Peer-Reviewed Letter
TIAGABINE FOR THE TREATMENT OF ANXIETY
Daniel Crane, M.D.
[Cephalon is on record saying that they believe that Gabitril will become their best-selling drug. (According to Cowen they have actually said that they believe that they believe that Gabitril will become larger than Provigil and Actiq combined). Pretty amazing considering that Gabitril was bought from Abbott for a mere 100 mUSD. Maybe anecdotal results like the ones quoted below is one of the reasons for the company's optimism.
I have copied this from Yahoo. The referenced abstract at PubMed actually turns up empty.]
Conventional antidepressants (which target noradrenergic, serotonergic, and dopaminergic systems in thecentral nervous system) and the benzodiazepines (which target the g-aminobutyric acid[GABA] system) are commonly used for the treatment of anxiety disorders. In addition to the benzodiazepines, other anticonvulsants, such as gabapentin and valproate, have been used in the treatment of anxiety.
Tiagabine hydrochloride (GABitril; Cephalon, West Chester, PA), a selective GABA-reuptake inhibitor (SGRI), increases GABA tone via a mechanism of action that is distinct from that of the otheranti-convulsants. Tiagabine is a highly selective inhibitor of the GAT-1 GABA transporter system, which is largely responsible for the reuptake of GABA from synaptic clefts to the presynaptic neurons and glia in the CNS. Tiagabine enhances the function of endogenously released GABA, is not associated with tolerance, dependence, and withdrawal symptoms, and appears to have little or no cognitive impairment at therapeutic doses. Preclinical studies suggest that tiagabine may have significant anti-anxiety properties. Additionally, there are case reports that suggest that tiagabine may be useful in the treatment of impulse control disorder (intermittent explosive disorder), schizoaffective dis-order, and bipolar depression.
To investigate the potential use of tiagabine for treatment of anxiety disorders and comorbid anxiety associated with other psychiatric disorders, ten patients received open-label treatment with tiagabine in a case-series study (Table 1). All patients had long-standing duration of anxiety and were considered to be refractory to treatment with conventional anxiolytic medications. Nine of the 10 patients were considered to be moderately to markedly ill, and one patient with MDD was considered to be severely ill. Five patients were not receiving any treatment with anti-anxiety medications before the start of tiagabine; the other five patients were taking either risperidone, clomipramine, paroxetine, or citalopram.
Patients initially received 2 mg of tiagabine daily (either as monotherapy or as adjunctive therapy) just before bedtime during the first week of treatment. The dosage of tiagabine was increased after the first week of treatment for patients who reported insufficient control of anxiety. Patients who received dosages greater than 2 mg/day took the full dosage just before bed-time or took tiagabine in divided doses of half before bedtime and half in the morning (elimination half-life range: 7–9 hr). Change in clinical condition after the 4-week treatment period was evaluated using the Clinical Global Impression of Change (CGI-C) scale.
At the end of the 4-week treatment period, 8 of 10 patients were receiving 2–4 mg of tiagabine daily, with the remaining two patients receiving 6–8 mg of tiagabine daily. The mean daily dosages of tiagabine were approximately the same in the group of patients who received tiagabine monotherapy (3.6 mg/day) and the group of patients who received tiagabine in combination with other medications for the treatment of anxiety (4.4 mg/day). Most of the patients reported marked improvement in clinical condition within 1 week of initiating treatment with tiagabine. After
4 weeks of treatment, all patients were rated as ‘‘much improved’’ or ‘‘very much improved’’ on the CGI-C scale.
At present, all ten patients have received tiagabine for at least 3 months. Control of anxiety symptomatology has been maintained in all ten patients over this period with no signs of tolerance to beneficial therapeutic ef fect. Tiagabine has been very well tolerated. None of the patients have reported adverse events considered to be related to treatment.
In summary, tiagabine, administered alone or in combination with other medications commonly used to treat anxiety, was highly effective for the treatment of anxiety disorders in this small group of patients who had responded unsatisfactorily to conventional therapeutic regimens. Longer follow-up is needed to determine whether the positive responses observed over the 1-month study period and the 2-month follow-up treatment period will be sustainable. Never-theless, the results are encouraging and suggest that
tiagabine may be effective for the treatment of anxiety in patients who are partially or completely refractory to conventional pharmacotherapy. The results further suggest that placebo-controlled clinical trials are warranted to determine the efficacy and safety of tiagabine for the treatment of anxiety disorders.
Correspondence to: Daniel Crane, 130 East 18th Street,
New York, NY 10003. E-mail: DLCrane115@earthlink.net
Received for publication 16 January 2002; Accepted 26 February
2003
DOI 10.1002/da.10104
Published online in Wiley InterScience (www.interscience.wiley.
com).
& & 2003 WILEY-LISS, INC.
ncbi.nlm.nih.gov |
