July 1, 2006
Psychiatric Times.
Mood Stabilizers and Novel Antipsychotics in the Treatment of Borderline Personality Disorder
Silvio Bellino, MD, Erika Paradiso, MD, and Filippo Bogetto, MD
Conclusions
Recent investigations of mood stabilizers in the treatment of BPD are promising and suggest that these drugs can be useful in clinical practice, particularly for controlling affective instability and impulsive aggression. However, further studies are needed to confirm the initial results and to ascertain whether some novel antipsychotics can be used for their mood-stabilizing effects in patients with BPD.
Future investigations should focus on a list of relevant topics: pilot studies of new drugs; controlled trials of drugs already tested in open case series; comparisons of new anticonvulsant agents with better-known mood stabilizers, such as lithium or valproate; head-to-head comparisons of novel and traditional antipsychotics to verify which differences in clinical effects and adverse events specifically occur in patients with BPD; maintenance studies to assess persistence of therapeutic effects in longlasting disorders such as BPD; add-on trials of mood stabilizers and novel antipsychotics in samples of patients with BPD who do not respond to firstline therapy with serotonergic antidepressants; and the relationship of clinical subtypes of patients with BPD (eg, affective labile, self-injurious, psychotoform) with response to drug treatment.
Dr Bellino is assistant professor of psychiatry, Dr Paradiso is a resident in psychiatry, and Dr Bogetto is professor of psychiatry and chairman in the department of neuroscience at the University of Turin in Italy.
Drs Bellino, Paradiso, and Bogetto report that they have no conflicts of interest with the subject matter of this article.
Drugs Mentioned in This Article
Carbamazepine (Carbatrol, Tegretol, others)
Clonazepam (Klonopin, Rivotril)
Clozapine (Clozaril)
Divalproex (Epival, Depakote)
Fluoxetine (Prozac)
Lamotrigine (Lamictal)
Lithium (Eskalith)
Olanzapine (Zyprexa)
Oxcarbazepine (Trileptal)
Phenytoin (Dilantin)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Tranylcypromine (Parnate)
Trifluoperazine (Stelazine)
Valproate/valproic acid (Depakote, others)
References
1. American Psychiatric Association. Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition,
Text Revision (DSM-IV-TR). Washington, DC:
American Psychiatric Association; 2000.
2. Clarkin JF, Yeomans FE, Kernberg OF. Psychotherapy
for Borderline Patients. New York: John Wiley
& Sons; 1999.
3. Livesley WJ. A practical approach to the treatment
of patients with borderline personality disorder.
Psychiatr Clin North Am. 2000;23:211-232.
4. American Psychiatric Association. Practice Guidelines
for the Treatment of Patients With Borderline
Personality Disorder. Washington, DC: American
Psychiatric Association; 2001.
5. Vieta E. Mood stabilization in the treatment of
bipolar disorder: focus on quetiapine. Hum Psychopharmacol.
2005;20:225-236.
6. Sachs GS. Bipolar mood disorder: practical strategies
for acute and maintenance phase treatment.
J Clin Psychopharmacol. 1996;16:32S-47S.
7. Keck PE Jr, McElroy SL, Richt N, Tohen M. What
makes a drug a primary mood stabilizer? Mol Psychiatry.
2002;7(suppl 1):S8-S14.
8. Ketter TA, Calabrese JR. Stabilization of mood
from below versus above baseline in bipolar disorder:
a new nomenclature. J Clin Psychiatry. 2002;
63:146-151.
9. Grof P. "Mood-stabilizers: the archeology of the
concept" by M Harris, S Chandran, N Chakraborty
and D Healy: a commentary. Bipolar Disord. 2003;
5:453-455.
10. Harris M, Chandran S, Chakraborty N, Healy D.
Mood stabilizers: the archeology of the concept.
Bipolar Disord. 2003;5:446-452.
11. Keck PE Jr, McElroy SL. Redefining mood stabilization.
J Affect Disord. 2003;73:163-169.
12. Mackinnon DF, Pies R. Affective instability as
rapid cycling: theoretical and clinical implications for
borderline personality and bipolar spectrum disorders. Bipolar Disord. 2006;8:1-14.
13. Zanarini MC, Frankenburg FR, Gunderson JG.
Pharmacotherapy of borderline outpatients. Compr
Psychiatry. 1988;29:372-378.
14. Gardner DL, Cowdry RW. Pharmacotherapy of
borderline personality disorder: a review. Psychopharmacol
Bull. 1989;25:515-523.
15. Goldberg SC. Prediction of change in borderline
personality disorder. Psychopharmacol Bull. 1989;
25:550-555.
16. Jope RS. Anti-bipolar therapy: mechanism of
action of lithium. Mol Psychiatry. 1999;4:117-128.
17. Links PS, Steiner M, Boiago I, et al. Lithium therapy
for borderline patients: preliminary findings.
J Clin Psychopharmacol. 1990;4:173-181.
18. Stein DJ. Drug treatment of the personality disorders.
Br J Psychiatry. 1992;161:167-184.
19. Ghaemi SN, Ko JY. Oxcarbazepine treatment of
bipolar disorder: a review of the literature. Primary
Psychiatry. 2002;9:55-59.
20. Gardner DL, Cowdry RW. Positive effects of carbamazepine
on behavioural dyscontrol in borderline
personality disorder. Am J Psychiatry. 1986;143:519-
522.
21. Cowdry RW, Gardner DL. Pharmacotherapy of
borderline personality disorder: alprazolam, carbamazepine,
trifluoperazine, and tranylcipromine. Arch
Gen Psychiatry. 1988;45:111-119.
22. Hori A. Pharmacotherapy for personality disorders.
Psychiatry Clin Neurosci. 1998;52:13-19.
23. Mattes J. Comparative effectiveness of carbamazepine
and propranolol for rage outbursts. J Neuropsychiatry
Clin Neurosci. 1990;2:159-164.
24. Kravitz HM, Fawcett J. Carbamazepine in the treatment
of affective disorders. Med Sci Res.1987;15:
1-8.
25. Blumer D, Heibronn M, Himmelhoch J. Indications
for carbamazepine in mental illness: atypical psychiatric
disorder or temporal lobe syndrome? Compr
Psychiatry. 1988;29:108-122.
26. Denicoff KD, Meglathery SB, Post RM, Tandeciarz
SI. Efficacy of carbamazepine compared with other
agents: a clinical practice survey. J Clin Psychiatry.
1994;55:70-76.
27. Emrich H. Studies with oxcarbazepine (Trileptal)
in acute mania. Int Clin Psychopharmacol. 1990;5
(suppl 1):83-88.
28. Hellewell JS. Oxcarbazepine (Trileptal) in the treatment
of bipolar disorders: a review of efficacy and
tolerability. J Affect Disord. 2002;72(suppl 1):S23-34.
29. Hummel B, Walden J, Stampfer R, et al. Acute
antimanic efficacy and safety of oxcarbazepine in an
open trial with an on-off-on design. Bipolar Disord.
2002;4:412-417.
30. Dietrich DE, Kropp S, Emrich HM. Oxcarbazepine
in the treatment of affective and schizoaffective
disorders. Fortschr Neurol Psychiatr. 2003;71:255-
264.
31. Evins AE. Efficacy of newer anticonvulsant
medications in bipolar spectrum mood disorders. J
Clin Psychiatry. 2003;64(suppl 8):9-14.
32. Ghaemi SN, Berv DA, Klugman J, et al. Oxcarbazepine
treatment of bipolar disorder. J Clin Psychiatry.
2003;64:943-945.
33. Perugi G, Toni C, Frare F, et al. An open case
study in Italy of oxcarbazepine, an effective mood
stabilizer, in patients with drug resistant/intolerant bipolar I disorders. Poster presented at the XVI Congress
of European College of Neuropsychopharmacology;
September 20-24, 2003; Prague.
34. Raja M, Azzoni A. Oxcarbazepine versus valproate
in mood and schizoaffective disorders. Int J Neuropsychopharm.
2003;6:409-414.
35. Benedetti A, Lattanzi L, Pini S, et al. Oxcarbazepine
as add-on treatment in patients with bipolar manic, mixed
or depressive episode. J Affect Disord.2004;79:273-277.
36. Spina E, Perugi G. Antiepileptic drugs: indications
other than epilepsy. Epileptic Disord. 2004;6:57-75.
37. Stahl SM. Anticonvulsants as mood stabilizers
and adjuncts to antipsychotics: valproate, lamotrigine,
carbamazepine, and oxcarbazepine and actions
at voltage-gated sodium channels. J Clin Psychiatry.
2004;65:738-739.
38. Yatham LN. Newer anticonvulsants in the treatment
of bipolar disorder. J Clin Psychiatry. 2004;
65(suppl 10):28-35.
39. Gentry JR, Hill C, Malcolm R. New anticonvulsants:
a review of applications for the management of substance
abuse disorders. Ann Clin Psychiatry. 2002;14:233-245.
40. Leweke FM, Gerth CW, Koethe D, et al. Oxcarbazepine
as an adjunct for schizophrenia. Am J Psychiatry.
2004;161:1130-1131.
41. Bellino S, Paradiso E, Bogetto F. Oxcarbazepine
in the treatment of borderline personality disorder:
a pilot study. J Clin Psychiatry. 2005;66:1111-1115.
42. Polc P. Enhancement of GABAergic inhibition: a
mechanism of action of benzodiazepines, phenobarbital,
valproate and L-cycloserine in the cat spinal
cord. Electroencephalogr Clin Neurophysiol. 1982;
36(suppl):188-198.
43. Wilcox JA. Divalproex sodium in the treatment of aggressive
behaviour. Ann Clin Psychiatry. 1994;6:17-20.
44. Wilcox JA. Divalproex sodium as a treatment for
borderline personality disorder. Ann Clin Psychiatry.
1995;7:33-37.
45. Stein DJ, Simeon D, Frenkel M, et al. An open
trial of valproate in borderline personality disorder.
J Clin Psychiatry. 1995;56:506-510.
46. Kavoussi RJ, Coccaro EF. Divalproex sodium for
impulsive aggressive behavior in patients with personality
disorder. J Clin Psychiatry.1998;59:676-680.
47. Hollander E, Allen A, Lopez RP, et al. A preliminary
double-blind, placebo-controlled trial of divalproex
sodium in borderline personality disorder.
J Clin Psychiatry. 2001;62:199-203.
48. Hollander E, Swann AC, Coccaro EF, et al. Impact
of trait impulsivity and state aggression on divalproex
versus placebo response in borderline personality
disorder. Am J Psychiatry. 2005;162:621-624.
49. 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.
50. Xie X, Hagan RM. Cellular and molecular actions
of lamotrigine: possible mechanisms of efficacy in bipolar
disorder. Neuropsychobiology. 1998;38:119-130.
51. Pinto OC, Akiskal HS. Lamotrigine as a promising
approach to borderline personality: an open case
series without concurrent DSM-IV major mood disorder.
J Affect Disord. 1998;51:333-343.
52. Green B. Lamotrigine in mood disorders. Curr
Med Res Opin. 2003;19:272-277.
53. Preston GA, Marchant BK, Reimherr FW, et al.
Borderline personality disorder in patients with bipolar
disorder and response to lamotrigine. J Affect
Disord. 2004;79:297-303.
54. Tritt K, Nickel C, Lahmann C, et al. Lamotrigine
treatment of aggression in female borderline-patients:
a randomized, double-blind, placebo-controlled study.
J Psychopharmacol. 2005;19:287-291.
55. Bowden CL, Brugger AM, Swann AC, et al. Efficacy
of divalproex vs lithium and placebo in the treatment
of mania: the Depakote Mania Study Group. JAMA.
1994;271:918-924.
56. Jarema M, Sartorius N. Treatment of bipolar disorders
with second generation antipsychotic medications.
Neuro Endocrinol Lett. 2005;26(suppl 1):5-7.
57. Malhi GS, Berk M, Bourin M, et al. Atypical mood
stabilizers: a typical role for atypical antipsychotics.
Acta Psychiatr Scand Suppl. 2005;(426):29-38.
58. Muzina DJ, Calabrese JR. Maintenance therapies
in bipolar disorder: focus on randomized controlled
trials. Aust N Z J Psychiatry. 2005;39:652-661.
59. Vieta E, Goikolea JM. Atypical antipsychotics:
newer options for mania and maintenance therapy.
Bipolar Disord. 2005;7(suppl 4):21-33.
60. Conus P, Berk M, McGorry PD. Pharmacological
treatment in the early phase of bipolar disorders:
what stage are we at? Aust N Z J Psychiatry. 2006;
40:199-207.
61. Frankenburg FR, Zanarini MC. Clozapine treatment
of borderline patients: a preliminary study.
Compr Psychiatry. 1993;34:402-405.
62. Chengappa KN, Baker RW, Sirri C. The successful
use of clozapine in ameliorating severe self-mutilating
in a patient with borderline personality disorder.
J Personal Disord. 1995;9:76-82.
63. Chengappa KN, Ebeling T, Kang JS, et al. Clozapine
reduces severe self-mutilation and aggression in
psychotic patients with borderline personality disorder.
J Clin Psychiatry. 1999;60:477-484.
64. Benedetti F, Sforzini L, Colombo C, et al. Lowdose
clozapine in acute and continuation treatment
of severe borderline personality disorder. J Clin
Psychiatry. 1998;59:103-107.
65. Swinton M. Clozapine in severe borderline personality.
J Forensic Psychiatry. 2001;12:580-591.
66. Kouzam HR, Donnelly NJ. Remission of selfmutilation
in a patient with borderline personality
during risperidone therapy. J Nerv Ment Dis.
1997;185:348-349.
67. Szighethy EM, Schulz SC. Risperidone in comorbid
borderline personality disorder and dysthymia.
J Clin Psychopharmacol. 1997;17:326-327.
68. Hirose S. Effective treatment of aggression and
impulsivity in antisocial personality disorder with
risperidone. Psych Clin Neurosci. 2001;55:161-162.
69. Rocca P, Marchiaro L, Cocuzza E, Bogetto F.
Treatment of borderline personality disorder with
risperidone. J Clin Psychiatry. 2002;63:241-244.
70. Bhana N, Foster RH, Olney R, Plosker GL.
Olanzapine: an updated review of its use in the management
of schizophrenia. Drugs. 2001;61:111-161.
71. 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.
72. Zanarini MC, Frankenburg FR. Olanzapine treatment
of female borderline personality disorder patients:
a double-blind, placebo-controlled pilot study.
J Clin Psychiatry. 2001;62:849-854.
73. Bogenschutz MP, Nurnberg HG. Olanzapine
versus placebo in the treatment of borderline personality
disorder. J Clin Psychiatry. 2004;65:104-109.
74. 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 ClinPsychiatry. 2004;65:903-907.
75. Soler J, Pascual JC, Barrachina J, et al. Doubleblind,
placebo-controlled study of dialectical behavior
therapy plus olanzapine for borderline personality
disorder. Am J Psychiatry. 2005;162:1221-1224.
76. Kufferle B, Tauscher J, Asenbaum S, et al. IBZM
SPECT imaging of striatal dopamine-2 receptors in
psychotic patients treated with the novel antipsychotic
substance quetiapine in comparison to
clozapine and haloperidol. Psychopharmacology.
1997;133:323-328.
77. Hellewell JSE, Cameron Hands D, McKellar J.
Seroquel: an effective atypical antipsychotic with no
greater EPS than placebo across the full dose range.
Schizophr Res. 1998;29:154.
78. Brecher M, Rak IW, Melvin K, et al. The longterm
effect of quetiapine (‘Seroquel’) monotherapy
on weight in patients with schizophrenia. Int J
Psychiatry Clin Pract. 2000;4:287-291.
79. Kapur S, Zipursky R, Jones C, et al. A positron
emission tomography study of quetiapine in schizophrenia:
a preliminary finding of an antipsychotic
effect with only transient high dopamine D2 receptor
occupancy. Arch Gen Psychiatry. 2000;57:553-
559.
80. Hilger E, Barnas C, Kasper S. Quetiapine in the
treatment of borderline personality disorder. World
J Biol Psychiatry. 2003;4:42-44.
81. Adityanjee A, Schulz SC. Clinical use of quetiapine
in disease states other than schizophrenia.
J Clin Psychiatry. 2002;63(suppl 13):32-38.
82. Villeneuve E, Lemelin S. Open-label study of atypical
neuroleptic quetiapine for treatment of borderline
personality disorder: impulsivity as main target.
J Clin Psychiatry. 2005;66:1298-1303.
83. Bellino S, Paradiso E, Bogetto F. Efficacy and
tolerability of quetiapine in the treatment of borderline
personality disorder: a pilot study. J Clin Psychiatry.
In press.
Evidence-based References
- Green B. Lamotrigine in mood disorders. Curr Med
Res Opin. 2003;19:272-277.
- Hollander E, Swann AC, Coccaro EF, et al. Impact of
trait impulsivity and state aggression on divalproex
versus placebo response in borderline personality
disorder. Am J Psychiatry. 2005;162:621-624. .
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