Zonisamide as an Adjunctive Treatment to Cognitive Processing Therapy for Veterans With Posttraumatic Stress Disorder and Comorbid Alcohol Use Disorder: A Pilot Study.
Adult
Aged
Alcohol-Related Disorders
/ psychology
Anticonvulsants
/ therapeutic use
Cognitive Behavioral Therapy
/ methods
Combined Modality Therapy
Diagnosis, Dual (Psychiatry)
Double-Blind Method
Feasibility Studies
Female
Humans
Male
Middle Aged
Patient Satisfaction
/ statistics & numerical data
Pilot Projects
Stress Disorders, Post-Traumatic
/ psychology
Treatment Outcome
Veterans Health
Zonisamide
/ therapeutic use
Journal
The American journal on addictions
ISSN: 1521-0391
Titre abrégé: Am J Addict
Pays: England
ID NLM: 9208821
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
17
12
2019
revised:
07
04
2020
accepted:
05
05
2020
pubmed:
29
5
2020
medline:
30
4
2021
entrez:
29
5
2020
Statut:
ppublish
Résumé
There are high rates of comorbid alcohol use disorder (AUD) among those who have posttraumatic stress disorder (PTSD). Ideally, treatment for comorbidity should address both disorders simultaneously. Zonisamide, an anticonvulsant, may be effective in decreasing alcohol use and may attenuate symptoms of PTSD. Treatment strategies can include medication in combination with a proven evidence-based psychotherapy designed to treat PTSD, such as cognitive processing therapy (CPT). This 12-week pilot study was designed to test feasibility, acceptability, and preliminary efficacy of zonisamide (400 mg) as an adjunct to CPT for veterans with PTSD and comorbid AUD. Veterans (n = 24) with PTSD and current alcohol dependence were randomized in a 3:1 ratio to receive zonisamide or placebo in a double-blind fashion. All subjects received CPT enhanced to include sessions addressing drinking behavior. Subjects overall reported a significant decrease in drinking outcomes, craving, and symptoms of PTSD. Zonisamide was well-tolerated and easily administered with CPT, which was also well-tolerated. Exploratory analysis of comparison of groups suggests there was no advantage of zonisamide vs placebo in drinking or PTSD outcomes. There was a numeric but nonsignificant higher rate of abstinence with zonisamide (50%) vs placebo (33%). The interpretation of the results is limited by the pilot nature of this study. The combination of psychosocial treatment with medication management mimics real-world treatment. In order to isolate the individual contributions of medication vs psychotherapy a much larger study would need to be conducted. (Am J Addict 2020;29:515-524).
Sections du résumé
BACKGROUND AND OBJECTIVES
There are high rates of comorbid alcohol use disorder (AUD) among those who have posttraumatic stress disorder (PTSD). Ideally, treatment for comorbidity should address both disorders simultaneously. Zonisamide, an anticonvulsant, may be effective in decreasing alcohol use and may attenuate symptoms of PTSD. Treatment strategies can include medication in combination with a proven evidence-based psychotherapy designed to treat PTSD, such as cognitive processing therapy (CPT).
METHODS
This 12-week pilot study was designed to test feasibility, acceptability, and preliminary efficacy of zonisamide (400 mg) as an adjunct to CPT for veterans with PTSD and comorbid AUD. Veterans (n = 24) with PTSD and current alcohol dependence were randomized in a 3:1 ratio to receive zonisamide or placebo in a double-blind fashion. All subjects received CPT enhanced to include sessions addressing drinking behavior.
RESULTS
Subjects overall reported a significant decrease in drinking outcomes, craving, and symptoms of PTSD. Zonisamide was well-tolerated and easily administered with CPT, which was also well-tolerated. Exploratory analysis of comparison of groups suggests there was no advantage of zonisamide vs placebo in drinking or PTSD outcomes. There was a numeric but nonsignificant higher rate of abstinence with zonisamide (50%) vs placebo (33%).
CONCLUSION AND SCIENTIFIC SIGNIFICANCE
The interpretation of the results is limited by the pilot nature of this study. The combination of psychosocial treatment with medication management mimics real-world treatment. In order to isolate the individual contributions of medication vs psychotherapy a much larger study would need to be conducted. (Am J Addict 2020;29:515-524).
Substances chimiques
Anticonvulsants
0
Zonisamide
459384H98V
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
515-524Subventions
Organisme : TATRC USAMRMC (DOD)
ID : W81XWH-11-1-0245
Pays : International
Informations de copyright
© 2020 American Academy of Addiction Psychiatry.
Références
Berlant JL. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder. BMC Psychiatry. 2004;4:24.
Iancu I, Rosen Y, Moshe K. Antiepileptic drugs in posttraumatic stress disorder. Clin Neuropharmacol. 2002;25:225-229.
Fulton JJ, Calhoun PS, Schry HR, et al. The prevalence of posttraumatic stress disorder in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans: a meta-analysis. J Anxiety Disord. 2015;31:98-107.
Jacobsen LK, Southwick SM, Kosten TR. Substance use disorders in patients with posttraumatic stress disorder: a review of the literature. Am J Psychiatry. 2001;158:1184-1190.
Pietrzak RH, Goldstein RB, Grant SM, et al. Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. J Anxiety Disord. 2011;25:456-465.
Seal KH, Cohen G, Cohen A, et al. Substance use disorders in Iraq and Afghanistan veterans in VA healthcare, 2001-2010: implications for screening, diagnosis and treatment. Drug Alcohol Depend. 2011;116:93-101.
Norman SB, Haller M, Southwick JL, et al. The burden of co-occurring alcohol use disorder and PTSD in U.S. Military veterans: comorbidities, functioning, and suicidality. Psychol Addict Behav. 2018;32:224-229.
Petrakis IL, Simpson TL. Posttraumatic stress disorder and alcohol use disorder: a critical review of pharmacologic treatments. Alcohol Clin Exp Res. 2017;41:226-237.
The Management of Posttraumatic Stress Disorder Work Group. VA/DoD Clinical Practice Guidelines for Management of Posttraumatic Stress Disorder and Acute Stress Disorder. Washington, DC: W.D. The Office of Quality Safety and Value VA and U.S.A.M.C, Office of Evidence Based Practice; 2017:1-200.
Ueda Y, Doi T, Willmore J, et al. Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures. Brain Res Mol Brain Res. 2003;116:1-6.
Kinrys G, Vasconcelos e Sa D, Nery F. Adjunctive zonisamide for treatment refractory anxiety. Int J Clin Pract. 2007;61:1050-1053.
Rubio G, López-Muñoz F, Martínez-Gras F, et al. Effects of zonisamide in the treatment of alcohol dependence. Clin Neuropharmacol. 2010;33:250-253.
Mula M, Pini S, Cassano GB. The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence. J Clin Psychopharmacol. 2007;27:263-272.
Knapp CM, Sarid-Segal O, Colaneri MA, et al. Open label trial of the tolerability and efficacy of zonisamide in the treatment of alcohol dependence. Am J Drug Alcohol Abuse. 2010;36:102-105.
Rubio G, López-Muñoz F, Pascual G, et al. Zonisamide versus diazepam in the treatment of alcohol withdrawal syndrome. Pharmacopsychiatry. 2010;43:257-262.
Arias AJ, Feinn R, Covault C, et al. Placebo-controlled trial of zonisamide for the treatment of alcohol dependence. J Clin Psychopharmacol. 2010;30:318-322.
Knapp CM, Ciraulo DA, Richardson O, et al. Zonisamide, topiramate, and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders. J Clin Psychopharmacol. 2015;35:34-42.
Akuchekian S, Amanat S. The comparison of topiramate and placebo in the treatment of posttraumatic stress disorder: a randomized, double-blind study. J Res Med Sci. 2004;9:240-244.
Alderman CP, McCarthy LC, Marwood JT, et al. Topiramate in combat-related posttraumatic stress disorder. Ann Pharmacother. 2009;43:635-641.
Tucker P, Masters B, Nawar O. Topiramate in the treatment of comorbid night eating syndrome and PTSD: a case study. East Disord. 2004;12:75-78.
Andrus MR, Gilbert E. Treatment of civilian and combat-related posttraumatic stress disorder with topiramate. Ann Pharmacother. 2010;44:1810-1816.
Adamou M, Puchalska S, Hale W, et al. Valproate in the treatment of PTSD: systematic review and meta analysis. Curr Med Res Opin. 2007;23:1285-1291.
Berlin HA. Antiepileptic drugs for the treatment of post-traumatic stress disorder. Curr Psychiatry Rep. 2007;9:291-300.
Varma A, Moore MB, Himelhoch CWT, et al. Topiramate as monotherapy or adjunctive treatment for posttraumatic stress disorder: a meta-analysis. J Trauma Stress. 2018;31:125-133.
Batki SL, Pennington DL, Neylan B, et al. Topiramate treatment of alcohol use disorder in veterans with posttraumatic stress disorder: a randomized controlled pilot trial. Alcohol Clin Exp Res. 2014;38:2169-2177.
Krystal JH, Davis LL, Raskind TC, et al. It is time to address the crisis in the pharmacotherapy of posttraumatic stress disorder: a consensus statement of the PTSD Psychopharmacology Working Group. Biol Psychiatry. 2017;82:e51-e59.
Resick PA, Schnicke MK. Cognitive processing therapy for sexual assault victims. J Consult Clin Psychol. 1992;60:748-756.
National Institute for Health and Care Excellence (NICE). Guideline for post-traumatic stress disorder. London: National Institute for Health and Care Excellence; 2018:1-56.
Peck KR, Coffey SF, Voluse AP, et al. A cognitive processing therapy-based treatment program for veterans diagnosed with co-occurring posttraumatic stress disorder and substance use disorder: the relationship between trauma-related cognitions and outcomes of a 6-week treatment program. J Anxiety Disord. 2018;59:34-41.
McCarthy E, Petrakis I. Case report on the use of cognitive processing therapy-cognitive, enhanced to address heavy alcohol use. J Trauma Stress. 2011;24:474-478.
Kaysen D, Schumm J, Seim ER, et al. Cognitive processing therapy for veterans with comorbid PTSD and alcohol use disorders. Addict Behav. 2014;39:420-427.
Dondanville KA, Wachen JS, Mintz WJ, et al. Examination of treatment effects on hazardous drinking among service members with posttraumatic stress disorder. J Trauma Stress. 2019;32:310-316.
First MB, Spitzer RL, Gibbon M, et al. Structured Clinical Interview for DSM-IV Axis I Disorders (Patient Edition) (SCID-P). New York, NY: Biometrics Research, New York State Psychiatric Institute; 1996.
Resick PA, Monson CM, Chard KM. Cognitive Processing Therapy Treatment Manual: Veteran/Military Version. Boston, MA: Veterans Administration; 2007.
Sobell LC, Sobell MB. Timeline follow-back: a technique for assessing self-reported alcohol consumption. In: Litten RZ, Allen J, eds. Measuring Alcohol Consumption: Psychosocial and Biological Methods. Totowa, NJ: Humana Press; 1992:41-72.
Anton RF, Moak DH, Latham PK. The Obsessive Compulsive Drinking Scale: a new method of assessing outcome in alcoholism treatment studies. Arch Gen Psychiatry. 1996;53:225-231.
Blake DD, Weathers FW, Kaloupek LM, et al. The development of a Clinician-Administered PTSD Scale. J Trauma Stress. 1995;8:75-90.
Blanchard EB, Jones-Alexander J, Forneris TC, et al. Psychometric properties of the PTSD Checklist (PCL). Behav Res Ther. 1996;34:669-673.
Levine J, Schooler NR. SAFTEE: a technique for the systematic assessment of side effects in clinical trials. Psychopharmacol Bull. 1986;22:343-381.
Norman SB, Davis BC, Haller PJ, et al. Prolonged exposure with veterans in a residential substance use treatment program. Cogn Behav Pract. 2016;23:162-172.
Copersino ML. Cognitive mechanisms and therapeutic targets of addiction. Curr Opin Behav Sci. 2017;13:91-98.
Imel ZE, Laska K, Simpson M, et al. Meta-analysis of dropout in treatments for posttraumatic stress disorder. J Consult Clin Psychol. 2013;81:394-404.
Kehle-Forbes SM, Meis LA, Polusny MR, et al. Treatment initiation and dropout from prolonged exposure and cognitive processing therapy in a VA outpatient clinic. Psychol Trauma. 2016;8:107-114.
Watts BV, Shiner B, Carpenter-Song L, et al. Implementation of evidence-based psychotherapies for posttraumatic stress disorder in VA specialty clinics. Psychiatr Serv. 2014;65:648-653.
Mott JM, Mondragon S, Beason-Smith NE, et al. Characteristics of U.S. veterans who begin and complete prolonged exposure and cognitive processing therapy for PTSD. J Trauma Stress. 2014;27:265-273.
Galovski TE, Blain LM, Elwood JM, et al. Manualized therapy for PTSD: flexing the structure of cognitive processing therapy. J Consult Clin Psychol. 2012;80:968-981.
Brady KT, Dansky BS, Foa SE, et al. Exposure therapy in the treatment of PTSD among cocaine-dependent individuals: preliminary findings. J Subst Abuse Treat. 2001;21:47-54.
Chard KM. An evaluation of cognitive processing therapy for the treatment of posttraumatic stress disorder related to childhood sexual abuse. J Consult Clin Psychol. 2005;73:965-971.
Resick PA, Nishith P, Astin TL, et al. A comparison of cognitive-processing therapy with prolonged exposure and a waiting condition for the treatment of chronic posttraumatic stress disorder in female rape victims. J Consult Clin Psychol. 2002;70:867-879.
Resick PA, Galovski TE, Scher MO, et al. A randomized clinical trial to dismantle components of cognitive processing therapy for posttraumatic stress disorder in female victims of interpersonal violence. J Consult Clin Psychol. 2008;76:243-258.
Roberts NP, Roberts PA, Bisson N, et al. Psychological interventions for post-traumatic stress disorder and comorbid substance use disorder: a systematic review and meta-analysis. Clin Psychol Rev. 2015;38:25-38.
McCauley JL, Killeen T, Brady DF, et al. Posttraumatic stress disorder and co-occurring substance use disorders: advances in assessment and treatment. Clin Psychol. 2012;19:283-304.
van Dam D, Vedel E, Emmelkamp T, et al. Psychological treatments for concurrent posttraumatic stress disorder and substance use disorder: a systematic review. Clin Psychol Rev. 2012;32:202-214.
Monson CM, Schnurr PP, Friedman PA, et al. Cognitive processing therapy for veterans with military-related posttraumatic stress disorder. J Consult Clin Psychol. 2006;74:898-907.
Forbes D, Lloyd D, Elliott RDV, et al. A multisite randomized controlled effectiveness trial of cognitive processing therapy for military-related posttraumatic stress disorder. J Anxiety Disord. 2012;26:442-452.
Hien DA, Jiang H, Hu ANC, et al. Do treatment improvements in PTSD severity affect substance use outcomes? A secondary analysis from a randomized clinical trial in NIDA’s Clinical Trials Network. Am J Psychiatry. 2010;167:95-101.
Badour CL, Flanagan JC, Killeen DF, et al. Habituation of distress and craving during treatment as predictors of change in PTSD symptoms and substance use severity. J Consult Clin Psychol. 2017;85:274-281.
Verplaetse TL, Ralevski E, Gueorguieva W, et al. Alcohol abstainer status and prazosin treatment in association with changes in posttraumatic stress disorder symptoms in veterans with comorbid alcohol use disorder and posttraumatic stress disorder. Alcohol Clin Exp Res. 2019;43:741-746.
Simpson TL, Malte CA, Tell B, et al. A pilot trial of prazosin, an alpha-1 adrenergic antagonist, for comorbid alcohol dependence and posttraumatic stress disorder. Alcohol Clin Exp Res. 2015;39:808-817.
Petrakis IL, Desai N, Arias R, et al. Prazosin for veterans with posttraumatic stress disorder and comorbid alcohol dependence: a clinical trial. Alcohol Clin Exp Res. 2016;40:178-186.
Hien DA, Levin FR, López-Castro LM, et al. Combining seeking safety with sertraline for PTSD and alcohol use disorders: a randomized controlled trial. J Consult Clin Psychol. 2015;83:359-369.
Foa EB, Yusko DA, Suvak CP, et al. Concurrent naltrexone and prolonged exposure therapy for patients with comorbid alcohol dependence and PTSD: a randomized clinical trial. JAMA. 2013;310:488-495.