CNS Drugs

, Volume 26, Issue 5, pp 391–401 | Cite as


Therapeutic Potential in Psychiatry
  • Olivia M. DeanEmail author
  • João Data-Franco
  • Francesco Giorlando
  • Michael Berk
Leading Article


Pharmacological interventions to treat psychiatric illness have previously focused on modifying dysfunctional neurotransmitter systems to improve symptoms. However, imperfect understanding of the aetiology of these heterogeneous syndromes has been associated with poor treatment outcomes for many individuals. Growing evidence suggests that oxidative stress, inflammation, changes in glutamatergic pathways and neurotrophins play important roles in many psychiatric illnesses including mood disorders, schizophrenia and addiction. These novel insights into pathophysiology allow new treatment targets to be explored. Minocycline is an antibiotic that can modulate glutamate-induced excitotoxicity, and has antioxidant, anti-inflammatory and neuroprotective effects. Given that these mechanisms overlap with the newly understood pathophysiological pathways, minocycline has potential as an adjunctive treatment in psychiatry. To date there have been promising clinical indications that minocycline may be a useful treatment in psychiatry, albeit from small trials most of which were not placebo controlled. Case reports of individuals with schizophrenia, psychotic symptoms and bipolar depression have shown serendipitous benefits of minocycline treatment on psychiatric symptoms. Minocycline has been trialled in open-label or small randomized controlled trials in psychiatry. Results vary, with findings supporting use in schizophrenia, but showing less benefit for nicotine dependence and obsessive-compulsive disorder. Given the limited data from rigorous clinical trials, further research is required. However, taken together, the current evidence suggests minocycline may be a promising novel therapy in psychiatry


Nitric Oxide Schizophrenia Traumatic Brain Injury Olanzapine Microglial Activation 
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.



No sources of funding were used to prepare this review. MB has received grant/research support from the NIH, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Organon, Novartis, Mayne Pharma and Servier; has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth; and served as a consultant to Astra Zeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck and Servier. FG has received grant/research support from the ASBD, AstraZeneca, Pfizer and the RANZCP. OD has received grant/research support from Simons Autism Foundation, Stanley Medical Research Institute, NHMRC and an ASBD/Servier grant. JF has no potential conflicts of interest.


  1. 1.
    Kim HS, Suh YH. Minocycline and neurodegenerative diseases. Behav Brain Res 2009; 196: 168–79PubMedCrossRefGoogle Scholar
  2. 2.
    Pae CU, Marks DM, Han C, et al. Does minocycline have antidepressant effect? Biomed Pharmacother 2008; 62: 308–11PubMedCrossRefGoogle Scholar
  3. 3.
    Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006; 97: 1634–58PubMedCrossRefGoogle Scholar
  4. 4.
    Maes M, De Vos N, Pioli R, et al. Lower serum vitamin E concentrations in major depression: another marker of lowered antioxidant defenses in that illness. J Affect Disord 2000; 58: 241–6PubMedCrossRefGoogle Scholar
  5. 5.
    Bilici M, Efe H, Koroglu MA, et al. Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 2001; 64: 43–51PubMedCrossRefGoogle Scholar
  6. 6.
    Selley ML. Increased (E)-4-hydroxy-2-nonenal and asymmetric dimethylarginine concentrations and decreased nitric oxide concentrations in the plasma of patients with major depression. J Affect Disord 2004; 80: 249–56PubMedCrossRefGoogle Scholar
  7. 7.
    Castro AA, Moretti M, Casagrande TS, et al. Neuropeptide S produces hyperlocomotion and prevents oxidative stress damage in the mouse brain: a comparative study with amphetamine and diazepam. Pharmacol Biochem Behav 2009; 91(4): 636–42PubMedCrossRefGoogle Scholar
  8. 8.
    Bitanihirwe BK, Woo TU. Oxidative stress in schizophrenia: an integrated approach. Neurosci Biobehav Rev 2011; 35: 878–93PubMedCrossRefGoogle Scholar
  9. 9.
    Villagonzalo KA, Dodd S, Dean O, et al. Oxidative pathways as a drug target for the treatment of autism. Expert Opin Ther Targets 2010; 14: 1301–10PubMedCrossRefGoogle Scholar
  10. 10.
    Tata DA, Yamamoto BK. Interactions between metham-phetamine and environmental stress: role of oxidative stress, glutamate and mitochondrial dysfunction. Addiction 2007; 102 Suppl. 1: 49–60CrossRefGoogle Scholar
  11. 11.
    Suzuki K, Kusumi I, Sasaki Y, et al. Serotonin-induced platelet intracellular calcium mobilization in various psychiatric disorders: is it specific to bipolar disorder? J Affect Disord 2001; 64: 291–6PubMedCrossRefGoogle Scholar
  12. 12.
    Dhir A, Kulkarni SK. Involvement of nitric oxide (NO) signaling pathway in the antidepressant action of bupropion, a dopamine reuptake inhibitor. Eur J Pharmacol 2007; 568: 177–85PubMedCrossRefGoogle Scholar
  13. 13.
    Kumar A, Garg R, Gaur V, et al. Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice. Indian J Pharmacol 2011; 43: 324–9PubMedCrossRefGoogle Scholar
  14. 14.
    Hashimoto K. The role of glutamate on the action of anti-depressants. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35(7): 1558–68PubMedCrossRefGoogle Scholar
  15. 15.
    Berk M, Kapczinski F, Andreazza AC, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 2011; 35: 804–17PubMedCrossRefGoogle Scholar
  16. 16.
    Luykx JJ, Laban KG, van den Heuvel MP, et al. Region and state specific glutamate downregulation in major depressive disorder: a meta-analysis of (1)H-MRS findings. Neurosci Biobehav Rev 2012 Jan; 36(1): 198–205PubMedCrossRefGoogle Scholar
  17. 17.
    Carlsson A. The neurochemical circuitry of schizophrenia. Pharmacopsychiatry 2006; 39 Suppl. 1: S10–4PubMedCrossRefGoogle Scholar
  18. 18.
    Kalivas PW, Lalumiere RT, Knackstedt L, et al. Glutamate transmission in addiction. Neuropharmacology 2009; 56 Suppl. 1: 169–73CrossRefGoogle Scholar
  19. 19.
    Berk M, Plein H, Belsham B. The specificity of platelet glutamate receptor supersensitivity in psychotic disorders. Life Sci 2000; 66: 2427–32PubMedGoogle Scholar
  20. 20.
    Berk M, Plein H, Ferreira D. Platelet glutamate receptor supersensitivity in major depressive disorder. Clin Neuro-pharmacol 2001; 24: 129–32Google Scholar
  21. 21.
    Liu Y, Ho RC, Mak A. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. Epub 2011 Aug 25Google Scholar
  22. 22.
    Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010; 67: 446–57PubMedCrossRefGoogle Scholar
  23. 23.
    Maes M, Yirmyia R, Noraberg J, et al. The inflammatory and neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 2009; 24: 27–53PubMedCrossRefGoogle Scholar
  24. 24.
    Wadee AA, Kuschke RH, Wood LA, et al. Serological observations in patients suffering from acute manic episodes. Hum Psychopharmacol 2002; 17: 175–9PubMedCrossRefGoogle Scholar
  25. 25.
    Potvin S, Stip E, Sepehry AA, et al. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry 2008; 63: 801–8PubMedCrossRefGoogle Scholar
  26. 26.
    Goncalves J, Martins T, Ferreira R, et al. Methamphetamine-induced early increase of IL-6 and TNF-alpha mRNA expression in the mouse brain. Ann N Y Acad Sci 2008; 1139: 103–11PubMedCrossRefGoogle Scholar
  27. 27.
    Goncalves J, Baptista S, Martins T, et al. Methamphetamine-induced neuroinflammation and neuronal dysfunction in the mice hippocampus: preventive effect of indomethacin. Eur J Neurosci 2010; 31: 315–26PubMedCrossRefGoogle Scholar
  28. 28.
    Maeng S, Hunsberger JG, Pearson B, et al. BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments. Proc Natl Acad Sci U S A 2008; 105: 8766–71PubMedCrossRefGoogle Scholar
  29. 29.
    Jarskog LF, Gilmore JH, Selinger ES, et al. Cortical bcl-2 protein expression and apoptotic regulation in schizophrenia. Biol Psychiatry 2000; 48: 641–50PubMedCrossRefGoogle Scholar
  30. 30.
    Bocchio-Chiavetto L, Bagnardi V, Zanardini R, et al. Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry 2010; 11: 763–73PubMedCrossRefGoogle Scholar
  31. 31.
    Ikeda Y, Yahata N, Ito I, et al. Low serum levels of brain-derived neurotrophic factor and epidermal growth factor in patients with chronic schizophrenia. Schizophr Res 2008; 101: 58–66PubMedCrossRefGoogle Scholar
  32. 32.
    Rakofsky JJ, Ressler KJ, Dunlop BW. BDNF function as a potential mediator of bipolar disorder and post-traumatic stress disorder comorbidity. Mol Psychiatry 2012 Jan; 17(1): 22–35PubMedCrossRefGoogle Scholar
  33. 33.
    Ekdahl CT, Claasen JH, Bonde S, et al. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci U S A 2003; 100: 13632–7PubMedCrossRefGoogle Scholar
  34. 34.
    Perera TD, Coplan JD, Lisanby SH, et al. Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J Neurosci 2007; 27: 4894–901PubMedCrossRefGoogle Scholar
  35. 35.
    Goshen I, Kreisel T, Ben-Menachem-Zidon O, et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 2008; 13: 717–28PubMedCrossRefGoogle Scholar
  36. 36.
    Ng F, Berk M, Dean O, et al. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 2008; 11: 851–76PubMedCrossRefGoogle Scholar
  37. 37.
    Leite LM, Carvalho AG, Ferreira PL, et al. Anti-inflammatory properties of doxycycline and minocycline in experimental models: an in vivo and in vitro comparative study. Inflammopharmacology 2011; 19: 99–110PubMedCrossRefGoogle Scholar
  38. 38.
    Garcia-Martinez EM, Sanz-Blasco S, Karachitos A, et al. Mitochondria and calcium flux as targets of neuroprotection caused by minocycline in cerebellar granule cells. Biochem Pharmacol 2010; 79: 239–50PubMedCrossRefGoogle Scholar
  39. 39.
    Ahuja M, Bishnoi M, Chopra K. Protective effect of minocycline, a semi-synthetic second-generation tetracycline against 3-nitropropionic acid (3-NP)-induced neurotoxicity. Toxicology 2008; 244: 111–22PubMedCrossRefGoogle Scholar
  40. 40.
    Kernt M, Neubauer AS, Eibl KH, et al. Minocycline is cytoprotective in human trabecular meshwork cells and optic nerve head astrocytes by increasing expression of XIAP, survivin, and Bcl-2. Clin Ophthalmol 2010; 4: 591–604PubMedCrossRefGoogle Scholar
  41. 41.
    Morimoto N, Shimazawa M, Yamashima T, et al. Mino-cycline inhibits oxidative stress and decreases in vitro and in vivo ischemic neuronal damage. Brain Res 2005; 1044: 8–15PubMedCrossRefGoogle Scholar
  42. 42.
    Homsi S, Federico F, Croci N, et al. Minocycline effects on cerebral edema: relations with inflammatory and oxidative stress markers following traumatic brain injury in mice. Brain Res 2009; 1291: 122–32PubMedCrossRefGoogle Scholar
  43. 43.
    Miyaoka T, Yasukawa R, Yasuda H, et al. Possible anti-psychotic effects of minocycline in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31: 304–7PubMedCrossRefGoogle Scholar
  44. 44.
    Schildknecht S, Pape R, Muller N, et al. Neuroprotection by minocycline caused by direct and specific scavenging of peroxynitrite. J Biol Chem 2010; 286: 4991–5002PubMedCrossRefGoogle Scholar
  45. 45.
    Pabreja K, Dua K, Sharma S, et al. Minocycline attenuates the development of diabetic neuropathic pain: possible anti-inflammatory and anti-oxidant mechanisms. Eur J Pharmacol 2011; 661: 15–21PubMedCrossRefGoogle Scholar
  46. 46.
    Kim SS, Kong PJ, Kim BS, et al. Inhibitory action of minocycline on lipopolysaccharide-induced release of nitric oxide and prostaglandin E2 in BV2 microglial cells. Arch Pharm Res 2004; 27: 314–8PubMedCrossRefGoogle Scholar
  47. 47.
    Kim BJ, Kim MJ, Park JM, et al. Reduced neurogenesis after suppressed inflammation by minocycline in transient cerebral ischemia in rat. J Neurol Sci 2009; 279: 70–5PubMedCrossRefGoogle Scholar
  48. 48.
    Bian Q, Kato T, Monji A, et al. The effect of atypical anti-psychotics, perospirone, ziprasidone and quetiapine on microglial activation induced by interferon-gamma. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 42–8PubMedCrossRefGoogle Scholar
  49. 49.
    Chang Y, Lee JJ, Hsieh CY, et al. Inhibitory effects of ketamine on lipopolysaccharide-induced microglial activation. Mediators Inflamm 2009; 2009: 705379PubMedCrossRefGoogle Scholar
  50. 50.
    Miyaoka T, Yasukawa R, Yasuda H, et al. Minocycline as adjunctive therapy for schizophrenia: an open-label study. Clin Neuropharmacol 2008; 31: 287–92PubMedCrossRefGoogle Scholar
  51. 51.
    Orio L, Llopis N, Torres E, et al. A study on the mechanisms by which minocycline protects against MDMA (‘ecstasy’)-induced neurotoxicity of 5-HT cortical neurons. Neurotox Res 2010; 18: 187–99PubMedCrossRefGoogle Scholar
  52. 52.
    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: 138–49PubMedCrossRefGoogle Scholar
  53. 53.
    Silva Bastos LF, Pinheiro de Oliveira AC, Magnus Schla-chetzki JC, et al. Minocycline reduces prostaglandin E synthase expression and 8-isoprostane formation in LPS-activated primary rat microglia. Immunopharmacol Immunotoxicol 2011; 33: 576–80PubMedCrossRefGoogle Scholar
  54. 54.
    Yang D, Liu X, Zhang R, et al. Increased apoptosis and different regulation of pro-apoptosis protein bax and anti-apoptosis protein bcl-2 in the olfactory bulb of a rat model of depression. Neurosci Lett 2011; 504: 18–22PubMedCrossRefGoogle Scholar
  55. 55.
    Garner SE, Eady EA, Popescu C, et al. Minocycline for acne vulgaris: efficacy and safety. Cochrane Database Syst Rev 2003; (1): CD002086Google Scholar
  56. 56.
    Tang CM, Hwang CS, Chen SD, et al. Neuroprotective mechanisms of minocycline against sphingomyelinase/ ceramide toxicity: roles of Bcl-2 and thioredoxin. Free Radic Biol Med 2011; 50: 710–21PubMedCrossRefGoogle Scholar
  57. 57.
    Homsi S, Piaggio T, Croci N, et al. Blockade of acute microglial activation by minocycline promotes neuroprotection and reduces locomotor hyperactivity after closed head injury in mice: a twelve-week follow-up study. J Neuro-trauma 2010; 27: 911–21Google Scholar
  58. 58.
    Investigators TNN-P. A pilot clinical trial of creatine and minocycline in early Parkinson disease: 18-month results. Clin Neuropharmacol 2008; 31: 141–50CrossRefGoogle Scholar
  59. 59.
    Liu Z, Fan Y, Won SJ, et al. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke 2007; 38: 146–52PubMedCrossRefGoogle Scholar
  60. 60.
    Shilling PD, Kuczenski R, Segal DS, et al. Differential regulation of immediate-early gene expression in the prefrontal cortex of rats with a high vs low behavioral response to methamphetamine. Neuropsychopharmacology 2006; 31: 2359–67PubMedCrossRefGoogle Scholar
  61. 61.
    Zhu S, Stavrovskaya IG, Drozda M, et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 2002; 417: 74–8PubMedCrossRefGoogle Scholar
  62. 62.
    Chen M, Ona VO, Li M, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 2000; 6: 797–801PubMedCrossRefGoogle Scholar
  63. 63.
    Goulden V, Glass D, Cunliffe WJ. Safety of long-term high-dose minocycline in the treatment of acne. Br J Dermatol 1996; 134: 693–5PubMedCrossRefGoogle Scholar
  64. 64.
    Zhang X, Xu Y, Wang J, et al. The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats. J Neural Transm. Epub 2011 Sep7Google Scholar
  65. 65.
    Morgado C, Pereira-Terra P, Cruz CD, et al. Minocycline completely reverses mechanical hyperalgesia in diabetic rats through microglia-induced changes in the expression of the potassium chloride co-transporter 2 (KCC2) at the spinal cord. Diabetes Obes Metab 2011; 13: 150–9PubMedCrossRefGoogle Scholar
  66. 66.
    Zhong J, Lee WH. Hydrogen peroxide attenuates insulin-like growth factor-1 neuroprotective effect, prevented by minocycline. Neurochem Int 2007; 51: 398–404PubMedCrossRefGoogle Scholar
  67. 67.
    Stirling DP, Koochesfahani KM, Steeves JD, et al. Minocycline as a neuroprotective agent. Neuroscientist 2005; 11: 308–22PubMedCrossRefGoogle Scholar
  68. 68.
    Kraus RL, Pasieczny R, Lariosa-Willingham K, et al. Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity. J Neurochem 2005; 94: 819–27PubMedCrossRefGoogle Scholar
  69. 69.
    Plein H, Berk M. The platelet as a peripheral marker in psychiatric illness. Hum Psychopharmacol 2001; 16: 229–36PubMedCrossRefGoogle Scholar
  70. 70.
    Nie H, Zhang H, Weng HR. Minocycline prevents impaired glial glutamate uptake in the spinal sensory synapses of neuropathic rats. Neuroscience 2010; 170: 901–12PubMedCrossRefGoogle Scholar
  71. 71.
    Molina-Hernandez M, Tellez-Alcantara NP, Perez-Garcia J, et al. Desipramine or glutamate antagonists synergized the antidepressant-like actions of intra-nucleus accumbens infusions of minocycline in male Wistar rats. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 1660–6PubMedCrossRefGoogle Scholar
  72. 72.
    Deak T, Bellamy C, D’Agostino LG, et al. Behavioral responses during the forced swim test are not affected by anti-inflammatory agents or acute illness induced by lipo-polysaccharide. Behav Brain Res 2005; 160: 125–34PubMedCrossRefGoogle Scholar
  73. 73.
    Watanabe T, Sagisaka H, Arakawa S, et al. A novel model of continuous depletion of glutathione in mice treated with L-buthionine (S,R)-sulfoximine. J Toxicol Sci 2003; 28:455–69PubMedCrossRefGoogle Scholar
  74. 74.
    Fujita Y, Ishima T, Kunitachi S, et al. Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antibiotic drug minocycline. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 336–9PubMedCrossRefGoogle Scholar
  75. 75.
    Chen H, Uz T, Manev H. Minocycline affects cocaine sensitization in mice. Neurosci Lett 2009; 452: 258–61PubMedCrossRefGoogle Scholar
  76. 76.
    Zhang L, Kitaichi K, Fujimoto Y, et al. Protective effects of minocycline on behavioral changes and neurotoxicity in mice after administration of methamphetamine. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1381–93PubMedCrossRefGoogle Scholar
  77. 77.
    Zhang L, Shirayama Y, Iyo M, et al. Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine. Neuropsychopharmacology 2007; 32: 2004–10PubMedCrossRefGoogle Scholar
  78. 78.
    Kelly DL, Vyas G, Richardson CM, et al. Adjunct minocycline to clozapine treated patients with persistent schizophrenia symptoms. Schizophr Res. Epub 2011 Aug 25Google Scholar
  79. 79.
    Levine J, Cholestoy A, Zimmerman J. Possible antidepressant effect of minocycline. Am J Psychiatry 1996; 153: 582PubMedGoogle Scholar
  80. 80.
    Chaves C, de Marque CR, Wichert-Ana L, et al. Functional neuroimaging of minocycline’s effect in a patient with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 550–2PubMedCrossRefGoogle Scholar
  81. 81.
    Tanibuchi Y, Shimagami M, Fukami G, et al. A case of methamphetamine use disorder treated with the antibiotic drug minocycline. Gen Hosp Psychiatry 2009; 32(5): 559.e1-3Google Scholar
  82. 82.
    Rodriguez CI, Bender Jr J, Marcus SM, et al. Minocycline augmentation of pharmacotherapy in obsessive-compulsive disorder: an open-label trial. J Clin Psychiatry 2010; 71:1247–9PubMedCrossRefGoogle Scholar
  83. 83.
    Sofuoglu M, Waters AJ, Mooney M, et al. Minocycline reduced craving for cigarettes but did not affect smoking or intravenous nicotine responses in humans. Pharmacol Biochem Behav 2009; 92: 135–40PubMedCrossRefGoogle Scholar
  84. 84.
    West R, Zatonski W, Cedzynska M, et al. Placebo-controlled trial of cytisine for smoking cessation. New Engl J Med 2011; 365: 1193–200PubMedCrossRefGoogle Scholar
  85. 85.
    Sofuoglu M, Mooney M, Kosten T, et al. Minocycline attenuates subjective rewarding effects of dextroamphetamine in humans. Psychopharmacology (Berl) 2011; 213: 61–8CrossRefGoogle Scholar
  86. 86.
    Khanzode SD, Dakhale GN, Khanzode SS, et al. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep 2003; 8: 365–70PubMedCrossRefGoogle Scholar
  87. 87.
    Kotan VO, Sarandol E, Kirhan E, et al. Effects of long-term antidepressant treatment on oxidative status in major depressive disorder: a 24-week follow-up study. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 1284–90PubMedCrossRefGoogle Scholar
  88. 88.
    Nishida A, Hisaoka K, Zensho H, et al. Antidepressant drugs and cytokines in mood disorders. Int Immunopharmacol 2002; 2: 1619–26PubMedCrossRefGoogle Scholar
  89. 89.
    Castren E, Rantamaki T. The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Dev Neurobiol 2010; 70: 289–97PubMedCrossRefGoogle Scholar
  90. 90.
    Otsuki K, Uchida S, Watanuki T, et al. Altered expression of neurotrophic factors in patients with major depression. J Psychiatr Res 2008; 42: 1145–53PubMedCrossRefGoogle Scholar
  91. 91.
    Lepping P, Delieu J, Mellor R, et al. Antipsychotic medication and oxidative cell stress: a systematic review. J Clin Psychiatry 2011; 72: 273–85PubMedCrossRefGoogle Scholar
  92. 92.
    Magalhaes PV, Dean OM, Bush AI, et al. Dimensions of improvement in a clinical trial of n-acetyl cysteine for bipolar disorder. Acta Neuropsychiatrica 2011; 23: 87–8CrossRefGoogle Scholar
  93. 93.
    Camfield DA, Sarris J, Berk M. Nutraceuticals in the treatment of obsessive compulsive disorder (OCD): a review of mechanistic and clinical evidence. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 887–95PubMedCrossRefGoogle Scholar
  94. 94.
    Sarris J, Camfield D, Berk M. Complementary medicine, self-help, and lifestyle interventions for Obsessive Compulsive Disorder (OCD) and the OCD spectrum: a systematic review. J Affect Disord. Epub 2011 May 25Google Scholar
  95. 95.
    Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci 2010; 36: 78–86Google Scholar
  96. 96.
    Berthold-Losleben M, Heitmann S, Himmerich H. Anti-inflammatory drugs in psychiatry. Inflamm Allergy Drug Targets 2009; 8: 266–76PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Olivia M. Dean
    • 1
    • 2
    • 3
    Email author
  • João Data-Franco
    • 2
    • 4
  • Francesco Giorlando
    • 3
  • Michael Berk
    • 1
    • 2
    • 3
    • 5
  1. 1.Deakin University, School of Medicine, Barwon HealthGeelongAustralia
  2. 2.Mental Health Research InstituteParkvilleAustralia
  3. 3.Department of PsychiatryUniversity of MelbourneParkvilleAustralia
  4. 4.Psychiatric DepartmentHospital Santa MariaLisbonPortugal
  5. 5.Orygen Youth Health Research CentreParkvilleAustralia

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