Skip to main content

Antidepressants in Schizophrenia: A Place for Them?

  • 1153 Accesses

Abstract

Antipsychotic monotherapy is often insufficient to achieve optimal outcome in schizophrenia. One of the numerous adjunctive psychopharmacological strategies proposed to overcome this drawback is a combination of an antipsychotic with an antidepressant. Existing evidence on the efficacy of such combination is ambiguous and varies by syndrome domains and antidepressant classes and—within a class—by individual compounds. The most dependable data favor—as a group—receptor-blocking antidepressants. Of these, mirtazapine demonstrates probably the most consistent beneficial effects, in particular for negative symptoms and cognitive deficits. While current guidelines warn about possible antidepressant-provoked psychotic exacerbation, no data today support these reservations, at least in chronic schizophrenia and when a contemporaneous antipsychotic therapy continues. Moreover, one randomized controlled trial (RCT) revealed an additive antipsychotic effect of an adjunctive antidepressant (mirtazapine) and, according to a recently published large cohort study concomitant antidepressants can reduce suicide rates and overall mortality of patients with schizophrenia. It appears hence that caution regarding the add-on antidepressant use recommended by current guidelines can be soon softened. Due to scarcity of data, conservative use of antidepressants may, however, be still justifiable in acute schizophrenia. If an antipsychotic-antidepressant combination is to be prescribed, a thorough knowledge of pharmacodynamic and pharmacokinetic (especially, regarding several CYP450 liver enzymes) interactions is essential to avoid adverse effects and complications.

A convincing amount of evidence is emerging on some previously unknown mechanisms of action beyond the classical neurotransmitter/monoamine receptor theory—findings that may boost research and development in the nearest future. For instance, the novel body of data on the proneuroplastic effect of antidepressants may help us to understand how an add-on antidepressant can improve neurocognition in chronic schizophrenia, and how antidepressant monotherapy can prevent psychosis in high-risk groups. More large RCTs with various combinations are needed to reveal the most feasible antidepressant therapy strategies for schizophrenia.

Keywords

  • Depressive Symptom
  • 5HT2 Receptor
  • Negative Symptom
  • Positive Symptom
  • Chronic Schizophrenia

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-94-007-5805-6_9
  • Chapter length: 21 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   169.00
Price excludes VAT (USA)
  • ISBN: 978-94-007-5805-6
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   219.99
Price excludes VAT (USA)
Hardcover Book
USD   219.99
Price excludes VAT (USA)

Abbreviations

AIMS:

Abnormal Involuntary Movement Scale

APA:

American Psychiatric Association

BDI:

Beck Depression Inventory

EPS:

Extrapyramidal Symptoms

FGA:

First-Generation Antipsychotic

HDRS:

Hamilton Depression Rating Scale

MDD:

Major Depressive Disorder

NICE:

National Institute for Health and Clinical Excellence

PANSS:

Positive and Negative Syndrome Scale

RCT:

Randomized Controlled Trial

SAS:

Simpson-Angus Scale

SGA:

Second Generation Antipsychotic

SNRI:

Selective Noradrenaline Reuptake Inhibitor

SSRI:

Selective Serotonin Reuptake Inhibitor

TCA:

Tricyclic Antidepressant

References

  1. Tandon R, Keshavan MS, Nasrallah HA (2008) Schizophrenia, “just the facts” what we know in 2008. 2. Epidemiology and etiology. Schizophr Res 102:1–18

    PubMed  CrossRef  Google Scholar 

  2. van Os J, Kapur S (2009) Schizophrenia. Lancet 374(9690):635–645

    PubMed  CrossRef  CAS  Google Scholar 

  3. Emsley R, Chiliza B, Schoeman R (2008) Predictors of long-term outcome in schizophrenia. Curr Opin Psychiatry 21:173–177

    PubMed  CrossRef  Google Scholar 

  4. Kane JM, Correll CU (2010) Pharmacologic treatment of schizophrenia. Dialogues Clin Neurosci 12:345–357

    PubMed  Google Scholar 

  5. Zink M, Englisch S, Meyer-Lindenberg A (2010) Polypharmacy in schizophrenia. Curr Opin Psychiatry 23:103–111

    PubMed  CrossRef  Google Scholar 

  6. Himelhoch S, Slade E, Kreyenbuhl J et al (2012) Antidepressant prescribing patterns among VA patients with schizophrenia. Schizophr Res 136:32–35

    PubMed  CrossRef  Google Scholar 

  7. American Psychiatric Association (2006) American Psychiatric Association practice guidelines for the treatment of psychiatric disorders: compendium 2006. PsychiatryOnline.com Online ISBN 0-89042-336-9

    Google Scholar 

  8. NICE (2009) Schizophrenia. Core interventions in the treatment and management of schizophrenia in primary and secondary care (update). National Institute for Clinical Excellence, London

    Google Scholar 

  9. Chakos MH, Glick ID, Miller AL et al (2006) Baseline use of concomitant psychotropic medications to treat schizophrenia in the CATIE trial. Psychiatr Serv 57:1094–1101

    PubMed  CrossRef  Google Scholar 

  10. Waehrens J, Gerlach J (1980) Antidepressant drugs in anergic schizophrenia. A double-blind cross-over study with maprotiline and placebo. Acta Psychiatr Scand 61:438–444

    PubMed  CAS  CrossRef  Google Scholar 

  11. Laruelle M, Abi-Dargham A, Casanova MF et al (1993) Selective abnormalities of prefrontal serotonergic receptors in schizophrenia. A postmortem study. Arch Gen Psychiatry 50:810–818

    PubMed  CAS  CrossRef  Google Scholar 

  12. Dean B, Hayes W, Opeskin K et al (1996) Serotonin receptors and the serotonin transporter in the schizophrenic brain. Behav Brain Res 73:169–175

    PubMed  CAS  CrossRef  Google Scholar 

  13. Meltzer HY (1999) Treatment of schizophrenia and spectrum disorders: pharmacotherapy, psychosocial treatments, and neurotransmitter interactions. Biol Psychiatry 46:1321–1327

    PubMed  CAS  CrossRef  Google Scholar 

  14. Meltzer HY, Massey BW (2011) The role of serotonin receptors in the action of atypical antipsychotic drugs. Curr Opin Pharmacol 11:59–67

    PubMed  CAS  CrossRef  Google Scholar 

  15. Berendsen HH, Broekkamp CL, Pinder RM (1998) Mirtazapine enhances the effect of haloperidol on apomorphine-induced climbing behaviour in mice and attenuates haloperidol-induced catalepsy in rats. Psychopharmacology (Berl) 135:284–289

    CAS  CrossRef  Google Scholar 

  16. Berk M, Ichim C, Brook S (2001) 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 16:87–92

    PubMed  CAS  CrossRef  Google Scholar 

  17. Duinkerke SJ, Botter PA, Jansen AA et al (1993) Ritanserin, a selective 5-HT2/1C antagonist, and negative symptoms in schizophrenia. A placebo-controlled double-blind trial. Br J Psychiatry 163:451–455

    PubMed  CAS  CrossRef  Google Scholar 

  18. Aparasu RR, Bhatara V, Gupta S (2005) U.S. national trends in the use of antipsychotics during office visits, 1998–2002. Ann Clin Psychiatry 17:147–152

    PubMed  CrossRef  Google Scholar 

  19. Boast C, Bartolomeo AC, Morris H et al (1999) 5HT antagonists attenuate MK801-impaired radial arm maze performance in rats. Neurobiol Learn Mem 71:259–271

    PubMed  CAS  CrossRef  Google Scholar 

  20. Sumiyoshi T, Matsui M, Nohara S et al (2001) Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment. Am J Psychiatry 158:1722–1725

    PubMed  CAS  CrossRef  Google Scholar 

  21. Sumiyoshi T, Park S, Jayathilake K et al (2007) Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: a randomized, double-blind, placebo-­controlled study. Schizophr Res 95:158–168

    PubMed  CrossRef  Google Scholar 

  22. Pitsikas N, Borsini F (1996) Itasetron (DAU 6215) prevents age-related memory deficits in the rat in a multiple choice avoidance task. Eur J Pharmacol 311:115–119

    PubMed  CAS  CrossRef  Google Scholar 

  23. Zhang ZJ, Kang WH, Li Q et al (2006) Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: a double-blind, randomized, placebo-controlled study. Schizophr Res 88:102–110

    PubMed  CrossRef  Google Scholar 

  24. Wadenberg ML, Wiker C, Svensson TH (2007) Enhanced efficacy of both typical and atypical antipsychotic drugs by adjunctive alpha2 adrenoceptor blockade: experimental evidence. Int J Neuropsychopharmacol 10:191–202

    PubMed  CAS  CrossRef  Google Scholar 

  25. Marcus MM, Wiker C, Frånberg O et al (2010) Adjunctive alpha2-adrenoceptor blockade enhances the antipsychotic-like effect of risperidone and facilitates cortical dopaminergic and glutamatergic, NMDA receptor-mediated transmission. Int J Neuropsychopharmacol 13:891–903

    PubMed  CAS  CrossRef  Google Scholar 

  26. Litman RE, Su TP, Potter WZ et al (1996) Idazoxan and response to typical neuroleptics in treatment-resistant schizophrenia. Comparison with the atypical neuroleptic, clozapine. Br J Psychiatry 168:571–579

    PubMed  CAS  CrossRef  Google Scholar 

  27. Inta D, Meyer-Lindenberg A, Gass P (2011) Alterations in postnatal neurogenesis and dopamine dysregulation in schizophrenia: a hypothesis. Schizophr Bull 37:674–680

    PubMed  CrossRef  Google Scholar 

  28. Jarskog LF, Lieberman JA (2006) Neuroprotection in schizophrenia. J Clin Psychiatry 67:e09

    PubMed  CrossRef  Google Scholar 

  29. Deng MY, McAlonan GM, Cheung C et al (2009) A naturalistic study of grey matter volume increase after early treatment in anti-psychotic naïve, newly diagnosed schizophrenia. Psychopharmacology (Berl) 206:437–446

    CAS  CrossRef  Google Scholar 

  30. Fumagalli F, Frasca A, Racagni G et al (2009) Cognitive effects of second-generation antipsychotics: current insights into neurochemical mechanisms. CNS Drugs 23:603–614

    PubMed  CAS  CrossRef  Google Scholar 

  31. Castrén E, Rantamäki T (2010) The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Dev Neurobiol 70:289–297

    PubMed  CrossRef  CAS  Google Scholar 

  32. Cornblatt BA, Lencz T, Smith CW et al (2007) Can antidepressants be used to treat the schizophrenia prodrome? Results of a prospective, naturalistic treatment study of adolescents. J Clin Psychiatry 68:546–557

    PubMed  CAS  CrossRef  Google Scholar 

  33. Salokangas R, Saarijarvi S, Taiminen T et al (1996) Citalopram as an adjuvant in chronic schizophrenia—a double-blind placebo-controlled study. Acta Psychiatr Scand 94:175–180

    PubMed  CAS  CrossRef  Google Scholar 

  34. Silver H, Barash I, Aharon N et al (2000) Fluvoxamine augmentation of antipsychotics improves negative symptoms in psychotic chronic schizophrenic patients: a placebo-controlled study. Int Clin Psychopharmacol 15:257–261

    PubMed  CAS  CrossRef  Google Scholar 

  35. Kirkpatrick B, Fenton WS, Carpenter WT et al (2006) The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull 32:214–219

    PubMed  CrossRef  Google Scholar 

  36. Erhart SM, Marder SR, Carpenter WT (2006) Treatment of schizophrenia negative symptoms: future prospects. Schizophr Bull 32:234–237

    PubMed  CrossRef  Google Scholar 

  37. Collins AD, Dundas J (1967) A double-blind trial of amitriptyline/perphenazine, perphenazine and placebo in chronic withdrawn inert schizophrenics. Br J Psychiatry 113:1425–1429

    PubMed  CAS  CrossRef  Google Scholar 

  38. Siris SG, Morgan V, Fagerstrom R et al (1987) Adjunctive imipramine in the treatment of postpsychotic depression. A controlled trial. Arch Gen Psychiatry 44:533–539

    PubMed  CAS  CrossRef  Google Scholar 

  39. Silver H, Nassar A (1992) Fluvoxamine improves negative symptoms in treated chronic schizophrenia: an add-on double-blind, placebo-controlled study. Biol Psychiatry 31:698–704

    PubMed  CAS  CrossRef  Google Scholar 

  40. Jockers-Scherubl MC, Bauer A, Godemann F et al (2005) Negative symptoms of schizophrenia are improved by the addition of paroxetine to neuroleptics: a double-blind placebo-controlled study. Int Clin Psychopharmacol 20:27–31

    PubMed  CAS  CrossRef  Google Scholar 

  41. Spina E, De Domenico P, Ruello C et al (1994) Adjunctive fluoxetine in the treatment of negative symptoms in chronic schizophrenic patients. Int Clin Psychopharmacol 9:281–285

    PubMed  CAS  CrossRef  Google Scholar 

  42. Goff DC, Midha KK, Sarid-Segal O (1995) A placebo-controlled trial of fluoxetine added to neuroleptic in patients with schizophrenia. Psychopharmacology (Berl) 117:417–423

    CAS  CrossRef  Google Scholar 

  43. Buchanan RW, Kirkpatrick B, Bryant N et al (1996) Fluoxetine augmentation of clozapine treatment in patients with schizophrenia. Am J Psychiatry 153:1625–1627

    PubMed  CAS  Google Scholar 

  44. Arango C, Kirkpatrick B, Buchanan RW (2000) Fluoxetine as an adjunct to conventional antipsychotic treatment of schizophrenia patients with residual symptoms. J Nerv Ment Dis 188:50–53

    PubMed  CAS  CrossRef  Google Scholar 

  45. Poyurovsky M, Pashinian A, Gil-Ad I et al (2002) Olanzapine-induced weight gain in patients with first-episode schizophrenia: a double-blind, placebo-controlled study of fluoxetine addition. Am J Psychiatry 159:1058–1060

    PubMed  CrossRef  Google Scholar 

  46. Bustillo JR, Lauriello J, Parker K et al (2003) Treatment of weight gain with fluoxetine in olanzapine-treated schizophrenic outpatients. Neuropsychopharmacology 28:527–529

    PubMed  CAS  CrossRef  Google Scholar 

  47. Lee MS, Kim YK, Lee SK et al (1998) A double-blind study of adjunctive sertraline in haloperidol-stabilized patients with chronic schizophrenia. J Clin Psychopharmacol 18:399–403

    PubMed  CAS  CrossRef  Google Scholar 

  48. Mulholland C, Lynch G, King DJ et al (2003) A double-blind, placebo-controlled trial of sertraline for depressive symptoms in patients with stable, chronic schizophrenia. J Psychopharmacol 17:107–112

    PubMed  CAS  CrossRef  Google Scholar 

  49. Friedman JI, Ocampo R, Elbaz Z et al (2005) The effect of citalopram adjunctive treatment added to atypical antipsychotic medications for cognitive performance in patients with schizophrenia. J Clin Psychopharmacol 25:237–242

    PubMed  CAS  CrossRef  Google Scholar 

  50. Schutz G, Berk M (2001) Reboxetine add on therapy to haloperidol in the treatment of schizophrenia: a preliminary double-blind randomized placebo-controlled study. Int Clin Psychopharmacol 16:275–278

    PubMed  CAS  CrossRef  Google Scholar 

  51. Poyurovsky M, Isaacs I, Fuchs C et al (2003) Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study. Am J Psychiatry 160:297–302

    PubMed  CrossRef  Google Scholar 

  52. Zoccali R, Muscatello MR, Cedro C et al (2004) The effect of mirtazapine augmentation of clozapine in the treatment of negative symptoms of schizophrenia: a double-blind, placebo-controlled study. Int Clin Psychopharmacol 19:71–76

    PubMed  CrossRef  Google Scholar 

  53. Joffe G, Terevnikov V, Joffe M et al (2009) Add-on mirtazapine enhances antipsychotic effect of first generation antipsychotics in schizophrenia: a double-blind, randomized, placebo-­controlled trial. Schizophr Res 108:245–251

    PubMed  CrossRef  Google Scholar 

  54. Abbasi SH, Behpournia H, Ghoreshi A et al (2010) The effect of mirtazapine add-on therapy to risperidone in the treatment of schizophrenia: a double-blind randomized placebo-controlled trial. Schizophr Res 116:101–106

    PubMed  CrossRef  Google Scholar 

  55. Singh SP, Singh V, Kar N et al (2010) Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. Br J Psychiatry 197:174–179

    PubMed  CrossRef  Google Scholar 

  56. Berk M, Gama CS, Sundram S et al (2009) Mirtazapine add-on therapy in the treatment of schizophrenia with atypical antipsychotics: a double-blind, randomised, placebo-controlled clinical trial. Hum Psychopharmacol 24:233–238

    PubMed  CAS  CrossRef  Google Scholar 

  57. Decina P, Mukherjee S, Bocola V et al (1994) Adjunctive trazodone in the treatment of negative symptoms of schizophrenia. Hosp Community Psychiatry 45:1220–1223

    PubMed  CAS  Google Scholar 

  58. Hayashi T, Yokota N, Takahashi T et al (1997) Benefits of trazodone and mianserin for patients with late-life chronic schizophrenia and tardive dyskinesia: an add-on, double-blind, placebo-controlled study. Int Clin Psychopharmacol 12:199–205

    PubMed  CAS  CrossRef  Google Scholar 

  59. Shiloh R, Zemishlany Z, Aizenberg D et al (2002) Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia. Int Clin Psychopharmacol 17:59–64

    PubMed  CAS  CrossRef  Google Scholar 

  60. Poyurovsky M, Koren D, Gonopolsky I et al (2003) Effect of the 5-HT2 antagonist mianserin on cognitive dysfunction in chronic schizophrenia patients: an add-on, double-blind placebo-controlled study. Eur Neuropsychopharmacol 13:123–128

    PubMed  CAS  CrossRef  Google Scholar 

  61. Terevnikov V, Stenberg JH, Joffe M et al (2010) More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial. Hum Psychopharmacol 25:431–438

    PubMed  CAS  CrossRef  Google Scholar 

  62. Joffe G, Appelberg B, Rimón R (1999) Adjunctive nefazodone in neuroleptic-treated schizophrenic patients with predominantly negative symptoms: an open prospective pilot study. Int Clin Psychopharmacol 14:233–238

    PubMed  CAS  CrossRef  Google Scholar 

  63. Poyurovsky M, Epshtein S, Fuchs C et al (2003) Efficacy of low-dose mirtazapine in neuroleptic-induced akathisia: a double-blind randomized placebo-controlled pilot study. J Clin Psychopharmacol 23:305–308

    PubMed  CAS  Google Scholar 

  64. An der Heiden W, Könnecke R, Maurer K (2005) Depression in the long-term course of schizophrenia. Eur Arch Psychiatry Clin Neurosci 255:174–184

    PubMed  CrossRef  Google Scholar 

  65. Buckley P, Miller B, Lehrer D et al (2009) Psychiatric comorbidities and schizophrenia. Schizophr Bull 35:383–402

    PubMed  CrossRef  Google Scholar 

  66. Heilä H, Isometsä E, Henriksson M et al (1997) Suicide and schizophrenia: a nationwide psychological autopsy study on age- and sex-specific clinical characteristics of 92 suicide victims with schizophrenia. Am J Psychiatry 154:1235–1242

    PubMed  Google Scholar 

  67. Radomsky E, Haas G, Mann J et al (1999) Suicidal behaviour in patients with schizophrenia and other psychotic disorders. Am J Psychiatry 156:1590–1595

    PubMed  CAS  Google Scholar 

  68. Zisook S, McAdams L, Kuck J et al (1999) Depressive symptoms in schizophrenia. Am J Psychiatry 156:1736–1743

    PubMed  CAS  Google Scholar 

  69. Whitehead C, Moss S, Cardno A, Lewis G (2002) Antidepressants for people with both schizophrenia and depression. Cochrane Database Syst Rev (2):CD002305. doi:10.1002/14651858.CD002305

  70. Tollefson G, Sanger T, Lu Y et al (1998) Depressive signs and symptoms in schizophrenia. A prospective blinded trial of olanzapine and haloperidol. Arch Gen Psychiatry 55:250–258

    PubMed  CAS  CrossRef  Google Scholar 

  71. Moller H (2005) Antidepressive effects of traditional and second generation antipsychotics: a review of the clinical data. Eur Arch Psychiatry Clin Neurosci 255:83–93

    PubMed  CrossRef  Google Scholar 

  72. Furtado V, Srihari V, Kumar A (2008) Atypical antipsychotics for people with both schizophrenia and depression. Cochrane Database Syst Rev CD005377

    Google Scholar 

  73. Leucht S, Heres S, Kissling W et al (2011) Evidence-based pharmacotherapy of schizophrenia. Int J Neuropsychopharmacol 14:269–284

    PubMed  CAS  CrossRef  Google Scholar 

  74. Siris SG, Bermanzohn PC, Gonzalez A et al (1991) The use of antidepressants for negative symptoms in a subset of schizophrenic patients. Psychopharmacol Bull 27:331–335

    PubMed  CAS  Google Scholar 

  75. Zisook S, Kasckow JW, Golshan S et al (2009) Citalopram augmentation for subsyndromal symptoms of depression in middle-aged and older outpatients with schizophrenia and schizoaffective disorder: a randomized controlled trial. J Clin Psychiatry 70:562–571

    PubMed  CAS  CrossRef  Google Scholar 

  76. Terevnikov V, Stenberg JH, Tiihonen J et al (2011) Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase. Hum Psychopharmacol Clin Exp 26:188–193

    CAS  Google Scholar 

  77. Kramer MS, Vogel WH, DiJohnson C et al (1989) Antidepressants in ‘depressed’ schizophrenic inpatients. A controlled trial. Arch Gen Psychiatry 46:922–928

    PubMed  CAS  CrossRef  Google Scholar 

  78. Wynchank D, Berk M (2003) Efficacy of nefazodone in the treatment of neuroleptic-induced extrapyramidal side effects: a double-blind randomised parallel group placebo-controlled trial. Hum Psychopharmacol Clin Exp 18:271–275

    CAS  CrossRef  Google Scholar 

  79. Goff DC, Hill M, Barch D (2011) The treatment of cognitive impairment in schizophrenia. Pharmacol Biochem Behav 99:245–253

    PubMed  CAS  CrossRef  Google Scholar 

  80. Keefe RS, Eesley CE, Poe MP (2005) Defining a cognitive function decrement in schizophrenia. Biol Psychiatry 57:688–691

    PubMed  CrossRef  Google Scholar 

  81. Szöke A, Trandafir A, Dupont ME et al (2008) Longitudinal studies of cognition in schizophrenia: meta-analysis. Br J Psychiatry 192:248–257

    PubMed  CrossRef  Google Scholar 

  82. Harvey PD, Cornblatt BA (2008) Pharmacological treatment of cognition in schizophrenia: an idea whose method has come. Am J Psychiatry 165:163–165

    PubMed  CrossRef  Google Scholar 

  83. Galletly C (2009) Recent advances in treating cognitive impairment. Psychopharmacology (Berl) 202:259–273

    CAS  CrossRef  Google Scholar 

  84. Stenberg JH, Terevnikov V, Joffe M et al (2010) Effects of add-on mirtazapine on neurocognition in schizophrenia: a double-blind, randomized, placebo-controlled study. Int J Neuropsychopharmacol 13:433–441

    PubMed  CAS  CrossRef  Google Scholar 

  85. Stenberg JH, Terevnikov V, Joffe M et al (2011) More evidence on proneurocognitive effects of add-on mirtazapine in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 35:1080–1086

    PubMed  CAS  CrossRef  Google Scholar 

  86. Cho SJ, Yook K, Kim B et al (2011) Mirtazapine augmentation enhances cognitive and reduces negative symptoms in schizophrenia patients treated with risperidone: a randomized controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 35:208–211

    PubMed  CAS  CrossRef  Google Scholar 

  87. Delle Chiaie R, Salviati M, Fiorentini S et al (2007) Add-on mirtazapine enhances effects on cognition in schizophrenic patients under stabilized treatment with clozapine. Exp Clin Psychopharmacol 15:563–568

    PubMed  CAS  CrossRef  Google Scholar 

  88. Poyurovsky M, Faragian S, Fuchs C et al (2009) Effect of the selective norepinephrine reuptake inhibitor reboxetine on cognitive dysfunction in schizophrenia patients: an add-on, double-blind placebo-controlled study. Isr J Psychiatry Relat Sci 46:213–220

    PubMed  Google Scholar 

  89. Tiihonen J, Suokas JT, Suvisaari JM et al (2012) Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia. Arch Gen Psychiatry 69:476–483

    PubMed  CAS  CrossRef  Google Scholar 

  90. Längle G, Steinert T, Weiser P et al (2012) Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment. Acta Psychiatr Scand 125:372–381

    PubMed  CrossRef  CAS  Google Scholar 

  91. Glick ID, Pham D, Davis JM (2006) Concomitant medications may not improve outcome of antipsychotic monotherapy for stabilized patients with non-acute schizophrenia. J Clin Psychiatry 67:1261–1265

    PubMed  CAS  CrossRef  Google Scholar 

  92. Yamada M, Yasuhara H (2004) Clinical pharmacology of MAO inhibitors: safety and future. Neurotoxicology 25:215–221

    PubMed  CAS  CrossRef  Google Scholar 

  93. Chang T, Fava M (2010) The future of psychopharmacology of depression. J Clin Psychiatry 71:971–975

    PubMed  CAS  CrossRef  Google Scholar 

  94. Möller H, Volz HP (1996) Drug treatment of depression in the 1990s. An overview of achievements and future possibilities. Drugs 52(5):625–638

    PubMed  CrossRef  Google Scholar 

  95. Rosenzweig-Lipson S, Beyer CE, Hughes ZA et al (2007) Differentiating antidepressants of the future: efficacy and safety. Pharmacol Ther 113:134–153

    PubMed  CAS  CrossRef  Google Scholar 

  96. Schellander R, Donnerer J (2010) Antidepressants: clinically relevant drug interactions to Be considered. Pharmacology 86:203–215

    PubMed  CAS  CrossRef  Google Scholar 

  97. Caccia S (1998) Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications. Clin Pharmacokinet 34:281–302

    PubMed  CAS  CrossRef  Google Scholar 

  98. Spina E, Santoro V, D’Arrigo C (2008) Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clin Ther 30:1206–1227

    PubMed  CAS  CrossRef  Google Scholar 

  99. Linnet K (1995) Comparison of the kinetic interactions of the neuroleptics perphenazine and zuclopenthixol with tricyclic antidepressives. Ther Drug Monit 17:308–311

    PubMed  CAS  CrossRef  Google Scholar 

  100. DeVane CL (2006) Antidepressant-drug interactions are potentially but rarely clinically significant. Neuropsychopharmacology 31:1594–1604

    PubMed  CAS  CrossRef  Google Scholar 

  101. Preskorn S, Werder S (2006) Detrimental antidepressant drug-drug interactions: Are they clinically relevant? Neuropsychopharmacology 31:1605–1612

    PubMed  CAS  CrossRef  Google Scholar 

  102. Lu ML, Lane HY, Chen KP et al (2000) Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients. J Clin Psychiatry 61:594–599

    PubMed  CAS  CrossRef  Google Scholar 

  103. Albers LJ, Ozdemir V, Marder SR et al (2005) Low-dose fluvoxamine as an adjunct to reduce olanzapine therapeutic dose requirements: a prospective dose-adjusted drug interaction strategy. J Clin Psychopharmacol 25:170–174

    PubMed  CAS  CrossRef  Google Scholar 

  104. Gillman PK (2007) Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol 151:737–748

    PubMed  CAS  CrossRef  Google Scholar 

  105. Bazire S (2009) Psychiatry psychotropic drug directory. Healthcomm UK Ltd., Aberdeen

    Google Scholar 

  106. Leucht S, Corves C, Arbter D et al (2009) Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373(9657):31–41

    PubMed  CAS  CrossRef  Google Scholar 

  107. Newcomer JW (2005) Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19(Suppl 1):81–93

    Google Scholar 

  108. Tatara A, Shimizu S, Shin N et al (2012 Apr 17) Modulation of antipsychotic-induced extrapyramidal side effects by medications for mood disorders. Prog Neuropsychopharmacol Biol Psychiatry [Epub ahead of print]

    Google Scholar 

  109. Gill HS, DeVane CL, Risch SC (1997) Extrapyramidal symptoms associated with cyclic antidepressant treatment: a review of the literature and consolidating hypotheses. J Clin Psychopharmacol 17:377–389

    PubMed  CAS  CrossRef  Google Scholar 

  110. Govoni S, Racchi M, Masoero E et al (2001) Extrapyramidal symptoms and antidepressant drugs: neuropharmacological aspects of a frequent interaction in the elderly. Mol Psychiatry 6:134–142

    PubMed  CAS  CrossRef  Google Scholar 

  111. Thanacoody HK, Thomas SH (2005) Tricyclic antidepressant poisoning: cardiovascular toxicity. Toxicol Rev 24:205–214

    PubMed  CAS  CrossRef  Google Scholar 

  112. Ray WA, Chung CP, Murray KT et al (2009) Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med 360:225–235

    PubMed  CAS  CrossRef  Google Scholar 

  113. Alvarez PA, Pahissa J (2010) QT alterations in psychopharmacology: proven candidates and suspects. Curr Drug Saf 5:97–104

    PubMed  CAS  CrossRef  Google Scholar 

  114. Hajós M, Fleishaker JC, Filipiak-Reisner JK et al (2004) The selective norepinephrine reuptake inhibitor antidepressant reboxetine: pharmacological and clinical profile. CNS Drug Rev 10:23–44

    PubMed  CrossRef  Google Scholar 

  115. Buckley NA, Sanders P (2000) Cardiovascular adverse effects of antipsychotic drugs. Drug Saf 23(3):215–228

    PubMed  CAS  CrossRef  Google Scholar 

  116. Pisani F, Oteri G, Costa C et al (2002) Effects of psychotropic drugs on seizure threshold. Drug Saf 25:91–110

    PubMed  CAS  CrossRef  Google Scholar 

  117. Ross S, Williams D (2005) Bupropion: risks and benefits. Expert Opin Drug Saf 4(6):995–1003

    PubMed  CAS  CrossRef  Google Scholar 

  118. Alldredge BK (1999) Seizure risk associated with psychotropic drugs: clinical and pharmacokinetic considerations. Neurology 53(5 Suppl 2):68–75

    Google Scholar 

Download references

Aknowledgements

The authors thank Jan-Henry Stenberg, PM, for providing the most up-­to-date information on the cognitive impairment in schizophrenia and its treatment.

The authors are also indebted to Kari Raaska, MD, PhD, for comprehensive consultations in the field of pharmacokinetics.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Viacheslav Terevnikov M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Terevnikov, V., Joffe, G. (2013). Antidepressants in Schizophrenia: A Place for Them?. In: Ritsner, M. (eds) Polypharmacy in Psychiatry Practice, Volume I. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5805-6_9

Download citation