谷氨酸系统相关药物在难治性强迫症治疗中的应用进展
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摘要
目前,选择性5-羟色胺再摄取抑制剂(SSRIs)是治疗强迫症的主要药物,但这些药物的疗效有限。经过两种或两种以上SSRIs足量足疗程治疗仍无效果的强迫症属于难治性强迫症,人们正在不断探索治疗难治性强迫症更有效的方法。谷氨酸系统失调与强迫症发病有关,参与强迫症的病理生理过程,且很多谷氨酸系统的调节药物被用于难治性强迫症的治疗,如N-甲基-D-天冬氨酸受体(NMDAR)拮抗剂和NMDAR激动剂等,其中一些药物也显示出显著的效果,这为难治性强迫症提供了新的治疗选择。
Currently,selective serotonin reuptake inhibitors( SSRIs) are the main treatment drugs for obsessive-compulsive disorder,but these drugs have limited efficacy. Refractory obsessive-compulsive disorder is an obsessive-compulsive disorder that has been treated with enough quantiy/courses of two or more SSRIs without effect. Therefore,people are constantly exploring more effective treatments for refractory obsessive-compulsive disorder. In recent years,there is increasing evidence that glutamate system disorders are associated with the pathogenesis of obsessive-compulsive disorder and are involved in the pathophysiological processes of obsessive-compulsive disorder. Moreover,many glutamate-related regulatory drugs have been used to treat refractory obsessive-compulsive disorder,such as N-methyl-D-aspartate receptor( NMDAR) antagonists and NMDAR agonists,some of which have shown significant effects,providing a new treatment option for refractory obsessivecompulsive disorder.
Currently,selective serotonin reuptake inhibitors( SSRIs) are the main treatment drugs for obsessive-compulsive disorder,but these drugs have limited efficacy. Refractory obsessive-compulsive disorder is an obsessive-compulsive disorder that has been treated with enough quantiy/courses of two or more SSRIs without effect. Therefore,people are constantly exploring more effective treatments for refractory obsessive-compulsive disorder. In recent years,there is increasing evidence that glutamate system disorders are associated with the pathogenesis of obsessive-compulsive disorder and are involved in the pathophysiological processes of obsessive-compulsive disorder. Moreover,many glutamate-related regulatory drugs have been used to treat refractory obsessive-compulsive disorder,such as N-methyl-D-aspartate receptor( NMDAR) antagonists and NMDAR agonists,some of which have shown significant effects,providing a new treatment option for refractory obsessivecompulsive disorder.
引文
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[3] Fernández-Guasti A,Ulloa RE,Nicolini H. Age differences in the sensitivity to clomipramine in an animal model of obsessive-compulsive disorder[J]. Psychopharmacology(Berl),2003,166(3):195-201.
[4] Hirschtritt ME,Bloch MH,Mathews CA. Obsessive-compulsive disorder:Advances in diagnosis and treatment[J]. JAMA,2017,317(13):1358-1367.
[5] Akyol Ardic U,Ercan ES,Kutlu A,et al. Successful treatment response with aripiprazole augmentation of SSRIs in refractory obsessive-compulsive disorder in childhood[J]. Child Psychiatry Hum Dev,2017,48(5):699-704.
[6] Masi G,Pfanner C,Brovedani P. Antipsychotic augmentation of selective serotonin reuptake inhibitors in resistant tic-related obsessive-compulsive disorder in children and adolescents:A naturalistic comparative study[J]. J Psychiatr Res,2013,47(8):1007-1012.
[7] Dold M,Aigner M,Lanzenberger R,et al. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessivecompulsive disorder:An update meta-analysis of double-blind,randomized,placebo-controlled trials[J]. Int J Neuropsychopharmacol,2015,18(9). pii:pyv047.
[8] Veale D,Miles S,Smallcombe N,et al. Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder:A systematic review and meta-analysis[J]. BMC Psychiatry,2014,14:317-330.
[9] Sobolevsky AI. Structure and gating of tetrameric glutamate receptors[J]. J Physiol,2015,593(1):29-38.
[10] Hansen KB,Yi F,Perszyk RE,et al. Structure,function,and allosteric modulation of NMDA receptors[J]. J Gen Physiol,2018,150(8):1081-1105.
[11] Kono M,Kakegawa W,Yoshida K,et al. Interneuronal NMDA receptors regulate long-term depression and motor learning in the cerebellum[J]. J Physiol,2019,597(3):903-920.
[12] Burguière E,Monteiro P,Mallet L,et al. Striatal circuits,habits,and implications for obsessive-compulsive disorder[J]. Curr Opin Neurobiol,2015,30:59-65.
[13] Del Casale A,Rapinesi C,Kotzalidis GD,et al. Executive functions in obsessive-compulsive disorder:An activation likelihood estimate meta-analysis of f MRI studies[J]. World J Biol Psychiatry,2016,17(5):378-393.
[14] Rasgon A,Lee WH,Leibu E,et al. Neural correlates of affective and non-affective cognition in obsessive compulsive disorder:A meta-analysis of functional imaging studies[J]. Eur Psychiatry,2017,46:25-32.
[15] Ting JT,Feng G. Neurobiology of obsessive-compulsive disorder:Insights into neural circuitry dysfunction through mouse genetics[J].Curr Opin Neurobiol,2011,21(6):842-848.
[16] Aida T,Yoshida J,Nomura M,et al. Astroglial glutamate transporter deficiency increases synaptic excitability and leads to pathological repetitive behaviors in mice[J]. Neuropsychopharmacology,2015,40(7):1569-1579.
[17] Mac Master FP. Translational neuroimaging research in pediatric obsessive-compulsive disorder[J]. Dialogues Clin Neurosci,2010,12(2):165-174.
[18] Nakao T,Okada K,Kanba S. Neurobiological model of obsessivecompulsive disorder:Evidence from recent neuropsychological and neuroimaging findings[J]. Psychiatry Clin Neurosci,2014,68(8):587-605.
[19] Brennan BP,Rauch SL,Jensen JE,et al. A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder[J]. Biol Psychiatry,2013,73(1):24-31.
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[21] Pittenger C,Bloch MH,Williams K. Glutamate abnormalities in obsessive compulsive disorder:Neurobiology,pathophysiology,and treatment[J]. Pharmacol Ther,2011,132(3):314-332.
[22] Egashira N,Okuno R,Harada S,et al. Effects of glutamate-related drugs on marble-burying behavior in mice:Implications for obsessive-compulsive disorder[J]. Eur J Pharmacol,2008,586(1/3):164-170.
[23] Wald R,Dodman N,Shuster L. The combined effects of memantine and fluoxetine on an animal model of obsessive compulsive disorder[J]. Exp Clin Psychopharmacol,2009,17(3):191-197.
[24] Yang Z,Zhou X,Zhang Q. Effectiveness and safety of memantine treatment for Alzheimer's disease[J]. J Alzheimers Dis,2013,36(3):445-458.
[25] Feusner JD,Kerwin L,Saxena S,et al. Differential efficacy of memantine for obsessive-compulsive disorder vs. Generalized anxiety disorder:An open-label trial[J]. Psychopharmacol Bull,2009,42(1):81-93.
[26] Ghaleiha A,Entezari N,Modabbernia A,et al. Memantine add-on in moderate to severe obsessive-compulsive disorder:Randomized double-blind placebo-controlled study[J]. J Psychiatr Res,2013,47(2):175-180.
[27] Haghighi M,Jahangard L,Mohammad-Beigi H,et al. In a doubleblind,randomized and placebo-controlled trial,adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders(OCD)[J]. Psychopharmacology(Berl),2013,228(4):633-640.
[28] Farnia V,Gharehbaghi H,Alikhani M,et al. Efficacy and tolerability of adjunctive gabapentin and memantine in obsessive compulsive disorder:Double-blind,randomized,placebo-controlled trial[J]. J Psychiatry Res,2018,104:137-143.
[29] Modarresi A,Sayyah M,Razooghi S,et al. Memantine augmentation improves symptoms in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder:A randomized controlled trial[J].Pharmacopsychiatry,2018,51(6):263-269.
[30] Bloch MH,Wasylink S,Landeros-Weisenberger A,et al. Effects of ketamine in treatment-refractory obsessive-compulsive disorder[J].Biol Psychiatry,2012,72(11):964-970.
[31] Rodriguez CI,Kegeles LS,Levinson A,et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder:Proof-of-concept[J]. Neuropsychopharmacology,2013,38(12):2475-2483.
[32] Adams TG,Bloch MH,Pittenger C. Intranasal ketamine and cognitive-behavioral therapy for treatment-refractory obsessivecompulsive disorder[J]. J Clin Psychopharmacol,2017,37(2):269-271.
[33] Greenberg WM,Benedict MM,Doerfer J,et al. Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults[J].J Psychiatr Res,2009,43(6):664-670.
[34] Wu PL,Tang HS,Lane HY,et al. Sarcosine therapy for obsessive compulsive disorder:A prospective,open-label study[J]. J Clin Psychopharmacol,2011,31(3):369-374.
[35] Mayer ML. Glutamate receptors at atomic resolution[J]. Nature,2006,440(7083):456-462.
[36] Wilhelm S,Berman N,Small BJ,et al. D-Cycloserine augmentation of cognitive behavior therapy for pediatric OCD:Predictors and moderators of outcome[J]. J Affect Disord,2018,241:454-460.
[37] Myers KM,Carlezon WA Jr,Davis M. Glutamate receptors in extinction and extinction-based therapies for psychiatric illness[J].Neuropsychopharmacology,2011,36(1):274-293.
[38] Andersson E,Hedman E,Enander J,et al. d-Cycloserine vs placebo as adjunct to cognitive behavioural therapy for obsessivecompulsive disorder and interaction with antidepressants:A randomized clinical trial[J]. JAMA Psychiatry,2015,72(7):659-667.
[39] Bonanno G,Giambelli R,Raiteri L,et al. Chronic antidepressants reduce depolarization-evoked glutamate release and protein interactions favoring formation of SNARE complex in hippocampus[J].J Neurosci,2005,25(13):3270-3279.
[40] de Leeuw AS,van Megen HJ,Kahn RS,et al. d-cycloserine addition to exposure sessions in the treatment of patients with obsessive-compulsive disorder[J]. Eur Psychiatry,2017,40(10):38-44.
[41] Pittenger C. Glutamate modulators in the treatment of obsessivecompulsive disorder[J]. Psychiatr Ann,2015,45(6):308-315.
[42] Takahashi K,Murasawa H,Yamaguchi K. Riluzole rapidly attenuates hyperemotional responses in olfactory bulbectomized rats,an animal model of depression[J]. Behav Brain Res,2011,216(1):46-52.
[43] Sugiyama A,Saitoh A,Iwai T,et al. Riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines[J]. Neuropharmacology,2012,62(8):2489-2498.
[44] Pittenger C,Bloch MH,Wasylink S,et al. Riluzole augmentation in treatment-refractory obsessive-compulsive disorder:A pilot randomized placebo-controlled trial[J]. J Clin Psychiatry,2015,76(8):1075-1084.
[45] Afshar H,Roohafza H,Mohammad-Beigi H,et al. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder:A randomized,double-blind,placebo-controlled trial[J].J Clin Psychopharmacol,2012,32(6):797-803.
[46] Bloch MH,Panza KE,Grant JE,et al. N-Acetylcysteine in the treatment of pediatric trichotillomania:A randomized,doubleblind,placebo-controlled add-on trial[J]. J Am Acad Child Adolesc Psychiatry,2013,52(3):231-240.
[47] Paydary K,Akamaloo A,Ahmadipour A,et al. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder:Randomized,double-blind,placebo-controlled trial[J].J Clin Pharm Ther,2016,41(2):214-219.
[48] Costa DLC,Diniz JB,Requena G,et al. Randomized,doubleblind,placebo-controlled trial of N-acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder[J]. J Clin Psychiatry,2017,78(7):e766-773.
[49] Van Ameringen M,Mancini C,Patterson B,et al. Topiramate augmentation in treatment-resistant obsessive-compulsive disorder:A retrospective,open-label case series[J]. Depress Anxiety,2006,23(1):1-5.
[50] Vinkers DJ,van der Wee NJ. Topiramate augmentation in treatmentresistant obsessive-compulsive disorder[J]. Tijdschr Psychiatr,2008,50(11):747-750.
[51] Thuile J,Even C,Guelfi JD. Topiramate may induce obsessivecompulsive disorder[J]. Psychiatry Clin Neurosci,2006,60(3):394.
[52] Mowla A,Khajeian AM,Sahraian A,et al. Topiramate augmentation in resistant OCD:A double-blind placebo-controlled clinical trial[J]. CNS Spectr,2010,15(11):613-617.
[53] Berlin HA,Koran LM,Jenike MA,et al. Double-blind,placebocontrolled trial of topiramate augmentation in treatment-resistant obsessive-compulsive disorder[J]. J Clin Psychiatry,2011,72(5):716-721.
[54] Afshar H,Akuchekian S,Mahaky B,et al. Topiramate augmentation in refractory obsessive-compulsive disorder:A randomized,double-blind,placebo-controlled trial[J]. Res Med Sci,2014,19(10):976-981.
[55] Bruno A,Micò U,Pandolfo G,et al. Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessivecompulsive disorder:A double-blind,placebo-controlled study[J].J Psychopharmacol,2012,26(11):1456-1462.
[2] Abramowitz JS. Presidential address:Are the obsessive-compulsive related disorders related to obsessive-compulsive disorder A critical look at DSM-5's new category[J]. Behav Ther,2018,49(1):1-11.
[3] Fernández-Guasti A,Ulloa RE,Nicolini H. Age differences in the sensitivity to clomipramine in an animal model of obsessive-compulsive disorder[J]. Psychopharmacology(Berl),2003,166(3):195-201.
[4] Hirschtritt ME,Bloch MH,Mathews CA. Obsessive-compulsive disorder:Advances in diagnosis and treatment[J]. JAMA,2017,317(13):1358-1367.
[5] Akyol Ardic U,Ercan ES,Kutlu A,et al. Successful treatment response with aripiprazole augmentation of SSRIs in refractory obsessive-compulsive disorder in childhood[J]. Child Psychiatry Hum Dev,2017,48(5):699-704.
[6] Masi G,Pfanner C,Brovedani P. Antipsychotic augmentation of selective serotonin reuptake inhibitors in resistant tic-related obsessive-compulsive disorder in children and adolescents:A naturalistic comparative study[J]. J Psychiatr Res,2013,47(8):1007-1012.
[7] Dold M,Aigner M,Lanzenberger R,et al. Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessivecompulsive disorder:An update meta-analysis of double-blind,randomized,placebo-controlled trials[J]. Int J Neuropsychopharmacol,2015,18(9). pii:pyv047.
[8] Veale D,Miles S,Smallcombe N,et al. Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder:A systematic review and meta-analysis[J]. BMC Psychiatry,2014,14:317-330.
[9] Sobolevsky AI. Structure and gating of tetrameric glutamate receptors[J]. J Physiol,2015,593(1):29-38.
[10] Hansen KB,Yi F,Perszyk RE,et al. Structure,function,and allosteric modulation of NMDA receptors[J]. J Gen Physiol,2018,150(8):1081-1105.
[11] Kono M,Kakegawa W,Yoshida K,et al. Interneuronal NMDA receptors regulate long-term depression and motor learning in the cerebellum[J]. J Physiol,2019,597(3):903-920.
[12] Burguière E,Monteiro P,Mallet L,et al. Striatal circuits,habits,and implications for obsessive-compulsive disorder[J]. Curr Opin Neurobiol,2015,30:59-65.
[13] Del Casale A,Rapinesi C,Kotzalidis GD,et al. Executive functions in obsessive-compulsive disorder:An activation likelihood estimate meta-analysis of f MRI studies[J]. World J Biol Psychiatry,2016,17(5):378-393.
[14] Rasgon A,Lee WH,Leibu E,et al. Neural correlates of affective and non-affective cognition in obsessive compulsive disorder:A meta-analysis of functional imaging studies[J]. Eur Psychiatry,2017,46:25-32.
[15] Ting JT,Feng G. Neurobiology of obsessive-compulsive disorder:Insights into neural circuitry dysfunction through mouse genetics[J].Curr Opin Neurobiol,2011,21(6):842-848.
[16] Aida T,Yoshida J,Nomura M,et al. Astroglial glutamate transporter deficiency increases synaptic excitability and leads to pathological repetitive behaviors in mice[J]. Neuropsychopharmacology,2015,40(7):1569-1579.
[17] Mac Master FP. Translational neuroimaging research in pediatric obsessive-compulsive disorder[J]. Dialogues Clin Neurosci,2010,12(2):165-174.
[18] Nakao T,Okada K,Kanba S. Neurobiological model of obsessivecompulsive disorder:Evidence from recent neuropsychological and neuroimaging findings[J]. Psychiatry Clin Neurosci,2014,68(8):587-605.
[19] Brennan BP,Rauch SL,Jensen JE,et al. A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder[J]. Biol Psychiatry,2013,73(1):24-31.
[20] Wu K,Hanna GL,Easter P,et al. Glutamate system genes and brain volume alterations in pediatric obsessive-compulsive disorder:A preliminary study[J]. Psychiatry Res,2013,211(3):214-220.
[21] Pittenger C,Bloch MH,Williams K. Glutamate abnormalities in obsessive compulsive disorder:Neurobiology,pathophysiology,and treatment[J]. Pharmacol Ther,2011,132(3):314-332.
[22] Egashira N,Okuno R,Harada S,et al. Effects of glutamate-related drugs on marble-burying behavior in mice:Implications for obsessive-compulsive disorder[J]. Eur J Pharmacol,2008,586(1/3):164-170.
[23] Wald R,Dodman N,Shuster L. The combined effects of memantine and fluoxetine on an animal model of obsessive compulsive disorder[J]. Exp Clin Psychopharmacol,2009,17(3):191-197.
[24] Yang Z,Zhou X,Zhang Q. Effectiveness and safety of memantine treatment for Alzheimer's disease[J]. J Alzheimers Dis,2013,36(3):445-458.
[25] Feusner JD,Kerwin L,Saxena S,et al. Differential efficacy of memantine for obsessive-compulsive disorder vs. Generalized anxiety disorder:An open-label trial[J]. Psychopharmacol Bull,2009,42(1):81-93.
[26] Ghaleiha A,Entezari N,Modabbernia A,et al. Memantine add-on in moderate to severe obsessive-compulsive disorder:Randomized double-blind placebo-controlled study[J]. J Psychiatr Res,2013,47(2):175-180.
[27] Haghighi M,Jahangard L,Mohammad-Beigi H,et al. In a doubleblind,randomized and placebo-controlled trial,adjuvant memantine improved symptoms in inpatients suffering from refractory obsessive-compulsive disorders(OCD)[J]. Psychopharmacology(Berl),2013,228(4):633-640.
[28] Farnia V,Gharehbaghi H,Alikhani M,et al. Efficacy and tolerability of adjunctive gabapentin and memantine in obsessive compulsive disorder:Double-blind,randomized,placebo-controlled trial[J]. J Psychiatry Res,2018,104:137-143.
[29] Modarresi A,Sayyah M,Razooghi S,et al. Memantine augmentation improves symptoms in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder:A randomized controlled trial[J].Pharmacopsychiatry,2018,51(6):263-269.
[30] Bloch MH,Wasylink S,Landeros-Weisenberger A,et al. Effects of ketamine in treatment-refractory obsessive-compulsive disorder[J].Biol Psychiatry,2012,72(11):964-970.
[31] Rodriguez CI,Kegeles LS,Levinson A,et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder:Proof-of-concept[J]. Neuropsychopharmacology,2013,38(12):2475-2483.
[32] Adams TG,Bloch MH,Pittenger C. Intranasal ketamine and cognitive-behavioral therapy for treatment-refractory obsessivecompulsive disorder[J]. J Clin Psychopharmacol,2017,37(2):269-271.
[33] Greenberg WM,Benedict MM,Doerfer J,et al. Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults[J].J Psychiatr Res,2009,43(6):664-670.
[34] Wu PL,Tang HS,Lane HY,et al. Sarcosine therapy for obsessive compulsive disorder:A prospective,open-label study[J]. J Clin Psychopharmacol,2011,31(3):369-374.
[35] Mayer ML. Glutamate receptors at atomic resolution[J]. Nature,2006,440(7083):456-462.
[36] Wilhelm S,Berman N,Small BJ,et al. D-Cycloserine augmentation of cognitive behavior therapy for pediatric OCD:Predictors and moderators of outcome[J]. J Affect Disord,2018,241:454-460.
[37] Myers KM,Carlezon WA Jr,Davis M. Glutamate receptors in extinction and extinction-based therapies for psychiatric illness[J].Neuropsychopharmacology,2011,36(1):274-293.
[38] Andersson E,Hedman E,Enander J,et al. d-Cycloserine vs placebo as adjunct to cognitive behavioural therapy for obsessivecompulsive disorder and interaction with antidepressants:A randomized clinical trial[J]. JAMA Psychiatry,2015,72(7):659-667.
[39] Bonanno G,Giambelli R,Raiteri L,et al. Chronic antidepressants reduce depolarization-evoked glutamate release and protein interactions favoring formation of SNARE complex in hippocampus[J].J Neurosci,2005,25(13):3270-3279.
[40] de Leeuw AS,van Megen HJ,Kahn RS,et al. d-cycloserine addition to exposure sessions in the treatment of patients with obsessive-compulsive disorder[J]. Eur Psychiatry,2017,40(10):38-44.
[41] Pittenger C. Glutamate modulators in the treatment of obsessivecompulsive disorder[J]. Psychiatr Ann,2015,45(6):308-315.
[42] Takahashi K,Murasawa H,Yamaguchi K. Riluzole rapidly attenuates hyperemotional responses in olfactory bulbectomized rats,an animal model of depression[J]. Behav Brain Res,2011,216(1):46-52.
[43] Sugiyama A,Saitoh A,Iwai T,et al. Riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines[J]. Neuropharmacology,2012,62(8):2489-2498.
[44] Pittenger C,Bloch MH,Wasylink S,et al. Riluzole augmentation in treatment-refractory obsessive-compulsive disorder:A pilot randomized placebo-controlled trial[J]. J Clin Psychiatry,2015,76(8):1075-1084.
[45] Afshar H,Roohafza H,Mohammad-Beigi H,et al. N-acetylcysteine add-on treatment in refractory obsessive-compulsive disorder:A randomized,double-blind,placebo-controlled trial[J].J Clin Psychopharmacol,2012,32(6):797-803.
[46] Bloch MH,Panza KE,Grant JE,et al. N-Acetylcysteine in the treatment of pediatric trichotillomania:A randomized,doubleblind,placebo-controlled add-on trial[J]. J Am Acad Child Adolesc Psychiatry,2013,52(3):231-240.
[47] Paydary K,Akamaloo A,Ahmadipour A,et al. N-acetylcysteine augmentation therapy for moderate-to-severe obsessive-compulsive disorder:Randomized,double-blind,placebo-controlled trial[J].J Clin Pharm Ther,2016,41(2):214-219.
[48] Costa DLC,Diniz JB,Requena G,et al. Randomized,doubleblind,placebo-controlled trial of N-acetylcysteine augmentation for treatment-resistant obsessive-compulsive disorder[J]. J Clin Psychiatry,2017,78(7):e766-773.
[49] Van Ameringen M,Mancini C,Patterson B,et al. Topiramate augmentation in treatment-resistant obsessive-compulsive disorder:A retrospective,open-label case series[J]. Depress Anxiety,2006,23(1):1-5.
[50] Vinkers DJ,van der Wee NJ. Topiramate augmentation in treatmentresistant obsessive-compulsive disorder[J]. Tijdschr Psychiatr,2008,50(11):747-750.
[51] Thuile J,Even C,Guelfi JD. Topiramate may induce obsessivecompulsive disorder[J]. Psychiatry Clin Neurosci,2006,60(3):394.
[52] Mowla A,Khajeian AM,Sahraian A,et al. Topiramate augmentation in resistant OCD:A double-blind placebo-controlled clinical trial[J]. CNS Spectr,2010,15(11):613-617.
[53] Berlin HA,Koran LM,Jenike MA,et al. Double-blind,placebocontrolled trial of topiramate augmentation in treatment-resistant obsessive-compulsive disorder[J]. J Clin Psychiatry,2011,72(5):716-721.
[54] Afshar H,Akuchekian S,Mahaky B,et al. Topiramate augmentation in refractory obsessive-compulsive disorder:A randomized,double-blind,placebo-controlled trial[J]. Res Med Sci,2014,19(10):976-981.
[55] Bruno A,Micò U,Pandolfo G,et al. Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessivecompulsive disorder:A double-blind,placebo-controlled study[J].J Psychopharmacol,2012,26(11):1456-1462.