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Adjunctive Antidepressant Drug Therapies in the Treatment of Negative Symptoms of Schizophrenia

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Summary

The negative symptoms of schizophrenia comprise one of several identified symptom clusters associated with the disorder. Although consensus on the precise components of the negative syndrome and on definitions for specific negative symptoms have not been reached, for the purpose of this review, negative symptoms include blunted affect, poverty of thought content and speech, apathy, social withdrawal and anergia. Negative symptoms are among the most disabling and treatment-resistant symptoms of schizophrenia, and various approaches to treatment have been taken, including augmentation of conventional antipsychotic treatment with antidepressants.

Assessment of the effect of treatments on negative symptoms can be problematic and, therefore, clinical trials need to be of adequate duration and systematic attempts need to be made to rule out secondary causes of negative symptoms that may mimic or exacerbate them.

Placebo-controlled studies of fluoxetine and fluvoxamine, which controlled for secondary negative symptoms, have demonstrated substantial improvement in negative symptoms compared with placebo. Significant exacerbation in psychotic symptoms was not reported in these controlled trials. This, therefore, represents a promising clinical option for treating negative symptoms.

It appears that the maximum benefit of antidepressant augmentation may not be achieved until at least 12 weeks after initiation of therapy. Therefore, trials of shorter duration may understate the potential efficacy of this combination.

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References

  1. Hwu HG, Tan H, Chen CC, et al. Negative symptoms at discharge and outcome: in schizophrenia. Br J Psychiatry 1995; 188: 61–7

    Google Scholar 

  2. McGlashan TH, Fenton WS. The positive-negative distinction in schizophrenia: review of natural history validators. Arch Gen Psychiatry 1992; 49: 63–71

    PubMed  CAS  Google Scholar 

  3. Fenton WS, McGlashan TH. Antecedents, symptom progression, and long-term outcome of the deficit syndrome in schizophrenia. Am J Psychiatry 1994; 151: 351–6

    PubMed  CAS  Google Scholar 

  4. Andreasen NC, Flaum M, Swayze II VW, et al. Positive and negative symptoms in schizophrenia: a critical reappraisal. Arch Gen Psychiatry 1990; 47: 615–21

    PubMed  CAS  Google Scholar 

  5. Strauss JS, Carpenter WT. The prediction of outcome in schizophrenia. II. Relationships between predictor and outcome variables: a report from the International Pilot Study of Schizophrenia. Arch Gen Psychiatry 1974; 31: 37–42

    PubMed  CAS  Google Scholar 

  6. Jackson JH. Remarks in the evolution and dissolution of the nervous system. J Mental Sci 1904; 33: 25–48

    Google Scholar 

  7. Kraepelin E. Dementia praecox and paraphrenia. Edinburgh: E&S Livingstone. 1919

    Google Scholar 

  8. Bleuler E. Dementia praecox of the group of schizophrenias. New York: International Universities Press. 1950

    Google Scholar 

  9. Kendell RE, Cooper JE, Gourlay AG. Diagnostic criteria of American and British psychiatrists. Arch Gen Psychiatry 1971; 25: 123–30

    PubMed  CAS  Google Scholar 

  10. Andreasen NC, Grove WM, Shapiro RW. Reliability of lifetime diagnosis: a multicenter collaborative perspective. Arch Gen Psychiatry 1981; 38: 400–5

    PubMed  CAS  Google Scholar 

  11. Crow TJ. Positive and negative schizophrenic symptoms and the role of dopamine. Br J Psychiatry 1980; 137: 383–6

    PubMed  CAS  Google Scholar 

  12. Crow TJ. Molecular pathology of schizophrenia: more than one process? BMJ 1980; 12: 66–8

    Google Scholar 

  13. Johnstone EC, Crow TJ, Frith CD. Cerebral ventricle size and cognitive impairment in chronic schizophrenia. Lancet 1976; 2: 924–6

    PubMed  CAS  Google Scholar 

  14. Johnstone E, Crow T, Frith C, et al. Mechanism of the antipsychotic effect on the treatment of acute schizophrenia. Lancet 1978; 1: 848–51

    PubMed  CAS  Google Scholar 

  15. Crow TJ. The two syndrome concept: origins and current status. Schizophr Bull 1985; 11: 471–86

    PubMed  CAS  Google Scholar 

  16. Andreasen NC. Scale for the Assessment of Negative Symptoms (SANS). Iowa City: University of Iowa. 1981

    Google Scholar 

  17. Andreasen NC, Olsen S. Negative v positive schizophrenia: definition and validation. Arch Gen Psychiatry 1982; 39: 789–94

    PubMed  CAS  Google Scholar 

  18. Andreasen NC. Negative symptoms in schizophrenia: definition and reliability. Arch Gen Psychiatry 1982; 39: 784–8

    PubMed  CAS  Google Scholar 

  19. Andreasen N, Olsen SA, Dennert JW. Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms. Am J Psychiatry 1982; 139: 297–302

    PubMed  CAS  Google Scholar 

  20. Andreasen NC, Arndt S, Alliger R, et al. Symptoms of schizophrenia: methods, meanings and mechanisms. Arch Gen Psychiatry 1995; 52: 341–51

    PubMed  CAS  Google Scholar 

  21. Arndt S, Alliger RJ, Andreasen NC. The distinction of positive and negative symptoms: the failure of a two-dimensional model. Br J Psychiatry 1991; 158: 317–22

    PubMed  CAS  Google Scholar 

  22. Arndt S, Andreasen NC, Flaum M, et al. A longitudinal study of symptom dimensions in schizophrenia: prediction and patterns of change. Arch Gen Psychiatry 1995; 52: 352–60

    PubMed  CAS  Google Scholar 

  23. Buchanan RW, Carpenter WT. Domains of psychopathology: an approach to the reduction of heterogeneity in schizophrenia. J Nerv Ment Dis 1994; 182: 193–204

    PubMed  CAS  Google Scholar 

  24. Buchanan RW, Strauss ME, Kirkpatrick B, et al. Neurospsychological impairments in deficit vs nondeficit forms of schizophrenia. Arch Gen Psychiatry 1994; 51: 804–11

    PubMed  CAS  Google Scholar 

  25. Carpenter WT, Heinrichs DW, Alphs LD. Treatment of negative symptoms. Schizophr Bull 1985; 11: 440–52

    PubMed  Google Scholar 

  26. Carpenter Jr WT, Heinrichs DW, Wagman AMI. Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatry 1988; 145: 578–83

    PubMed  Google Scholar 

  27. Johnstone EC, Owens DGC, Firth CD, et al. The relative stability of positive and negative features in chronic schizophrenia. Br J Psychiatry 1986; 150: 60–4

    Google Scholar 

  28. Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res 1987; 23: 99–110

    Google Scholar 

  29. Kay SR, Singh MM. The positive-negative distinction in drug-free schizophrenic patients: stability, response to neuroleptics and prognostic significance. Arch Gen Psychiatry 1989; 46: 711–8

    PubMed  CAS  Google Scholar 

  30. Kibel DA, Laffont I, Liddle PF. The composition of the negative syndrome of chronic schizophrenia. Br J Psychiatry 1993; 162: 744–50

    PubMed  CAS  Google Scholar 

  31. Kirkpatrick B, Buchanan R, McKenney P. The schedule for the deficit syndrome: an instrument for research in schizophrenia. Psychiatry Res 1989; 30: 119–23

    PubMed  CAS  Google Scholar 

  32. Kirkpatrick B, Buchanan RW. The neural basis of the deficit syndrome of schizophrenia. J Nerv Ment Dis 1990; 178: 545–55

    PubMed  CAS  Google Scholar 

  33. Liddle PF. The symptoms of chronic schizophrenia: a re-examination of the positive-negative dichotomy. Br J Psychiatry 1987; 151: 145–51

    PubMed  CAS  Google Scholar 

  34. Miller DD, Arndt SV, Andreasen NC. Alogia attentional impairment and inappropriate affect: their status in the dimensions of schizophrenia. Compr Psychiatry 1993; 34: 221–6

    PubMed  CAS  Google Scholar 

  35. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington. DC: American Psychiatric Association. 1994

    Google Scholar 

  36. Peralta V, de Leon J, Cuesta MJ. Are there more than two syndromes in schizophrenia? A critique of the positive-negative dichotomy. Br J Psychiatry 1992; 161: 335–43

    PubMed  CAS  Google Scholar 

  37. Van der Does AJW, Linszen DH, Dingemans PM, et al. A dimensional and categorical approach to the symptomatology of recent onset schizophrenia. J Nerv Ment Dis 1993; 181: 744–9

    PubMed  Google Scholar 

  38. Keefe RSE, Harvey PD, Lenzenweger MF, et al. Empirical assessment of the factorial structure of clinical symptoms in schizophrenia: negative symptoms. Psychiatry Res 1992; 44: 153–65

    PubMed  CAS  Google Scholar 

  39. Peralta V, Cuesta MJ, de Leon J. An empirical analysis of latent structures underlying schizophrenic symptoms: a four-syndrome model. Biol Psychiatry 1994; 36: 726–36

    PubMed  CAS  Google Scholar 

  40. Johnstone EC, Frith CD, Crow TJ, et al. The Northwick Park ‘functional’ psychosis study: diagnosis and treatment response. Lancet 1988; II(8603): 119–25

    Google Scholar 

  41. Kirkpatrick B, Buchanan RW. Anhedonia and the deficit syndrome of schizophrenia. Psychiatry Res 1988; 31: 25–30

    Google Scholar 

  42. Moller H. The negative component in schizophrenia. Acta Psychiatr Scand 1995; 91: 11–4

    Google Scholar 

  43. Sommers A. ‘Negative symptoms’: conceptual and methodological problems. Schizophr Bull 1985; 11: 364–79

    PubMed  CAS  Google Scholar 

  44. Overall JE, Gorham DR. The brief psychiatric rating scale (BPRS). Psychol Rep 1962; 10: 799–812

    Google Scholar 

  45. Alphs LD, Summerfelt A, Lann H, et al. The negative symptom assessment: a new instrument to assess negative symptoms of schizophrenia. Psychopharmacol Bull 1989; 25: 159–63

    PubMed  CAS  Google Scholar 

  46. Iager A, Kirsch D, Wyatt R. A negative symptom rating scale. Psychiatry Res 1986; 16: 27–36

    Google Scholar 

  47. Czobor P, Bitter I, Volavka J. Relationship between the Brief Psychiatric Rating Scale and the Scale for Assessment of Negative Symptoms: a study of their correlation and redundancy. Psychiatry Res 1990; 36: 129–39

    Google Scholar 

  48. Thiemann S, Csernansky J, Berger P. Rating scales in research: the case of negative symptoms. Psychiatry Res 1987; 20: 47–55

    PubMed  CAS  Google Scholar 

  49. Fenton WS, McGlashman TH. Testing systems for assessment of negative symptoms in schizophrenia. Arch Gen Psychiatry 1992; 49: 179–84

    PubMed  CAS  Google Scholar 

  50. Brown KW, White T. The association among negative symptoms, movement disorders, and frontal lobe psychological deficits in schizophrenic patients. Biol Psychiatry 1991; 30: 1182–90

    PubMed  CAS  Google Scholar 

  51. Mortimer AM, Lund CE, McKenna PJ. The positive:negative dichotomy in schizophrenia. Br J Psychiatry 1990; 157: 41–9

    PubMed  CAS  Google Scholar 

  52. Moller HJ, van Praag HM, Aufdembrinke B, et al. Negative symptoms in schizophrenia: considerations for clinical trials. Working group on negative symptoms in schizophrenia. Psychopharmacology 1994; 115: 221–8

    PubMed  CAS  Google Scholar 

  53. Siris S. Diagnosis of secondary depression in schizophrenia: implications for DSM-IV. Schizophrenia Bull 1991; 17: 75–97

    CAS  Google Scholar 

  54. Van Putten T, May PRA. ‘Akinetic depression’ in schizophrenia. Arch Gen Psychiatry 1978; 35: 1101–7

    PubMed  Google Scholar 

  55. Marder SR, Van Putten T, Mintz J, et al. Costs and benefits of two doses of fluphenazine. Arch Gen Psychiatry 1984; 41: 1025–9

    PubMed  CAS  Google Scholar 

  56. Kane JM, Woerner M, Sarantakos S. Depot neuroleptics: a comparative review of standard, intermediate, and low dose regimen. J Clin Psychiatry 1986; 47 Suppl. 5: S30–3

    Google Scholar 

  57. Harvey PD, Putnam KM, Davidson M, et al. Brief neuroleptic discontinuation and clinical symptoms in Kraepelinian and non-Kraepelinian chronic schizophrenic patients. Psychiatry Res 1991; 38: 285–92

    PubMed  CAS  Google Scholar 

  58. Miller DD, Flaum M, Arndt S, et al. Effect of antipsychotic withdrawal on negative symptoms in schizophrenia. Neuropsychopharmacology 1994; 11: 11–20

    PubMed  CAS  Google Scholar 

  59. Kuck J, Zisook S, Moranville JT, et al. Negative symptomatology in schizophrenic outpatients. J Nerv Ment Dis 1992; 180: 510–5

    PubMed  CAS  Google Scholar 

  60. Kulhara P, Avasthi A, Chadda R, et al. Negative and depressive symptoms in schizophrenia. Br J Psychiatry 1989; 154: 207–11

    PubMed  CAS  Google Scholar 

  61. Pogue-Geile MF, Harrow M. Negative and positive symptoms in schizophrenia and depression: a follow-up. Schizophrenia Bull 1984; 10: 371–87

    CAS  Google Scholar 

  62. Siris S, Adan F, Cohen M, et al. Postpsychotic depression and negative symptoms: an investigation of syndromal overlap. Am J Psychiatry 1988; 12: 1532–7

    Google Scholar 

  63. Newcomer JW, Faustman WO, Yeh W, et al. Distinguishing depression and negative symptoms in unmedicated patients with schizophrenia. Psychiatry Res 1989; 31: 243–50

    Google Scholar 

  64. Kramer M, Vogel W, DiJohnson C, et al. Antidepressants in ‘depressed’ schizophrenic inpatients: a controlled trial. Arch Gen Psychiatry 1989; 46: 922–8

    PubMed  CAS  Google Scholar 

  65. Prusoff VA, Williams DH, Weissman MM, et al. Treatment of secondary depression in schizophrenia. Arch Gen Psychiatry 1979; 36: 569–75

    PubMed  CAS  Google Scholar 

  66. Plasky P. Antidepressant usage in schizophrenia. Schizophr Bull 1991; 17: 649–57

    PubMed  CAS  Google Scholar 

  67. Hogarty GE, McEvoy JP, Ulrich RF, et al. Pharmacotherapy of impaired affect in recovering schizophrenic patients. Arch Gen Psychiatry 1995; 52: 29–41

    PubMed  CAS  Google Scholar 

  68. Siris SG, Rifkin AE, Reardon GT. Response of postpsychotic depression to adjunctive imipramine or amitriptyline. J Clin Psychiatry 1982; 43: 485–6

    PubMed  CAS  Google Scholar 

  69. Siris SG, Adan F, Cohen M, et al. Targeted treatment of depression-like symptoms in schizophrenia. Psychopharmacol Bull 1987; 23: 85–9

    PubMed  CAS  Google Scholar 

  70. Siris SG, Morgan V, Fagerstrom R, et al. Adjunctive imipramine in the treatment of postpsychotic depression. Arch Gen Psychiatry 1987; 44: 533–9

    PubMed  CAS  Google Scholar 

  71. Siris SG, Mason SE, Bermanzohn PC, et al. Adjunctive imipramine maintenance in post-psychotic depression/negative symptoms. Psychopharmacol Bull 1990; 26: 91–4

    PubMed  CAS  Google Scholar 

  72. Siris SG, Bermanzohn PC, Gonzalez A, et al. The use of antidepressants for negative symptoms in a subset of schizophrenic patients. Psychopharmacol Bull 1991; 27: 331–5

    PubMed  CAS  Google Scholar 

  73. Siris S, Bermazohn P, Mason S, et al. Maintenance imipramine therapy for secondary depression in schizophrenia. Arch Gen Psychiatry 1994; 51: 109–15

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  75. Spina E, De Domenico P, Ruello C, et al. Adjunctive fluoxetine in the treatment of negative symptoms in chronic schizophrenic patients. Int Clin Psychopharmacol 1994; 9: 281–5

    PubMed  CAS  Google Scholar 

  76. Goff D, Midha K, Sarid-Segal O, et al. A placebo-controlled trial of fluoxetine added to neuroleptic in patients with schizophrenia. Psychopharmacology 1995; 117: 417–23

    PubMed  CAS  Google Scholar 

  77. Bucci L. The negative symptoms of schizophrenia and the monoamine oxidase inhibitors. Psychopharmacology 1987; 91: 104–8

    PubMed  CAS  Google Scholar 

  78. Goff D, Renshaw P, Sarid-Segal O, et al. A placebo-controlled trial of 1-deprenyl for tardive dyskinesia. Biol Psychiatry 1993; 33: 700–6

    PubMed  CAS  Google Scholar 

  79. Collins A, Dundas I. A double-blind trial of amitriptyline/perphenazine, perphenazine and placebo in chronic withdrawn inert schizophrenics. Br J Psychiatry 1967; 113: 1425–9

    PubMed  CAS  Google Scholar 

  80. Decina P, Mukherjee S, Bocola V, et al. Adjunctive trazodone in the treatment of negative symptoms of schizophrenia. Hosp Community Psychiatry 1994; 45: 1220–3

    PubMed  CAS  Google Scholar 

  81. Waehrens J, Gerlach J. Antidepressant drugs in anergic schizophrenia. Acta Psychiatr Scand 1980; 61: 438–44

    PubMed  CAS  Google Scholar 

  82. Goff DC, Brotman AW, Waites M, et al. Trial of fluoxetine added to neuroleptics for treatment-resistant schizophrenic patients. Am J Psychiatry 1990; 147: 492–4

    PubMed  CAS  Google Scholar 

  83. Goldman MB, Janecek HM. Adjunctive fluoxetine improves global function in chronic schizophrenia. J Neuropsychiatry Clin Neurosci 1990; 2: 429–31

    PubMed  CAS  Google Scholar 

  84. Silver H, Kaplan A, Kushnir M. Fluvoxamine augmentation in chronic schizophrenia: an open exploratory study. Hum Psychopharmacol 1995; 10: 59–63

    Google Scholar 

  85. Perenyi A, Goswami U, Frecska E, et al. L-Deprenyl in treating negative symptoms of schizophrenia [letter]. Psychiatry Res 1992; 42: 189–91

    PubMed  CAS  Google Scholar 

  86. Yamagami S, Soejima K. Effect of maprotiline combined with conventional neuroleptics against negative symptoms of chronic schizophrenia. Drugs Exp Clin Res 1989; 4: 171–6

    Google Scholar 

  87. Mizuki Y, Kajimura N, Kai S, et al. Effects of mianserin in chronic schizophrenia. Prog Neuropsych Bioi Psychiatry 1992; 16: 517–28

    CAS  Google Scholar 

  88. Kuniyoshi M, Nakamura J, Miura C, et al. Effectiveness of concomitant setiptiline maleate (TecipulR) on negative symptoms of schizophrenia. Prog Neuropsych Biol Psychiatry 1994; 18: 339–46

    CAS  Google Scholar 

  89. Goff D, Midha K, Brotman A, et al. Elevation of plasma concentrations of haloperidol after addition of fluoxetine. Am J Psychiatry 1991; 148: 790–2

    PubMed  CAS  Google Scholar 

  90. Goff D, Baldessarini R. Drug interactions with antipsychotic agents. J Clin Psychopharmacol 1993; 13: 57–67

    PubMed  CAS  Google Scholar 

  91. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed., rev. Washington, DC: American Psychiatric Association, 1987

    Google Scholar 

  92. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions. I. Antidepressants and antipsychotics. J Clin Psychopharmacol 1990; 10: 48–50

    PubMed  CAS  Google Scholar 

  93. Goff D, Baldessarini R. Antipsychotics. In: Ciraulo D, Shader R, Greenblatt D, et al. editors. Drug interactions in psychiatry. Baltimore: Williams & Wilkins. 1995: 129–74

    Google Scholar 

  94. Knoll J. Deprenyl (selegiline): the history of its development and pharmacological action. Acta Neurol Scand 1983; Suppl. 95: 57–94

    Google Scholar 

  95. Venables P. A short scale for rating ‘activity-withdrawal’ in schizophrenics. J Ment Sci 1957; 103: 197–9

    PubMed  CAS  Google Scholar 

  96. Itoh H. Clinical study on the psychotropic affects of caerulein: an open clinical trial in chronic schizophrenic patients. Keio J Med 1982; 31: 71

    PubMed  CAS  Google Scholar 

  97. Heykants J. The pharmacokinetics of risperidone in humans: a summary. J Clin Psychiatry 1994; 55 Suppl.: 13–7

    PubMed  Google Scholar 

  98. Pollock B, Mulsant B, Sweet R. Prospective cytochrome phenotyping for neuroleptic treatment in dementia. Psychopharmacol Bull 1995; 31: 327–31

    PubMed  CAS  Google Scholar 

  99. Spina E, Martines C, Caputi A. Debrisoquine oxidation phenotype during neuroleptic monotherapy. Eur J Clin Pharmacal 1991; 41: 467–70

    CAS  Google Scholar 

  100. Byerly M, DeVane L. Pharmacokinetics of clozapine and risperidone: a review of the literature. J Clin Psychopharmacol 1996; 16: 177–87

    PubMed  CAS  Google Scholar 

  101. Fischer V, Vogels B, Maurer G, et al. The antipsychotic clozapine is metabolized by the polymorphic human microsomal and recombinant cytochrome P450 2D6. J Pharmacol Exp Ther 1992; 260 (3): 1355–60

    PubMed  CAS  Google Scholar 

  102. Fonne-Pfister R, Meyer UA. Xenobiotic and endobiotic inhibitors of cytochrome P-4SOdbl function, the target of the debrisoquine/sparteine type polymorphism. Biochem Biophys Pharmacol 1988; 37: 3829–35

    CAS  Google Scholar 

  103. Jerling M. The use of therapeutic drug monitoring data to document kinetic drug interactions: an example with amitriptyline and nortriptyline. Ther Drug Mon 1994; 16: 1–12

    CAS  Google Scholar 

  104. Crewe HK, Lennard MS, Tucker GT, et al. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 activity in human liver. Br J Clin Pharmacol 1992; 34: 262–5

    PubMed  CAS  Google Scholar 

  105. von Moltke LL, Greenblatt DJ, Court MH, et al. Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. J Clin Psychopharmacol 1995; 15: 125–32

    Google Scholar 

  106. Brosen K, Skjelbo E, Rasmussen B, et al. Fluvoumine is a potent inhibitor of cytochrome P4501A2. Biochem Pharmacol 1993; 46: 1211–4

    Google Scholar 

  107. Gram LF, Overo KF. Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. BMJ 1972; 1: 463–5

    PubMed  CAS  Google Scholar 

  108. Gram LF, Overo K, Kirk L. Influence of neuroleptics and benzodiazepines on metabolism of tricyclic antidepressants in man. Am J Psychiatry 1974; 1: 11: 863–6

    Google Scholar 

  109. Brosen K, Gram LF. Clinical significance of the sparteine/debrisoquine oxidation polymorphism. Eur J Clin Pharmacol 1989; 36: 5: 17–47

    Google Scholar 

  110. Nelson JC, Jatlow PI. Neuroleptic effect on desipramine steady-state plasma concentrations. Am J Psychiatry 1980; 137: 1232–4

    PubMed  CAS  Google Scholar 

  111. Bock JL, Nelson JC, Gray S, et al. Desipramine hydroxylation: variability and effect of antipsychotic drugs. Clin Pharmacol Ther 1983; 33: 322–8

    PubMed  CAS  Google Scholar 

  112. Siris SG, Cooper TB, Rifkin AE, et al. Plasma imipramine concentrations in patients receiving concomitant fluphenazine decanoate. Am J Psychiatry 1982; 1: 19: 104–6

    Google Scholar 

  113. Loga S, Curry C, Lader M. Interaction of chlorpromazine and nortriptyline in patients with schizophrenia. Clin Pharmacokinet 1981; 6: 454–62

    PubMed  CAS  Google Scholar 

  114. El-Yousef MK, Manier DH. Tricyclic antidepressants and phenothiazines [letter]. JAMA 1974; 229: 1419

    PubMed  CAS  Google Scholar 

  115. Centorrino F, Baldessarini RJ, Kando J, et al. Serum concentrations of clozapine and its major metabolites: effects of cotreatment with fluoxetine or valproate. Am J Psychiatry 1994; 151: 123–5

    PubMed  CAS  Google Scholar 

  116. Lipinski JF, Mallya G, Zimmerman P, et al. Fluoxetine-induced akathisia: clinical and theoretical implications. J Clin Psychiatry 1989; 50: 339–42

    PubMed  Google Scholar 

  117. Balsara JJ, Jadhav JH, Muley MP, et al. Effect of drugs influencing central serotonergic mechanisms on methamphetamine- induced stereotyped behavior in the rat. Psychopharmacology 1979; 64: 303–7

    PubMed  CAS  Google Scholar 

  118. Korsgaard S, Gerlach J, Christensson E. Behavioral aspects of serotonin-dopamine interaction in the monkey. Eur J Pharmacol 1985; 118: 245–52

    PubMed  CAS  Google Scholar 

  119. Kane JM. Risperidone. Am J Psychiatry 1994; 151: 802–3

    PubMed  CAS  Google Scholar 

  120. Kane JM, Mayerhnff D. Do negative symptoms respond to pharmacological treatment? Br J Psychiatry 1989; 155 Suppl. 7: 115–8

    Google Scholar 

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    A. Eden Evins & Donald C. Goff

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Evins, A.E., Goff, D.C. Adjunctive Antidepressant Drug Therapies in the Treatment of Negative Symptoms of Schizophrenia. CNS Drugs 6, 130–147 (1996). https://doi.org/10.2165/00023210-199606020-00005

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