Many reports show evidence of the disruption of central noradrenergic activity in the etiology of schizophrenia. A few studies show positive effects of a specific α2 -agonist, clonidine, on cognition and on positive and negative symptoms of schizophrenia. In this report, we tried clonidine for the treatment of auditory hallucinations in a patient with schizophrenia who had low compliance with antipsychotic treatment. At the end of seven days, auditory hallucinations decreased dramatically. Moreover, almost all auditory hallucinations disappeared at 6-months follow-up. This is the first case report showing the efficacy of clonidine monotherapy on auditory hallucinations in schizophrenia. However, the mechanism of action of clonidine remains hypothetical. The dramatic improvement observed in this case in the absence of any adverse effects suggests that controlled trials of the effect of clonidine on auditory hallucinations may be of clinical importance.
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Tracy DK, Shergill SS. Mechanisms underlying auditory hallucinations-understanding perception without stimulus. Brain Sci 2013; 3:642-669.
Yamamoto K, Hornykiewicz O. Proposal for a noradrenaline hypothesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28:913-922.
Powchik P, Davidson M, Haroutunian V, Gabriel SM, Purohit DP, Perl DP, Harvey PD, Davis KL. Postmortem studies in schizophrenia. Schizophr Bull 1998; 24:325-341.
Oranje B, Glenthoj BY. Clonidine normalizes sensorimotor gating deficits in patients with schizophrenia on stable medication. Schizophr Bull 2013; 39:684-691.
Friedman JI, Adler DN, Davis KL. The role of norepinephrine in the pathophysiology of cognitive disorders: potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer’s disease. Biol Psychiatry 1999; 46:1243-1252.
Litman RE, Pickar D. Noradrenergic systems: a target for augmenting pharmacotherapy: In Breier A (editor). The New Pharmacotherapy of Schizophrenia. Washington: American Psychiatric Press, 1996, 133-152.
Kruiper C, Glenthoj BY, Oranje B. Effects of clonidine on MMN and P3a amplitude in schizophrenia patients on stable medication. Neuropsychopharmacology 2019; 44:1062-1067.
Maas JW, Miller AL, Tekell JL, Funderburg L, Silva JA, True J, Velligan D, Berman N, Bowden CL. Clonidine plus haloperidol in the treatment of schizophrenia/psychosis. J Clin Psychopharmacol 1995; 15:361-364.
Freedman R, Kirch D, Bell J, Adler LE, Pecevich M, Pachtman E, Denver P. Clonidine treatment of schizophrenia: double-blind comparison to placebo and neuroleptic drugs. Acta Psychiatr Scand 1982; 65:35-45.
Fields RB, Van Kammen DP, Peters JL, Rosen J, Van Kammen WB, Nugent A, Stipetic M, Linnoila M. Clonidine improves memory function in schizophrenia independently from change in psychosis. Preliminary findings. Schizophr Res 1988; 1:417-423.
Naguy A. Clonidine use in psychiatry: panacea or panache. Pharmacology 2016; 98:87-92.
Dardennes RM, Al Anbar NN, Rouillon F. Successful augmentation of clozapine-resistant treatment of schizophrenia with clonidine. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34:724-725.
Yasaei R, Saadabadi A. Clonidine. StatPearls [Internet]. Treasure Island FL; StatPearls Publishing, 2019.
Wlodarczyk A, Szarmach J, Cubala WJ, Wiglusz MS. Benzodiazepines in combination with antipsychotic drugs for schizophrenia: GABA-ergic targeted therapy. Psychiatr Danub 2017; 29(Suppl.3):345-348.
Sommer IE, Slotema CW, Daskalakis ZJ, Derks EM, Blom JD, van der Gaag M. The treatment of hallucinations in schizophrenia spectrum disorders. Schizophr Bull 2012; 38:704-714.
Lechin F, van der Dijs B, Gomez F, Valls JM, Acosta E, Arocha L. Pharmacomanometric studies of colonic motility as a guide to the chemotherapy of schizophrenia. J Clin Pharmacol 1980; 20:664-671.
Lerner AG, Finkel B, Oyffe I, Merenzon I, Sigal M. Clonidine treatment for hallucinogen persisting perception disorder. Am J Psychiatry 1998; 155:1460.