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Pregabalin (Lyrica) vs. Gabapentin (Neurontin)

Lyrica (pregabalin) and Neurontin (gabapentin) are both classified as “gabapentinoids” (i.e. α2δ ligands).  As gabapentinoids, Lyrica (pregabalin) and Neurontin (gabapentin) are chemical analogues of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) that interact with α2δ subunit-containing voltage-dependent calcium channels.

Development of gabapentin (Neurontin) was initiated in the 1970s by chemists at the pharmaceutical company Parke-Davis – and the chemical was first formally described in 1975.  The synthesis of pregabalin (Lyrica) was initiated between 1988 and 1990 by Ryszard Andruszkiewicz (a researcher) in collaboration with Richard Bruce Silverman (a medicinal chemist) at Northwestern University whereafter its rights were acquired by Parke-Davis.

Neurontin (gabapentin) was first approved by the U.S. FDA in 1993 for the treatment of epilepsy; subsequently in 2002 for the treatment of postherpetic neuralgia; and again in 2011 (in a prodrug format) for the treatment of restless leg syndrome (RLS).  Lyrica (pregabalin) is intended to be the successor to Neurontin (gabapentin) and was first approved by the U.S. FDA in 2004 for the treatment of epilepsy; diabetic neuropathic pain; and postherpetic neuralgia.

Lyrica (Pregabalin) vs. Neurontin (Gabapentin)

Included below is a chart which highlights general attributes of Lyrica (pregabalin) and Neurontin (gabapentin).  Assessing this chart should aid persons in understanding obvious similarities and differences between these gabapentinoids.

 LyricaNeurontin
IngredientPregabalinGabapentin
Drug classificationGabapentinoid (α2δ)Gabapentinoid (α2δ)
Approved medical usesDiabetic neuropathic pain.

Postherpetic neuralgia.

Partial onset seizures (adjunct).

Fibromyalgia.

Neuropathic pain associated with spinal cord injury.
Postherpetic neuralgia.

Partial onset seizures (adjunct).
Off-label usesAlcohol use disorder. Alcohol withdrawal. Anxiety disorders. Hot flashes. Insomnia. Migraine (prophylaxis). Multiple sclerosis-related pain and spasticity. Pruritus. Restless leg syndrome (RLS). Smoking cessation. Tremor (essential or orthostatic).Alcohol use disorder. Alcohol withdrawal. Anxiety disorders. Hot flashes. Insomnia. Migraine (prophylaxis). Multiple sclerosis-related pain and spasticity. Neuropathic pain. Nystagmus (acquired pendular or infantile). Pruritus. Restless leg syndrome (RLS). Smoking cessation. Tremor (essential or orthostatic).
Bioavailability~90% (oral)27% to 60% (Oral) (Bioavailability of gabapentin is inversely proportionate to dose and increases if ingested with a high-protein meal)
FormatsCapsule. Oral solution. (Standard-release)

Tablet. (Controlled-release)
Capsule. Tablet. Oral solution. (Standard-release)

Tablet. (Extended-release)
DosagesCapsule: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg

Oral solution: 20 mg/mL

Tablet (Controlled-release): 82.5 mg, 165 mg, 330 mg
Capsule: 100 mg, 300 mg, 400 mg

Tablet: 600 mg, 800 mg

Oral solution: 250 mg/5mL

Tablet (Extended-release): 300 mg, 600 mg
ManufacturersPfizer Inc.Parke-Davis (Pfizer Inc.)
Legal statusSchedule V (U.S.)Rx (Prescription)-only (U.S.)
Mechanism of actionInhibits α2δ-subunits (α2δ-1 and α2δ-2) of voltage-dependent calcium channels (VDCC).

Dose-dependently increases L-glutamic acid decarboxylase (GAD) expression within the brain.

Modulates branched-chain aminotransferase (BCAT) activation.

Inhibits GABA aminotransferase (GABA-T) and glutamate dehydrogenase (GDH).

Increases GABA synthesis and non-synaptic neurotransmission of GABA.

Decreases glutamate synthesis and neurotransmission of glutamate.
Inhibits α2δ-subunits (α2δ-1 and α2δ-2) of voltage-dependent calcium channels (VDCC).

Dose-dependently increases L-glutamic acid decarboxylase (GAD) expression within the brain.

Modulates branched-chain aminotransferase (BCAT) activation.

Inhibits GABA aminotransferase (GABA-T) and glutamate dehydrogenase (GDH).

Increases GABA synthesis and non-synaptic neurotransmission of GABA.

Decreases glutamate synthesis and neurotransmission of glutamate.
Generic version (?)No.Yes.
Half-Life~6.3 hours~6.5 hours
Common side effectsDizziness. Somnolence. Dry mouth. Edema. Blurred vision. Weight gain. Difficulty concentrating. Increased appetite.Dizziness. Somnolence. Edema (peripheral). Ataxia. Fatigue. Nystagmus. Fever. Nausea. Vomiting. Hostility.
Date approved (U.S.)20041993
Duration of effect8 to 14 hours (standard)

24 hours (controlled-release)
5 to 8 hours (standard)

24 hours (extended-release)
MetabolismN/A (Not significantly metabolized).N/A (Not significantly metabolized).
Onset of action40 to 120 minutes30 to 90 minutes
Dosage equivalence (approximation)50 mg300 mg

Note: The information reported in the above chart might be subject to inaccuracies and/or end up “outdated.” If you have additional questions regarding Lyrica (pregabalin) and/or Neurontin (gabapentin) – contact a medical doctor and/or pharmacist.

Lyrica (Pregabalin) vs. Neurontin (Gabapentin): What are the general differences?

General differences between Lyrica and Neurontin include: release dates; official (FDA-approved) medical uses; dosing, potency, and formatting; bioavailability; onset & duration of action; elimination half-life; side effects (incidence rates); and legal status (in the U.S.). As was previously mentioned, pregabalin (Lyrica) was synthesized in 1990 and approved for medical use in the U.S. in 2004.

Gabapentin (Neurontin) was synthesized in the 1970s and approved for medical use in the U.S. in 1993 – making it the predecessor to pregabalin (Lyrica).  The official FDA-authorized medical uses for pregabalin (Lyrica) and gabapentin (Neurontin) include: postherpetic neuralgia and partial onset seizures (as an adjunct), however, only pregabalin is FDA-authorized to treat: diabetic neuropathic pain; fibromyalgia; and neuropathic pain associated with spinal cord injury.

Although pregabalin (Lyrica) and gabapentin (Neurontin) are both available in the formats of capsule and oral solution – there are a greater number of dosing increments for pregabalin capsules (8 total) than dosing increments for gabapentin capsules (3 total).  That said, unlike pregabalin, gabapentin is also manufactured in tablet format providing 2 additional dosing increments.

Moreover, while pregabalin (Lyrica) and gabapentin (Neurontin) have extremely similar mechanisms of action, some studies suggest that the former (pregabalin) exhibits approximately 6-fold greater affinity for α2δ subunit-containing voltage-dependent calcium channels (VDCCs) – than the latter (gabapentin).  Other sources estimate that pregabalin is 2-to-4-fold and 3-to-10-fold more potent than gabapentin as an analgesic and anticonvulsant, respectively.

The oral bioavailability of pregabalin (Lyrica) at ~90% is significantly greater than that of gabapentin (Neurontin) ranging from ~27% to ~60% (depending on dosage and whether administered with a high-fat meal).  (The oral bioavailability of pregabalin (Lyrica) is not affected by dosage or whether administered with a meal).

Because pregabalin (Lyrica) is understood to be more bioavailable and potent in its voltage-dependent calcium channel modulation than gabapentin (Neurontin) – the recommended dosages of pregabalin to treat medical conditions are lower than those of gabapentin.  Some sources estimate that a dose of ~50 mg pregabalin (Lyrica) might be roughly equivalent to ~300 mg gabapentin (Neurontin).

Furthermore, there might be subtle differences in the respective onsets of action associated with pregabalin (Lyrica) and gabapentin (Neurontin).  Pregabalin is estimated to take effect within 40 to 120 minutes of administration – and that gabapentin is estimated to take effect within 30 to 60 minutes of administration.

Although pregabalin (Lyrica) might “kick in” slightly slower than gabapentin (Neurontin), the duration of action for standard pregabalin is longer (8 to 14 hours) than the duration of action for standard gabapentin (5 to 8 hours).  There appears to be a modest difference in the average elimination half-life of pregabalin (~6.3 hours) relative to the average elimination half-life of gabapentin (~6.5 hours).

There are also subtle differences in the incidence rates of side effects associated with pregabalin (Lyrica) and gabapentin (Neurontin).  According to side effect data compiled by the FDA, pregabalin is more likely (than gabapentin) to cause: blurred vision, weight gain, difficulty concentrating, dry mouth, and increased appetite – and gabapentin is more likely (than pregabalin) to cause: ataxia, fatigue, nystagmus, fever, nausea, vomiting, and hostility.

Abuse Liability & Addiction Potential

Both pregabalin (Lyrica) and gabapentin (Neurontin) are understood to exhibit modest abuse liability and addiction potential.  Based on current knowledge of pregabalin and gabapentin pharmacodynamics, respectively, some may argue that these medications have zero clinically-relevant abuse liability or addiction potential.

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A systematic review Bonnet and Scherbaum (2017) which included 106 studies involving pregabalin and/or gabapentin reported that there were no data to substantiate addiction risk associated with gabapentinoids.  Researchers suggested that gabapentinoids like pregabalin and gabapentin lack significant “rewarding properties” necessary for induction of addiction.

The aforementioned review also noted that, in the medical literature, there are only 4 cases in which gabapentinoid-related dependence occurred in persons without a history of substance abuse.  Moreover, none of the data compiled by researchers indicate that patients deliberately request gabapentinoids for the treatment of medical conditions (such as commonly occurs with addictive substances).

The researchers did state that pregabalin (Lyrica) appears slightly more addictive than gabapentin (Neurontin) in aspects such as: magnitude of behavioral dependence symptoms; transitions from prescription to self-administration; and durability of self-administration.  It was noted that the principal population at risk of gabapentinoid addiction consists of persons with a history of substance use disorders (especially opioid users and poly-drug users).

An earlier systematic review by Smith et al. (2016) examined 33 publications (23 case studies and 11 epidemiological reports) from the U.S., U.K., Germany, Finland, India, South Africa, and France – to determine risk of gabapentinoid abuse and addiction.  According to extracted data, the prevalence of gabapentin misuse in the general population is approximately 1%.

Smith et al. reported that, among misusers of gabapentin: (1) 40% to 65% are persons with a legitimate prescription; and (2) 15% to 22% are persons who abuse opioids.  Moreover, it was documented that varying gabapentin dosages may induce subjective psychological and/or physical effects analogous to opioids, benzodiazepines, and/or psychedelics – all of which are regulated substances.

According to Smith et al., the most common reason for misusing gabapentin was to attain a recreational intoxication (“high”).  Similar to the findings by Bonnet and Scherbaum (2017), persons at highest risk for misusing gabapentin were individuals with histories of drug abuse.

Based on systematic reviews and side effect data, gabapentinoids (pregabalin and gabapentin) are suggested to exhibit limited or negligible abuse and addiction potential.  However, it’s reasonable to surmise that experts might be underestimating the occurrence of pregabalin and/or gabapentin abuse/misuse across the general population.

Many cases of gabapentinoid abuse/misuse are not reported to medical doctors, and of the small percentage of reported cases, an even smaller percentage end up formally documented (e.g. in a published “case report”).  Additionally, patients receiving pregabalin or gabapentin aren’t routinely “drug tested” to detect whether these agents are being administered as is medically directed – and gabapentin can be easily refilled without an appointment (due to its availability as a standard prescription in the U.S.).

Furthermore, while some may claim that gabapentinoids (pregabalin and gabapentin) are incapable of activating reward pathways in the brain to induce psychological reinforcement (thereby increasing addiction risk), this claim is controversial.  According to Schifano (2004), pregabalin and gabapentin might reduce excitatory neurotransmission while simultaneously activating the dopaminergic reward system.

If this is the case, select pregabalin and/or gabapentin users may experience a unique combination of psychological and/or physical effects that are perceived as pleasurable, including: calmness or relaxation; euphoria or positive mood; and/or increased sociability.  Experiencing these effects may significantly increase risk of future abuse and addiction.

Because pregabalin (Lyrica) is absorbed faster, more bioavailable, and of greater potency than gabapentin (Neurontin), pregabalin users may be at greater risk of abuse and/or addiction relative to gabapentin users.  Schifano also noted that misusers of pregabalin or gabapentin tend to have histories of recreational poly-drug misuse and generally administer 3-to-20-fold the clinically-recommended dosages of these agents.

Assuming pregabalin is more potent than gabapentin (at the respective recommended dosages to treat similar medical conditions), perhaps it makes logical sense that pregabalin (Lyrica) is classified as a “Schedule V” substance in the United States – whereas gabapentin (Neurontin) remains a standard prescription (Rx) medication.  In clinical trials of pregabalin, euphoria was reported in 4% of pregabalin recipients (versus 1% of placebo recipients); other trials have reported euphoria occurring in 1% to 12% of pregabalin recipients.

In clinical trials of gabapentin, euphoria was not reported in a significant percentage of gabapentin recipients relative to placebo recipients.  Additionally, although pregabalin and gabapentin exhibit similar primary mechanisms of action, some studies suggest that pregabalin exerts nearly 6-fold the inhibition of α2δ subunit-containing voltage-dependent calcium channels (VDCCs) relative to gabapentin.

What’s more, pregabalin has been reported as 2-to-4-fold and 3-to-10-fold more potent than gabapentin as an analgesic and anticonvulsant, respectively.  Considering the higher occurrence rates of euphoria among pregabalin users (relative to gabapentin users) and the stronger action of pregabalin on α2δ subunit-containing VDCCs (relative to gabapentin users), one would expect pregabalin (Lyrica) to exhibit greater abuse/addiction potential than gabapentin (Neurontin) when administered at therapeutic doses.

Although clinically-recommended dosages of pregabalin may yield greater abuse/addiction potential than clinically-recommended dosages of gabapentin, if the dosage of gabapentin is increased to a supratherapeutic level – it’s abuse/addiction potential likely exceeds that of pregabalin (at clinically-recommended dosages).  Furthermore, because gabapentin (as a standard prescription) is slightly easier to attain than pregabalin (a Schedule V substance), its misuse may be more common relative to the misuse of pregabalin.

It’s also possible that: (1) trials involving gabapentin underreported the incidence of euphoria (as a side effect) and/or (2) therapeutic doses of pregabalin (Lyrica) aren’t much different in potency than therapeutic doses of gabapentin (Neurontin).  For example, 300 mg pregabalin might be only slightly more potent than 900 mg gabapentin in the treatment of postherpetic neuralgia (PHN) – such that each regimen could result in abuse/addiction in susceptible populations.

In 2017, the United Kingdom opted to modify the legal classification of pregabalin and gabapentin from standard prescriptions to “Class C” controlled substances.  This reclassification was implemented in response to increases in rates of addiction, misuse, and deaths associated with the administration of pregabalin and gabapentin.

Overall, assuming that pregabalin and gabapentin are administered in accordance with proper medical instruction, risk of abuse/addiction is extremely low.  Nonetheless, clinically-recommended dosages of pregabalin (Lyrica) are more potent than the clinically-recommended dosages of gabapentin (Neurontin) – making the abuse/addiction potential of the former (pregabalin) slightly greater than that of the latter (gabapentin).

For this reason, the United States FDA has classified pregabalin (Lyrica) as a Schedule V substance – while gabapentin (Neurontin) remains available as a standard prescription.  As a Schedule V substance, pregabalin (Lyrica): (1) has a lower abuse potential than Schedule IV substances; (2) has accepted medical uses in the U.S.; and (3) can lead to limited dependence (physical and/or psychological) if abused.

Risk of pregabalin or gabapentin abuse/misuse and addiction increases among persons: (1) with histories of drug abuse/misuse; and/or (2) who administer gabapentinoids with other substances (e.g. opioids; alcohol; amphetamines; benzodiazepines).  That said, pregabalin and gabapentin are not among the most addictive drugs in mainstream pharmaceutical use.

Approved Medical Uses & Off-Label Uses

In the United States, pregabalin (Lyrica) and gabapentin (Neurontin) are both approved by the Food and Drug Administration (FDA) as standalone treatments in postherpetic neuralgia and as adjunct treatments in partial onset seizures.  The U.S. FDA-authorized medical uses of gabapentin (Neurontin) are limited to the 2 aforementioned conditions (postherpetic neuralgia and partial onset seizures).

The U.S. FDA-authorized medical uses of pregabalin (Lyrica) are not limited to the 2 aforementioned conditions (postherpetic neuralgia and partial onset seizures).  Pregabalin is authorized by the U.S. FDA to treat 3 additional conditions including: diabetic neuropathic pain; fibromyalgia; and neuropathic pain associated with spinal cord injury.

Although some medical doctors perceive pregabalin and gabapentin as being interchangeable treatment options for all conditions, it is necessary to underscore the fact that only pregabalin is officially indicated to treat: diabetic neuropathic pain; fibromyalgia; and neuropathic pain associated with spinal cord injury.  In total, pregabalin is FDA-approved to treat 5 medical conditions – whereas gabapentin is FDA-approved to treat 2 medical conditions.

Despite differences between pregabalin and gabapentin in their respective FDA-approved medical uses, both medications are regularly utilized “off-label” to treat medical conditions for which their FDA-approvals are lacking.  As off-label interventions, the only noteworthy difference between pregabalin and gabapentin is that gabapentin needs to be prescribed off-label to treat: diabetic neuropathic pain; fibromyalgia; and neuropathic pain associated with spinal cord injury.

Because pregabalin is approved by the U.S. FDA to treat those conditions, it need not be prescribed “off-label” in their treatment.  Shared off-label uses for pregabalin (Lyrica) and gabapentin (Neurontin) include: alcohol use disorder; alcohol withdrawal; anxiety disorders; hot flashes; insomnia; migraine prophylaxis; nystagmus (acquired pendular or infantile); opioid withdrawal; pain and spasticity in multiple sclerosis; pruritus (itching); restless leg syndrome (RLS); smoking cessation; tremor (essential or orthostatic).

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In sum, there aren’t substantial differences between pregabalin (Lyrica) and gabapentin (Neurontin) in the medical conditions for which each is prescribed off-label.  Similar off-label uses for pregabalin and gabapentin is to be expected considering that the medications exhibit similar primary mechanisms of action involving modulation of α2δ subunit-containing voltage-dependent calcium channels (VDCC).

Cost: What are the prices?

As of current (August 2018) there are slight differences in the respective prices of Lyrica (pregabalin) and Neurontin (gabapentin) – mostly attributable to the fact that Lyrica (pregabalin) is not yet available as a generic, whereas Neurontin (gabapentin) is sold as a low-cost generic.  When Lyrica (pregabalin) becomes available as a generic (which is expected later in 2018), its price [as a generic] is unlikely to significantly differ from the price of generic Neurontin (gabapentin).

Lyrica Cost (Brand Name)

Capsules

  • 25 mg (60 capsules): $442 to $471
  • 50 mg (60 capsules): $439 to $471
  • 75 mg (60 capsules): $439 to $471
  • 100 mg (60 capsules): $439 to $471
  • 150 mg (60 capsules): $439 to $471
  • 200 mg (60 capsules): $439 to $471
  • 225 mg (60 capsules): $439 to $471
  • 300 mg (60 capsules): $439 to $471

Oral solution

  • 473 mL bottle (20 mg/mL): $919 to $986

Neurontin Cost (Brand Name)

Capsules

  • 100 mg (90 capsules): $198 to $211
  • 300 mg (90 capsules): $482 to $518
  • 400 mg (90 capsules): $576 to $620

Tablets

  • 600 mg (90 tablets): $911 to $975
  • 800 mg (90 tablets): $1088 to $1169

Oral solution

  • 120 mL bottle (250 mg/5 mL): $109 to $114

Gabapentin Cost (Generic Neurontin)

Capsules

  • 100 mg (90 capsules): $10 to $27
  • 300 mg (90 capsules): $11 to $32
  • 400 mg (90 capsules): $13 to $55

Tablets

  • 600 mg (90 tablets): $19 to $41
  • 800 mg (90 tablets): $21 to $39

Oral solution

  • 120 mL bottle (250 mg/5 mL): $15 to $24

If directly comparing the cost of “brand name” Lyrica capsules to the cost of “brand name” Neurontin capsules/tablets, it seems as though brand name Lyrica is (1) more expensive than brand name Neurontin among low-dose users; and (2) less expensive than brand name Neurontin among high-dose users.  It is known that 50 mg Lyrica is approximately equal to 300 mg Neurontin – and that 100 mg Lyrica is approximately equal to 600 mg Neurontin.

A 30-day supply of Lyrica at a dosage of 50 mg per day ranges from $442 to $471, whereas a 30-day supply of Neurontin at a dosage of 300 mg per day ranges from $198 to $211 – making Neurontin the significantly cheaper option.  Similarly, a 30-day supply of Lyrica at a dosage of 100 mg per day ranges in price from $439 to $471, whereas a 30-day supply of Neurontin at a dosage of 600 mg per day ranges in price from $241 to $345 – making Neurontin the cheaper option.

However, at higher dosages, brand name Lyrica capsules become notably cheaper than brand name Neurontin capsules/tablets.  The standard daily dosage of Lyrica in the management of postherpetic neuralgia is 300 mg which equates to approximately 1800 mg per day of Neurontin.  A 30-day supply of Lyrica capsules at a dosage of 300 mg per day ranges in price from $442 to $471, whereas a 30-day supply of Neurontin capsules/tablets at a dosage of 1800 mg per day ranges in price from $911 to $975 – making Lyrica the significantly cheaper option.

In the event that large daily doses of a “brand name” gabapentinoid (Lyrica or Neurontin) become necessary to manage a medical condition, brand name Lyrica would be a significantly better deal than brand name Neurontin.  This is because the cost of brand name Lyrica is not “dose-dependent” such that capsules of the highest-dose (300 mg) aren’t priced differently than capsules of the lowest-dose (25 mg) – and the cost of brand name Neurontin is “dose-dependent” such that the highest-dose tablet (800 mg) is significantly more expensive than the lowest-dose capsule (100 mg).

If comparing the cost of brand name Lyrica oral solution to that of brand name Neurontin oral solution, brand name Lyrica oral solution is slightly cheaper (assuming potency of dosing is approximately equal).  Specifically, the cost of 100 mg Lyrica oral solution ranges from $9.71 to $10.42 per dose, whereas the cost of [an approximately equivalent] Neurontin dose (600 mg) oral solution ranges from $10.90 to $11.40 per dose.

The cost of gabapentin (generic Neurontin) is significantly lesser than brand name Neurontin of identical dosage and capsule/tablet count.  At most pharmacies, gabapentin (generic Neurontin) sells for: $10 to $55 for 90 capsules; $19 to $39 for 90 tablets; and $15 to $24 for a 120 mL bottle of oral solution (250 mg/5 mL).

Though pregabalin (generic Lyrica) is slated to hit the market between 2018 and 2019, it is unknown as to whether it will be cheaper (at dosages of approximately equal potency) to gabapentin (generic Neurontin).  That said, pregabalin (generic Lyrica) in capsule and oral solution formats will likely be significantly less expensive than brand name Lyrica – and likely analogous in price to gabapentin (generic Neurontin).

Everything considered, standard Lyrica capsules are cheaper than standard Neurontin capsules/tablets at moderate-to-high doses (e.g. 300 mg/day of Lyrica vs. 1800 mg/day Neurontin) – whereas standard Neurontin capsules/tablets are cheaper than standard Lyrica capsules at low doses (100 mg/day of Lyrica vs. 600 mg/day of Neurontin).  The cost of brand name Lyrica oral solution doesn’t differ much from that of brand name Neurontin oral solution – but the former (Lyrica) is slightly cheaper than the latter (Neurontin).

Since only Neurontin is available as a generic (gabapentin) which can be attained for a significantly lower cost than Lyrica, most would regard gabapentin as being significantly more cost-effective (until generic Lyrica i.e. pregabalin becomes available).  For this reason, it makes logical sense for medical professionals to favor the utilization of gabapentin (generic Neurontin) relative to Lyrica (brand name) in the treatment of medical conditions for which either agent could be prescribed – in effort to preserve patient finances.

Note: The prices listed above for Lyrica (pregabalin) and Neurontin (gabapentin) may be subject to future fluctuation and/or inaccuracies.  Moreover, know that the prices of Lyrica (pregabalin) and Neurontin (gabapentin) may be subject to significant variation among retailing pharmacies.

Dosages & Formats

Pregabalin and gabapentin are each manufactured in multiple formats and a variety of dosage increments.  Standard pregabalin (Lyrica) is manufactured in 2 formats: capsules and oral solution – whereas standard gabapentin (Neurontin) is manufactured in 3 formats: capsules; tablets; and oral solution.

Standard pregabalin (Lyrica) capsules are available in 8 dosage increments of: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mgStandard gabapentin (Neurontin) capsules are available in 3 dosage increments of: 100 mg, 300 mg, and 400 mg.

Oral pregabalin (Lyrica) solution is available in one 473 mL bottle and offers one dosage increment of 20 mg/mL.  Oral gabapentin (Neurontin) solution is available in size-customizable bottles and offers one dosage increment of 250 mg/5 mL.

Although standard pregabalin (Lyrica) and standard gabapentin (Neurontin) are both available in capsule and oral solution formats, gabapentin is also sold in an additional tablet format.  Gabapentin (Neurontin) tablets are available in 2 dosage increments of: 600 mg and 800 mg.

Standard pregabalin (Lyrica) formats are considered “immediate-release” and exhibit an average onset of action ranging from 40 to 120 minutes and an average duration of effect ranging from 8 to 14 hours.  Standard gabapentin (Neurontin) formats are also considered “immediate-release” and exhibit an average onset of action ranging from 30 to 90 minutes and an average duration of effect ranging from 5 to 8 hours.

If solely comparing the standard immediate-release versions of pregabalin and gabapentin, one might perceive pregabalin as advantageous over gabapentin on the basis of its longer duration of action.  A longer duration of action allows for less frequent administration (twice per day; b.i.d.) relative to gabapentin (thrice per day; t.i.d.) which is generally more convenient for users (remembering to take 2 pills vs. 3 pills).

That said, persons who only require intermittent or “as-needed” administration of gabapentinoids might actually prefer to use gabapentin instead of pregabalin on the basis of its shorter duration of action.  For example, gabapentin might be preferred over pregabalin by a person with social anxiety who wishes to control his/her anxiety for a short-term event (e.g. 4 to 6 hours) – but doesn’t want to be under the influence of the medication (and deal with its side effects) for hours after the event has ended.

Because standard pregabalin capsules are available in a greater number of dosing increments (8 total) relative to standard gabapentin capsules and tablets combined (5 total), some might perceive pregabalin as favorable over gabapentin in the aspect of dosing.  The greater number of dosing increments for pregabalin may decrease the likelihood that users need to split capsules while titrating in effort to find an optimal (tolerable and effective) dose.

However, because gabapentin users have access to tablets as an alternative to capsules and oral solution (whereas pregabalin users do not), it’s reasonable to state that gabapentin is favorable over pregabalin in its variety of formatting options.  Certain individuals might also prefer using gabapentin tablets instead of capsules on the basis that tablets are easier to split for dosage adjustments (relative to capsules which require pouring out and/or measuring powder).

Worthy of additional mention is the fact that pregabalin and gabapentin are each available in “longer-acting” formulations that facilitate a therapeutic effect of ~24 hours.  Long-acting pregabalin is sold under the brand name Lyrica CR (pregabalin controlled-release) – and long-acting gabapentin is sold under the brand names Gralise (gabapentin extended-release) and Horizant (gabapentin enacarbil extended-release).

Pregabalin controlled-release is available in capsules at 3 dosage increments of: 82.5 mg; 165 mg; and 330 mgGabapentin extended-release and gabapentin enacarbil extended-release are available in tablets at 2 dosage increments of: 300 mg and 600 mg.

If comparing the long-acting formulations of pregabalin and gabapentin, one might perceive pregabalin controlled-release (CR) as being advantageous over gabapentin extended-release – as a result of its additional dosing increment (3 dosing increments for pregabalin CR vs. 2 dosing increments for gabapentin ER).  The additional dosing increment with pregabalin controlled-release should make it easier for users to find an optimal (tolerable and effective) dose – relative to the two dosing increments for gabapentin extended-release.

In summary, pregabalin might be preferred over gabapentin as a result of its longer duration of action (in standard formats) and greater number of dosing options (in standard and long-acting formats).  Conversely, gabapentin might be preferred over pregabalin as a result of its shorter duration of action (in standard formats); availability in tablets (in standard formats); and availability in two slightly different extended-release formulations (gabapentin ER vs. gabapentin enacarbil ER).

Efficacy: Is Pregabalin (Lyrica) more effective than Gabapentin (Neurontin)?

It remains unknown as to whether the efficacy of pregabalin (Lyrica) significantly differs from the efficacy of gabapentin (Neurontin) in the management of any specific medical condition(s).  Because postherpetic neuralgia (PHN) and partial onset seizures are the only conditions for which both pregabalin (Lyrica) and gabapentin (Neurontin) are approved to treat, medical doctors and consumers are probably most interested in determining how their respective efficacies compare in the management of these conditions.

Postherpetic Neuralgia (PHN)

It is important to underscore the fact that both pregabalin (Lyrica) and gabapentin (Neurontin) have proven to be safe, tolerable, and effective in large-scale, randomized, controlled trials – for the treatment of postherpetic neuralgia.  As a result, both medications have received official approval from the U.S. FDA as interventions for postherpetic neuralgia.

Below are brief synopses of studies in which the efficacies of pregabalin and gabapentin were compared in the treatment of postherpetic neuralgia.  (For additional information about a particular study, click the link cited below each synopsis).

2016: The Cost-Effectiveness of Pregabalin Versus Gabapentin for Peripheral Neuropathic Pain (pNeP) and Postherpetic Neuralgia (PHN) in China.

Wang et al. conducted a study to assess the cost-effectiveness of pregabalin (Lyrica) relative to gabapentin (Neurontin) for the management of postherpetic neuralgia (and peripheral neuropathic pain) in 1000 Chinese patients with these diagnoses.  For this study, researchers sent a questionnaire to 11 Chinese opinion leaders (general practitioners and specialists) in effort to estimate pre-treatment distribution of pain scores for postherpetic neuralgia.

Additionally, researchers examined results of large-scale, randomized, controlled trials involving pregabalin and gabapentin – to determine their respective efficacies in the management of postherpetic neuralgia.  Using a 12-week simulation model, researchers reported that pregabalin (~372 mg/day) is more effective than gabapentin (~2400 mg/day) in the treatment of postherpetic neuralgia.

Superior efficacy of pregabalin (Lyrica) over gabapentin (Neurontin) in the treatment of postherpetic neuralgia was evidenced by: (1) greater reduction of postherpetic neuralgia pain scores (an additional ~0.7 points on an 11-point scale) at the end of 12 weeks; and (2) greater number of days with over 30%, 40%, and 50% pain reduction.  By percentage, pregabalin users exhibited a ~58.2% reduction in pain associated with postherpetic neuralgia (from baseline), whereas gabapentin users exhibited a ~36% reduction in pain associated with postherpetic neuralgia (from baseline) – over 12 weeks.

Data from this study support the idea that pregabalin might be more effective than gabapentin (even if average gabapentin dosages are more potent) for the treatment of postherpetic neuralgia.  Despite the aforementioned findings (indicating that pregabalin might be superior to gabapentin in postherpetic neuralgia), there are some limitations that warrant discussion.

Limitations associated with this study include: (1) efficacies of pregabalin and gabapentin were determined using data extracted from studies with different parameters (dosing regiments, durations, participant numbers, etc.); (2) potentially-inaccurate estimates calculated by researchers; (3) funding by Pfizer Inc. (a company that stood to benefit financially from showcasing the superiority of pregabalin); (4) research and authorship by paid consultants and employees of Pfizer Inc.; and (5) some data based upon questionnaire results (questionnaires are notoriously inaccurate).

Hypothetically assuming that poor methods and/or limitations didn’t affect the study outcome, it would seem as though pregabalin may be more useful than gabapentin in the treatment of postherpetic neuralgia.  However, considering the suboptimal methods and serious limitations of this study, we cannot be confident that the results (suggesting that pregabalin is more efficacious than gabapentin) are accurate and clinically-relevant.

2013: Pregabalin versus gabapentin in the management of peripheral neuropathic pain associated with post-herpetic neuralgia and diabetic neuropathy: a cost effectiveness analysis for the Greek healthcare setting.

Athanasakis et al. conducted a study to assess the cost-effectiveness of pregabalin relative to gabapentin in the treatment of postherpetic neuralgia and peripheral neuropathic pain.  The study employed a dynamic simulation model which estimated the costs and outcomes of pregabalin and gabapentin treatment in a hypothetical sample of 1000 patients with postherpetic neuralgia or painful diabetic neuropathy.

In this simulation model, each patient was randomly allocated an average pretreatment pain score (based on an 11-point visual analogue scale) using data from an actual distribution of pain levels reported in randomized, double-blind, controlled trials.  It was reported that researchers accounted for the established efficacies of each medication and simulated daily pain intensity (allowing for random calculation of outcomes).

Results of this simulation study suggested that pregabalin was more effective than gabapentin for the treatment of postherpetic neuralgia.  The superior efficacy of pregabalin over gabapentin was evidenced by: (1) a greater reduction in the number of days with moderate-to-severe pain; and (2) greater quality of life – over a 12-week period – among pregabalin users relative to gabapentin users.

That said, there are numerous limitations associated with this study, including: (1) more potent pregabalin dosing (~457 mg/day) relative to gabapentin (~2400 mg/day); (2) extraction of efficacy data from studies with different parameters (dosing regiments, durations, participant numbers, etc.); (3) use of questionnaire data (questionnaires frequently yield unreliable data); (4) possibly-inaccurate estimations and calculations from researchers; (5) funding by Pfizer (a pharmaceutical company who stood to benefit financially from proving the superiority of pregabalin over gabapentin); and (6) the study was conducted and authored by Pfizer employees.

Assuming the study outcome was unaffected by suboptimal methods and/or limitations, it would seem as though pregabalin is superior to gabapentin as a treatment for postherpetic neuralgia.  That said, because there are serious limitations associated with this study, we cannot be confident that the results (suggesting that pregabalin is more effective than gabapentin in postherpetic neuralgia) are accurate or clinically-relevant.

2011: Replacement of gabapentin with pregabalin in postherpetic neuralgia therapy.

Ifuku et al. conducted a study examining the magnitude of pain relief (i.e. effectiveness) of gabapentin and pregabalin in the treatment of postherpetic neuralgia.  For this study, 32 patients diagnosed with postherpetic neuralgia (who had been receiving gabapentin treatment) were transitioned from gabapentin to pregabalin at one-sixth the dosage (in effort to maintain approximately equal potencies of action).

After 2 weeks of pregabalin treatment, researchers interviewed patients to determine: visual analogue scale (VAS) pain scores; shifts in onset of action and/or duration of action after transition to pregabalin; and incidence rates of common side effects.  Dosage of pregabalin was increased [after transition from gabapentin] in 22 patients who requested increases due to insufficient symptom relief.

Results indicated that visual analogue scale (VAS) pain scores did not significantly change after the transition from gabapentin to pregabalin.  Furthermore, most patients reported that there were no differences between gabapentin and pregabalin in onset and duration of action – but some claimed that onset of action became quicker and/or duration of action increased.

However, in the 22 patients who received increased pregabalin dosages after the transition (due to insufficient symptom relief), visual analogue scale (VAS) pain scores significantly decreased.  Based on the findings in this study, there are no differences in the respective efficacies of gabapentin and pregabalin in the treatment of pain associated with postherpetic neuralgia.

Although increasing pregabalin dosage (to a potency that exceeds the prior gabapentin dosage) led to significant reductions in visual analogue scale (VAS) pain scores, this does not support the idea that pregabalin is more effective than gabapentin in the management of postherpetic neuralgia.  Perhaps similar results would’ve occurred if users were transitioned from pregabalin to gabapentin – followed by increasing the gabapentin dosage (to a potency that exceeds a prior pregabalin dosage).

Limitations associated with this study include: (1) small sample size; (2) no transition from pregabalin to gabapentin (only from gabapentin to pregabalin); and (3) short duration (2 weeks).  Overall, there are no data from this study to substantiate the idea that gabapentin and pregabalin differ in efficacy for the treatment of pain resulting from postherpetic neuralgia.

Verdict: It remains unknown as to whether pregabalin (Lyrica) and gabapentin (Neurontin) differ in efficacy for the treatment of postherpetic neuralgia (PHN)

In summary, there are few studies that’ve attempted to compare the efficacy of pregabalin to that of gabapentin in the treatment of postherpetic neuralgia.  Of the studies comparing these agents, none involved equal comparisons: 2 utilized model simulations based upon preexisting trial data and 1 implemented a transition from gabapentin to pregabalin (but not vice-versa).

Various limitations associated with these studies included: (1) unequal potency (of dose) comparisons; (2) inflexible dosing; (3) indirect comparisons; (4) data extraction (from studies with parameter disparities); (5) inclusion of questionnaire data; (6) research and authorship by Pfizer Inc. employees; (7) potential reporting bias, sponsorship bias; and/or publication bias.

In the 2 simulation trials, pregabalin was reported to be more effective than gabapentin, however, these were “simulations” conducted with questionnaire data by Pfizer Inc. employees – not legitimate head-to-head comparisons.  Moreover, in the standalone trial involving a transition from gabapentin to pregabalin (of an equally-potent dose), no differences were reported in respective efficacies of these medications for postherpetic neuralgia.

At this time, there’s no convincing evidence to substantiate the recommendation that pregabalin is superior to gabapentin in the treatment of postherpetic neuralgia.  Unless a large-scale, randomized controlled trial proves otherwise, pregabalin and gabapentin should be regarded by medical professionals as equally efficacious interventions for postherpetic neuralgia.

Partial onset seizures

Pregabalin (Lyrica) and gabapentin (Neurontin) are both approved by the FDA to treat partial onset seizures when administered as an adjunct (i.e. “add-on”) to a first-line anticonvulsant.  Below are brief synopses of studies in which the efficacies of pregabalin and gabapentin were compared (indirectly or directly) in the treatment of partial onset seizures.

2016: Adjunctive pregabalin vs gabapentin for focal seizures: Interpretation of comparative outcomes.

French et al. organized a randomized, double-blind, parallel group study to compare the respective adjunct efficacies of pregabalin and gabapentin in the treatment of partial-onset seizures.  For this study, adults with refractory partial-onset seizures were monitored for a 6-week baseline period and then assigned at random to receive either: pregabalin (flexible-dose) OR gabapentin (flexible-dose) – for a 21-week duration.

To determine the respective adjunct efficacies of pregabalin and gabapentin in treating partial onset seizures, researchers tracked the percentage (%) change in 28-day seizure rate from baseline to treatment phase.  A total of 484 patients participated in the trial (242 received pregabalin and 242 received gabapentin), and 359 patients completed the treatment phase (187 received pregabalin and 172 received gabapentin).

The average percentage (%) reductions in 28-day seizure rates were as follows: 47.7% reductions among pregabalin users – and 45.28% reductions among gabapentin users.  Results indicated that pregabalin and gabapentin appear to be equally effective adjunct treatments for partial onset seizures.

Although researchers expected adjunct pregabalin to be more efficacious than adjunct gabapentin in the management of partial onset seizures (due to prior modeling of trials), this study provided Class II evidence that pregabalin is not superior to gabapentin in reducing seizure frequency.

2010: Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships.

Delahoy et al. conducted a meta-analysis in effort to compare the effectiveness of pregabalin to that of gabapentin (at approximately equally-potent dosages) in the treatment of refractory partial epilepsy.  For the meta-analysis, researchers compiled data from 8 randomized controlled trials (over 12 weeks in duration): 4 trials involving pregabalin (versus a placebo) and 4 trials involving gabapentin (versus a placebo).

Of interest to researchers were “responder rates” (responses were defined as at least 50% reductions in number of seizures from baseline) and “change in seizure-free days” (from baseline) over a 28-day period.  Data from all trials were evaluated with an indirect comparison approach wherein the placebo served as a common comparator.

Researchers performed a base-case analysis (using intention-to-treat last observation carried forward method) and two sensitivity analyses (among completer and responder populations).  Results of the base-case analysis indicated that users of 300 mg pregabalin exhibited higher “response rates” than users of 1200 mg gabapentinand users of 600 mg pregabalin exhibited higher “response rates” than users of 1800 mg gabapentin.

Although sensitivity analyses substantiated the findings of the base-case analysis, the sensitivity analyses did not find statistical significance between pregabalin and gabapentin.  Nevertheless, it was further reported that all pregabalin doses (150 mg to 600 mg) were more effective than corresponding gabapentin dosages (900 mg to 2400 mg) for “seizure-free days” (from baseline) over a 28-day period.

Researchers concluded that there’s a trend to suggest that adjunct pregabalin may be more effective than adjunct gabapentin in treatment of seizures.  Still, there are some serious limitations associated with this study including: (1) efficacy estimates were based on indirect comparisons; (2) data were extracted from trials with different characteristics (duration, sample specifics, dosing regimens, concurrent substance use, etc.); (3) potentially-inaccurate comparisons in potency of dosing (e.g. 150 mg pregabalin may be more potent than 600 mg gabapentin); and (4) competing interests (the meta-analysis was funded by Pfizer Inc., included data from 8 studies funded by Pfizer Inc., and authors of the study were Pfizer Inc. employees).

In summary, this study suggests that pregabalin could be more effective than gabapentin as an adjunct treatment in refractory partial epilepsy.  However, reflecting upon the lack of statistical significance in “response rates” between pregabalin and gabapentin plus the myriad of limitations – it’s unreasonable to suggest that one medication (pregabalin or gabapentin) is more effective than the other as an adjunct treatment for epilepsy.

Verdict: Pregabalin and Gabapentin are equally effective adjuncts in the treatment of partial onset seizures

At this time, there’s no convincing evidence to suggest that pregabalin and gabapentin differ in efficacy for the management of partial onset seizures.  The meta-analysis conducted by Delahoy et al. (2010) suggested that pregabalin might be more effective than gabapentin in the treatment of partial onset seizures, however, sensitivity analyses revealed no statistically-significant differences in the efficacies of pregabalin and gabapentin.

Additionally, the meta-analysis was full of limitations including: (1) indirect comparisons of pregabalin and gabapentin; (2) unequal potency-of-dose comparisons; (3) funding by Pfizer Inc.; (4) research and authorship by Pfizer Inc. employees; (5) use of data in the meta-analysis from 8 Pfizer Inc.-funded studies.  Even if the meta-analysis by Delahoy et al. (2010) would’ve reported greater efficacy for pregabalin (relative to gabapentin) in the treatment of partial onset seizures, the findings would be difficult to trust.

The most reliable data regarding the respective efficacies of pregabalin and gabapentin in the treatment of partial onset seizures were derived from a study by French et al. (2016).  This study was long-term (6-week baseline phase & 21-week treatment phase); large-scale (484 patients), and utilized randomization.

Results of the study indicated that pregabalin and gabapentin treatment yield similar reductions in 28-day seizure rates (47.7% pregabalin vs. 45.28% gabapentin).  This study provided Class II evidence to suggest that pregabalin and gabapentin do not differ in efficacy as adjuncts for the treatment of partial onset seizures.

What about efficacy for other medical conditions? Pregabalin vs. Gabapentin

In the U.S., pregabalin (Lyrica) is officially approved for the treatment of diabetic neuropathic pain; fibromyalgia; and neuropathic pain in spinal cord injury – whereas gabapentin is not.  Though gabapentin (Neurontin) is not authorized by the FDA to treat neuropathic pain or fibromyalgia, it is regularly prescribed as an off-label intervention for these conditions.

For this reason, many persons remain curious as to whether there are significant differences in the respective efficacies of pregabalin and gabapentin in the management of neuropathic pain and/or fibromyalgia.  Included below are summaries of studies in which the efficacies of pregabalin and gabapentin are discussed and/or compared for neuropathic pain and fibromyalgia.

Neuropathic pain

2012: Evaluation of efficacy and safety of gabapentin, duloxetine, and pregabalin in patients with painful diabetic peripheral neuropathy.

Devi et al. organized a study to compare the efficacy of gabapentin (GBP), pregabalin (PGB), and duloxetine (DLX) in the treatment of painful diabetic peripheral neuropathy (DPNP).  For the study, 152 patients with a history of DPNP-related pain (minimum 40-mm score on visual analogue scale (VAS)) were assigned at random to receive gabapentin, pregabalin, or duloxetine for a 12-week duration.

The primary endpoint was DPNP-related pain score on an 11-point visual analogue scale (VAS), and secondary endpoints included: sleep interference scores, patient global impression of change, and clinical global impression of change.  Of the 152 participants: 50 received gabapentin; 52 received pregabalin; and 50 received duloxetine.

Results indicated that all 3 treatments (gabapentin, pregabalin, duloxetine) significantly: (1) reduced 11-point visual analogue pain scale (VAS) scores; (2) decreased sleep interference; and (3) improved patient and clinical global impressions of change.  While there were trends for greater pain reduction, superior sleep improvement, and faster onset of therapeutic action with pregabalin (relative to gabapentin and duloxetine), there were no statistically-significant differences in outcomes between groups to suggest that one treatment was more or less effective than the others.

Researchers concluded that monotherapy with gabapentin, pregabalin, and duloxetine provide significant pain relief among patients with DPNP.  The findings of this study indicate that pregabalin and gabapentin do not differ in efficacy for the management of neuropathic pain.

2010: Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy.

Toth organized a study to assess the effect of substituting gabapentin with pregabalin patients with peripheral neuropathy-related neuropathic pain.  In the study, 47 patients served as a gabapentin control group – and 69 transitioned from gabapentin to pregabalin: 33 “gabapentin responders” and 36 “gabapentin nonresponders” (i.e. a 4-week treatment failed to reduce pain by 30% from baseline).

Among the 69 patients who switched to pregabalin, additional pain relief of ~25% was observed after 6 months and 12 months (relative to prior gabapentin treatment) – regardless of whether the patients were “responders” or “nonresponders” to gabapentin.  It was concluded that pregabalin may provide additional pain relief relative to gabapentin in the treatment of neuropathic pain.

Despite the suggestion by authors of this study that pregabalin may be more efficacious than gabapentin in the treatment of neuropathic pain, there are major limitations to consider.  Limitations associated with this study include: (1) no transition from pregabalin to gabapentin (only from gabapentin to pregabalin); (2) uneven treatment periods (short-term gabapentin use prior to transition but long-term pregabalin use); (3) unblinded status of patient assessments; (4) no control group; (5) small sample size; (6) possible placebo-like effect (upon transition to pregabalin); (7) author received support from Pfizer Inc. (manufacturer of pregabalin).

2009: Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.

Quilici et al. conducted a meta-analysis indirectly comparing the efficacies of gabapentin (GPB); pregabalin (PGB); duloxetine (DLX); and amitriptyline (AMT) – in the treatment of diabetic peripheral neuropathic pain (DPNP).  More specifically, researchers extracted data from high-quality, randomized, placebo-controlled trials to compare the respective magnitudes of therapeutic efficacy (relative to a placebo) – associated with each intervention.

It was reported that 3 studies with duloxetine; 6 with pregabalin; 2 with gabapentin; and zero with amitriptyline met inclusion criteria for the meta-analysis.  Using random-effects and fixed-effects analyses, researchers stated that gabapentin, pregabalin, and duloxetine were all more effective than a placebo in the treatment of diabetic peripheral neuropathic pain.

Researchers concluded that gabapentin, pregabalin, and duloxetine are of comparable efficacy in the treatment of diabetic peripheral neuropathic pain.  This study supports the idea that gabapentin and pregabalin are equally efficacious in the management of diabetic neuropathic pain.

Verdict: Pregabalin (Lyrica) might be slightly more effective than Gabapentin (Neurontin) for neuropathic pain

In studies that’ve directly or indirectly compared the efficacy of pregabalin to gabapentin for the treatment of neuropathic pain, none have proven that one medication (pregabalin or gabapentin) exhibits superior efficacy relative to the other.  In a meta-analysis by Quilici et al. (2009), gabapentin, pregabalin, and duloxetine were reported as equally efficacious in the management of diabetic peripheral neuropathic pain (DPNP).

In the small-scale study by Toth (2010), it appeared as though pregabalin might be more efficacious than gabapentin in the treatment of neuropathic pain, however, Toth acknowledged that the study was full of notable limitations (unequal comparison, no blinding of patient assessments, small sample, support from Pfizer, etc.) such that no clinical recommendations could be made from its results.

The most useful data for comparing the head-to-head efficacies of pregabalin and gabapentin in the treatment of neuropathic pain were derived from a study by Devi et al. (2012).  The study by Devi et al. directly compared gabapentin, pregabalin, and duloxetine among 152 patients with neuropathic pain over a 12-week period.

Results of this study reported no statistically-significant differences between groups in pain reduction to suggest that one medication was more efficacious than another.  That said, there were trends for: quicker pain relief, greater sleep enhancement, and a larger degree of pain reduction among pregabalin users – versus gabapentin users and duloxetine users.

Because trends reveal that pregabalin may be faster-acting and reduce pain to a greater extent than gabapentin – it’s reasonable to hypothesize that pregabalin might be [negligibly] more useful (on average) than gabapentin in the management of neuropathic pain.  Nonetheless, from a clinical perspective, there’s no strong evidence to suggest that pregabalin is more efficacious than gabapentin in the management of neuropathic pain (despite FDA-approval of the former (pregabalin) and lack thereof for the latter (gabapentin)).

Fibromyalgia

Because pregabalin (Lyrica) is FDA-approved to treat fibromyalgia and gabapentin (Neurontin) is not, it’s reasonable to suggest that pregabalin is a medically-superior treatment choice (over gabapentin) among persons with fibromyalgia.  Although pregabalin may be a superior treatment recommendation versus gabapentin for fibromyalgia (on the basis of its FDA-approval), it is unclear as to whether it is legitimately more efficacious for this condition.

As of current, there’s only one moderately-sized, randomized, double-blind, placebo-controlled, 12-week trial by Arnold et al. (2007) that’s evaluated the efficacy of gabapentin in fibromyalgia.  In the trial by Arnold et al., 150 patients with fibromyalgia were assigned at random to receive either: 1200 mg to 2400 mg of gabapentin per day (75 patients) OR a placebo (75 patients).

Results of the trial indicated that gabapentin recipients exhibited significantly: (1) greater reductions in fibromyalgia-related pain and (2) higher response rates after 12 weeks (from baseline) – relative to placebo recipients.  Arnold et al. concluded that gabapentin appears efficacious in the management of fibromyalgia-related symptoms.

To date, no well-designed studies have directly compared pregabalin and gabapentin in the treatment of fibromyalgia.  For this reason, it remains unknown as to whether pregabalin and gabapentin differ in therapeutic efficacy for the treatment of fibromyalgia.

Note: Both pregabalin and gabapentin are regularly prescribed off-label for conditions like alcohol use disorder, alcohol withdrawal, anxiety disorders, insomnia, pruritus, restless leg syndrome (RLS), and tremor.  Given their similar: (1) mechanisms of action and (2) efficacies in the treatment of medical conditions for which they’ve received FDA-approval – it’s unreasonable to assume that one agent would be substantially more efficacious, on average, (relative to the other) as an “off-label” medical treatment.

Mechanism of action (Pharmacodynamics)

Pharmacodynamic research indicates that pregabalin (Lyrica) and gabapentin (Neurontin) exhibit identical primary mechanisms of action, functioning as inhibitors of α2δ-subunit-containing voltage-dependent calcium channels (VDCCs).  More specifically, pregabalin and gabapentin penetrate the blood-brain barrier (BBB) and bind to α2δ-1 and α2δ-2 subunits of N-type, L-type, P-type, Q-type (and possibly R-type) voltage-dependent calcium channels to reduce their expression and activation.

A reduction in activation of voltage-dependent calcium channels (VDCCs) [facilitated by pregabalin and gabapentin] simultaneously (1) bolsters inhibitory neurotransmission and (2) reduce excitatory neurotransmission to induce a combination of: analgesic, anticonvulsant, anxiolytic, and sedative effects.  Researchers believe that the primary neurochemical action (voltage-dependent calcium channel inhibition) of pregabalin and gabapentin accounts for a majority of their therapeutic effects in the management of medical conditions (e.g. nerve pain, seizures, anxiety, restlessness, etc.).

Though the primary neurochemical action facilitated by pregabalin and gabapentin is identical, the magnitude of this action differs between the medications.  A study by Jones and Sorkin (1998) indicates that pregabalin inhibits voltage-dependent calcium channels (VDCCs) to nearly 6-fold the extent of gabapentin (assuming equal dosing).

In addition to inhibiting α2δ-subunits of voltage-dependent calcium channels, pregabalin and gabapentin exhibit a host of similar (non-primary) neurochemical actions, including: glutamic acid decarboxylase (GAD) upregulation; cytosolic branched-chain aminotransferase (BCATc) competitive inhibition; GABA aminotransferase (GABA-T) inhibition; glutamate dehydrogenase (GDH) inhibition; neuropeptide (substance P and CGRP) modulation; NMDA receptor inhibition; neural connectivity modulation.

  • Upregulation of glutamic acid decarboxylase (GAD), an enzyme implicated in the production of GABA (gamma-aminobutyric acid) is understood to increase GABA synthesis and signaling.
  • Competitive inhibition of cytosolic branched-chain aminotransferase (BCATc) is understood to reduce the synthesis of excitatory neurotransmitters like glutamate.
  • Inhibition of GABA aminotransferase (GABA-T), an enzyme implicated in the degradation and metabolism of GABA, increases intraneuronal concentrations of GABA.
  • Inhibition of glutamate dehydrogenase (GDH), an enzyme implicated in the production of glutamate, is understood to reduce glutamatergic signaling.
  • Modulation of neuropeptides like substance P and CGRP (calcitonin gene-related peptide) may help reduce and/or counteract preexisting inflammation.
  • NMDA receptor inhibition has been demonstrated with both pregabalin and gabapentin – and is understood to generate an antinociceptive effect.
  • Neural connectivity is subject to modulation as a result of regular (i.e. daily) pregabalin and/or gabapentin administration.

In response to the aforementioned secondary neurochemical actions facilitated by pregabalin and gabapentin: (1) inhibitory (GABAergic) neurotransmission increases; and (2) excitatory (glutamatergic) neurotransmission decreases.  It is hypothesized that these secondary actions might potentiate analgesic, anticonvulsant, anxiolytic, and/or sedative effects resulting from the primary neurochemical action (voltage-dependent calcium channel inhibition).

Other hypothesized secondary neurochemical actions for both pregabalin and gabapentin include: voltage-gated potassium channel modulation; cytokine modulation; excitatory amino acid transporter 3 (EAAT) modulation; GABA-B heteroreceptor modulation; reactive oxygen species (ROS) and reactive nitrogen species (RNS) modulation; and voltage-gated sodium channel modulation.  Although pregabalin and gabapentin share common secondary neurochemical actions, it remains unclear as to whether there’s a difference in respective magnitudes of their secondary neurochemical effects.

Moreover, while pregabalin and gabapentin share many common secondary neurochemical actions, research has unveiled subtle pharmacodynamic disparities between these agents.  For example, according to Manville and Abbott (2018), gabapentin is a potent activator of the voltage-gated potassium channels (VGPCs) KCNQ2/3; KCNQ3; and KCNQ5 – whereas pregabalin does not activate (at standard doses) or inhibits (at high doses) KCNQ2/3.

Other research suggests that while both pregabalin and gabapentin interact with excitatory amino-acid transporter 3 (EAAT3), the former (pregabalin) appears to increase its activation – whereas the latter (gabapentin) appears to decrease its activation.  As a result of deviating interactions with EAAT3, pregabalin might reduce glutamate to a greater extent than gabapentin (which might increase glutamate in certain regions).

Preliminary evidence suggests that gabapentin modulates monoamine concentrations by: (1) increasing norepinephrine secretion in the locus coeruleus and spinal cord; (2) inhibiting dopamine secretion in the caudate nucleus; (3) increasing serotonin concentrations in the peripheral (without altering melatonin); and (4) decreasing total catecholamine secretion in response to stress.  It is unknown as to whether pregabalin modulates monoamine concentrations in similar ways as gabapentin.

To recap: Pregabalin and gabapentin exhibit identical primary mechanisms of action as inhibitors of α2δ-subunit-containing voltage-dependent calcium channels.  Pregabalin is more potent than gabapentin (by approximately 6-fold) in its magnitude of voltage-dependent calcium channel inhibition.

Shared secondary neurochemical targets for pregabalin and gabapentin include: GAD; BCATc; GABA-T; GDH; NMDA receptors; EAAT3; and voltage-gated potassium channels.  Pregabalin and gabapentin both modulate neural connectivity; cytokine concentrations; and neuropeptides (substance P and CGRP).

It is hypothesized that both pregabalin and gabapentin might also modulate: voltage-gated sodium channels; reactive oxygen/nitrogen species; and GABA-B heteroreceptors.  Preliminary evidence suggests that pregabalin and gabapentin differ in action upon select voltage-gated potassium channels and EAAT3.

Subtle differences between pregabalin and gabapentin in pharmacodynamics may explain why there are trends for superior therapeutic efficacy and/or faster onsets of action associated with pregabalin (relative to gabapentin).  Additionally, slight pharmacodynamic disparities between these agents might explain why certain individuals respond better to one medication (i.e. find it more tolerable and effective) relative to the other.

Metabolism & Half-Life

There are no significant differences between pregabalin (Lyrica) and gabapentin (Neurontin) in metabolism.  Neither pregabalin nor gabapentin is subject to hepatic metabolism by cytochrome P450 (CYP450) enzymes – and neither agent interferes with the hepatic metabolism of concomitantly-administered substances.

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Some evidence suggests that a negligible quantity (less than 2%) of pregabalin and gabapentin may undergo renal metabolism prior to elimination.  That said, a majority (over 98%) of ingested pregabalin and gabapentin doses will remain unchanged during excretion.

In addition to there being no relevant difference between pregabalin and gabapentin in metabolism (or lack thereof), there’s no significant difference between these medications in elimination half-life.  Pharmacokinetic research by Bockbrader et al. (2010) suggests that both pregabalin and gabapentin exhibit elimination half-lives of approximately 6 hours.

According to StatPearls, the average elimination half-life of pregabalin is 6.3 hours and the average elimination half-life of gabapentin is 6.5 hours (ranging from 5 to 7 hours).  These half-life figures suggest that pregabalin will remain in one’s system for ~1.44 days, and gabapentin will remain in one’s system for ~1.48 days – following discontinuation.

Though pregabalin and gabapentin negligibly differ in elimination half-life, the agents significantly differ in oral bioavailability (percentage of the medication that exerts a physiologic effect).  The oral bioavailability of pregabalin is ~90% – whereas the oral bioavailability of gabapentin ranges from ~27% to ~60%.

According to Bockbrader et al. (2010), the oral bioavailability of pregabalin is ~90% regardless of its dosage, whereas the oral bioavailability of gabapentin ranges from ~27% to ~60% and is inversely proportionate to its dosage (smaller doses exhibit higher bioavailability than larger doses).  Moreover, some evidence suggests that consuming food with gabapentin (particularly high-protein and/or high-fat) might increase its bioavailability.

Popularity

If considering the respective historical popularities of pregabalin (Lyrica) and gabapentin (Neurontin), gabapentin has been the disproportionately more popular prescription medication.  In the United States, pregabalin (Lyrica) was first approved by the FDA for medical use in 2004 whereas gabapentin (Neurontin) was first approved by the FDA for medical use in 1993.

According to ClinCalc DrugStats Database, around ~43.3 million prescriptions were filled for gabapentin in 2015 within the United States – whereas around ~10.2 million prescriptions were filled for pregabalin in 2015 within the United States.  More specifically, gabapentin was ranked as the 13th most-prescribed medication in 2015 throughout the U.S. and pregabalin was ranked as the 79th most-prescribed medication in 2015 throughout the U.S.

There are numerous reasons as to why gabapentin is currently, and has historically, been more popular than pregabalin, including: (1) its release ~11 years prior to that of pregabalin; (2) its status as the only “gabapentinoid” medication available (for ~11 years prior to gabapentin); (3) its ability to treat the same medical conditions as pregabalin; (4) its availability as a generic prior to pregabalin; and (5) its classification as a “standard prescription” medication (rather than a Schedule V substance like pregabalin).

Although the future popularity of pregabalin will likely eventually increase (when it becomes available as a generic), it’s unclear as to whether the future popularity of pregabalin will ever exceed that of gabapentin.  Reasons the popularity of pregabalin might increase in future years include: (1) its higher potency (relative to gabapentin); (2) its longer duration of action (relative to gabapentin); (3) its availability in a greater number of dosing increments (than gabapentin); (4) its FDA-approval to treat more conditions (than gabapentin); and (5) its potentially-superior efficacy in the treatment of medical conditions (relative to that of gabapentin).

Substantial shifts in the respective popularities of pregabalin and gabapentin would likely occur if: (1) pregabalin were reclassified as a “standard prescription” (rather than a “Schedule V” controlled-substance) OR (2) gabapentin were reclassified as a “Schedule V” controlled-substance (rather than a “standard prescription).  Since Schedule V controlled-substances like pregabalin are more difficult to attain (and require more doctor visits for refills – which can be costly) versus “standard prescriptions” like gabapentin, many patients and medical doctors prefer using gabapentin over pregabalin whenever possible.

Side effects

According to U.S. FDA Access Data, the most common pregabalin (Lyrica) side effects include: dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, difficulty concentrating, and increased appetite.  According to the U.S. FDA Access Data, the most common gabapentin (Neurontin) side effects include: dizziness, somnolence, edema (peripheral), ataxia, fatigue, nystagmus, fever, nausea, vomiting, and hostility.

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Reflecting upon the most common side effects reported by U.S. FDA Access Data for pregabalin (Lyrica) and gabapentin (Neurontin), respectively, it seems as though there are notable similarities in common side effects for these medications.  Common side effects for both pregabalin (Lyrica) and gabapentin (Neurontin) include: dizziness, somnolence, and edema.

Furthermore, while there may be differences in common side effects (occurring in at least 5% of users) for pregabalin (Lyrica) and gabapentin (Neurontin), adverse effects reported for both medications include: appetite changes; blurred vision; cognitive impairment; constipation; depression; dry mouth; fever; headache; incoordination; nausea; nystagmus; weight gain; sexual dysfunction; suicidality; and vomiting.  An overlap in side effects for pregabalin (Lyrica) and gabapentin (Neurontin) is likely attributable to their identical primary mechanism of action (involving inhibition of α2δ-subunits of voltage-dependent calcium channels).

Nevertheless, assuming the common side effects for pregabalin (Lyrica) and gabapentin (Neurontin) reported by U.S. FDA Access Data are reliable, it appears as though there are various differences between these medications in their respective common side effects.  Specifically, it seems as though pregabalin (Lyrica) may be more likely than gabapentin (Neurontin) to cause dry mouth, blurred vision, weight gain, difficulty concentrating and increased appetite (as side effects).

Oppositely, it seems as though gabapentin (Neurontin) may be more likely than pregabalin (Lyrica) to cause ataxia (i.e. incoordination), fatigue, nystagmus (involuntary eye movements), fever, nausea, vomiting, and hostility (as side effects).  Differences in the occurrence rates of side effects for pregabalin and gabapentin is probably attributable to subtle disparities between these medications in: (1) pharmacodynamics; (2) potency and bioavailability; (3) chemical structure; and/or (4) onset and/or duration of action.

That said, differences in the occurrence rates of side effects for pregabalin and gabapentin may be less significant than available medical literature suggests.  As of current, there are no convincing data to substantiate the idea that pregabalin is significantly more tolerable (i.e. causes fewer side effects) than gabapentin – or vice-versa.

An authorless report from 2005 stated that “the adverse effects profile of pregabalin is similar to that of gabapentin” and includes mainly neurophysiologic reactions (dizziness and drowsiness).  The report further stated that pregabalin, analogous to gabapentin, can cause weight gain and peripheral edema in elderly persons.

However, a study by Ghai et al. (2011) involving 90 women with abdominal hysterectomy pain reported that pregabalin is associated with fewer dose-related adverse reactions than gabapentin.  Researchers speculate that its predictable bioavailability and linear pharmacokinetic profile might be reasons as to why pregabalin might be slightly more tolerable than gabapentin.

Additionally, a study by Devi et al. (2012) in which pregabalin, gabapentin, and duloxetine were directly compared in the treatment of peripheral neuropathy (among 152 patients) reported no significant differences in adverse reactions among users of these medications.  In the aforementioned study, both pregabalin and gabapentin caused mild adverse reactions of dizziness and nausea/vomiting – but only gabapentin caused additional reactions of weight gain and somnolence in 2 and 1 users, respectively.

Because no large-scale, randomized controlled trials have directly compared the acceptability/tolerability of pregabalin and gabapentin, it’s unclear as to whether one medication is significantly more tolerable than the other (especially when administered at equally-potent doses OR flexible-doses).  There are some trends from research to suggest that pregabalin might be slightly more tolerable than gabapentin (on average).

Furthermore, some researchers speculate that high-dose gabapentin may be less tolerable than an equally-potent dose of pregabalin on the basis of gabapentin’s descending bioavailability at high doses.  Essentially, because the body cannot use a large percentage of high-dose gabapentin, the circulating excess (unused portion) could theoretically increase risk of adverse reactions and/or the severities of preexisting side effects.

In summary, both pregabalin and gabapentin are generally considered safe and well-tolerated medications when administered in accordance with instruction from a licensed medical doctor.  Though some hypothesize that pregabalin might be better tolerated than gabapentin (assuming potency of dosing is equal) due to its higher, dose-independent bioavailability – there’s no evidence from large-scale trials to support this hypothesis.

Withdrawal

In the event that an individual discontinues pregabalin (Lyrica) or gabapentin (Neurontin) treatment after a moderate- or long-term, the former user may experience an array of disconcerting physical and psychological withdrawal symptoms.  Although withdrawal symptoms can occur in any former users of pregabalin or gabapentin, withdrawal symptoms tend to be most prevalent and of greatest severity among those who rapidly discontinue treatment (without tapering) after regular high-dose, long-term use.

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It is extremely common for former pregabalin (Lyrica) and gabapentin (Neurontin) to report withdrawal symptoms that persist for weeks after the date of treatment cessation.  In some cases, withdrawal symptoms will linger for months beyond the date of treatment cessation such that former users end up experiencing “Post-Acute Withdrawal Syndrome” (PAWS).

Common withdrawal symptoms associated with both pregabalin (Lyrica) and gabapentin (Neurontin) include: anxiety; cognitive impairment; depression; diarrhea; fatigue; flu-like symptoms; insomnia; mood changes; muscle aches; nausea; rebound symptoms (of the medical condition for which the gabapentinoid was prescribed); restlessness; and vomiting.

Many former users of pregabalin and gabapentin report that discontinuation symptoms significantly interfere with their ability to function in academic, occupational and/or social settings.  The cause of discontinuation symptoms (associated with pregabalin and gabapentin) is imbalanced physiology – attributable to physiology gradually transitioning from a gabapentinoid-adapted state to sober homeostasis.

More specifically, anyone who uses pregabalin or gabapentin regularly for a moderate- or long-term will undergo physiologic adaptation to its presence and neurochemical actions.  Hypothesized physiologic adaptations that might occur and/or accumulate with regular pregabalin or gabapentin administration, include: (1) downregulation of α2δ subunits of voltage-dependent calcium channels; (2) altered mRNA and protein levels of α2δ subunits; (3) decreased endogenous GABA production via enzymes; (4) increased endogenous glutamate production via enzymes; and (5) upregulation of NMDA receptors.

Once a person has accrued substantial physiologic adaptation to pregabalin or gabapentin, continued administration of the medication becomes required to preserve existing physiologic (particularly neurochemical) stability.  When pregabalin or gabapentin is ceased, the aforementioned physiologic adaptations linger – and physiologic activation ends up grossly imbalanced.

Imbalanced physiologic activation lingering from pregabalin or gabapentin cessation is what causes noticeable physical and/or psychological reactions characterized as “withdrawal symptoms.”  Although physiologic activation will eventually adjust or revert back to pre-gabapentinoid homeostasis, this homeostatic reversion requires time (weeks, months, etc.).

Only when a former user’s physiology has completely returned to homeostasis (from a gabapentinoid-adapted state) will discontinuation symptoms abate.  As of current, it is unclear as to whether specific withdrawal symptoms and/or withdrawal symptom severities differ significantly between users of pregabalin and users of gabapentin.

Considering the fact that pregabalin and gabapentin exert an identical primary mechanism of action (inhibiting α2δ-subunits of voltage-dependent calcium channels), it’s unlikely that specific withdrawal symptoms and/or withdrawal symptom severities would differ significantly between these agents – especially if dosages utilized throughout treatment were of equal potency and rates of discontinuation were similar.  As of current, there’s no medical literature suggesting that discontinuation symptoms differ in severity or duration among pregabalin and gabapentin users.

In the event that there are differences between pregabalin and gabapentin in: specific withdrawal symptoms; severities of withdrawal symptoms; and/or duration of withdrawal – these differences are likely to be subtle or clinically insignificant (assuming we control for potency of dosage, duration of treatment, and/or discontinuation rate).  If the differences in withdrawal symptoms between pregabalin and gabapentin are significant, this might be attributable to disparities in potency of dosing; treatment duration; discontinuation rates; and other variables.

Nonetheless, because standard pregabalin doses are more potent than standard gabapentin doses for similar medical conditions like postherpetic neuralgia (e.g. pregabalin 300 mg/day vs. gabapentin 900 mg/day – making the former dose approximately double as potent as the latter), it’s reasonable to expect that pregabalin users might experience harsher withdrawal symptoms (on average) due to the higher potency of medically-recommended doses (relative to gabapentin).

Similarities (Summary): Pregabalin (Lyrica) vs. Gabapentin (Neurontin)

Included below is a brief recap of similarities associated with pregabalin and gabapentin.  Noteworthy similarities between pregabalin and gabapentin include: drug classification; efficacy; elimination half-life; formatting; mechanism of action; medical uses; metabolism; side effects; and withdrawal symptoms.

  • Drug classification: Both pregabalin (Lyrica) and gabapentin (Neurontin) are formally classified as “gabapentinoids.” This classification indicates that pregabalin and gabapentin are: (1) synthetic analogues of the neurotransmitter gamma-aminobutyric acid (GABA); and (2) interact with α2δ subunit-containing voltage-dependent calcium channels.
  • Efficacy: Presently, there are no quality data to suggest that pregabalin and gabapentin differ in efficacy (magnitude of therapeutic effect and response rates) for the management of any medical condition – especially when administered at equipotent dosages. Though some studies have reported that pregabalin might be slightly more effective than gabapentin for the treatment of certain conditions – these reports were either: (1) based on “trends” (rather than statistical significance) or (2) derived from low-quality studies.
  • Elimination half-life: Pharmacokinetic research by Bockbrader et al. (2010) suggests that pregabalin (Lyrica) and gabapentin (Neurontin) exhibit similar elimination half-lives of around ~6 hours. Medication information provided by StatPearls suggests that pregabalin has an elimination half-life of around ~6.3 hours – and gabapentin has an elimination half-life of around ~6.5 hours.  Though there may be a marginal difference in the average elimination half-lives of pregabalin and gabapentin, the difference (~0.2 hours) isn’t substantial.
  • Formatting: The formatting of pregabalin (Lyrica) and gabapentin (Neurontin) is extremely similar. Both medications are manufactured in “capsule” and “oral solution” formats.  Additionally, pregabalin and gabapentin are available as long-acting (24-hour) formulations: pregabalin controlled-release (CR) and gabapentin extended-release (ER).  (The only subtle formatting difference between these agents is that gabapentin is manufactured in “tablets” at high doses – whereas pregabalin isn’t).
  • Manufacturers: Both pregabalin (Lyrica) and gabapentin (Neurontin) were manufactured by Pfizer Inc. Technically, gabapentin (Neurontin) was first manufactured by Parke-Davis, a pharmaceutical company acquired by Pfizer Inc. in 2000.  Furthermore, though pregabalin (Lyrica) was originally owned by Parke-Davis, it was solely manufactured by Pfizer Inc.
  • Medical uses: Though pregabalin (Lyrica) and gabapentin (Neurontin) differ slightly in their respective FDA-authorized indications, pregabalin and gabapentin are generally used to treat similar medical conditions – and are regarded as equally useful interventions. Medical conditions commonly treated with pregabalin and gabapentin include: postherpetic neuralgia; partial onset seizures; neuropathic pain; fibromyalgia; and restless leg syndrome.
  • Metabolism: Neither pregabalin (Lyrica) nor gabapentin (Neurontin) undergo hepatic metabolism or interact with hepatic enzymes (e.g. CYP450). Although a small percentage of each agent (less than 2%) undergoes renal metabolism, a majority of ingested pregabalin and gabapentin will remain unchanged within the body.
  • Mechanism of action: The principal mechanism of action exhibited by pregabalin and gabapentin is identical. Both medications function as inhibitors of α2δ subunit-containing voltage-dependent calcium channels (VDCCs).  Inhibition of α2δ subunit-containing voltage-dependent calcium channels is understood to generate a bulk of, possibly all of, the therapeutic anticonvulsant, antinociceptive, anxiolytic, and sedative effects associated with these agents.
  • Potential for abuse or addiction: Despite disparities in the U.S. scheduling of pregabalin (Schedule V substance) and gabapentin (standard prescription), both medications have a modest potential for abuse and addiction. Abuse and addiction potential of pregabalin and gabapentin increases among individuals with a history of poly-drug use and/or substance use disorders (particularly opioid use disorder).
  • Side effects: The side effect profiles of pregabalin (Lyrica) and gabapentin (Neurontin) are similar – likely due to their identical primary mechanisms of action (involving inhibition of α2δ subunit-containing voltage-dependent calcium channels). The three most common side effects that occur with pregabalin and gabapentin include: dizziness, somnolence, and edema.  Other adverse reactions associated with these agents include: appetite change, blurred vision, cognitive deficits, constipation, depression, dry mouth, fever, headache, loss of coordination, nausea, nystagmus, sexual dysfunction, suicidal thoughts, vomiting, and weight gain.
  • Tolerability: In studies that’ve compared the tolerability of pregabalin (Lyrica) and gabapentin (Neurontin), no clinically-relevant differences have been discovered. Pregabalin and gabapentin appear to be equally-tolerable medications (causing similar rates and magnitudes of adverse reactions) when administered at therapeutic doses for the treatment of medical conditions.
  • Withdrawal: Since pregabalin (Lyrica) and gabapentin (Neurontin) exhibit identical primary mechanisms of action (modulation of α2δ-containing voltage-dependent calcium channels), there shouldn’t be significant differences between these medications in the magnitude, occurrence rates, and/or durations of their respective discontinuation symptoms. Former users of pregabalin and gabapentin can experience severe and/or protracted symptoms following treatment cessation – especially if treatment was long-term, involved high doses, and/or ended abruptly (i.e. “cold turkey”).

Note: If you know of additional similarities between pregabalin (Lyrica) and gabapentin (Neurontin) that weren’t mentioned in the above summary, feel free to share them in the comments.

Differences (Summary): Pregabalin (Lyrica) vs. Gabapentin (Neurontin)

Included below is a brief recap of differences between pregabalin and gabapentin.  Noteworthy differences between pregabalin and gabapentin include: bioavailability; duration of effect; FDA-approved uses; legal status; and popularity.

  • Bioavailability: There’s a significant difference between the oral bioavailability of pregabalin (Lyrica) and the oral bioavailability of gabapentin (Neurontin). The oral bioavailability of pregabalin is ~90% regardless of its dosing and/or whether administered with food.  The oral bioavailability of gabapentin ranges from ~27% to ~60% and is inversely proportionate to dose plus increases when administered with a high-protein meal.
  • Developers: Although rights to pregabalin (Lyrica) were eventually acquired by the pharmaceutical company Parke-Davis, pregabalin was developed by Richard Bruce Silverman (a medicinal chemist at Northwestern University) in collaboration with Ryszard Andruszkiewicz (a researcher). In comparison, gabapentin (Neurontin) was developed by chemists directly employed through the pharmaceutical company Parke-Davis.
  • Dosing: There is a slight difference in the number of standard dosing increments (i.e. options) for pregabalin (Lyrica) and gabapentin (Neurontin). Pregabalin capsules are manufactured in 8 total dosing increments – whereas gabapentin capsules plus tablets are only manufactured in 5 total dosing increments.  Additionally, long-acting pregabalin controlled-release (CR) is available in 3 dosing increments – whereas long-acting gabapentin extended-release (ER) is available in just 2 dosing increments.
  • Duration of effect: Standard pregabalin (Lyrica) exhibits a longer duration of effect than standard gabapentin (Neurontin). Specifically, it is estimated that standard pregabalin is active for 8 to 14 hours – and that standard gabapentin is active for 5 to 8 hours.  For this reason, standard pregabalin is generally administered twice per day (b.i.d.) and standard gabapentin is generally administered thrice per day (t.i.d.) – among persons who require “all-day” symptom management.
  • FDA approved uses: Although pregabalin (Lyrica) and gabapentin (Neurontin) function similarly and are generally regarded as interchangeable interventions for most medical conditions, the medications differ in their official FDA-authorized indications. Pregabalin is FDA-approved to treat 5 medical conditions, including: diabetic neuropathic pain; postherpetic neuralgia; partial onset seizures; fibromyalgia; and spinal cord injury-related neuropathic pain.  Gabapentin is approved to treat 2 medical conditions, namely: postherpetic neuralgia and partial onset seizures.
  • Ingredients: The active ingredient in the medications Lyrica and Lyrica CR is the chemical “pregabalin” – and the active ingredient in the medications Neurontin and Gralise is the chemical “gabapentin.” Though pregabalin and gabapentin are similar in that each is a synthetic GABA analogue, each contains a different active chemical.
  • Legal status: The legal status of pregabalin (Lyrica) currently differs slightly from that of gabapentin (Neurontin) in the United States. Pregabalin is classified as a “Schedule V” controlled-substance – whereas gabapentin is classified as a standard “prescription medication.”  Differences in the scheduling of pregabalin and gabapentin is related to: (1) euphoria occurring as an adverse reaction in pregabalin clinical trials (not gabapentin trials); and (2) pregabalin exerting a ~6-fold stronger effect (on voltage-dependent calcium channels) relative to gabapentin; and (3) pregabalin maintaining its high bioavailability (~90%) at high doses (whereas gabapentin does not).
  • Onset of action (?): It is unclear as to whether there are significant differences between pregabalin (Lyrica) and gabapentin (Neurontin) in their respective onsets of neurochemical action – and onsets of therapeutic action. Online reports estimate that the initial neurochemical action of pregabalin becomes noticeable within 40 to 120 minutes (post-administration) – and the initial neurochemical action of gabapentin becomes noticeable within 30 to 90 minutes (post-administration).  However, pharmacokinetic research indicates that pregabalin is absorbed quicker than gabapentin – and some (low quality) comparison studies have reported quicker onsets of both initial neurochemical action and therapeutic action with pregabalin relative to gabapentin.
  • Popularity: In the United States, the popularity of gabapentin (Neurontin) has been significantly greater than that of pregabalin (Lyrica) – despite the fact that the latter (pregabalin) is approved by the FDA to treat a greater number of medical conditions. As of 2015, gabapentin was prescribed over 43.3 million times and pregabalin was prescribed over 10.2 million times.  Differences in the popularities of these agents are likely attributable to disparities in scheduling (Schedule V vs. standard prescription) and generic availability.

Note: If you know of additional differences between pregabalin (Lyrica) and gabapentin (Neurontin) that weren’t mentioned in the above summary, feel free to share them in the comments.

Which medication is “better”? (Pregabalin or Gabapentin)

If attempting to determine whether pregabalin (Lyrica) or gabapentin (Neurontin) is “better” (on average) relative to the other, it’s necessary to reflect upon variables that prospective users and/or medical professionals deem important, including: average cost; effectiveness in the treatment of medical conditions; formatting and dosing; onset and duration of action; official (FDA-approved) medical uses; side effects and tolerability; and withdrawal severity.

In many of these variables, there aren’t clinically-significant differences between pregabalin and gabapentin.  Pregabalin and gabapentin are generally similar in: (1) efficacy (magnitude of therapeutic effect and response rates); (2) formatting (capsules/oral solution; short-acting/long-acting); (3) medical uses (postherpetic neuralgia; partial onset seizures; neuropathic pain; fibromyalgia; restless leg syndrome); (4) metabolism (lack thereof); (5) elimination half-life (~6 hours); (6) side effects (profiles are similar); (7) tolerability (dropout rates are similar).

Due to these similarities, most medical doctors regard pregabalin (Lyrica) and gabapentin (Neurontin) as equally useful and likely-interchangeable treatment options.  Nevertheless, some individuals might have developed preferences for one medication relative to the other.

Why Pregabalin instead of Gabapentin?

One might perceive pregabalin (Lyrica) as modestly favorable over gabapentin (Neurontin) on the basis of its: (1) higher bioavailability; (2) longer duration of action; (3) greater number of FDA-approved uses; (4) greater number of dosing options; and/or (5) potentially-faster onset of therapeutic action; (6) potentially-superior efficacy.

1. Higher bioavailability: The oral bioavailability of pregabalin (Lyrica) is high (~90%) regardless of dosing and/or whether administered with food – whereas the oral bioavailability of gabapentin (Neurontin) fluctuates between moderate (~60%) and low (~27%) depending on: dosing (bioavailability is inversely proportionate to dose) and food intake (high protein meals increase its bioavailability).

Since pregabalin is significantly more bioavailable than gabapentin (especially at high doses), the former (pregabalin) may be safer, more tolerable, and/or more efficacious than the latter (gabapentin).  Because the body is unable to use a noteworthy percentage of ingested gabapentin (especially at high doses), the circulating excess (unused portion) might increase risk of toxicity and/or provoke adverse reactions.

Moreover, persons who require high and/or supratherapeutic doses of gabapentinoids for symptom management might achieve significantly better responses with pregabalin than gabapentin as a result of bioavailability disparities.  Pregabalin maintains a ~90% bioavailability at high doses – whereas the bioavailability of gabapentin continues dropping with dose escalation.

2. Longer duration of action: Another reason some patients and/or medical doctors might prefer pregabalin (Lyrica) over gabapentin (Neurontin) is its longer duration of action (in standard format). In standard format, pregabalin (Lyrica) exhibits an average duration of action from 8 to 14 hours – whereas gabapentin (Neurontin) exhibits an average duration of action from 5 to 8 hours.

The longer duration of action associated with pregabalin (8 to 14 hours) relative to gabapentin (5 to 8 hours) might be preferred by patients because symptoms can be managed throughout the day with less frequent dosing.  For a full day of symptom management, pregabalin (Lyrica) generally requires twice-daily dosing (b.i.d.) whereas gabapentin (Neurontin) generally requires thrice-daily dosing (t.i.d.).

Less frequent dosing may improve rates of treatment adherence as it’s easier for some individuals to remember to administer a medication twice per day (e.g. morning and evening) – rather than thrice per day (e.g. morning, afternoon, evening).  In other words, twice-per-day dosing with pregabalin is probably more convenient for most than thrice-per-day dosing with gabapentin.

3. FDA-approved uses: Though pregabalin (Lyrica) and gabapentin (Neurontin) are generally utilized interchangeably and are both approved by the U.S. FDA to treat postherpetic neuralgia and partial onset seizures, pregabalin is approved by the U.S. FDA to treat 3 conditions that gabapentin is not. Specifically, pregabalin FDA-approved to treat: diabetic neuropathic pain; fibromyalgia; and spinal cord injury-related neuropathic pain – whereas gabapentin is not.

To receive FDA approval as a treatment for the aforementioned conditions (diabetic neuropathic pain; fibromyalgia; and spinal cord injury-related neuropathic pain), pregabalin had to prove its efficacy in numerous large-scale, randomized controlled trials.  Because pregabalin has proven effective [in large-scale, well-designed trials] for the management of diabetic neuropathic pain; fibromyalgia; and spinal cord injury-related neuropathic pain – but gabapentin has not, it’s fair to suggest that pregabalin is a superior “treatment choice” (relative to gabapentin) for these conditions.

4. Dosing options: There are a greater number of dosing options for pregabalin (Lyrica) than gabapentin (Neurontin). Standard pregabalin is sold in 8 total dosing increments (25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg) – whereas standard gabapentin is sold in 5 total dosing increments (100 mg, 300 mg, 400 mg, 600 mg, 800 mg).

Additionally, long-acting pregabalin (controlled-release) is sold in 3 total dosing increments (82.5 mg, 165 mg, 330 mg) – whereas long-acting gabapentin (extended-release) is sold in 2 total dosing increments (300 mg and 600 mg).  A greater number of dosing options for pregabalin should increase odds of pregabalin users finding a tolerable and effective dose without emptying powder from capsules and/or splitting pills – relative to gabapentin users.

5. Faster onset of action (?): There’s some evidence to suggest that pregabalin (Lyrica) may exhibit faster onsets of neurochemical and therapeutic action than gabapentin (Neurontin). Pharmacokinetic studies suggest that pregabalin is absorbed quicker than gabapentin and reaches peak plasma concentrations quicker (within 1 hour) than gabapentin (within 3 to 4 hours).

Moreover, some comparison studies have reported pregabalin users experiencing quicker average remission of symptoms (i.e. therapeutic responses) than gabapentin users.  Although it’s unclear as to whether pregabalin exhibits a significantly quicker onset of therapeutic action than gabapentin, the fact that it might be a faster-acting medication than gabapentin is yet another reason to favor its use (over gabapentin).

6. Slightly superior efficacy (?): Several comparison studies (indirect simulation and direct) have suggested that pregabalin (Lyrica) might be superior over gabapentin (Neurontin) in efficacy. For example, a simulation study (based off of magnitude of effect in clinical trials) suggested that pregabalin is likely more effective than gabapentin in the treatment of postherpetic neuralgia.

Another study documented a trend for better efficacy with pregabalin in the treatment of partial onset seizures – relative to gabapentin.  Additionally, a randomized controlled trial comparing pre-treatment pregabalin and gabapentin in the management of perioperative pain (among 90 women who underwent hysterectomy) reported that pregabalin (300 mg) was significantly more efficacious than gabapentin (900 mg).

Moreover, it’s reasonable to suspect that pregabalin is more effective than gabapentin if high doses (particularly supratherapeutic dosages) are ever required due to its high bioavailability (90%) irrespective of dosing – compared to the diminishing bioavailability of gabapentin at high doses (27%).  Because studies suggest that pregabalin might be more effective than gabapentin (but none suggest the opposite), the potentially-superior efficacy of pregabalin makes it favorable over the gabapentin.

Why Gabapentin instead of Pregabalin?

One might perceive gabapentin (Neurontin) as modestly favorable over pregabalin (Lyrica) on the basis of its: (1) lower abuse potential; (2) shorter duration of action; (3) availability as a standard prescription; (4) greater number of formatting options; (5) lower cost.

1. Lower abuse potential (?): Another reason some patients and/or medical doctors might prefer using gabapentin over pregabalin is related to its lower abuse/addiction potential. Support for the idea that gabapentin may carry lower risk of abuse/addiction than pregabalin includes: (1) the bioavailability of gabapentin is inversely proportionate to dose (pregabalin retains its high bioavailability irrespective of dose); (2) the ~6-fold lower magnitude of voltage-dependent calcium channel modulation facilitated by gabapentin relative to equally-dosed pregabalin; and (3) the lack of “euphoria” reported in gabapentin clinical trials (“euphoria” occurred in pregabalin clinical trials).

Since the bioavailability of gabapentin precipitously decreases at high doses (due to saturation of its transport mechanism), persons who intentionally abuse/misuse gabapentin (such as by ingesting a supratherapeutic dose) may experience a “ceiling-like effect” whereby its neurochemical effect basically plateaus at a high dose.  The plateau of gabapentin’s neurochemical effect might prevent select users from experiencing euphoria and/or reward center activation that could foster abuse or addiction.

Moreover, even among persons who experience euphoria from abusing/misusing gabapentin, its ceiling-like effect likely sets a tolerance threshold – whereby higher tolerance levels cannot be reached after tolerance to the ceiling dose occurs.  It’s also possible that the diminishing bioavailability of gabapentin at high doses decreases toxicity among misusers.

In comparison to gabapentin, the bioavailability of pregabalin remains at ~90% regardless of its dosing (no ceiling-like effect occurs at high doses).  As a result, persons who deliberately misuse/abuse pregabalin (such as by ingesting a supratherapeutic dose) will endure significantly greater neurochemical modulation of voltage-dependent calcium channels (VDCCs) relative to lower doses – such that there’s a markedly higher likelihood of experiencing euphoria (leading to further abuse/addiction) and/or toxicity.

It is also understood that euphoria did not occur in clinical trials of gabapentin (yet euphoria occurred in clinical trials of pregabalin).  This suggests that there could be neurochemical actions unique to pregabalin that increase its abuse/addiction potential and/or neurochemical actions unique to gabapentin that decrease its abuse/addiction potential (relative to pregabalin).

2. Shorter duration of action: Though some individuals prefer pregabalin’s longer duration of action (8 to 14 hours) over gabapentin’s shorter duration of action (5 to 8 hours) – others prefer the opposite. For example, persons who use gabapentinoids “as needed” for intermittent and/or short-term management of medical symptoms might only require symptom management for 4 to 6 hours – making gabapentin a potentially-superior choice over pregabalin.

Individuals who solely require short-term symptom management might like the fact that gabapentin controls symptoms for a predictably brief duration (5 to 8 hours) – and then it wears off (such that users aren’t under its influence and/or enduring medication-related side effects all day).  In comparison, users of pregabalin will be under its influence and prone to treatment-related side effects for a bulk of the day (8 to 14 hours) – which may be less preferable.

It may also be likely that the shorter duration of action associated with gabapentin among infrequent or “as needed” users decreases likelihood of tolerance onset – relative to pregabalin.  Essentially, intermittent use of a medication with a shorter duration of action (gabapentin) should allow the body to recover (or shift towards homeostasis to a greater extent) “between doses” relative to intermittent use of a medication with a longer duration of action (pregabalin).

3. Standard prescription: The fact that gabapentin (Neurontin) is available in the United States as a “standard prescription” might lead some individuals to prefer its usage over that of pregabalin (Lyrica). As a standard prescription, gabapentin is slightly easier for patients to attain and refill than pregabalin (which is classified as a Schedule V controlled-substance).

Assuming patients with chronic medical conditions (e.g. neuropathic pain) require long-term treatment with gabapentinoids, patients might save themselves money and time by opting to use gabapentin instead of pregabalin.  Gabapentin prescriptions can be filled electronically and refilled without frequent follow-up doctor appointments.

In comparison, Schedule V substances like pregabalin can only be refilled a maximum of 5 times within 6 months before additional doctor appointments are needed for further refills.  Because doctor appointments are expensive and could be reduced with gabapentin relative to pregabalin, using gabapentin may prove to be more cost-effective for certain patients.

4. Formatting options: Although gabapentin is available in fewer total dosing increments than pregabalin, gabapentin offers a greater number of formatting options than pregabalin. Standard-release gabapentin is available in capsules, tablets, and oral solution (3 formats) – whereas standard-release pregabalin is only available in capsules and oral solution (2 formats).

The availability of standard-release gabapentin in “tablet” format might be perceived as a noteworthy advantage relative to standard-release pregabalin formatting options).  Unlike standard-release capsules (which contain powder), standard-release gabapentin tablets can be conveniently and precisely split (e.g. with a pill cutter) by persons who wish to modify or titrate dosing.

Since only gabapentin is available in standard-release tablet format (and pregabalin is not), pregabalin users who wish to precisely adjust dosing will need to: (1) carefully empty powder from capsules (while avoiding spills) and (2) measure out specific quantities of powder for ingestion – this takes time, increases risk of dosing errors, and/or could be perceived as a hassle.

Moreover, users of gabapentin might be able to save a modest amount on annual prescription costs by splitting 600 mg or 800 mg tablets into smaller increments – rather than purchasing exact-dose capsules.  Also worth mentioning is the fact that gabapentin is available in multiple long-acting (24-hour) formats, including: Gralise (gabapentin extended-release) and Horizant (gabapentin enacarbil).

In comparison, pregabalin is only available in one long-acting (24-hour) formulation of Lyrica CR (pregabalin controlled-release).  The availability of gabapentin in multiple long-acting preparations might be perceived as favorable relative to the standalone long-acting preparation of pregabalin – based on the fact that patients have an alternative if the first long-acting preparation tested exhibits suboptimal efficacy and/or tolerability.

5. Lower cost: Another reason patients and/or medical professionals prefer using gabapentin (Neurontin) over pregabalin (Lyrica) is related to its significantly lower cost. Neurontin has been available as a low-cost generic (gabapentin) since 2004, whereas Lyrica is not yet available as a generic (pregabalin). (Prognosticators expect Lyrica to become available as a generic in December 2018).

Until pregabalin becomes available as a generic, it will be preferable for most patients (who require gabapentinoid treatment) to use generic gabapentin for the sake preserving finances.  The average cost for a 30-day supply of “brand name” Lyrica ranges from $439 to $471 – whereas the average cost for a 30-day supply of gabapentin (generic Neurontin) ranges from $10 to $39.

Over the course of a 1-year span, prescription expenses for daily Lyrica users will exceed $5200 – whereas prescription expenses for daily gabapentin (generic Neurontin) users will range from $120 to $468.  Assuming a person has poor health insurance, using gabapentin could result in thousands-of-dollars in annual savings (relative to using Lyrica).

Deciding whether to use Lyrica (pregabalin) or Neurontin (gabapentin)…

If we assume that there are no clinically-relevant differences between pregabalin and gabapentin in aspects of efficacy and tolerability, the most logical reasons to select one medication over the other would likely be: lower cost; favorable legal scheduling; and preferred duration of action.  Since gabapentin is available as a low-cost generic (pregabalin is not) and is considered a “standard prescription” (pregabalin is a “Schedule V” substance), it would make sense for patients and practitioners to favor the use of gabapentin.

That said, if a patient’s insurance covers the full cost of pregabalin and/or pregabalin becomes available as a low-cost generic (priced analogously to gabapentin) AND the patient sees his/her medical doctor the same number of times per year as he/she would with gabapentin (such as to incur the same financial toll in doctor appointment expenses), then it makes sense to favor neither medication unless one intervention is supported by stronger data for the treatment of a particular medical condition.

If we assume that there are no differences between pregabalin and gabapentin in cost (prescriptions plus annual doctor appointments expenses required to attain prescriptions) and that there might be differences in pregabalin and/or gabapentin in efficacy and/or tolerability – then it makes sense to favor the use of pregabalin.  Why? Because there are data suggesting that pregabalin might be faster-acting, more effective, and/or more tolerable than gabapentin in the treatment of various medical conditions – but no data to suggest the opposite.

However, in patients with a history of substance use disorders, it makes sense to favor the use of gabapentin relative to pregabalin (assuming a gabapentinoid is absolutely necessary for symptom management).  Why? Because the bioavailability of gabapentin decreases at high doses (minimizing odds of a euphoriant effect from abuse/misuse) whereas the high bioavailability of pregabalin is retained at all doses (increasing odds of a euphoriant effect from abuse/misuse).

It is worth noting that some individuals could benefit from using pregabalin and gabapentin: (1) as a combination treatment, (2) each at a different time of day, and/or (3) on a rotational schedule (e.g. gabapentin for one month, pregabalin for the second month, etc.).  In theory, most individuals should find that equipotent doses of pregabalin and gabapentin induce similar subjective and objective effects.

Nonetheless, it’s possible that some individuals will respond significantly better to pregabalin (relative to gabapentin) – and others will respond significantly better to gabapentin (relative to pregabalin).  Disparities in responses to equipotent doses of pregabalin and gabapentin might be explained by subtle differences in their respective bioavailabilities and pharmacodynamics.

Which medication do you prefer: Pregabalin or Gabapentin?

If you have experience with the gabapentinoid medications – pregabalin (Lyrica) and gabapentin (Neurontin), leave a comment regarding whether you: (A) prefer one medication over the other OR (B) have no substantial preference for using one medication over the other.  Reflecting upon your experiences with each medication, what would you rate each intervention on a scale of 1 to 10 (with “1” being “worst” and “10” being “best”) in the domains of “efficacy” (1 to 10) and “tolerability” (1 to 10).

In the event that you’ve developed a strong preference for either pregabalin (Lyrica) or gabapentin (Neurontin) relative to the other, what are your reasons for this preference?  Reasons for preferring one gabapentinoid over the other might include: superior symptom management; fewer side effects; and/or lower cost.

If you’re a person who found one gabapentinoid (pregabalin or gabapentin) to be superior over the other in efficacy and/or tolerability, have you considered that these differences might be explained by disparities in treatment-related variables like: potency of dosing (e.g. more potent with one medication relative to the other); concurrent substance use (e.g. using another medication during pregabalin treatment and not gabapentin treatment); neurochemistry at baseline (e.g. using pregabalin with zero substance use 90 days prior – and gabapentin after recently discontinuing a psychiatric medication)?

In order for others to best understand your respective experiences with pregabalin (Lyrica) and gabapentin (Neurontin), feel free to provide additional details like: the average lengths of treatments; dosages administered throughout each treatment; concurrent substance use throughout each treatment; and the medical conditions for which pregabalin and gabapentin were prescribed.

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