Pharmacotherapy of Personality Disorders

Yıl 2012, Cilt: 2 Sayı: 1, 34 - 46, 01.01.2012

Demet Güleç Öyekçin Deniz Yıldız

https://doi.org/10.5455/jmood.20120328094704

Öz

Objective: Prevalence of personality disorders have been reported as 10-13% in general population, 30-50% in psychiatric patients, and 15% in psychiatric outpatients. The most common personality disorders are respectively borderline, antisocial, schizotypal, and avoidant. There has been no specific pharmacological approach for the treatment of personality disorders that have different clinical features with various co-morbid psychiatric disorders. The aim of this report is to review the efficacy of psychotropic medications used for the treatment of personality disorders. Methods: By using “borderline, antisocial, schizotypal, narcissistic, obsessive compulsive, avoidant personality, and pharmacotherapy” as keywords at the Pubmed database we primarily searched for the double blind, placebo controlled, randomized trials and also included some of the open label trials. Results: Most of the research on this topic was on pharmacotherapy of borderline personality disorder. Polypharmacy, that has been used widely in treatment of these cases, has been reported ineffective in most of the patients. The antidepressants have been replaced by mood stabilizers. The antidepressants and mood stabilizers have been reported to decrease mood symptoms like anger, depression, dysphoria, and to enhance adherence to psychotherapy. The most effective mood stabilizer was divalproex. The antipsychotics have been recommended to be used at psychotic and behavioral symptomatology. At the treatment of antisocial personality disorder CBT is recommended and there was no evidence based pharmacotherapy. In the treatment of schizotypal personality disorder, the antipsychotics have been reported effective. Pergolide and guanfacine have been reported to be useful in the treatment of cognitive disorders. The first line treatment options of avoidant personality disorder are venlafaxine and SSRIs. Conclusions: Most of the studies in literature have been focused at borderline personality disorder that has been difficult to treat. According to the guidelines, psychotherapy is the first line treatment for personality disorders. Pharmacotherapy has been reported to increase the efficiency of psychotherapy in BPD which presents with various symptoms of mood, cognition, and behavior. The studies in the literature report that Polypharmacy is not useful for these patients contrary to the popular belief. The research about other personality disorders is limited. More clear understanding of etiopathogenesis of personality disorders; would be helpful in development of more effective pharmacological agents in their treatment.

Anahtar Kelimeler

-

Kişilik Bozukluklarında İlaç Tedavisi

Öz

Giriş: Kişilik bozukluğunun genel toplumda yaygınlığı %10-13, psikiyatrik tanı alan hastalarda %30-50, psikiyatri kliniğine başvuranlarda ise %15 olarak bildirilmektedir. En sık görülen kişilik bozuklukları sırasıyla; borderline kişilik bozukluğu (BKB), antisosyal kişilik bozukluğu (ASKB), şizotipal kişilik bozukluğu (SKB)ve kaçıngan kişilik bozukluğu (KKB) olarak tanımlanmaktadır. Klinikte farklı belirtiler ve çeşitli ruhsal bozukluklarla karşımıza çıkan kişilik bozukluklarının özgül bir farmakoterapisi bulunmamaktadır. Bu yazında kişilik bozukluğu tedavisinde kullanılan psikotrop ilaçların ekinliğinin gözden geçirilmesi amaçlanmıştır. Yöntem: Pubmed arama motorunda borderline, antisosyal, şizotipik, narsisistik, şizoid, obsesif kompulsif, kaçıngan kişilik bozukluğu ve farmakoterapi anahtar kelimeleri kullanılarak 1980 ve 2011 yılları arasında ingilizce dilde yayınlanmış olan öncelikle çift–kör, randomize, plasebo kontrollü çalışmalar araştırılmıştır, konuyla ilişkili açık uçlu çalışmaların bir kısmına yer verilmiştir. Bulgular: Yapılan tarama sonucunda bu konuda yapılan araştrımaların çoğunun borderline kişilik bozukluğu (BKB) tedavisiyle ilişkili olduğu görülmüştür. BKB’de yaygın olarak kullanılan çoklu ilaç kullanımının tedavide etkin olmadığı belirtilmektedir. Antidepresan tedavinin yerini mizaç düzenleyiciler almaktadır. Antidepresan ve mizaç dengeleyecilerin öfke, depresyon, disfori gibi ‘mizaç’ belirtilerini azalttığı ve psikoterapi uygulamalarını kolaylaştırdığı belirtilmektedir. Mizaç düzenleyicilerden özellikle divalproik asitin daha etkili olduğu bildirilmektedir. Antipsikotik tedavilerin psikotik belirtilerin ve davranış bozukluklarının ortaya çıktığı durumlarda kullanılması önerilmektedir. Antisosyal kişilik bozukluğunun temel tedavisi Bilişsel Davranışçı Terapi (BDT) olarak tanımlanmaktadır ve farmakoterapisine yönelik kanıta dayalı veriler oldukça sınırlıdır. Şizotipal kişilik bozukluğu tedavisinde ise antipsikotik ilaçların yararlı olduğu bildirilmekte ve bu hastalarda sıklıkla izlenen bilişsel bozuklukların tedavisinde pergolid ve guanfasinin gibi ilaçların yararlı olabildiği belirtilmektedir. Kaçıngan kişilik bozukluğu tedavisinde ise ilk seçenek olarak venlafaksin ve serotonin geri alım inhibitörlerinin yaralı olduğu bildirilmektedir. Sonuç: Literatürde araştırmaların büyük çoğunluğu klinik uygulamada da sıklıkla zorluk yaşandığı bilinen borderline kişilik bozukluğunun tedavisine odaklanmıştır. Tedavi klavuzlarında kişilik bozukluklarının psikoterapiyle tedavisi önerilmektedir. Özellikle farklı psikiyatrik belirtilerle karşımıza çıkabilen BKB’ye özgü olan mizaç, davranış, bilişsel bozuklukların tedavisinde farmakoterapinin psikoterapiden yararlanımı arttırdığı belirtilmektedir. Çoklu psikotrop kullanımının bu hasta grubunda sanıldığının aksine yararının olmadığı saptanmıştır. Diğer kişilik bozukluklarıyla yapılan araştırmalar ise sınırlı sayıdadır. Kişilik bozukluklarının etiyopatogenizinin daha iyi anlaşılması bu konuda daha etkin farmakoterapi seçeneklerinin gelişmesini sağlayacaktır.

Anahtar Kelimeler

borderline kişilik bozukluğu, farmakoterapi, kişilik bozuklukları

Kaynakça

• Spitzer RL, Gibbon M, W, Skodol AE, Williams JBW, Michael B, First MB. Case Book. A Learning Companian to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Version. American Psychiatric Publishing Inc.2002
• American Psychiatric Association. Diagnostic and statistical manual of mental disorders 4th ed. Washington, DC 1994.
• Widiger TA, Weissman MM. Epidemiology of borderline personality disorder. Hosp Community Psychiatry 1991; 42:1015-1021.
• Rinne T, Van den Brink W, Wouters L, van Dyck R. SSRI treatment of borderline personality disorder: a randomized, placebo- controlled clinical trial for female patients with borderline personality disorder. Am J Psychiatry 2002;159:2048-2054.
• Gross R, Olfson M, Gameroff M, Shea S, Feder A, Fuentes M, Lantigua R, Weissman MM. Borderline personality disorder in primary care. Arch Intern Med 2002; 14: 162:53-60.
• Vedat Ş. DSM-5 Taslak tanı ölçütlerine genel bir bakış: “Batı cephesinde yeni bir şey yok”mu? Klinik Psikiyatri Dergisi 2010; 13:196-208.
• American Psychiatric Association DSM-V development (2010) http://www.dsm5.org Proposed Revisions/Pages/Personality and PersonalityDisorders.aspx.
• Cloninger C.R, Svrakic DM, Przybeck TR. A psychological model of temperament and character. Arch Gen Psychiatry 1993;50: 975-990.
• Hori A. Pharmacotherapy for personality disorders. Psychiatry Clin Neurosci 1998; 52: 13-19.
• Lenzenweger MF, Lane MC, Loranger AW, Kessler RC. DSM- IV personality disorders in the National Comorbidity Survey Replication. Biol Psychiatry 2007; 62: 553-564.
• Al-Alem L, Omar HA. Borderline personality disorder: an overview of history, diagnosis and treatment in adolescents. Int J Adolesc Med Health 2008;20:395-404.
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.(DSM-IV) (1994) Washington D.C: American Psychiatric Association. Türkçe çevirisi: E Köroğlu ve ark. Ankara Hekimler Yayın birliği.
• McGlashan TH, Grilo CM, Skodol AE, Gunderson JG, Shea MT, Morey LC, Zanarini MC, Stout RL. The Collaborative Longitudinal Personality Disorders Study: baseline Axis I/II and II/II diagnostic cooccurrence. Acta Psychiatr Scand 2000;102:256-264.
• Sansone RA, Sansone LA. Gender Patterns in Borderline Personality Disorder Innov Clin Neurosci 2011;8:16-20.
• Soloff PH, Lynch KG, Kelly TM. Childhood abuse as a risk factor for suicidal behavior in borderline personality disorder. J Pers Disord 2002;16:201-214.
• Black DW, Blum N, Pfohl B, Hale N. Suicidal behavior in borderline personality disorder: prevalence, risk factors, prediction and prevention. J Pers Disord 2004;18:226-239.
• Akiskal HS. Demystifying borderline personality: critique of the concept and unorthodox reflections on its natural kinship with the bipolar spectrum. Acta Psychiatr Scand 2004;110:401-407.
• Paris J, Gunderson J, Weinberg I. The interface between borderline personality disorder and bipolar spectrum disorders. Compr Psychiatry 2007;48:145-154.
• American Psychiatric Association. Practic guideline for the treatment of patients with borderline personality disorder: Treatment recommandations for patients with borderline personality disorder: executive summary of recomandations, Washington DC 2001, p:2
• Abraham PF, Calabrese JR. Research report Evidenced-based pharmacologic treatment of borderline personality disorder: A shift from SSRIs to anticonvulsants and atypical antipsychotics? J Affect Disord 2008; 111:21-30.
• Zanarini MC, Frankenburg FR, Reich DB, Silk KR, Hudson JI, McSweeney LB. The subsyndromal phenomenology of borderline personality disorder: a 10-year follow-up study. Am J Psychiatry 2007;164:929-935.
• Feurino L, Silk KR.State of the Art in the Pharmacologic Treatment of Borderline Personality Disorder. Curr Psychiatry Rep 2011;13:69-75.
• Mercer D, Douglass AB, Links PS. Meta-analyses of mood stabilizers, antidepressants and antipsychotics in the treatment of borderline personality disorder: effectiveness for depression and anger symptoms. J Pers Disord 2009;23:156-174.
• Pittenger C, Duman RS. Stress, depression, and neuroplasticity: A convergence of mechanisms. Neuropsychopharmacology 2008; 33:88-109.
• Glenn AL, Raine A. The neurobiology of psychopathy. Psychiatr Clin North Am 2008; 31: 463-475.
• Salzman C, Wolfson AN, Schatzberg A, Looper J, Henke R, Albanese M, Schwartz J, Miyawaki. Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder. J Clin Psychopharmacol 1995;15:23-29.
• Coccaro EF, Kavoussi RJ. Fluoxetine and impulsive aggressive behavior in personality-disordered subjeets. Arch Gen Psychiatry 1997; 54: 1081-1088.
• Simpson EB, Yen S, Costello E, Rosen K, Begin A, Pistorello J, Pearlstein T. Combined dialectical behavior therapy and fluoxetine in the treatment of borderline personality disorder. J Clin Psychiatry 2004; 65: 379-385.
• Kool S, Dekker J, Duijsens IJ, de Jonghe F, Puite B. Effieacy of combined therapy and pharmacotherapy for depressed patients with or without personality disorders. Harv Rev Psychiatry 2003; 1:133-141.
• Norden MJ. Fluoxetine in borderline personality disorder. Prog Neuorpsychopharmacol Biol Psychiatr 1989, 13: 885-893.
• Cornelius JR, Soloff PH, Perel JM, Ulrich RF. Fluoxetine trial in borderline personality disorder. Psychopharmacol Bull 1990; 26:151-154.
• Markowitz PJ, Calabrese, Schulz SC, Meltzer HY. Fluoxetine in the treatment of borderline and schizotypal personality disorders. Am J Psychiatry 1991;148:1064-1067.
• Zanarini MC, Frankenburg FR, Parachini EA. A preliminary, randomized trial of fluoxetine, olanzapine, and the olanzapine fluoxetine combination in women with borderline personality disorder. J Clin Psychiatry 2004;65:903-907.
• Bellino S, Paradiso E, Bozzatello P, Bogetto F. Efficacy and tolerability of duloxetine in borderline personality disorder a pilot study. J Psychopharmacol 2010; 24: 333-339.
• Frankenburg FR, Zanarini MC. Clozapine treatment in borderline patients: a preliminary study. Compr Psychiatry 1993; 34: 402-405.
• Benedetti F, Sforzini L, Colombo C, Maffei C, Smeraldi E. Low- dose clozapine in acute and continuation treatment of severe borderline personality disorder. J Clin Psychiatry 1998;59:103-107.
• Schulz SC, Camlin KL, Berry SA, Jesberger JA. Olanzapine safety and efficacy in patients with borderline personality disorder and comorbid dysthymia. Biol Psychiatry 1999;46: 1429-1435.
• Schulz SC, Zanarini MC, Bateman A, Bohus M, Detke HC, Trzaskoma Q, Tanaka Y, Lin D, Deberdt W, Corya S. Olanzapine for the treatment of borderline personality disorder: variable dose 12-week randomised double-blind placebo-controlled study. Br J Psychiatry 2008;193:485-492.
• Nickel MK, Muehlbacher M, Nickel C, Kettler C, Pedrosa Gil F, Bachler E, Buschmann W, Rother N, Fartacek R, Egger C, Anvar J, Rother WK, Loew TH, Kaplan P.Aripiprazole in the treatment of patients with borderline personality disorder: a double-blind, placebo-controlled study. Am J Psychiatry. 2006;163:833-838.
• Johnson DM, Shea MT, Yen S, Battle CL, Zlotnick C, Sanislow CA, Grilo CM, Skodol AE, Bender DS, McGlashan TH, Gunderson JG, Zanarini MC. Gender differences in borderline personality disorder: findings from the Collaborative Longitudinal Personality Disorders Study. Compr Psychiatry 2003;44: 284-292.
• Zanarini MC, Frankenburg FR, Dubo ED, Sickel AE, Trikha A, Levin A, Reynolds V. Axis I comorbidity of borderline personality disorder. Am J Psychiatry 1998;155:1733–1739.
• Hollander, E, Allen A, Lopez RP, Bienstock C, Grossman R, Siever L, Margolin L, Stein D. A preliminary double blind placebo- controlled trial of divalproex sodium in borderline personality disorder. J Clin Psychiatry 2001; 62:199-203.
• Frankenburg FR, Zanarini MC. Divalproex sodium treatment of women with borderline personality disorder and bipolar II disorder: a double-blind placebo-controlled pilot study. J Clin Psychiatry 2002;63:442-446.
• Hollander E, Tracy KA, Swann AC, Coccaro EF, McElroy SL, Wozniak P, Sommerville KW, Nemeroff CB. Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders. Neuropsychopharmacology 2003; 28:1186-1197.
• Hollander E. Swann AC. Coccaro EF. Jiang P. Smith TB. Impac of trait impulsivity and state agression on divalproex versus plasebo response in borderline personality disorder. Am J Psychiatry 2005; 162:621-624.
• De la Fuente JM, Lotstra F. A trial of karbamazepine in borderline personality disorder. Eur Neuropsychopharmacol 1994;4:479-486.
• Cowdry RW, Gardner DL. Pharmacotherapy of borderline personality disorder: alprazolam, carbamazepine, trifluoperazine and tranylcypromine. Arch Gen Psychiatry 1988; 45:111-119.
• Reich DB, Zanarini MC, Bieri KA. A preliminary study of lamotrigine in the treatment of affective instability in borderline personality disorder. Int Clin Psychopharmacol 2009; 24:270-275.
• Saunders EFH, Silk K. Personality trait dimensions and the pharmacologic treatment of borderline personality disorder. J Clin Psychopharm 2009; 29:461-467.
• Zanarini MC, Frankenburg FR. Omega-3 fatty acid treatment of women with borderline personality disorder: a double blind placebo controlled pilot study. Am J Psychiatry 2003;160:167-169.
• Philipsen A, Richter H, Schmahl C, Peters J, Rüsch N, Bohus M, Lieb K. Clonidine in acute aversive inner tension and self-injurious behavior in female patients with borderline personality disorder. J Clin Psychiatry 2004; 65:1414-1419.
• Ziegenhorn AA, Roepke S, Schommer NC, Merkl A, Danker-Hopfe H, Perschel FH, Heuser I, Anghelescu IG, Lammers CH. Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial. Psychopharmacology 2009;29:170-173.
• Rodrigo C, Rajapakse S, Jayananda G.The ‘antisocial’ person: an insight in to biology, classification and current evidence on treatment. Ann Gen Psychiatry 2010; 9:31.
• Shirtcliff EA, Vitacco MJ, Graf AR, Gostisha AJ, Merz JL, Zahn- Waxler C. Neurobiology of Empathy and Callousness: Implications for the Development of Antisocial Behavior. Behav Sci Law 2009; 27:137-171.
• Marsh AA, Finger EC, Mitchell DG, Reid ME, Sims C, Kosson DS, Towbin KE, Leibenluft E, Pine DS, Blair RJ. Reduced amygdala response to fearful expressions in children and adolescents with callous-unemotional traits and disruptive behavior disorders. Am J Psychiatry 2008;165:712-720.
• Rhee SH, Waldman ID. Genetic and environmental influences on antisocial behavior: a metaanalysis of twin and adoption studies. Psychol Bull 2002;128:490-529.
• National Institute for Health and Clinical Excellence: Antisocial Personality Disorder: treatment, management and prevention Volume 77. London, UK: National Collaborating Center for Mental Health; 2009.
• Ripoll LH, Triebwasser J, Siever LJ. Evidence-based pharmacotherapy for personality disorders. Int J Neuropsychopharmacol 2011; 15:1-32.
• Barratt ES, Stanford MS, Felthous AR, Kent TA. The effects of phenytoin on impulsive and premeditated aggression: a controlled study. J Clin Psychopharmacol 1997;17:341-349.
• Hirose S. Effective treatment of aggression and impulsivity in antisocial personality disorder with risperidone. Psychiatry Clin Neurosci 2001; 55:161-162.
• Savitz J, Van der Merwe L, Newman TK, Stein DJ, Ramesar R. Catechol-o-methyltransferase genotype and childhood trauma may interact to impact schizotypal personality traits. Behav Genet 2010;40:415-423.
• Suzuki M, Zhou SY, Hagino H, Takahashi T, Kawasaki Y, Nohara S, Yamashita I, Matsui M, Seto H, Kurachi M. Volume reduction of the right anterior limb of the internal capsule in patients with schizotypal disorder. Psychiatry Res 2004;130:213-225.
• McClure MM, Barch DM, Romero MJ, Minzenberg MJ, Triebwasser J, Harvey PD, Siever LJ. The effects of guanfacine on context processing abnormalities in schizotypal personality disorder. Biol Psychiatry 2007;61:1157-1160.
• McClure MM, Harvey PD, Goodman M, Triebwasser J, New A, Koenigsberg HW, Sprung LJ, Flory JD, Siever LJ. Pergolide treatment of cognitive deficits associated with schizotypal personality disorder: continued evidence of the importance of the dopamine system in the schizophrenia spectrum. Neuropsychopharmacology 2010;35:1356-1362.
• Koenigsberg HW, Reynolds D, Goodman M, New AS, Mitropoulou V, Trestman RL, Silverman J, Siever LJ. Risperidone in the treatment of schizotypal personality disorder. J Clin Psychiatry 2003;64:628-634.
• Tillfors M, Furmark T, Ekselius L, Fredrikson M. Social phobia and avoidant personality disorder: One spectrum disorder? Nord J Psychiatry 2004;58: 147-152.
• Alden LE, Laposa JM, Taylor CT, Ryder AG. Avoidant personality disorder: current status and future directions. J Pers Disord 2002;16:1-29.
• Stein MB, Pollack MH, Bystritsky A, Kelsey JE, Mangano RM. Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial. Psychopharmacology (Berl) 2005;177:280-288.
• Allgulander C, Mangano R, Zhang J, Dahl AA, Lepola U, Sjödin I, Emilien G. Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel- group comparison with paroxetine. Hum Psychopharmacol 2004;19:387-396.
• Van Ameringen M, Oakman J, Mancini C, Pipe B, Chung H. Predictors of response in generalized social phobia: effect of age of onset. J Clin Psychopharmacol 2004;24:42-48.
• Davidson JR. Pharmacotherapy of social anxiety disorder: what does the evidence tell us? J Clin Psychiatry 2006;67:20-26.
• Pande AC, Davidson JR, Jefferson JW, Janney CA, Katzelnick DJ, Weisler RH, Greist JH, Sutherland SM. Treatment of social phobia with gabapentin: a placebo-controlled study. J Clin Psychopharmacol 1999;19:341–348.
• Pande AC, Feltner DE, Jefferson JW, Davidson JR, Pollack M, Stein MB, Lydiard RB, Futterer R, Robinson P, Slomkowski M, DuBoff E, Phelps M, Janney CA, Werth JL. Efficacy of the novel anxiolytic pregabalin in social anxiety disorder. J Clin Psychopharmacol 2004; 24:141–149.
• Montgomery SA, Nil R, Dürr-Pal N, Loft H, Boulenger JP. A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder. J Clin Psychiatry 2005;66:1270-1278.
• Liebowitz MR, Gelenberg AJ, Munjack D. Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder. Arch Gen Psychiatry 2005;62:190-198.
• Kasper S, Stein DJ, Loft H, Nil R. Escitalopram in the treatment of social anxiety disorder: randomised, placebo-controlled, flexible- dosage study. Br J Psychiatry 2005;186:222-226.
• Stein MB, Fyer AJ, Davidson JR, Pollack MH, Wiita B. Fluvoxamine treatment of social phobia (social anxiety disorder): a double- blind, placebo-controlled study. Am J Psychiatry 1999;156:756- 760.
• Katzelnick DJ, Kobak KA, Greist JH, Jefferson JW, Mantle JM, Serlin RC. Sertraline for social phobia: a double-blind, placebo- controlled crossover study. Am J Psychiatry 1995;152:1368-1371.
• Van Ameringen MA, Lane RM, Walker JR, Bowen RC, Chokka PR, Goldner EM, Johnston DG, Lavallee YJ, Nandy S, Pecknold JC, Hadrava V, Swinson RP. Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study. Am J Psychiatry 2001;158:275-281.
• Stein DJ, Versiani M, Hair T, Kumar R. Efficacy of paroxetine for relapse prevention in social anxiety disorder: a 24-week study. Arch Gen Psychiatry 2002;59:1111-1118.
• Leichsenring F, Leibing E, Kruse J, New AS, Leweke F. Borderline personality disorder. Lancet 2011;377:74-84.
• Herpertz SC, Zanarini M, Schulz CS, Siever L, Lieb K, Möller HJ. WFSBP Task Force on Personality Disorders; World Federation of Societies of Biological Psychiatry (WFSBP). World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of personality disorders. World J Biol Psychiatry 2007;8:212-244.
• Kingsbury SJ, Yi D, Simpson GM. Psychopharmacology: Rational and Irrational Polypharmacy. Psychiatr Serv 2001; 52:1033-1036.
• Pascual JC, Martín-Blanco A, Soler J, Ferrer A, Tiana T, Alvarez E, Pérez V.A naturalistic study of changes in pharmacological prescription for borderline personality disorder in clinical practice: from APA to NICE guidelines. Int Clin Psychopharmacol 2010;25:349-355.