During the course of psychotic disorders, patients often suffer from intercurrent
major depressive episodes (MDEs), and suicides frequently occur. This constellation
challenges further improvements in psychopharmacological therapy. The antidepressant
duloxetine was recently introduced as a novel reuptake inhibitor of serotonin and
noradrenaline. We provide the first reports on duloxetine treatment of MDEs in the
course of psychotic disorders. In two cases this substance was successfully involved
as an add-on to antipsychotic treatment consisting of clozapine or amisulpride. We
achieved a response of the MDEs, as reflected by psychopathological rating scales.
A significant rise in the clozapine serum level was detected, most likely because
of pharmacokinetic interactions. Overall, the application of duloxetine was well tolerated;
therefore, further investigations in prospective studies seem to be recommendable.
Abbreviations
CDSS:Calgary Depression Scale for Schizophrenia
GP:Global Psychopathology
HAMD:Hamilton Depression Scale
MDE:Major Depressive Episode
PANSS:Positive and Negative Syndrome Scale
SANS:Scale for the Assessment of Negative Symptoms
SSNRI:Selective Serotonin and Noradrenaline Reuptake Inhibitor
References
- 1
Addington D, Addington J, Atkinson M.
A psychometric comparison of the Calgary Depression Scale for Schizophrenia and the
Hamilton Depression Rating Scale.
Schizophr Res.
1996;
19
205-212
- 2
Addington D, Addington J, Maticka-Tyndale E, Joyce J.
Reliability and validity of a depression rating scale for schizophrenics.
Schizophr Res.
1992;
6
201-208
- 3
An der Heiden W, Könnecke R, Maurer K, Ropeter D, Haefner H.
Depression in the long-term course of schizophrenia.
Eur Arch Psychiatry Clin Neurosci.
2005;
255
174-184
- 4
Caccia S.
Biotransformation of post-clozapine antipsychotics: pharmacological implications.
Clin Pharmacokinetics.
2000;
38
393-414
- 5
Detke M J, Lu Y, Goldstein D J, Hayes J R, Demitrack M A.
Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind
placebo-controlled trial.
J Clin Psychiatry.
2002;
63
308-315
- 6
Deuschle M, Krumm B, Bindeballe N, Colla M, Hamann B, Lederbogen F, Gilles M, Heuser I.
Open-label non-randomized versus double-blind randomized antidepressive treatment:
what are the advantages of clinical decision over randomization.
Pharmacopsychiatry.
2004;
37
299-302
- 7
Gaebel W, Janssen B, Riesbeck M.
Modern treatment concepts in schizophrenia.
Pharmacopsychiatry.
2003;
36 Suppl. 3
S168-S175
- 8
Goldstein D J, Lu Y, Detke M J, Wiltse C, Mallinckrodt C, Demitrack M A.
Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison
with paroxetine.
J Clin Psychopharmacol.
2004;
24
389-399
- 9
Kohler C G, Lallart E A.
Postpsychotic depression in schizophrenia patients.
Curr Psychiatry Rep.
2002;
4
273-278
- 10
Kuo F, Gillespie T A, Kulanthaivel P, Lantz R J, Ma T W, Nelson D L, Threlkeld P G,
Wheeler W J, Yi P, Zmijewski M.
Synthesis and biological activity of some known and putative duloxetine metabolites.
[Erratum appears in Bioorg Med Chem Lett. 2004 Oct 18;14(20):5233].
Bioorg Med Chem Lett.
2004;
14
3481-3486
- 11
Lantz R J, Gillespie T A, Rash T J, Kuo F, Skinner M, Kuan H Y, Knadler M P.
Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects.
Drug Metabol Disposition.
2003;
31
1142-1150
- 12
Lehman A F, Lieberman J A, Dixon L B, McGlashan T H, Miller A L, Perkins D O, Kreyenbuhl J,
American Psychiatric A ssociation, and Steering Committee on Practice G uidelines.
Practice guideline for the treatment of patients with schizophrenia, second edition.
Am J Psychiatry.
2004;
161
1-56
- 13
Mallinckrodt C H, Raskin J, Wohlreich M M, Watkin J G, Detke M J.
The efficacy of duloxetine: a comprehensive summary of results from MMRM and LOCF_ANCOVA
in eight clinical trials.
BMC Psychiatry.
2004;
4
26
- 14
Mazeh D, Shahal B, Saraf R, Melamed Y.
Venlafaxine for the treatment of depressive episode during the course of schizophrenia.
J Clin Psychopharmacol.
2004;
24
653-655
- 15
McGlashan T H, Waltrip R W.
2nd. Postpsychotic depression.
Am J Psychiatry.
1991;
148
545-547
- 16
Palmer B A, Pankratz S, Bostwick J M.
The lifetime risk of suicide in schizophrenia.
Arch Gen Psychiatry.
2005;
62
247-253
- 17
Preskorn S H.
Duloxetine.
J Psychiatr Pract.
2004;
10
375-385
- 18
Repo-Tiihonen E, Eloranta A, Hallikainen T, Tiihonen J.
Effects of Venlafaxine treatment on clozapine plasma levels in schizophrenic patients.
Neuropsychobiology.
2005;
51
173-176
- 19
Silver H.
Selective serotonin re-uptake inhibitor augmentation in the treatment of negative
symptoms of schizophrenia.
Expert Op Pharmacother.
2004;
5
2053-2058
- 20
Siris S G.
Diagnosis of secondary depression in schizophrenia: implications for DSM-IV.
Schizophr Bull.
1991;
17
75-98
- 21
Skinner M H, Kuan H Y, Pan A, Sathirakul K, Knadler M P, Gonzales C R, Yeo K P, Reddy S,
Lim M, Ayan-Oshodi M, Wise S D.
Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers.
Clin Pharmacol Therapeutics.
2003;
73
170-177
- 22
Spina E, Avenoso A, Scordo M G, Ancione M, Madia A, Levita A.
No effect of reboxetine on plasma concentrations of clozapine, risperidone, and their
active metabolites.
Ther Drug Monitoring.
2001;
23
675-678
- 23
Van de Kar L D, Rittenhouse P A, Li Q, Levy A D.
Serotonergic regulation of renin and prolactin secretion.
Beh Brain Res.
1996;
73
203-208
- 24
Zoccali R, Muscatello M R, Cedro C, Neri P, La Torre D, Spina E, Di Rosa A E, Meduri M.
The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms
of schizophrenia: a double-blind, placebo-controlled study.
Int Clin Psychopharmacol.
2004;
19
71-76
Mathias Zink (MD)
Central Institute of Mental Health
P.O. Box: 12 21 20
D-68072 Mannheim
Germany
Phone: ++49-621-1703 2911
Fax: ++49-621-1703 1205
Email: mathias.zink@zi-mannheim.de