Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder

Jeffrey L Berlant, Jeffrey L Berlant

Abstract

Background: In order to confirm therapeutic effects of topiramate on posttraumatic stress disorder (PTSD) observed in a prior study, a new prospective, open-label study was conducted to examine acute responses in chronic, nonhallucinatory PTSD.

Methods: Thirty-three consecutive newly recruited civilian adult outpatients (mean age 46 years, 85% female) with DSM-IV-diagnosed chronic PTSD, excluding those with concurrent auditory or visual hallucinations, received topiramate either as monotherapy (n = 5) or augmentation (n = 28). The primary measure was a change in the PTSD Checklist-Civilian Version (PCL-C) score from baseline to 4 weeks, with response defined as a >/= 30% reduction of PTSD symptoms.

Results: For those taking the PCL-C at both baseline and week 4 (n = 30), total symptoms declined by 49% at week 4 (paired t-test, P < 0.001) with similar subscale reductions for reexperiencing, avoidance/numbing, and hyperarousal symptoms. The response rate at week 4 was 77%. Age, sex, bipolar comorbidity, age at onset of PTSD, duration of symptoms, severity of baseline PCL-C score, and monotherapy versus add-on medication administration did not predict reduction in PTSD symptoms. Median time to full response was 9 days and median dosage was 50 mg/day.

Conclusions: Promising open-label findings in a new sample converge with findings of a previous study. The use of topiramate for treatment of chronic PTSD, at least in civilians, warrants controlled clinical trials.

Figures

Figure 1
Figure 1
Mean percentage symptom reduction at week 4. Symptom reduction in those 30 subjects who completed a PCL-C at baseline and after 4 weeks. *Paired t-test, P < 0.001 versus baseline. PTSD = posttraumatic stress disorder; PCL-C = PTSD Checklist-Civilian Version.

References

    1. Breslau N. The epidemiology of posttraumatic stress disorder: what is the extent of the problem? J Clin Psychiatry. 2001;62:16–22.
    1. van der Kolk BA. The psychobiology of posttraumatic stress disorder. J Clin Psychiatry. 1997;58:16–24.
    1. Iancu I, Rosen Y, Moshe K. Antiepileptic drugs in posttraumatic stress disorder. Clin Neuropharmacol. 2002;25:225–229. doi: 10.1097/00002826-200207000-00006.
    1. Berlant J. Antiepileptic treatment of posttraumatic stress disorder. Primary Psychiatry. 2003;10:41–49.
    1. Davidson JR. Biological therapies for posttraumatic stress disorder: an overview. J Clin Psychiatry. 1997;58:29–32.
    1. Berlant J, van Kammen DP. Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report. J Clin Psychiatry. 2002;63:15–20.
    1. DeLorenzo RJ, Sombati S, Coulter DA. Effects of topiramate on sustained repetitive firing and spontaneous recurrent seizure discharges in cultured hippocampal neurons. Epilepsia. 2000;41:S40–44.
    1. Zona C, Ciotti MT, Avoli M. Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells. Neurosci Lett. 1997;231:123–126. doi: 10.1016/S0304-3940(97)00543-0.
    1. McLean MJ, Bukhari AA, Wamil AW. Effects of topiramate on sodium-dependent action-potential firing by mouse spinal cord neurons in cell culture. Epilepsia. 2000;41:S21–24.
    1. Taverna S, Sancini G, Mantegazza M, Franceschetti S, Avanzini G. Inhibition of transient and persistent Na+ current fractions by the new anticonvulsant topiramate. J Pharmacol Exp Ther. 1999;288:960–968.
    1. Wu SP, Tsai JJ, Gean PW. Frequency-dependent inhibition of neuronal activity by topiramate in rat hippocampal slices. Br J Pharmacol. 1998;125:826–832.
    1. Zhang X, Velumian AA, Jones OT, Carlen PL. Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia. 2000;41:S52–60.
    1. White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH. Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Res. 1997;28:167–179. doi: 10.1016/S0920-1211(97)00045-4.
    1. White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH. Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia. 2000;41:S17–20.
    1. Gibbs JW, III, Sombati S, DeLorenzo RJ, Coulter DA. Cellular actions of topiramate: blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia. 2000;41:S10–S16.
    1. Skradski S, White HS. Topiramate blocks kainate-evoked cobalt influx into cultured neurons. Epilepsia. 2000;41:S45–S47.
    1. Wauquier A, Zhou S. Topiramate: a potent anticonvulsant in the amygdala-kindled rat. Epilepsy Res. 1996;24:73–77. doi: 10.1016/0920-1211(95)00105-0.
    1. Amano K, Hamada K, Yagi K, Seino M. Antiepileptic effects of topiramate on amygdaloid kindling in rats. Epilepsy Res. 1998;31:123–128. doi: 10.1016/S0920-1211(98)00021-7.
    1. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. 4. Washington, DC: American Psychiatric Association; 1994.
    1. Hamner MB. Psychotic features and combat-associated PTSD. Depress Anxiety. 1997;5:34–38. doi: 10.1002/(SICI)1520-6394(1997)5:1<34::AID-DA6>;2-5.
    1. Hamner MB, Frueh BC, Ulmer HG, Arana GW. Psychotic features and illness severity in combat veterans with chronic posttraumatic stress disorder. Biol Psychiatry. 1999;45:846–852. doi: 10.1016/S0006-3223(98)00301-1.
    1. Blanchard EB, Jones-Alexander J, Buckley TC, Forneris CA. Psychometric properties of the PTSD Checklist (PCL) Behav Res Ther. 1996;34:669–673. doi: 10.1016/0005-7967(96)00033-2.
    1. Weathers FW, Keane TM, Davidson JR. Clinician-administered PTSD scale: a review of the first ten years of research. Depress Anxiety. 2001;13:132–156. doi: 10.1002/da.1029.
    1. Lipper S, Davidson JR, Grady TA, Edinger JD, Hammett EB, Mahorney SL, Cavenar JO., Jr Preliminary study of carbamazepine in post-traumatic stress disorder. Psychosomatics. 1986;27:849–854.
    1. Fesler FA. Valproate in combat-related posttraumatic stress disorder. J Clin Psychiatry. 1991;52:361–364.
    1. Clark RD, Canive JM, Calais LA, Qualls CR, Tuason VB. Divalproex in posttraumatic stress disorder: an open-label clinical trial. J Trauma Stress. 1999;12:395–401. doi: 10.1023/A:1024797014210.
    1. Petty F, Davis LL, Nugent AL, Kramer GL, Teten A, Schmitt A, Stone RC. Valproate therapy for chronic, combat-induced posttraumatic stress disorder. J Clin Psychopharmacol. 2002;22:100–101. doi: 10.1097/00004714-200202000-00021.
    1. Otte C, Wiedemann K, Yassouridis A, Kellner M. Valproate monotherapy in the treatment of civilian patients with non-combat-related posttraumatic stress disorder: an open-label study. J Clin Psychopharmacol. 2004;24:106–108. doi: 10.1097/01.jcp.0000106234.36344.a4.
    1. Hertzberg MA, Butterfield MI, Feldman ME, Beckham JC, Sutherland SM, Connor KM, Davidson JR. A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biol Psychiatry. 1999;45:1226–1229. doi: 10.1016/S0006-3223(99)00011-6.
    1. Hamner MB, Brodrick PS, Labbate LA. Gabapentin in PTSD: a retrospective, clinical series of adjunctive therapy. Ann Clin Psychiatry. 2001;13:141–146. doi: 10.1023/A:1012281424057.
    1. Berlant JL. Topiramate in posttraumatic stress disorder: preliminary clinical observations. J Clin Psychiatry. 2001;62:60–63.
    1. Corman CL, Leung NM, Guberman AH. Weight gain in epileptic patients during treatment with valproic acid: a retrospective study. Can J Neurol Sci. 1997;24:240–244.

Source: PubMed

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