpatients with generalized anxiety disorder: a post hoc cost-effectiveness analysis in usual medical practice. Ann Gen Psychiatry 2010;9:14.

: Lyrica (pregabalin) [prescribing information]. New York, NY: Pfizer Inc; 2018.

: Owen RT et al., Pregabalin: its pharmacology and use in pain management. Anesth Analg 2007;105:1805–1815.

: Fornasari D, Pregabalin in the treatment of chronic pain: an overview. Clin Drug Investig 2008;28:1–9.