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Sense and non-sense of polypharmacy: increasing efficacy, decreasing compliance?

Published online by Cambridge University Press:  16 April 2020

Patrice Boyer*
Affiliation:
Hôpital de la Salpétrière, Pavillon Clérambault, UMR 7593 CNRS, Paris75013, France
*
*Corresponding author. E-mail address:[email protected] (E Boyer).
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Extract

The objective in managing patients with schizophrenia is to provide effective control of symptoms and enable the patient to reintegrate into society. Pharmacotherapy should, therefore, aim to provide optimum symptom control with minimal side effects using a simple dosage regimen. Ideally, this would be achieved through the use of a single agent. Some patients are successfully managed with a single antipsychotic drug, but it is often necessary or thought to be necessary to use a combination of agents to provide effective treatment. One European survey reported that most patients receive two to three psychotropic agents on average, but at least 5-22% receive five or more agents [53]. Unfortunately, the addition of more agents increases the risk of drug interactions, adverse events and non-compliance. This is amplified by the paucity of evidence-based medicine currently available to guide physicians in the use of combinations of agents, and the tendency of polypharmaceutical practice to be mostly driven by personal preference, clinical experience and marketing. This article therefore briefly looks at the feasibility of using various drug classes as adjunctive therapy in patients with schizophrenia.

Type
Research Article
Copyright
Copyright © 2003 European Psychiatric Association

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References

Anand, A, Chamey, DSet al. Attenuation of the neuropsychiatrie effects of ketamme with lamotrigine: support for hyperglutamatergic effects of iV-mefhyl-D-aspartate receptor antagonists. Arch Gen Psychiatry 2000;57(3):270–6.CrossRefGoogle Scholar
Angrist, B, Peselow, Eet al. Partial improvement in negative schizophrenic symptoms after amphetamine. Psychopharmacology 1982:78(2):128–30.CrossRefGoogle ScholarPubMed
Angrist, B, Rotrosen, Jet al. Differential effects of amphetamine and neuroleptics on negative vs. positive symptoms in schizophrenia. Psychopharmacology 1980;72(1): 17–19.CrossRefGoogle Scholar
Arango, C, Kirkpatrick, Bet al. Fluoxetine as an adjunct to conventional antipsychotic treatment of schizophrenia patients with residual symptoms. J Nerv Ment Dis 2000;188(1):50–3.CrossRefGoogle ScholarPubMed
Arnsten AFT, Cai, JXet al. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: Evidence for alpha-2 receptor subtypes. J Neurosci 1988;8:4287–97.Google Scholar
Bergeron, R, Meyer, TMet al. Modulation of N-methyl-D-aspartate receptor function by glycine transport. Proc Natl Acad Sci USA 1998:95(26): 15730–4CrossRefGoogle ScholarPubMed
Berk, M, Ichim, Cet al. Efficacy of mirtazapine add-on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Int Clin Psychopharmacol 2001;16(2):87–92.CrossRefGoogle ScholarPubMed
Bezchlibnyk-Butler, KZ, Remington, GJ. Antiparkinsonian drugs in the treatment of neuroleptic-induced extrapyramidal symptoms. Can J Psychiatry/Rev Can Psychiatrie 1994:39(2):74–84.CrossRefGoogle ScholarPubMed
Bottlender, R, Sato, Tet al. Negative symptoms in depressed and schizophrenic patients: how do they differ? J Clin Psychiatry 2003; 64(8):954–8.CrossRefGoogle ScholarPubMed
Bottlender, R, Strauss, Aet al. Prevalence and background factors of depression in first-admitted schizophrenic patients. Acta Psychiatr Scand 2000;101(2):153–60.CrossRefGoogle ScholarPubMed
Buchanan, RW, Kirkpatrick, Bet al. Fluoxetine augmentation of clozapine treatment in patients with schizophrenia. Am J Psychiatry 1996;153(12):1625–7.Google ScholarPubMed
Burns, T, Chabannes, JPet al. Switching antipsychotic medications: general recommendations and switching to amisulpride Curr Med Res Opin 2002;18(4):201–8.CrossRefGoogle ScholarPubMed
Casey, D.Neuroleptic-induced acute extrapyramidal symptoms and tardive dyskinesia in schizophrenia. 1st edition. Hirsch, S, Weinberger, D Eds. Oxford: Blackwell; 1995. p. 546–65.Google Scholar
Casey, DE, Daniel, DGet al. Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. Neuropsychopharmacology 2003;28(1) 182–92.CrossRefGoogle ScholarPubMed
Castner, SA, Williams, GVet al. Reversal of antipsychotic-induced working memory deficits by short-term dopamine D, receptor stimulation. Science 2000;287(5460):2020–2.CrossRefGoogle Scholar
Csernansky, JG, Riney, SJet al. Double-blind comparison of alprazolam, diazepam, and placebo for the treatment of negative schizophrenic symptoms. Arch Gen Psychiatry 1988;45(7):655–9.CrossRefGoogle ScholarPubMed
Duinkerke, SJ, Botter, PA. et al. Ritanserin, a selective 5-HT2/nC antagonist, and negative symptoms in schizophrenia. A placebo-controlled double-blind trial. Br J Psychiatry 1993;163:451–5.CrossRefGoogle Scholar
Fields, RB, Van Kammen, DPet al. Clonidine improves memory function in schizophrenia independently from change in psychosis. Preliminary findings. Schizophr Res 1988;1(6) 417–23.CrossRefGoogle ScholarPubMed
Fisch, RZ.Trihexyphenidyl abuse: therapeutic implications for negative symptoms of schizophrenia? Acta Psychiatr Scand 1987;75(1): 91–4.CrossRefGoogle ScholarPubMed
Foster, S, Kessel, Jet al. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. Int Clin Psychopharmacol 1997;12(3):175–9.CrossRefGoogle Scholar
Freundenreich, , Goff, DC. Antipsychotic combination therapy in schizophrenia: a review of efficacy and risks of current combinations. Acta Psychiatr Scand 2002;106:323–30.CrossRefGoogle Scholar
Friedman, JI, Adler, DNet al. The role of norepinephrine m the pathophysiology of cognitive disorders: potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer's disease Biol Psychiatry 1999:46(9): 1243–52.CrossRefGoogle Scholar
Friedman, JI, Adler, DNet al. Guanfacine treatment of cognitive impairment in schizophrenia. Neuropsychopharmacology 2001; 25(3):402–9.CrossRefGoogle Scholar
Friedman, JI, Ault, Ket al. Pimozide augmentation for the treatment of schizophrenic patients who are partial responders to clozapine. Biol Psychiatry 1997;42(6):522–3.CrossRefGoogle ScholarPubMed
Goff, DC, Brotman, AWet al. Trial of fluoxetine added to neuroleptics for treatment-resistant schizophrenic patients. Am J Psychiatry 1990; 147 (4):492–4.Google ScholarPubMed
Goff, DC, Midha, KKet al. A placebo-controlled trial of fluoxetine added to neuroleptic in patients with schizophrenia. Psychopharmacology 1995;117(4):417–23.CrossRefGoogle ScholarPubMed
Goff, DC, Tsai, G.et al. D-cycloserine added to clozapine for patients with schizophrenia. Am J Psychiatry 1996;153(12);1628–30.Google ScholarPubMed
Goff, DC, Tsai, Get alA placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry 1999:56(1):21–7.CrossRefGoogle ScholarPubMed
Goldberg, TE, Bigelow, LBet al. Cognitive and behavioral effects of the coadministration of dextroamphetamine and haloperidol in schizophrenia. Am J Psychiatry 1991;148(1):78–84.Google Scholar
Goldman, MB, Janecek, HMAdjunctive fluoxetine improves global function in chronic schizophrenia. J Neuropsychiatry Clin Neurosci 1990;2(4):429–31.Google ScholarPubMed
Goldman-Rakic, PS, Lidow, MSet al. Overlap of dopaminergic, adrenergic, and serotoninergic receptors and complementarity of their subtypes in primate prefrontal cortex. J Neurosci 1990;10(7): 2125–38.CrossRefGoogle ScholarPubMed
Goldman-Rakic, PS, Muly III, ECet al. D, receptors in prefrontal cells and circuits. Brain Res Rev 2000;31(2/3):295–301.CrossRefGoogle ScholarPubMed
Gupta, S, Sonnenberg, SJet al. Olanzapine augmentation of clozapine. Ann Clin Psychiatry 1998;10(3):113–15.CrossRefGoogle ScholarPubMed
Heresco-Levy, U, Javitt, DCet al. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry 1999;56(1):29–36CrossRefGoogle ScholarPubMed
Hirsch, SR, Jolley, AGet al. Dysphoric and depressive symptoms in chronic schizophrenia. Schizophr Res 1989;2(3):259–64.CrossRefGoogle ScholarPubMed
Hogarty, , McEvoy, JPet al. Pharmacotherapy of impaired affect in recovering schizophrenic patients. Arch Gen Psychiatry 1995; 52(1):29–41.CrossRefGoogle ScholarPubMed
Homtner, DW, Zahn, TPet al. Prazosin, a specific alpha-1-noradrenergic receptor antagonist, has no effect on symptoms but increases autonomic arousal in schizophrenic patients. Psychiatry Res 1984:11(3):193–204Google Scholar
Kanter, GL, Yerevaman, Blet al. Case report of a possible interaction between neuroleptics and carbamazepine. Am J Psychiatry 1984; 141(9):1101–2.Google ScholarPubMed
Kramer, MS, Vogel, WHet al. Antidepressants in ‘depressed’ schizophrenic inpatients. A controlled trial. Arch Gen Psychiatry 1989;46(10):922–8.CrossRefGoogle ScholarPubMed
Lee, MS, Kim, YKet al. A double-blind study of adjunctive sertraline in haloperidol-stabihzed patients with chronic schizophrenia. J Clin Psychopharmacol 1998;18(5):399–403.CrossRefGoogle ScholarPubMed
Leucht, S, McGrath, Jet al. Carbamazepine for schizophrenia and schizoaffective psychoses. Cochrane Database Systematic Reviews, The Cochrane Library; 2003.CrossRefGoogle Scholar
Litman, RE, Su, TPet al. Idazoxan and response to typical neuroleptics in treatment-resistant schizophrenia. Comparison with the atypical neuroleptic, clozapine. Br J Psychiatry 1996;168(5):571–9.CrossRefGoogle ScholarPubMed
Marcus, MM, Nomikos, GGet al. Effects of atypical antipsychotic drugs on dopamine output in the shell and core of the nucleus accum-bens: role of 5-HT(2A1 and alpha-(l)-adrenoceptor antagonism. Eur Neuropsychopharmacol 2000;10(4):245–53.CrossRefGoogle Scholar
Mathew, RJ, Wilson, WH. Changes in cerebral blood flow and mental state after amphetamine challenge in schizophrenic patients. Neurop-sychobiology 1989;21 (3): 117–23.CrossRefGoogle ScholarPubMed
Matthiasson, P, Erlandsson, Ket al. Amisulpride augmentation of clozapine and striatal dopamine D2 receptor binding potential. A l23I-IBZM SPET study. Schizophr Res 2002,53(3):208–9.Google Scholar
Moghaddam, B, Adams, Bet al. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 1997,17(8):2921–7.CrossRefGoogle ScholarPubMed
Mowerman, S, Siris, SGAdjunctive loxapine in a clozapine-resistant cohort of schizophrenic patients. Ann Clin Psychiatry 1996;8(4). 193–7.CrossRefGoogle Scholar
Munro, J, O'Sullivan, D, Andrews, Cet al. 1999. Active monitoring of 12 760 resistant clozapine recipients in the UK and Ireland: beyond pharmacovigilance. Br J Psychiatry 1999;175:576–80.CrossRefGoogle ScholarPubMed
Okubo, Y, Suhara, Tet al. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 1997;385(6617):634–6.CrossRefGoogle ScholarPubMed
Okuma, T, Yamashita, Iet al. A double-blind study of adjunctive car-bamazepine versus placebo on excited states of schizophrenic and schizoaffective disorders. Acta Psychiatr Scand 1989;80(3):250–9.CrossRefGoogle Scholar
Raskin, S, Katz, Get al. Clozapine and risperidone: combination/augmentation treatment of refractory schizophrenia: a preliminary observation. Acta Psychiatr Scand 2000:101(4):334–6.CrossRefGoogle ScholarPubMed
Reyntjens, A, Gelders, YGet al. Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin-S, receptor blocker. Drug Dev Res 1986;8:205–11.CrossRefGoogle Scholar
Rittmannsberger, H, Meise, Uet al. Polypharmacy in psychiatric treatment. Patterns of psychotropic drug use in Austrian psychiatrie clinics. Eur Psychiatry 1999;14(1):33–40CrossRefGoogle Scholar
Rosse, RB, Theut, SKet al. Glycine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: an open-label, pilot study. Clin Neuropharmacol 1989;12(5):416–24.CrossRefGoogle Scholar
Sanfihpo, M, Wolkin, Aet al. Amphetamine and negative symptoms of schizophrenia. Psychopharmacology 1996;123(2):211–14.CrossRefGoogle Scholar
Schmidt, CJ, Fadayel, GM. The selective 5-HT2A receptor antagonist, MDL 100,907, increases dopamine efflux in the prefrontal cortex of the rat. Eur J Pharmacol 1995:273(3): 273–9.CrossRefGoogle ScholarPubMed
Schulz, SC, Thompson, PAet al. Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients. J Clin Psychiatry 1999;60(6) 366–72.CrossRefGoogle ScholarPubMed
Sharif, ZA.Common treatment goals of antipsychotics: acute treatment. J Clin Psychiatry 1998;59(19):5–8.Google ScholarPubMed
Shiloh, R, Zemishlany, Z.et al. Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia. Int Clin Psycho-pharmacol 2002;17(2):59–64.CrossRefGoogle ScholarPubMed
Silver, H, Barash, Iet al. Fluvoxamine augmentation of antipsychotics improves negative symptoms in psychotic chronic schizophrenic patients: a placebo-controlled study Int Clin Psychopharmacol 2000;15(5):257–61.CrossRefGoogle ScholarPubMed
Silver, H, Nassar, A.Fluvoxamine improves negative symptoms in treated chronic schizophrenia: an add-on double-blind, placebo-controlled study. Biol Psychiatry 1992;31(7):698–704.CrossRefGoogle ScholarPubMed
Silver, H, Shmugliakov, N.Augmentation with fluvoxamine but not maprotiline improves negative symptoms in treated schizophrenia: evidence for a specific serotonergic effect from a double-blind study. J Clin Psychopharmacol 1998;18(3):208–11CrossRefGoogle Scholar
Sins, SG, Bermanzohn, PCet al. The use of antidepressants for negative symptoms in a subset of schizophrenic patients. Psychopharmacol Bull 1991;27(3):331–5.Google Scholar
Siris, SG, Bermanzohn, PCet al. Maintenance imipramine therapy for secondary depression in schizophrenia. A controlled trial. Arch Gen Psychiatry 1994;51(2):109–15.CrossRefGoogle ScholarPubMed
Spina, E, De Domenico, Pet al. Adjunctive fluoxetine in the treatment of negative symptoms in chronic schizophrenic patients Int Clin Psychopharmacol 1994;9(4):281–5.CrossRefGoogle ScholarPubMed
Strauss, ME, Reynolds, KSet al. Effects of anticholinergic medication on memory in schizophrenia. Schizophr Res 1990;3(2) 127–9CrossRefGoogle Scholar
Stubbs, JH, Haw, CMet al. Augmentation with sulpiride for a schizophrenic patient partially responsive to clozapine. Acta Psychiatr Scand 2000;102(5):390–3.CrossRefGoogle ScholarPubMed
Svensson, TH, Mathe, JMet alMode of action of atypical neuroleptics in relation to the phencyclidine model of schizophrenia: role of 5-HT2 receptor and alpha 1-adrenoceptor antagonism. J Clin Psychopharmacol 1995;15(1): 11S-18SCrossRefGoogle ScholarPubMed
Taiminen, TJ, Syvalahti, Eet al. Citalopram as an adjuvant in schizophrenia: further evidence for a serotonergic dimension in schizophrenia. Int Clm Psychopharmacol 1997;12(1):31–5.CrossRefGoogle Scholar
Tandon, R, Greden, JF. Cholinergic hyperactivity and negative schizophrenic symptoms. A model of cholinergic/dopaminergic interactions in schizophrenia. Arch Gen Psychiatry 1989;46(8):745–53.CrossRefGoogle Scholar
Tandon, R, Greden, JFet alTreatment of negative schizophrenic symptoms with trihexyphenidyl. J Clin Psychopharmacol 1988;8(3): 212–15.CrossRefGoogle ScholarPubMed
Terao, T, Oga, T.et al. Lithium addition to neuroleptic treatment in chrome schizophrenia: a randomized, double-blind, placebo-controlled, cross-over study Acta Psychiatr Scand 1995;92(3):220–4.CrossRefGoogle Scholar
Thienhaus, OJ, Allen, Aet al. Anticholinergic serum levels and cognitive performance. Eur Arch Psychiatry Clin Neurosci 1990, 240(1):28–33.CrossRefGoogle ScholarPubMed
Tracy, JI, Monaco, Cet al. Anticholinergicity and cognitive processing in chronic schizophrenia. Biol Psychology 2001;56(1):1-22.CrossRefGoogle ScholarPubMed
Tsai, GE, Yang, Pet al. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 1998;44(11): 1081–9.CrossRefGoogle ScholarPubMed
Tsai, GE, Yang, Pet al. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry 1999; 156(11): 1822–5.Google ScholarPubMed
van Kammen, DP, Boronow, JJ. Dextro-amphetamine diminishes negative symptoms in schizophrenia Int Clin Psychopharmacol 1988:3(2);] 11–21.CrossRefGoogle Scholar
Wassef, AA, Dott, SGet al. Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia. J Clin Psychopharmacol 2000;20(3):357–61CrossRefGoogle ScholarPubMed
Wilson, WH.Addition of lithium to haloperidol in non-affective, antipsychotic non-responsive schizophrenia: a double blind, placebo controlled, parallel design clinical trial. Psychopharmacology 1993;111(3):359–66.CrossRefGoogle ScholarPubMed
Wolkowitz, OM, Pickar, D.Benzodiazepines in the treatment of schizophrenia: a review and reappraisal. Am J Psychiatry 1991;148(6). 714–26.Google ScholarPubMed
Ziegenbein, M, Rosenthal, Pet al. Coadministration of clozapine and amisulpride in psychotic patients. Eur Psychiatry 2002;17(1):99CrossRefGoogle Scholar
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