Gabapentin (Neurontin) is becoming to be the "Swiss Army knife" of neurologic drugs. The drug is approved for partial and generalized adult seizures, but continues to show effectiveness in the treatment of a variety of ailments from mood disorders to diabetes-related neuropathy. Its potential use in psychiatric disorders include 1. bipolar disorder, especially the manic, mixed and rapid cycling type; 2. schizoaffective disorder; 3. impulsive aggression; 4. states of benzodiazepine, sedative, and alcohol withdrawal; and 5. anxiety disorders such as generalized anxiety disorder, panic disorder, social phobia, and borderline personality disorder with anxiety and depressive features.

In one study[1] of 4 patients (2 men and 2 women, aged 36-54 years old), diagnoses of panic disorder and generalized anxiety disorder, without response to one or more meds such as Zoloft, Paxil, Norpramin, Xanax, Valium, and Wellbutrin, Neurontin was added to their drug regimen, dosage range from 200 mg/day (100 mg twice daily) to 1200 mg/day (divided doses). All 4 experienced marked reduction of their panic attacks or level of anxiety. One patient (1200 mg/day) had her dose lowered to 400 mg twice daily because of sedation. The authors state that Neurontin appears to be safe and effective treatment of anxiety.

Neurontin was also used to treat anxiety and depression in patients with borderline personality disorder. One study was done by Rosen et al.[2] involving 12 female outpatients who had at least 4 out of 5 borderline features and presented with significant anxiety. They were given Neurontin as part of their medication regimen. Measures of depression (Beck Depression Inventory) and anxiety (State and Trait Anxiety Scores) were given to patients before the Neurontin was added. Those assessments also were conducted 8 weeks later. Neurontin was increased to an average dose of 900 mg daily. The results indicate a significant decrease in both depression and anxiety scores. They concluded that Neurontin may play a useful role in the treatment of patients with borderline personality disorder, especially for those who exhibit severe anxiety. The authors suggested that large, placebo-controlled trials be conducted to clarify the effectiveness of Neurontin in this type of patients.

In another study[3], this time using Neurontin in patients with social phobia, AC Pande and others used a randomly-assigned, double-blind, placebo-controlled, parallel-group study with 69 patients. They were given either Neurontin, flexible dose between 900 mg/day and 3600 mg/day in three divided doses, or placebo for 14 weeks. Neurontin patients' symptoms were reduced significantly vs. those of placebo patients, based on clinician- and patient-rated scales. Common side effects of Neurontin reported during this trial were dizziness, dry mouth, drowsiness, nausea, flatulence, and decreased libido. There were no serious side effects reported. According to the researchers, this is the first demonstration of a nonbenzodiazepine anticonvulsant drug showing effectiveness in a placebo-controlled trial for social phobia. They recommended more studies to confirm Neurontin's effect in this type of patients. (Social phobia is also known as social anxiety disorder. About 10 million Americans suffer from this condition. For these people, they go through life everyday suffering because of the dreaded fear of meeting or interacting with other people. They are sometimes labeled "people allergic to people." Paxil is the first SSRI approved for social phobia.)

In another study[4], involving 5 cases, ages and sexes unknown, Neurontin in combination with Prozac was found beneficial in OCD (obssessive-compulsive disorder) patients with partial or incomplete response to the SSRI. The dose ranged from 900 mg three times a day for 6 weeks and titrated upward to a maximum of 3600 mg daily in divided doses. All patients reported marked subjective improvement in anxiety, OCD symptoms, sleep and mood within 2 weeks of starting Neurontin. Neurontin was also found to reduce the frequency of migraine headaches in one patient.

Neurontin's dose used for anxiety disorders is generally lower than that for bipolar disorder (manic type). For anxiety disorders, doses ranging from 300 mg to 1200 mg daily (divided doses) are usually enough to alleviate anxiety. For bipolar disorder (usually as an add-on to another mood stabilizer), the usual dose is between 900 to 4200 mg daily, divided doses.

Geriatric psychiatrists and physicians specializing in the treatment of the elderly are now beginning to appreciate the potential of Neurontin's calming effect in the confused and agitated elderly patients. Of course, doctors are now commonly using Neurontin for control of neuropathies (e.g., diabetic neuropathy).

A few things you should know about Neurontin. It is not metabolized by the liver and has no active metabolites (daughter compounds). It is eliminated through the kidneys unchanged. So you must have a good kidney function to take this drug. It has a short half-life of 6 to 7 hours (must be taken in divided doses during the day for adequate coverage) and it reaches a steady state blood level in about 2 to 3 days.

The most common side effects, usually occur after start of treatment or increase in dose are drowsiness, unsteadiness, dizziness, and fatigue. Tolerance (side effects fade away) usually develops to these side effects but may persists sometimes. Neurontin itself weakly interacts with the other drugs. However, you should avoid the following drugs while on Neurotin: 1. cimetidine (Tagamet) will increase Neurontin's blood level; 2. antacids with aluminum/magnesium contents will reduce Neurontin's absorption leading to decrease bioavailability and effectiveness; 3. alcohol will increase sedating effect.

No routine laboratory tests are required during Neurontin treatment. However, make sure your kidneys are working well. One more thing, a case of thyroiditis was reported with the use of Neurontin in a 28-year-old woman with rapid cycling bipolar and normal baseline thyroid function.[5] Further clinical experience with Neurontin should help clarify whether use of this drug is associated with a significant risk of thyroid disturbance.

Sources:

1] Gabapentin used to treat anxiety disorders. American Journal of Psychiatry 1998;155:992-993.

2] Gabapentin used to treat BPD: In: Psychopharmacology Update, July 1999.

3] Gabapentin for social phobia. In: Primary Psychiatry, August 1999.

4] Gabapentin/fluoxetine combination helpful for OCD. Journal of Clinical Psychiatry 1998;59:9.

5] Frye M, et al: Possible gabapentin-induced thyroiditis (letter). Journal of Clinical Psychopharmacology 1999;19(February):94-95.

There may be some substance to the notion that gabapentin (Neurontin) has anti-panic effect. The following is the latest study conducted to attest this.

GABAPENTIN FOR PANIC DISORDER

Modest anti-panic effects were observed in a subset of more severely affected patients with anxiety disorder with gabapentin (Neurontin) treatment.

Subjects (103) in this multicenter study met DSM-IV criteria for panic disorder with or without agoraphobia, and had at least 1 panic attack per week for 3 weeks before screeing. All psychotropic drugs were discontinued, and patients were randomized to 8 weeks of flexible-dose gabapentin at 600-3600 mg/day (52 subjects) or placebo (51 subjects). Treatment efficacy was measured using the multidimensional Panic and Agoraphobia (PAS), with treatment response defined as a >50% (greater than 50%) decrease in the score from baseline.

For the group as a whole, declines in PAS scores and response rates did not differ between gabapentin and placebo. However, among the subgroup (61 subjects) with more severe symptoms (baseline PAS >20), gabapentin treatment resulted in a significantly greater decrease in PAS scores compared with placebo (-10 vs. -5 points, p=0.04). Response rates did not differ between placdebo- and gabapentin-treated patients with PAS scores of <20 (less than 20). Gabapentin was generally well tolerated, with somnolence and headache the most frequently reported adverse effects.

CONCLUSION: Gabapentin has been shown in preclinical studies to have anti-anxiety effects comparable to those of benzodiazepines. However, results of this study suggest that gabapentin may be useful in some patients with panic disorder.

Reference:

Pande A, et al: Placebo-controlled study of gabapentin treatment of panic disorder. Journal of Clinical Psychopharmacology 2000;20(August):467-471.

FYI: This study was funded by Parke-Davis, maker of Neurontin.

Although oversimplified the below post by an MD is interesting:

Neurontin (Gabapentin) is quickly becoming known as the "Swiss Army
Knife" of both psychiatry and neurology. Although its only FDA-
approved indication if for adjunct treatment of partial complex
seizures, its utility spans an incredibly broad spectrum. In vivo,
Neurontin increases GABA turnover and increases whole blood
serotonin. GABA receptors are those that are targeted by the
benzodiazepines (ie Valium, Klonopin, Xanax) as well as by alcohol.
Action at the GABA receptor is inhibitory, and therefore results in
relaxation, and control of anxiety symptoms (overly-simplified).
Beauclair and colleagues noted that Neurontin (in a dose of 200-1800
mg/day) resulted in improvement in a number of anxiety-related
symptoms including somatic complaints, panic attacks, obsessive-
compulsive symptoms, psychotic anxiety, and generalized anxiety in 18
psychotic patients. As you can see, although the published studies
for Neurontin in anxiety are positive they were done in a very select
patient population. However, our institution has non-psychotic
patients enrolled in a study to determine Neurontin's utility in
generalized anxiety disorder.
Neurontin's usefulness in chronic pain syndromes is already
well documented, despite not being FDA approved. Although it has
never been formally studied (that I know of) for the neurovascular
pain in rosacea, one would suspect it to be beneficial. Other
medications that could be beneficial for this type of pain include
Tegretol (carbamazepine) and Elavil (amitryptiline). Tegretol is
approved for the treatment of trigeminal neuralgia (a pain syndrome
of the face involving the distribution of the trigeminal nerve).
Although Neurontin has yet to be fully studied, preliminary
results for its use in anxiety disorders are very promising. Of
particular note, it is a medication which is not prone to addiction
or dependence (in stark contrast to the benzodiazapines ie Klonopin,
Xanax, etc). In addition, it is completely safe in liver disease as
it is metabolized completely by the kidneys. The side effect profile
of Neurontin is incredibly benign in comparison to other
neuropsychiatric medications. However, Neurontin's dose needs to be
steadily increased into the range of at least 1200mg-1800mg/day to be
effective. Any dose less than this may not indicate an adequate trial
of the drug if symptoms are unhelped. Shoot for the 1800mg/day in
three divided doses (Can't be taken all at once given the drug's
short half life).
Hope this information was somewhat helpful as
neuropsychopharmacology is my area of interest. Don't ask any
questions of emu oil or the like though. My rosacea regimen is
Doxycycline 100mg once a day and MetroCream twice a day, wash with
warm water (not glamorous, but medically proven to be successful in
*most* patients).

Brown University Department of Psychiatry and Human Behavior
Providence, Rhode Island.