Gabapentin chemical structure

Drug of the Month:
Gabapentin

Many uses, but NOT a “mood stabilizer”



Gabapentin is a medication that has many uses, especially for anxiety and insomnia, but it is frequently misused as if it was a mood stabilizer that could be used by itself in bipolar illness. It’s important to know when to use it and also to realize that it shouldn’t be used primarily as a mood stabilizer.


Clinical efficacy and inefficacy

Gabapentin was first FDA indicated for epilepsy. Very quickly it began to be used for many non-indicated purposes.  Some of this use outside of epilepsy was based on a certain amount of clinical wisdom, with the observation that gabapentin was effective for anxiety and pain. These anxiety and pain symptoms often occurred in the context of depression, however, and this led to the misinterpretation by many clinicians that this medication might be effective for mood illnesses per se. The PL editor was one of those who published clinical experience suggesting possible benefits on mood conditions. The company which marketed this medication in the 1990s then began to market those uses to  clinicians, which is outside of federal regulations.  This led to a backlash from the FDA and those who are critical of the pharmaceutical industry.

In the last decade, the opposite scenario evolved. Critics began to claim that gabapentin was useless for anything except epilepsy. The truth is somewhere in between.

Gabapentin is experiencing something of a renaissance. It’s being used for anxiety, insomnia, menopausal symptoms, chronic pain syndrome, and once again mood and bipolar illness.

It’s the PL view that all of these uses are potentially valid, but it’s very important not to use this medication as a primary mood stabilizer in bipolar illness. It was studied about a decade ago in multiple studies of acute mania, and it was proven to be equivalent to placebo. It has never been proven to be effective for bipolar depression  or in prophylaxis of mood episodes. Therefore it is inappropriate to use this medication as if it was similar to lithium or valproate or lamotrigine. This is a mistake: It is not effective for bipolar illness.

Nevertheless it is useful for anxiety, whether symptomatically or as part of a larger anxiety illness. It’s sedating and probably helpful for insomnia in some persons, although it has not been carefully studied in that condition. It’s very well proven for pain syndromes and also beneficial for persons with substance abuse who may have anxiety-related self-medication.

Biological mechanism

Gabapentin stimulates a receptor subunit of GABA, which likely produces its anxiety benefits. It is not definitively known if this mechanism is the reason for its other benefits such as   anticonvulsant effects.

Fig 1. Gabapentin (1-(aminomethyl)cyclohexaneacetic acid) and GABA (4-aminobutanoic acid) structures. Gabapentin contains an additional 5-carbon closed chain forming a non-aromatic ring. Despite similarity, gabapentin agonism relates only to specific types of GABAB receptors.

Fast facts: Gabapentin


Typical dose: 300-900 mg/d (range 100-2000)

Biological mechanism: GABA agonist

Typical side effects: sedation, nausea 

Less common but important side effects: none

Medically important side effects:  none

Clinically proven efficacy: Treatment of anxiety, alcohol/cocaine withdrawal, diabetic neuropathy, epilepsy

Side effects and dosing

The main benefit of this medication is that it has very few side effects, and none that are known to be medically important or harmful long-term. Its main nuisance side effects are nausea and sedation. Dosing has a very broad range, which can be good in terms of being able to reduce the dose greatly to a point that is tolerable for most people. Sensitive individuals usually begin at 100 mg nightly, but for the average patient, 300 mg is a standard starting dose. For anxiety and pain and insomnia, typical final dose will be about 300 to 900 mg nightly. PL recommends giving all the medication at night, even though it has a short half-life of about four hours. This short half-life may be relevant for anxiety, in which case multiple daily dosing may be needed. If given for other purposes, a single evening dose may be sufficient.


The PL Bottom Line

  • Gabapentin is a versatile medication, which can be helpful for anxiety and insomnia.
  • It is proven ineffective for mania and should NOT be given as a “mood stabilizer.”

PL Reflection

We have strength enough to endure the troubles of others.  

Duc de La Rochefoucauld

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