A controlled trial of propoxyphene and naltrexone in patients with tourette's syndrome

To investigate the effect of drugs acting on the endogenous opioid system, we studied 10 adults with Tourette's syndrome who received propoxyphene hydrochloride (260 mg/day), naltrexone hydrochloride (50 mg/day), and placebo in a double‐blinded, randomized clinical trial. Using a self‐report scale (Tourette's Syndrome Symptom List), subjects noted a significant (p < 0.04) lessening of tics after treatment with naltrexone when compared with placebo. An improvement in performance on the Trail Making B test, a measure of attention and visuomotor sequencing and planning, occurred after receiving naltrexone when compared with placebo (p < 0.08) or propoxyphene (p < 0.02). The Trail Making B test best discriminated the treatments (p < 0.02, analysis of variance). No other treatment effects were observed for several other measures of tic severity, attentional ability, or obsessive‐compulsive symptoms. Our findings indicate that pharmacological manipulation of the endogenous opioid system does influence symptoms of Tourette's syndrome.

[1]  R. Kurlan,et al.  Opiate therapy and self‐harming behavior in tourette's syndrome , 1991, Movement disorders : official journal of the Movement Disorder Society.

[2]  H. Singer,et al.  Tourette's syndrome: A neurochemical analysis of postmortem cortical brain tissue , 1990, Annals of neurology.

[3]  J. McGinty,et al.  Differential modulation of striatonigral dynorphin and enkephalin by dopamine receptor subtypes , 1990, Brain Research.

[4]  R. Kurlan Tourette's syndrome , 1989, Neurology.

[5]  R. Kurlan,et al.  Opiate withdrawal unmasks Tourette's syndrome. , 1988, Clinical neuropharmacology.

[6]  B. H. Herman,et al.  Naltrexone decreases self‐injurious behavior , 1987, Annals of neurology.

[7]  C. Gordon,et al.  Naloxone in Gilles de la Tourette's syndrome , 1987, Annals of neurology.

[8]  C. Tanner,et al.  Clonidine and Gilles de la Tourette's syndrome: Double‐blind study using objective rating methods , 1987, Annals of neurology.

[9]  P. Spencer,et al.  Recognizing neurotoxic disease , 1987, Neurology.

[10]  R. Sandyk,et al.  Naloxone abolishes obsessive-compulsive behavior in Tourette's syndrome. , 1987, The International journal of neuroscience.

[11]  Suzanne N. Haber,et al.  Gilles de la Tourette's syndrome A postmortem neuropathological and immunohistochemical study , 1986, Journal of the Neurological Sciences.

[12]  J. C. Stoof,et al.  Blockade of D-2 dopamine receptors strongly enhances the potency of enkephalins to inhibit dopamine-sensitive adenylate cyclase in rat neostriatum: involvement of delta- and mu-opioid receptors , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  H. Ågren,et al.  TRH tests with analyses of TSH, prolactin, and GH responses in subtypes of patients with major depressive disorders , 1986, Acta psychiatrica Scandinavica.

[14]  R. Sandyk Naloxone withdrawal exacerbates Tourette syndrome. , 1986, Journal of clinical psychopharmacology.

[15]  S. Chokroverty,et al.  Opioid responsiveness in patients with neuroleptic‐induced akathisia , 1986, Movement disorders : official journal of the Movement Disorder Society.

[16]  R. Sandyk The effects of naloxone in tourette's syndrome , 1985, Annals of neurology.

[17]  P. Spano,et al.  Dopamine enhances Met-enkephalin efflux from rat striatal slices , 1984, Brain Research.

[18]  J. Cubells,et al.  Evidence for a role of endogenous opioids in the nigrostriatal system: Influence of naloxone and morphine on nigrostriatal dopaminergic supersensitivity , 1983, Brain Research.

[19]  Aghajanian Gk Central noradrenergic neurons: a locus for the functional interplay between alpha-2 adrenoceptors and opiate receptors. , 1982 .

[20]  D. Cooper,et al.  Opiate Receptor‐Mediated Inhibition of Adenylate Cyclase in Rat Striatal Plasma Membranes , 1982, Journal of neurochemistry.

[21]  C. Chavkin,et al.  Dynorphin is a specific endogenous ligand of the kappa opioid receptor. , 1982, Science.

[22]  M. Bergner,et al.  The Sickness Impact Profile: Development and Final Revision of a Health Status Measure , 1981, Medical care.

[23]  J. Nazzaro,et al.  Selective inhibition of mesolimbic behavioral supersensitivity by naloxone. , 1980, European journal of pharmacology.

[24]  J. Schwartz Opiate receptors on catecholaminergic neurones in brain , 1979, Trends in Neurosciences.

[25]  W. Weiner,et al.  Gilles de la Tourette syndrome after long‐term chlorpromazine therapy , 1978, Neurology.

[26]  H. Lal,et al.  Narcotic dependence, narcotic action and dopamine receptors. , 1975, Life sciences.

[27]  G. S. Mudholkar,et al.  Mebutamate as a hypnotic: Clinical trial and statistical considerations , 1973, Clinical pharmacology and therapy.

[28]  H. Loh,et al.  Neuroanatomical and chemical correlates of naloxone-precipitated withdrawal. , 1973, Advances in biochemical psychopharmacology.

[29]  J. Cooper The Leyton Obsessional Inventory , 1970, Psychological Medicine.

[30]  A. Benton,et al.  COMPARATIVE STUDIES OF SOME PSYCHOLOGICAL TESTS FOR CEREBRAL DAMAGE , 1965, The Journal of nervous and mental disease.

[31]  R. B. Mefferd,et al.  Repetitive Psychometric Measures , 1959 .