1,070
Views
24
CrossRef citations to date
0
Altmetric
Review

Drug repurposing and emerging adjunctive treatments for schizophrenia

, MD, , MD & , MD

Bibliography

  • Tandon R, Gaebel W, Barch DM, et al. Definition and description of schizophrenia in the DSM-5. Schizophr Res 2013;150(1):3-10
  • Collins PY, Patel V, Joestl SS, et al. Grand challenges in global mental health. Nature 2011;475(7354):27-30
  • Robinson DG, Woerner MG, McMeniman M, et al. Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry 2004;161(3):473-9
  • Harrison G, Hopper K, Craig T, et al. Recovery from psychotic illness: a 15- and 25-year international follow-up study. Br J Psychiatry 2001;178:506-17
  • Miyamoto S, Miyake N, Jarskog LF, et al. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Mol Psychiatry 2012;17(12):1206-27
  • Seeman P. Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. Neuropsychopharmacology 1992;7(4):261-84
  • Sommer IE, van Westrhenen R, Begemann MJ, et al. Efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia: an update. Schizophr Bull 2014;40(1):181-91
  • Torrey EF, Davis JM. Adjunct treatments for schizophrenia and bipolar disorder: what to try when you are out of ideas. Clin Schizophr Relat Psychoses 2012;5(4):208-16
  • Bumb JM, Enning F, Leweke FM. Repurposed drugs for the treatment of schizophrenia and bipolar disorders. Curr Top Med Chem 2013;13(18):2364-85
  • Tuominen HJ, Tiihonen J, Wahlbeck K. Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev 2006(2):CD003730
  • Krystal JH, Karper LP, Seibyl JP, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994;51(3):199-214
  • Deutsch SI, Schwartz BL, Schooler NR, et al. Targeting alpha-7 nicotinic neurotransmission in schizophrenia: a novel agonist strategy. Schizophr Res 2013;148(1-3):138-44
  • Begemann MJ, Dekker CF, van Lunenburg M, et al. Estrogen augmentation in schizophrenia: a quantitative review of current evidence. Schizophr Res 2012;141(2-3):179-84
  • Hafner H. Gender differences in schizophrenia. Psychoneuroendocrinology 2003;28(Suppl 2):17-54
  • Leweke FM, Schneider U, Thies M, et al. Effects of synthetic delta9-tetrahydrocannabinol on binocular depth inversion of natural and artificial objects in man. Psychopharmacology (Berl) 1999;142(3):230-5
  • Seillier A, Advani T, Cassano T, et al. Inhibition of fatty-acid amide hydrolase and CB1 receptor antagonism differentially affect behavioural responses in normal and PCP-treated rats. Int J Neuropsychopharmacol 2010;13(3):373-86
  • Adams CE, Awad GA, Rathbone J, et al. Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev 2014;1:CD000284
  • Tardy M, Huhn M, Engel RR, et al. Perphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2014;10:CD009369
  • Correll CU, Leucht S, Kane JM. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. Am J Psychiatry 2004;161(3):414-25
  • Heres S, Davis J, Maino K, et al. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. Am J Psychiatry 2006;163(2):185-94
  • Kane JM, Correll CU. Past and present progress in the pharmacologic treatment of schizophrenia. J Clin Psychiatry 2010;71(9):1115-24
  • Leucht S, Komossa K, Rummel-Kluge C, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry 2009;166(2):152-63
  • Mailman RB, Murthy V. Third generation antipsychotic drugs: partial agonism or receptor functional selectivity? Curr Pharm Des 2010;16(5):488-501
  • Leweke FM, Odorfer TM, Bumb JM. Medical needs in the treatment of psychotic disorders. Handb Exp Pharmacol 2012(212):165-85
  • Correll CU, Robinson DG, Schooler NR, et al. Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study. JAMA Psychiatry 2014;71(12):1350-63
  • Leung JY, Barr AM, Procyshyn RM, et al. Cardiovascular side-effects of antipsychotic drugs: the role of the autonomic nervous system. Pharmacol Ther 2012;135(2):113-22
  • Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013;382(9896):951-62
  • Meyer-Lindenberg A. From maps to mechanisms through neuroimaging of schizophrenia. Nature 2010;468(7321):194-202
  • Laan W, Grobbee DE, Selten JP, et al. Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2010;71(5):520-7
  • Weiser M, Burshtein S, Fodoreanu L, et al. A randomized trial administering aspirin, minocycline or pramipexole vs placebo as add-on to antipsychotics in patients with schizophrenia or schizoaffective disorder [abstract]. Neuropsychopharmacology 2012;28:314-446
  • Nitta M, Kishimoto T, Muller N, et al. Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia: a meta-analytic investigation of randomized controlled trials. Schizophr Bull 2013;39(6):1230-41
  • Akhondzadeh S, Tabatabaee M, Amini H, et al. Celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and placebo-controlled trial. Schizophr Res 2007;90(1-3):179-85
  • Muller N, Krause D, Dehning S, et al. Celecoxib treatment in an early stage of schizophrenia: results of a randomized, double-blind, placebo-controlled trial of celecoxib augmentation of amisulpride treatment. Schizophr Res 2010;121(1-3):118-24
  • Muller N, Riedel M, Scheppach C, et al. Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am J Psychiatry 2002;159(6):1029-34
  • Rapaport MH, Delrahim KK, Bresee CJ, et al. Celecoxib augmentation of continuously ill patients with schizophrenia. Biol Psychiatry 2005;57(12):1594-6
  • Rappard F, Muller N. Celecoxib add-on does not have beneficial antipsychotic effects over risperidone alone in schizophrenia [abstract]. Neuropsychopharmacology 2004;29:183-241
  • Berk M, Copolov D, Dean O, et al. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry 2008;64(5):361-8
  • Bulut M, Savas HA, Altindag A, et al. Beneficial effects of N-acetylcysteine in treatment resistant schizophrenia. World J Biol Psychiatry 2009;10(4 Pt 2):626-8
  • Farokhnia M, Azarkolah A, Adinehfar F, et al. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol 2013;36(6):185-92
  • Chaudhry IB, Hallak J, Husain N, et al. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol 2012;26(9):1185-93
  • Levkovitz Y, Mendlovich S, Riwkes S, et al. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry 2010;71(2):138-49
  • Liu F, Guo X, Wu R, et al. Minocycline supplementation for treatment of negative symptoms in early-phase schizophrenia: a double blind, randomized, controlled trial. Schizophr Res 2014;153(1-3):169-76
  • Khodaie-Ardakani MR, Mirshafiee O, Farokhnia M, et al. Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study. Psychiatry Res 2014;215(3):540-6
  • Kulkarni J, Riedel A, de Castella AR, et al. Estrogen - a potential treatment for schizophrenia. Schizophr Res 2001;48(1):137-44
  • Akhondzadeh S, Nejatisafa AA, Amini H, et al. Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 2003;27(6):1007-12
  • Louza MR, Marques AP, Elkis H, et al. Conjugated estrogens as adjuvant therapy in the treatment of acute schizophrenia: a double-blind study. Schizophr Res 2004;66(2-3):97-100
  • Kulkarni J, de Castella A, Fitzgerald PB, et al. Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry 2008;65(8):955-60
  • Kulkarni J, de Castella A, Headey B, et al. Estrogens and men with schizophrenia: is there a case for adjunctive therapy? Schizophr Res 2011;125(2-3):278-83
  • Ghafari E, Fararouie M, Shirazi HG, et al. Combination of estrogen and antipsychotics in the treatment of women with chronic schizophrenia: a double-blind, randomized, placebo-controlled clinical trial. Clin Schizophr Relat Psychoses 2013;6(4):172-6
  • Kulkarni J, Gavrilidis E, Wang W, et al. Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age. Mol Psychiatry 2014. [Epub ahead of print]
  • Bergemann N, Mundt C, Parzer P, et al. Estrogen as an adjuvant therapy to antipsychotics does not prevent relapse in women suffering from schizophrenia: results of a placebo-controlled double-blind study. Schizophr Res 2005;74(2-3):125-34
  • Kulkarni J, Gurvich C, Lee SJ, et al. Piloting the effective therapeutic dose of adjunctive selective estrogen receptor modulator treatment in postmenopausal women with schizophrenia. Psychoneuroendocrinology 2010;35(8):1142-7
  • Usall J, Huerta-Ramos E, Iniesta R, et al. Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry 2011;72(11):1552-7
  • Kianimehr G, Fatehi F, Hashempoor S, et al. Raloxifene adjunctive therapy for postmenopausal women suffering from chronic schizophrenia: a randomized double-blind and placebo controlled trial. Daru 2014;22:55
  • Huerta-Ramos E, Iniesta R, Ochoa S, et al. Effects of raloxifene on cognition in postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. Eur Neuropsychopharmacol 2014;24(2):223-31
  • Meyer-Lindenberg A, Domes G, Kirsch P, et al. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci 2011;12(9):524-38
  • Feifel D, Macdonald K, Nguyen A, et al. Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biol Psychiatry 2010;68(7):678-80
  • Pedersen CA, Gibson CM, Rau SW, et al. Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia. Schizophr Res 2011;132(1):50-3
  • Modabbernia A, Rezaei F, Salehi B, et al. Intranasal oxytocin as an adjunct to risperidone in patients with schizophrenia: an 8-week, randomized, double-blind, placebo-controlled study. CNS Drugs 2013;27(1):57-65
  • Lee MR, Wehring HJ, McMahon RP, et al. Effects of adjunctive intranasal oxytocin on olfactory identification and clinical symptoms in schizophrenia: results from a randomized double blind placebo controlled pilot study. Schizophr Res 2013;145(1-3):110-15
  • Cacciotti-Saija C, Langdon R, Ward PB, et al. A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis. Schizophr Bull 2015;41(2):483-93
  • Gibson CM, Penn DL, Smedley KL, et al. A pilot six-week randomized controlled trial of oxytocin on social cognition and social skills in schizophrenia. Schizophr Res 2014;156(2-3):261-5
  • Buchanan RW, Javitt DC, Marder SR, et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry 2007;164(10):1593-602
  • Heresco-Levy U, Javitt DC. Comparative effects of glycine and D-cycloserine on persistent negative symptoms in schizophrenia: a retrospective analysis. Schizophr Res 2004;66(2-3):89-96
  • Heresco-Levy U, Javitt DC, Ermilov M, et al. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry 1999;56(1):29-36
  • Heresco-Levy U, Javitt DC, Ermilov M, et al. Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Br J Psychiatry 1996;169(5):610-17
  • Evins AE, Fitzgerald SM, Wine L, et al. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry 2000;157(5):826-8
  • Tsai G, Yang P, Chung LC, et al. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 1998;44(11):1081-9
  • Heresco-Levy U, Javitt DC, Ebstein R, et al. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry 2005;57(6):577-85
  • Kantrowitz JT, Malhotra AK, Cornblatt B, et al. High dose D-serine in the treatment of schizophrenia. Schizophr Res 2010;121(1-3):125-30
  • Weiser M, Heresco-Levy U, Davidson M, et al. A multicenter, add-on randomized controlled trial of low-dose d-serine for negative and cognitive symptoms of schizophrenia. J Clin Psychiatry 2012;73(6):e728-34
  • Goff DC, Cather C, Gottlieb JD, et al. Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study. Schizophr Res 2008;106(2-3):320-7
  • Goff DC, Herz L, Posever T, et al. A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients. Psychopharmacology (Berl) 2005;179(1):144-50
  • Goff DC, Henderson DC, Evins AE, et al. A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia. Biol Psychiatry 1999;45(4):512-14
  • Goff DC, Tsai G, Levitt J, et al. A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry 1999;56(1):21-7
  • Goff DC, Tsai G, Manoach DS, et al. Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia. Am J Psychiatry 1995;152(8):1213-15
  • Evins AE, Amico E, Posever TA, et al. D-Cycloserine added to risperidone in patients with primary negative symptoms of schizophrenia. Schizophr Res 2002;56(1-2):19-23
  • Heresco-Levy U, Ermilov M, Shimoni J, et al. Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine, or risperidone in schizophrenia. Am J Psychiatry 2002;159(3):480-2
  • Goff DC, Leahy L, Berman I, et al. A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. J Clin Psychopharmacol 2001;21(5):484-7
  • Goff DC, Lamberti JS, Leon AC, et al. A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology 2008;33(3):465-72
  • Tsai G, Lane HY, Yang P, et al. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 2004;55(5):452-6
  • Lane HY, Chang YC, Liu YC, et al. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry 2005;62(11):1196-204
  • Lane HY, Lin CH, Huang YJ, et al. A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophrenia. Int J Neuropsychopharmacol 2010;13(4):451-60
  • Lane HY, Huang CL, Wu PL, et al. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia. Biol Psychiatry 2006;60(6):645-9
  • Sreekumar A, Poisson LM, Rajendiran TM, et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 2009;457(7231):910-14
  • Umbricht D, Alberati D, Martin-Facklam M, et al. Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study. JAMA Psychiatry 2014;71(6):637-46
  • Brauser D. Bitopertin disappoints as schizophrenia treatment. Medscape Medical News-Psychiatry. 2014. Available from: http://www.medscape.com/viewarticle/826805 - vp_2 [Cited 15 November 2014]
  • Singh SP, Singh V. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs 2011;25(10):859-85
  • Tuominen HJ, Tiihonen J, Wahlbeck K. Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis. Schizophr Res 2005;72(2-3):225-34
  • Veerman SR, Schulte PF, de Haan L. The glutamate hypothesis: a pathogenic pathway from which pharmacological interventions have emerged. Pharmacopsychiatry 2014;47(4-5):121-30
  • Homayoun H, Moghaddam B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 2007;27(43):11496-500
  • Patil ST, Zhang L, Martenyi F, et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med 2007;13(9):1102-7
  • Kinon BJ, Zhang L, Millen BA, et al. A multicenter, inpatient, phase 2, double-blind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia. J Clin Psychopharmacol 2011;31(3):349-55
  • Adams DH, Kinon BJ, Baygani S, et al. A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia. BMC Psychiatry 2013;13:143
  • Adams DH, Zhang L, Millen BA, et al. Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: a Phase 3, Multicenter, Double-Blind Comparison. Schizophr Res Treatment 2014;2014:758212
  • Kinon B, Millen BA, Downing L, et al. LY, 2140023 monohydrate in the treatment of patients with schizophrenia: results of 2 clinical trials assessing effi cacy in treating acutely ill and those with prominent negative symptoms. 14th International Congress on Schizophrenia Research; Schizophrenia Bull 2013; p. 1-358
  • Sommer IE, Begemann MJ, Temmerman A, et al. Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. Schizophr Bull 2012;38(5):1003-11
  • Tiihonen J, Wahlbeck K, Kiviniemi V. The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophr Res 2009;109(1-3):10-14
  • Davidson M. Nicotine receptor agonist(s) (nAChR) in schizophrenia-A new way forward to treat schizophrenia or backing up the wrong tree again? ECNP 2014;Berlin; 2014
  • Roh S, Hoeppner SS, Schoenfeld D, et al. Acute effects of mecamylamine and varenicline on cognitive performance in non-smokers with and without schizophrenia. Psychopharmacology (Berl) 2014;231(4):765-75
  • Shim JC, Jung DU, Jung SS, et al. Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo-controlled trial. Neuropsychopharmacology 2012;37(3):660-8
  • Smith RC, Lindenmayer JP, Davis JM, et al. Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder. Schizophr Res 2009;110(1-3):149-55
  • Williams JM, Anthenelli RM, Morris CD, et al. A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry 2012;73(5):654-60
  • Evins AE, Cather C, Pratt SA, et al. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA 2014;311(2):145-54
  • Pachas GN, Cather C, Pratt SA, et al. Varenicline for smoking cessation in schizophrenia: safety and effectiveness in a 12-week, open-label trial. J Dual Diagn 2012;8(2):117-25
  • Lindenmayer JP, Khan A. Galantamine augmentation of long-acting injectable risperidone for cognitive impairments in chronic schizophrenia. Schizophr Res 2011;125(2-3):267-77
  • Sacco KA, Creeden C, Reutenauer EL, et al. Effects of galantamine on cognitive deficits in smokers and non-smokers with schizophrenia. Schizophr Res 2008;103(1-3):326-7
  • Dyer MA, Freudenreich O, Culhane MA, et al. High-dose galantamine augmentation inferior to placebo on attention, inhibitory control and working memory performance in nonsmokers with schizophrenia. Schizophr Res 2008;102(1-3):88-95
  • Buchanan RW, Conley RR, Dickinson D, et al. Galantamine for the treatment of cognitive impairments in people with schizophrenia. Am J Psychiatry 2008;165(1):82-9
  • Lee SW, Lee JG, Lee BJ, et al. A 12-week, double-blind, placebo-controlled trial of galantamine adjunctive treatment to conventional antipsychotics for the cognitive impairments in chronic schizophrenia. Int Clin Psychopharmacol 2007;22(2):63-8
  • Deutsch SI, Schwartz BL, Schooler NR, et al. First administration of cytidine diphosphocholine and galantamine in schizophrenia: a sustained alpha7 nicotinic agonist strategy. Clin Neuropharmacol 2008;31(1):34-9
  • Schubert MH, Young KA, Hicks PB. Galantamine improves cognition in schizophrenic patients stabilized on risperidone. Biol Psychiatry 2006;60(6):530-3
  • Sacco KA, Termine A, Dudas MM, et al. Neuropsychological deficits in nonsmokers with schizophrenia: effects of a nicotinic antagonist. Schizophr Res 2006;85(1-3):213-21
  • Preskorn SH, Gawryl M, Dgetluck N, et al. Normalizing effects of EVP-6124, an alpha-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J Psychiatr Pract 2014;20(1):12-24
  • Lieberman JA, Dunbar G, Segreti AC, et al. A randomized exploratory trial of an alpha-7 nicotinic receptor agonist (TC-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacology 2013;38(6):968-75
  • Olincy A, Freedman R. Nicotinic mechanisms in the treatment of psychotic disorders: a focus on the alpha7 nicotinic receptor. Handb Exp Pharmacol 2012(213):211-32
  • Kalra EK. Nutraceutical--definition and introduction. AAPS PharmSci 2003;5(3):E25
  • Amminger GP, Schafer MR, Papageorgiou K, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry 2010;67(2):146-54
  • Emsley R, Myburgh C, Oosthuizen P, et al. Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Am J Psychiatry 2002;159(9):1596-8
  • Peet M, Horrobin DF; Group EEMS. A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. J Psychiatr Res 2002;36(1):7-18
  • Sivrioglu EY, Kirli S, Sipahioglu D, et al. The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study. Prog Neuropsychopharmacol Biol Psychiatry 2007;31(7):1493-9
  • Berger GE, Proffitt TM, McConchie M, et al. Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. J Clin Psychiatry 2007;68(12):1867-75
  • Fenton WS, Dickerson F, Boronow J, et al. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry 2001;158(12):2071-4
  • Peet M, Brind J, Ramchand CN, et al. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr Res 2001;49(3):243-51
  • Bentsen H, Osnes K, Refsum H, et al. A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia. Transl Psychiatry 2013;3:e335
  • Emsley R, Chiliza B, Asmal L, et al. A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia. Schizophr Res 2014;158(1-3):230-5
  • Emsley R, Niehaus DJ, Koen L, et al. The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial. Schizophr Res 2006;84(1):112-20
  • Godfrey PS, Toone BK, Carney MW, et al. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990;336(8712):392-5
  • Levine J, Stahl Z, Sela BA, et al. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry 2006;60(3):265-9
  • Hill M, Shannahan K, Jasinski S, et al. Folate supplementation in schizophrenia: a possible role for MTHFR genotype. Schizophr Res 2011;127(1-3):41-5
  • Roffman JL, Lamberti JS, Achtyes E, et al. Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia. JAMA Psychiatry 2013;70(5):481-9
  • Lerner V, Miodownik C, Kaptsan A, et al. Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients: a double-blind, placebo-controlled study. J Clin Psychiatry 2002;63(1):54-8
  • Rathbone J, Zhang L, Zhang M, et al. Chinese herbal medicine for schizophrenia: cochrane systematic review of randomised trials. Br J Psychiatry 2007;190:379-84
  • Rathbone J, Zhang L, Zhang M, et al. Chinese herbal medicine for schizophrenia. Cochrane Database Syst Rev 2005(4):CD003444
  • Bisogno T, Hanus L, De Petrocellis L, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 2001;134(4):845-52
  • Zuardi AW, Hallak JE, Dursun SM, et al. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol 2006;20(5):683-6
  • Miyamoto S, Jarskog LF, Fleischhacker WW. Alternative pharmacologic targets for the treatment of schizophrenia: results from phase I and II trials. Curr Opin Psychiatry 2013;26(2):158-65
  • Leweke FM, Giuffrida A, Wurster U, et al. Elevated endogenous cannabinoids in schizophrenia. Neuroreport 1999;10(8):1665-9
  • Giuffrida A, Leweke FM, Gerth CW, et al. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology 2004;29(11):2108-14
  • Koethe D, Giuffrida A, Schreiber D, et al. Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. Br J Psychiatry 2009;194(4):371-2
  • Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry 2012;2:e94
  • Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353(12):1209-23
  • Jones PB, Barnes TR, Davies L, et al. Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006;63(10):1079-87
  • Kahn RS, Fleischhacker WW, Boter H, et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008;371(9618):1085-97
  • Fenton WS, Blyler CR, Heinssen RK. Determinants of medication compliance in schizophrenia: empirical and clinical findings. Schizophr Bull 1997;23(4):637-51
  • Porcelli S, Balzarro B, Serretti A. Clozapine resistance: augmentation strategies. Eur Neuropsychopharmacol 2012;22(3):165-82
  • Tiihonen J, Leucht S. Clozapine resistance--augmentation strategies. Eur Neuropsychopharmacol 2013;23(4):338
  • Hiemke C, Baumann P, Bergemann N, et al. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: update 2011. Pharmacopsychiatry 2011;44(6):195-235

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.