The use of pharmacological treatments for people with personality disorder: A systematic review of randomized controlled trials
Corresponding Author
Conor Duggan
University of Nottingham, Nottingham, UK
Section of Forensic Mental Health, Division of Psychiatry, University of Nottingham, Duncan Macmillan House, Porchester Road, Nottingham, NG3 6AA, UKSearch for more papers by this authorNick Huband
Nottinghamshire Healthcare NHS Trust, Porchester Road, Nottingham, UK
Search for more papers by this authorNadja Smailagic
Nottinghamshire Healthcare NHS Trust, Porchester Road, Nottingham, UK
Search for more papers by this authorMichael Ferriter
Nottinghamshire Healthcare NHS Trust, Porchester Road, Nottingham, UK
Search for more papers by this authorCorresponding Author
Conor Duggan
University of Nottingham, Nottingham, UK
Section of Forensic Mental Health, Division of Psychiatry, University of Nottingham, Duncan Macmillan House, Porchester Road, Nottingham, NG3 6AA, UKSearch for more papers by this authorNick Huband
Nottinghamshire Healthcare NHS Trust, Porchester Road, Nottingham, UK
Search for more papers by this authorNadja Smailagic
Nottinghamshire Healthcare NHS Trust, Porchester Road, Nottingham, UK
Search for more papers by this authorMichael Ferriter
Nottinghamshire Healthcare NHS Trust, Porchester Road, Nottingham, UK
Search for more papers by this authorAbstract
Background This is a companion paper to our earlier review of psychological treatments for people with personality disorder that examined the evidence from randomized controlled trials (RCTs). Here, we report on the evidence of pharmacological treatments from RCTs for people with personality disorder. As in the previous report, this paper incorporates information from an earlier review that examined the evidence to 2002, and extends it to December 2006. As in the previous paper, this review restricts itself to the findings from RCTs, and excludes evidence from other study designs; however, details of these other studies will be posted in the National Personality Disorder Institute Website (http://www.pdinstitute.org.uk).
Aim This study aimed to examine the evidence from RCTs to justify intervening with pharmacological treatments in people with personality disorder.
Method Fifteen electronic databases (including MEDLINE, EMBASE and PsycINFO) were searched to the end of December 2006 for any RCT of a pharmacological intervention for participants meeting DSM or ICD criteria for personality disorder. Outcomes were grouped using a similar symptomological categorization to that suggested by Soloff in 1998.
Results This methodology identified 35 trials for inclusion. The main positive findings were those favouring the use of anticonvulsants to reduce aggression, and of anti-psychotics to reduce cognitive perceptual and mental state disturbance. However, there were major methodological deficiencies in the trial designs, including small numbers of participants and limited duration of treatment and follow-up.
Conclusion This review identifies a very limited evidence base to justify intervening with drugs in this group. Reasons why this should be so are examined that relate to fundamentally differing conceptualizations of how any intervention might impact in an individual with personality disorder. Copyright Ā© 2008 John Wiley & Sons, Ltd.
REFERENCES
- Arndt, I. O., Dorozynski, L., McLellan, A. T., Woody, G. E., & O'Brien, C. P. (1992). Controlled study of desipramine treatment of cocaine dependence in methadone treated patients. Archives of General Psychiatry, 49, 888ā893.
- Arndt, I. O., McClellan, A. T., Dorozynsky, L., Woody, G. E., & O'Brien, C. P. (1994). Desipramine treatment for cocaine dependence: Role of antisocial personality disorder. Journal of Nervous and Mental Disease, 182/3, 151ā156.
- Battaglia, J., Wolff, T. K., Wagner-Johnson, D. S., Rush, A. J., Carmody, T. J., & Basco, M. R. (1999). Structured diagnostic assessment and depot fluphenazine treatment of multiple suicide attempters in the emergency department. International Clinical Psychopharmacology, 14/6, 361ā372.
- Benjamin, L. S. (1993). Interpersonal diagnosis and treatment of personality disorders. New York, NY: Guilford Press.
- Binks, C. A., Fenton, M., McCarthy, L., Lee, T., Adams, C. E., & Duggan, C. (2006). Pharmacological interventions for people with borderline personality disorder. Cochrane database of systematic reviews 2006, Issue 1. Art. No. CD005653. DOI: 10.1002/14651858.CD005653.
- Bogenschutz, M. P., & Nurnberg, G. (2004). Olanzapine versus placebo in the treatment of borderline personality disorder. Journal of Clinical Psychiatry, 65/1, 104ā109.
- Coccaro, E. F., & Kavoussi, R. J. (1997). Fluoxetine and impulsive aggressive behaviour in personality-disordered subjects. Archives of General Psychiatry, 54, 1081ā1088.
- Cornelius, J. R., Soloff, P. H., Perel, J. M., Ulrich, R. F. (1990). Fluoxetine trial in borderline personality disorder. Psychopharmacology Bulletin, 26, 151ā154.
- Cowdry, R. W., & Gardner, D. L. (1989). Pharmacotherapy of borderline personality disorder: Alprazolam, carbamazepine, trifluoperazine and tranylcypromine. Archives of General Psychiatry, 45, 111ā119.
- De la Fuente, J. M., & Lotstra, F. (1994). A trial of carbamazepine in borderline personality disorder. European Neuropsychopharmacology, 4, 479ā486.
- Duggan, C., Huband, N., Smailagic, N., Ferriter, M., & Adams, C. (2007). The use of psychological treatments for people with personality disorder: A systematic review of randomized controlled trials. Personality and Mental Health, 1, 95ā125.
- Elkin, I., Shea, M. T., Watkins, J. T., Imber, S. D., Sotsky, S. M., Collins, J. F., Glass, D. R., Pilkonis, P. A., Lever, W. R., Dochesty, J. P., Fiester, S. J., & Parloff, M. B. (1989). National Institute of Mental Health Treatment of Depression Collaborative Research Program: General effectiveness of treatments. Archives of General Psychiatry, 46, 971ā982.
- Faltus, F. (1984). The positive effect of alprazolam in the treatment of three patients with borderline personality disorder. American Journal of Psychiatry, 141, 802ā803.
- Frankenburg, F. R., & Zanarini, M. C. (2002). Divalproex sodium treatment of women with borderline personality disorder and bipolar II disorder: A double-blind placebo-controlled pilot study. Journal of Clinical Psychiatry, 63/5, 442ā446.
- Goldberg, S. C., Schulz, S. C., Schulz, P. M., Resnick, R. J., Hamer, R. M., & Friedel, R. O. (1986). Borderline and schizotypal personality disorders treated with low-dose thiothixene vs. placebo. Archives of General Psychiatry, 43, 680ā686.
- Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in meta-analyses. British Medical Journal, 327, 557ā560.
- Higgins, J. P. T., & Green, S. (Eds.), (2006). Cochrane handbook for systematic reviews of interventions 4.2.6 [updated September 2006]. The Cochrane Library, Issue 4. Chichester, UK: John Wiley & Sons, Ltd.
- Hollander, E., Allen, A., Lopez, R. P., Bienstock, C. A., Grossman, R., Siever, L. J., Merkatz, L., & Stein, D. J. (2001). A preliminary double-blind, placebo-controlled trial of divalproex sodium in borderline personality disorder. Journal of Clinical Psychiatry, 62/3, 199ā203.
- Hollander, E., Tracy, K. A., Swann, A. C., Coccaro, E. F., McElroy, S. L., Wozniak, P., Sommerville, K. W., & Nemeroff, C. B. (2003). Divalproex in the treatment of impulsive aggression: Efficacy in cluster B personality disorders. Neuropsychopharmacology, 28/6, 1186ā1197.
- Hollander, E., Swann, A. C., Coccaro, E. F., Jiang, P., & Smith, T. B. (2005). Impact of trait impulsivity and state aggression on divalproex versus placebo response in borderline personality disorder. American Journal of Psychiatry, 162/3, 621ā624.
- Joyce, P. R., Mulder, R. T., Luty, S. E., Mackenzie, J. M., Sullivan, P. F., & Cloninger, R. C. (2003). Borderline personality disorder in major depression: Symptomatology, temperament, character, differential drug response, and 6-month outcome. Comprehensive Psychiatry, 44/1, 35ā43.
- Kavouissi, R. J., Lui, J., & Coccaro, E. F. (1994). An open trial of sertraline in personality disordered patients with impulsive aggression. Journal of Clinical Psychiatry, 55/4, 137ā141.
- Koenigsberg, H. W., Reynolds, D., Goodman, M., New, A. S., Mitropoulou, V., Trestman, R. L., Silverman, J., & Siever, L. J. (2003). Risperidone in the treatment of schizotypal personality disorder. Journal of Clinical Psychiatry, 64/6, 628ā634.
- Leal, J., Ziedonis, D., & Kosten, T. (1994). Antisocial personality disorder as a prognostic factor for pharmacotherapy of cocaine dependence. Drug and Alcohol Dependence, 35, 31ā35.
- Leone, N. F. (1982). Response of borderline patients to loxapine and chlorpromazine. Journal of Clinical Psychiatry, 43/4, 148ā150.
- Lewis, A. (1974). Psychopathic personality: A most elusive category. Psychological Medicine 4, 133ā140.
-
Links, P. (1990). Lithium therapy for borderline patients. Journal of Personality Disorders, 4, 173ā181.
10.1521/pedi.1990.4.2.173 Google Scholar
- Loew, T. H., Nickel, M. K., Muehlbacher, M., Kaplan, P., Nickel, C., Kettler, C., Fartacek, R., Lahmann, C., Buschmann, W., Tritt, K., Bachler, E., Mitterlehner, F., Gil, F. P., Leiberich, P., Rother, W. K., & Egger, C. (2006). Topiramate treatment for women with borderline personality disorder: A double-blind, placebo-controlled study. Journal of Clinical Psychopharmacology, 26/1, 61ā66.
- Markovitz, P. J., & Wagner, S. L. (1995). Venlafaxine in the treatment of borderline personality disorder. Psychopharmacology Bulletin, 31/4, 773ā777.
- Markovitz, P. J., Calabrese, J. R., Schulz, S. C., & Melzer, H. Y. (1991). Fluoxetine in the treatment of borderline and schizotypal personality disorders. American Journal of Psychiatry, 148, 1064ā1067.
- Marks, I. M. (1986). Behavioural psychotherapy: Pocketbook of clinical management. Bristol, UK: John Wright.
- Montgomery, S. A., Roy, D., & Montgomery, D. B. (1983). The prevention of recurrent suicidal acts. British Journal of Clinical Pharmacology, 15, 183ā185.
- National Institute for Clinical Excellence (2002). Schizophrenia: Core interventions in the treatment and management of schizophrenia in primary and secondary care (NICE guideline). London: National Institute for Clinical Excellence.
- Nickel, M. K., Nickel, C., Mitterlehner, F. O., Tritt, K., Lahamann, C., Leiberich, P. K., Rother, W. K., & Loew, T. H. (2004). Topiramate treatment of aggression in female borderline personality disorder patients: A double-blind, placebo-controlled study. Journal of Clinical Psychiatry, 65/11, 1515ā1519.
- Nickel, M. K., Nickel, C., Kaplan, P., Lahmann, C., Muhlbacher, M., Tritt, K., Krawczvk, J., Leiberich, P. K., Rother, W. K., & Rother, K. (2005). Treatment of aggression with topiramate in male borderline patients: A double-blind, placebo-controlled study. Biological Psychiatry, 57/5, 495ā499.
- Nickel, M. K., Muechlbacher, M., Nickel, C., Kettler, C., Gil, F. P., Bachler, E., Buschmann, W., Rother, N., & Fartacek, R. (2006). Aripiprazole in the treatment of patients with borderline personality disorder: A double-blind, placebo-controlled study. American Journal of Psychiatry, 163/5, 833ā838.
- Oosterbaan, D. B., van Balkom, A. J. L. M., Spinhoven, P. H., Van Oppen, P., & Van Dyck, R. (2001). Cognitive therapy versus moclobemide in social phobia: A controlled study. Clinical Psychology & Psychotherapy, 8, 263ā273.
- Parsons, B., Quitkin, F. M., McGrath, P. J., Stewart, J. W., Tricamo, E., Ocepek-Welikson, K., Harrison, W., Rabkin, J. G., Wager, S. G., & Nunes, E. (1989). Phenelzine, imipramine and placebo in borderline patients meeting criteria for atypical depression. Psychopharmacology Bulletin, 25, 524ā534.
- Philipsen, A., Schmahl, C., & Lieb, K. (2004a). Naloxone in the treatment of acute dissociative states in female patients with borderline personality disorder. Pharmacopsychiatry, 37, 196ā199.
- Philipsen, A., Richter, H., Schmahl, C., Peters, J., Rusch, N., Bohus, M., & Lieb, K. (2004b). Clonidine in acute aversive inner tension and self-injurious behavior in female patients with borderline personality disorder. Journal of Clinical Psychiatry, 65/10, 1414ā1419.
- Powell, B. J., Campbell, J. L., Landon, J. F., Liskow, B. I., Thomas, H. M., Nickel, E. J., Dale, T. M., Penick, E. C., Samuelson, S. D., & Lacoursiere, R. B. (1995). A double-blind, placebo-controlled study of nortriptyline and bromocriptine in male alcoholics subtyped by comorbid psychiatric disorders. Alcoholism: Clinical & Experimental Research, 19/2, 462ā468.
- Rinne, T., van den Brink, W., Wouters, L., & Van Dyck, R. (2002). SSRI treatment of borderline personality disorder: A randomized, placebo-controlled clinical trial for female patients with borderline personality disorder. American Journal of Psychiatry, 159/12, 2048ā2054.
- Salzman, C., Wolfson, A. N., Schatzberg, A., Looper, J., Henke, R., Albanese, M., Schwartz, J., & Miyawaki, E. (1995). Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder. Journal of Clinical Psychopharmacology, 15/1, 23ā29.
- Serban, G., & Siegel, S. (1984). Response of borderline and schizotypal patients to small doses of thiothixene and haloperidol. American Journal of Psychiatry, 141/11, 1455ā1458.
- Simpson, E. B., Yen, S., Costello, E., Rosen, K., Begin, A., Pistorello, J., & Pearlstein, T. (2004). Combined dialectical behavior therapy and fluoxetine in the treatment of borderline personality disorder. Journal of Clinical Psychiatry, 65/3, 379ā385.
- Skodol, A. E., Gunderson, J. G., Shea, T. M., McGlashan, T. H., Morey, L. C., Sanislow, C. A., Bender, D. S., Grilo, C. M., Zanarini, M. C., Yen, S., Pagano, M. E., & Stout, R. L. (2005). The collaborative longitudinal personality disorders study (CLPS). Journal of Personality Disorders, 19, 487ā504.
- Soler, J., Pascual, J. C., Campins, J., Barrachina, J., Puigdemont, D., Alvarez, E., & Perez, V. (2005). Double-blind, placebo-controlled study of dialectical behavior therapy plus olanzapine for borderline personality disorder. American Journal of Psychiatry, 162/6, 1221ā1224.
- Soloff, P. H. (1998). Symptom-oriented psychopharmacology for personality disorders. Journal of Practical Psychiatry and Behavioral Health, 4/1, 3ā11.
- Soloff, P., George, A., Nathan, R. S., Schulz, P. M., Ulrich, R. F., & Perel, J. M. (1986b). Progress in pharmacotherapy of borderline disorders: A double-blind study of amitryptyline, haloperidol, and placebo. Archives of General Psychiatry, 43, 691ā697.
- Soloff, P. H., George, A., Nathan, S., Schulz, P. M., Ulrich, R. F., & Perel, J. M. (1986c). Amitriptyline and haloperidol in unstable and schizotypal borderline disorders. Psychopharmacology Bulletin, 22/1, 177ā182.
- Soloff, P. H., George, A., Nathan, R. S., Schulz, P. M., Cornelius, J. R., Herring, J., & Perel, J. M. (1989). Amitriptyline versus haloperidol in borderlines: Final outcomes and predictors of response. Journal of Clinical Psychopharmacology, 9/4, 238ā246.
- Soloff, P. H., Cornelius, J., Georger, A., Swami, N., Perel, J. M., & Ulrich, R. F. (1993). Efficacy of phenelzine and haloperidol in borderline personality disorder. Archives of General Psychiatry, 50/5, 377ā385.
- Stein, D. J., Simeon, D., Frenkel, M., Islan, M. N., & Hollander, E. (1995). An open trial of valproate in borderline personality disorder. Journal of Clinical Psychiatry, 56, 506ā510.
- Tritt, K., Nickel, C., Lahmann, K., Leiberich, P. K., Rother, W. K., Loew, T. H., & Nickel, M. K. (2005). Lamotrigine treatment of aggression in female borderline-patients: A randomized, double-blind, placebo-controlled study. Journal of Psychopharmacology, 19/3, 287ā291.
- Tupin, J. P., Smith, D. B., Clanon, T. L., Kim, L. I., Nugent, A., & Groupe, A. (1973). Long-term use of lithium in aggressive disorders. Comprehensive Psychiatry, 14, 311ā317.
- Tyrer, P., & Duggan, C. (2008). NICE guidelines for the treatment of personality disorder. Psychiatry (in press).
- Verkes, R. J., Van der Mast, R. C., Hengeveld, M. W., Tuyl, J. P., Zwinderman, A. H., & Van Kempen, G. M. (1998). Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major depression. American Journal of Psychiatry, 155/4, 543ā547.
-
Wilcox, J. A. (1995). Divalproex sodium as a treatment for borderline personality disorder. Annals of Clinical Psychiatry, 7/1, 33ā37.
10.3109/10401239509149022 Google Scholar
- Zanarini, M. C., & Frankenburg, F. R. (2001). Olanzapine treatment of female borderline personality disorder patients: A double-blind, placebo-controlled pilot study. Journal of Clinical Psychiatry, 62/11, 849ā854.
- Zanarini, M. C., & Frankenburg, F. R. (2003). Omega-3 fatty acid treatment of women with borderline personality disorder: A double-blind, placebo-controlled pilot study. American Journal of Psychiatry, 160/1, 167ā169.
- Zanarini, M. C., Frankenburg, F. R., & Parachini, E. A. (2004). A preliminary, randomized trial of fluoxetine, olanzapine, and the olanzapineāfluoxetine combination in women with borderline personality disorder. Journal of Clinical Psychiatry, 65/7, 903ā907.
- Zanarini, M. C., Frankenburg, F. R., Hennen, J., Bradford Reich, D., & Silk, K. B. (2005). The McLean study of adult development (MSAD). Journal of Personality Disorders, 19, 505ā523.