Pharmacopsychiatry 2001; 34(4): 137-141
DOI: 10.1055/s-2001-15872
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Adjunctive Dopamine Agonists in Treatment-Resistant Bipolar II Depression: an Open Case Series

G. Perugi1 , C. Toni1 , G. Ruffolo1 , F. Frare1 , H. Akiskal2
  • 1Department of Psychiatry, University of Pisa, Italy
  • 2International Mood Disorder Center, Department of Psychiatry at the University of California at San Diego, La Jolla, USA
Further Information

Publication History

Publication Date:
31 December 2001 (online)

Objective: Previous studies and case observations have suggested that dopamine agonists (DAAs) such as pramipexole (PPX) and ropinirole (RPN) might be effective for major depression, but their adjunctive use in treatment-resistant bipolar II depression has not yet been specifically addressed. Method: A chart review was conducted on 18 patients with a DSM-III-R bipolar NOS (Bipolar II) major depressive episode who were admitted to the day-hospital of the Department of Psychiatry at the University of Pisa. DAAs were added to ongoing treatments with conventional antidepressants and mood stabilizers to which patients had no responded after a period of at least 8 weeks. Clinical state and adverse effects were assessed at each visit. Final improvement in CGI scores of 1 or 2 were considered as responders. Results: Mean DAA trial duration was 17.6 (sd = 7.8, range 4 - 34) weeks, with a mean final dose of 1.23 ± 0.32 mg/day (range, 0.75 - 1.50 mg/day) for PPX, and 2.97 ± 0.99 mg/day (range, 1.50 - 5.00 mg/day) for RPN. DAAs were well tolerated and did not show any negative interaction with concomitant psychotropic medications. Only one patient became worse (final CGI = 5), and had to interrupt PPX due to nausea, increased agitation and irritability. Eight patients (44.4 %) were considered responders (4 with PPX and 4 with RPN): 5 showed marked improvement (CGI = 1), and 3 showed moderate improvement (CGI = 2); another 5 (27.8 %) manifested a transient response not sustained up to the end. The initial and final scores of CGI severity scale for all patients (responders and non-responders combined) were, respectively, 5.33 ± 0.7 and 3.94 ± 1.3 (mean ± S.D). The mean change according to the CGI severity scale was statistically significant (t = 4.74. p < 0.0002). Conclusion: From the results, PPX and RPN appear to be well tolerated and potentially useful in the adjunctive treatment of drug-resistant bipolar II depression.

Literatur

  • 1 Agnoli A, Ruggieri S, Casacchia M. Restatement and perspectives of ergot alkaloids in clinical neurology and psychiatry.  Pharmacol. 1978;  16 (1) 174-188
  • 2 Bode L, Dietrich E, Stoyloff R, Emrich H M, Ludwig H. Amantadine and human Borna disease virus in an infected patient with bipolar depression.  Lancet. 1997;  349 178-179
  • 3 Bouckoms A, Mangini L. Pergolide. An antidepressant Adjuvant for Mood Disorders.  Psychopharmacol Bull. 1993;  29 207-211
  • 4 Bouras N, Bridges P K. Bromocriptine and depression.  Curr Med Res Opin. 1982;  8 150-153
  • 5 Cassano G B, Akiskal H S, Musetti L, Perugi G, Soriani A, Mignani V. Psychopathology, Temperament and Past Course in Primary Major Depressions. 2. Toward a redefinition of bipolarity with a New Semi structured Interview for Depression.  Psychopat. 1989;  22 278-288
  • 6 Cassano G B, Musetti L, Perugi G, Mignani V, Soriani A, McNair D M, Akiskal H S. Major depression subcategories: their potentiality for clinical research. In: Sanofi Group (eds) Diagnosis and treatment of depression. Quo Vadis?. Montpelier, France; Sanofi Group 1987: 91-175
  • 7 Colonna L, Petit M, Lepine J P. Bromocriptine in affective disorders.  J Affect Disord. 1979;  1 173-177
  • 8 Ferszt R, Kühl K-P, Bode L, Severus E W, Winzer B, Berghofer A, Beelilitz G, Brodhun B, Müler-Oerlinghausen B, Ludwig H. Amantadine revisited: an open trial of amantadine sulfate treatment on chronically depressed patients with Borna disease virus infection.  Pharmacopsychiat. 1999;  32 142-147
  • 9 Ferszt R, Severus E, Bode L, Brehm M, Kühl K-P, Berzewski H, Ludwig H. Activated Borna disease virus in affective disorders.  Pharmacopsychiat. 1999;  32 93-98
  • 10 Goldberg J F, Frye M A, Dunn R T. Pramipexole in refractory bipolar depression.  Am J Psychiatry (Letter). 1999;  156 798
  • 11 Goodman W K, Corrigan M, Evans D. Pramipexole in the treatment of major depression. Abstract presented at the congress of “European federation of Neurological Societies”. Siviglia, Spain; September 1998
  • 12 Guy W. Adult Demogrpahic and Personal Inventory. In: Guy W (ed) ECDEU Assessment Manual for Psychopharmacology. Washington, DC; U.S. Government Printing Office 1976
  • 13 Huber T J, Dietrich D, Emrich H M. Possible use of amantadine in depression.  Pharmacopsychiat. 1999;  32 47-55
  • 14 Kapur S, Mann J J. Role of the dopaminergic system in depression.  Biol Psychiatry. 1992;  32 1-17
  • 15 Kasper S, Barnas C, Heiden A, Volz H P, Laakmann G, Zeit H, Pfolz H. Pramipexole as adjunct to haloperidol in schizophrenia: safety and efficacy.  Eur Neuropsychopharmacol. 1997;  7 65-70
  • 16 Little K Y. Amphetamine, but not methylphenidate, predicts antidepressant response.  J Clin Psychopharmacol. 1988;  8 177-183
  • 17 Nordin C, Siwers B, Bertilsson L. Bromocriptine in depressive disorder: clinical and biochemical effects.  Acta Psychiatr Scand. 1981;  64 25-33
  • 18 Nurnberger J J, Simmons-Ailing S, Kessler L. Separate mechanisms for behavioral cardiovascular and hormonal responses to dextroamphetamine in man.  Psychopharmacol. 1984;  84 200-204
  • 19 Parkes J D, Calver D M, Zilkha K J, Knill-Jones R P. Conrolled trial of amantadine hydrochloride in Parkinson's Disease.  Lancet. 1970;  1 259-262
  • 20 Parkinson Study Group . Safety and efficacy of pramipexole in early Parkinson disease: a randomized dose-ranging study.  J Am Med Ass. 1997;  278 125-130
  • 21 Perugi G, Akiskal H S, Micheli C, Musetti L, Paiano A, Quilici C, Rossi L, Cassano G B. Clinical subtypes of bipolar mixed states: validating a broader European definition in 143 cases.  J Affective Dis. 1997;  43 169-180
  • 22 Perugi G, Akiskal H S, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A, Vignoli S, Bemi E. The high prevalence of “soft” bipolar (II) features in atypical depression.  Comprehen Psychiatry. 1998;  39 (2) 63-71
  • 23 Perugi G, Musetti L, Simonini E, Piagentini F, Cassano G B, Akiskal H S. Gender-mediated clinical features of depressive illness. The importance of temperamental differences.  Br J Psychiatry. 1990;  157 835-841
  • 24 Post R M, Gerner R H, Carman J S. Effects of a dopamine agonist piribedil in depressed patients.  Arch Gen Psychiatry. 1978;  35 609-615
  • 25 Rizzo M, Bioandrate P, Tognoni G, Morselli P L. Amantadine in depression: relationship between behavioral effects and plasma levels.  Eur J Clin Pharmacol. 1973;  5 226-228
  • 26 Rosenbaum J F, Fava M, Nierenberg A A, Sachs G S. Treatment-Resistant Mood Disorders. In: Gabbard GO (ed) Treatment of Psychiatric Disorders II (II ed). Vol. 46. Washington, DC; American Psychiatric Press 1995: 1275-1328
  • 27 Rott R, Herzog S, Fleischer B, Winokur H, Amsterdam J, Dyson W, Koprowski H. Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders.  Science. 1985;  228 755-756
  • 28 Schatzberg A F, Cole J O, DeBattista C. Manual of Clinical Psychopharmacology, 3rd Edition. Washington, DC; American Psychiatric Press 1997
  • 29 Schwab R S, England A C, Poskanzer D C, Young R R. Amantadine in the treatment of Parkinson's disease.  J Am Med Association. 1969;  208 1168-1170
  • 30 Silverstone T. Response to bromocriptine distinguishes bipolar from unipolar depressions.  Lancet. 1984;  1 903-904
  • 31 Szegedi A, Hillert A, Wetzel H, Klieser E, Gaebel W, Benkert O. Pramipexole, a dopamine agonist, in major depression: Antidepressant effects and tolerability in an open-label study with multiple doses.  Clin Neuropharmacol. 1997;  20 (1) S36-S45
  • 32 Theohar C, Fischer-Cornelssen K, Brosch H, Fischer E K, Petrovic D. A comparative, multicenter trial between bromocriptine and amitriptyline in the treatment of endogenous depression.  Arzneimittelforschung. 1982;  32 (7) 783-787
  • 33 Vale S, Espejel M A, Dominguez J C. Amantadine in depression.  Lancet. 1971;  21-437
  • 34 Waehrens J, Gerlach J. Bromocriptine and imipramine in endogenous depression: a double-blind controlled trial in outpatients.  J Affect Disord. 1981;  3 193-202
  • 35 Willner P. Dopamine and depression: a review of recent evidence. I. Empirical studies.  Brain Res. 1983;  287 211-224

Giulio Perugi,MD 

Institute of Psychiatry
University of Pisa

Via Roma 67
56100 Pisa
Italy

Phone: + 50-992647

Fax: + 50-21581

Email: gperugi@psico.med.unipi.it

    >