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P.3.016 Oxcarbazepine, topiramate and lamotrigine in the treatment of alcohol craving
Clinical neuropsychopharmacology The significance of differences between average measurements in the two groups was assessed using Student’s t-test. Significance was set at p < 0.05. Statistical analysis was performed using the STATA Data Analyses Tool: Regression statistics; Two-sample t test with equal variances, Bartlett’s test for equal variances, Bonferroni test. Results: The levels of vitamin B12 and folic acid were found to be normal for all patients. The mean level of Hcy was 11.94±5.6 mmol/L for patients with schizophrenia spectrum disorders and 11.26±3.3 mmol/L for patients with affective disorders versus 7.47±2.9 mmol/L for controls. The highest level of Hcy in the schizophrenia patients was seen in those with an episodic-recurrent disease course, in particular for acute onset and pronounced affect. For the group with affective disorders the highest level was seen in patients with depressive symptoms with anxiety and in patients with mixed affective disorders (r = −0.58; p < 0.01). No associations were found between patient groups, the level of Hcy and MTHFR gene polymorphism. Conclusions: These data suggest a potential link between Hcy level and pronounced affect in schizophrenia and affective disorders, as well as disease severity and course. However, no association was found between Hcy level, schizophrenia and affective disorders and the MTHFR 677C→T polymorphism. Reference(s) [1] Bottiglieri T., Laundy M., Crellin R., Toone B.K., Carney M.W., Reynolds E.H.: Homocysteine, folate, methylation, and monoamine metabolism in depression. Journal of Neurology, Neurosurgery and Psychiatry 2000, 69:228–232. [2] Bolander-Gouaille C., Bottiglieri T. Homocysteine. Related vitamins and neuropsychiatric disorders. Second edition. Springer-Verlag France 2007:15−29. [3] Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. Journal of Psychopharmacology 2005; 19:59−65.
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P.3.016 Oxcarbazepine, topiramate and lamotrigine in the treatment of alcohol craving B. Bajovic1 ° , N. Zivkovic2 , G. Djokic3 , D. Pavicevic4 . Neuropsychiatry Hospital “Dr Laza Lazarevic”, K department, Belgrade, Serbia; 2 Neuropsychiatry Hospital “Dr Laza Lazarevic”, M department, Belgrade, Serbia; 3 Neuropsychiatry Hospital “Dr Laza Lazarevic”, Scientific Research Centre, Belgrade, Serbia; 4 Neuropsychiatry Hospital “Dr Laza Lazarevic”, Intensive Care Unit, Belgrade, Serbia 1
Substance use disorders (SUD) are both very common and very severe psychiatric disorders, with a high prevalence in the general population. It is supposed that the midbrain dopaminergic system and neuroadaptive changes in almost all neurotransmitter systems have significant roles in the neurobiochemical basis of SUD. Oxcarbazepine (OXC) blocks voltage-sensitive sodium channels and reduces high-voltage activated calcium currents in striatal and cortical neurons. Topiramate (TPA) is a modulator of voltage-sensitive sodium channels; its mechanism of action is uncertain, altough it does potentiate GABA activity in the brain. Lamotrigine (LTG) blocks voltagedependent sodium channels and reduces the release of excitatory neurotransmitters, in particular that of glutamate. Aim of this study was to investigate the efficacy of the antiepileptics/mood stabilisers OXC, TPA and LTG in the treatment of alcohol-induced craving. Methods: This prospective clinical study included 182 patients with ICD-10 criteria for alcohol dependence, who were randomly divided into four groups − a control group (C), N = 40, and three experimental groups: Oxcarbazepine (O), N = 51; Topiramate (T), N = 42 and Lamotrigine (L), N = 49. Patients were observed for 6 months in hospital and outpatient conditions, according to a specially designed protocol, which included the clinical score on the alcohol craving scale (ACS). The control group was treated with symptomatic therapy, and the experimental groups were treated with symptomatic therapy and OXC (600–1200 mg/24 h), TPA (100– 200 mg/24 h), and LTG (75–200 mg/24 h), respectively. Results: There was no statistical significance in pretrial scores between the groups, p = 0.847 for ACS. In all experimental groups there was a statistically significant reduction in ACS score versus baseline both after 30 days (p = 0.001) and after 180 days (p = 0.001). There was no statistically significant reduction in ACS score between 30 and 180 days (p = 0.724). Results of ACS reduction between all experimental groups are as follows: O vs. C,
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p = 0.001 after 30 and 180 days (highly statistically significant); O vs. T, p = 0.011 after 30 and p = 0.009 after 180 days (highly statistically significant); O vs. L, p = 0.856 after 30 and p = 0.232 after 180 days (not statistically significant); L vs. C, p = 0.001 after 30 and 180 days (highly statistically significant); L vs. T, p = 0.021 after 30 and p = 0.039 after 180 days (highly statistically significant); T vs. C, p = 0.001 after 30 and 180 days (highly statistically significant). After 180 days ACS reduction was significant in all four groups: 78.41% in O; 71.82% in L; 69.52% in T and 57.11% in C. The relapse rate was significantly lower in all three experimental groups than in the control group. No severe side effects were observed during this study. Conclusion: OXC, TPA and LTG have potent anticraving effect in alcohol dependents. OXC, TPA and LTG are efficacious in reducing ACS score. At the end of the study OXC showed the best efficacy. OXC, TPA and LTG all three significantly lowered the risk of relapse in comparison with the control group. Reference(s) [1] Johnson BA, Swift RM, Ait-Daoud N, DiClemente CC, Javors MA, Malcolm RJ Jr. Development of novel pharmacotherapies for the treatment of alcohol dependence: focus on antiepileptics. Alcohol Clin Exp Res 2004. 28 (2): 295–301. [2] Mason BJ, Shaham Y, Weiss F, Le AD. Stress, alcohol craving, and relapse risk: mechanisms and viable treatment targets. Alcohol 2009. 43 (7): 541–543. [3] Boykoff N., Schneekloth TD, Hall-Flavin D, Loukianova L, Karpyak VM, Stevens SR, Biernacka JM, Mrazek DA, Frye MA. Gender differences in the relationship between depressive symptoms and craving in alcoholism. Am J Addict. 2010. 19 (4): 352–356. P.3.017 Human impulsivity is not associated with variation in presynaptic striatal dopamine synthesis capacity P.R.A. Stokes1 ° , A. Benecke1 , J.P. Shotbolt2 , D.J. Nutt1 , O.D. Howes2 , A.R. Lingford-Hughes1 . 1 Imperial College London, Neuropsychopharmacology Unit 5th Floor Burlington Danes Building, London, United Kingdom; 2 Imperial College London, Psychiatric Imaging Group MRC Clinical Sciences Centre, London, United Kingdom Introduction: Impulsivity is a personality trait which encompasses the tendency to initiate actions without forethought and the inability to inhibit inappropriate behaviour. Impulsivity plays an important role in a number
of psychiatric disorders including substance misuse and addiction, ADHD and impulse control disorders. Increased levels of trait impulsivity in healthy human volunteers are associated with decreased midbrain dopamine D2 /D3 receptor availability and greater amphetamine induced striatal dopamine release [1]. Moreover, healthy human TT homozygotes of the dopamine D2 receptor polymorphism C957T, which affects postsynaptic striatal receptor density, show higher levels of dysfunctional impulsivity [2]. Although there is increasing evidence that variation in postsynaptic striatal dopamine function influences human impulsivity, no studies have so far examined whether this is the case for presynaptic striatal dopamine function. Aims: To determine whether human impulsivity is associated with variation in presynaptic striatal dopamine synthesis capacity using [18F]-DOPA positron emission tomography (PET). Methods: 20 healthy volunteers (11 males, mean age 37 years (SD: 14)) were recruited to the study. Each volunteer underwent one [18F]-DOPA PET scan to determine presynaptic dopamine synthesis capacity. Volunteers were scanned using a high resolution ECAT EXACT3D PET scanner. All scans were corrected for head movement using frame by frame realignment. Normalised striatal functional subdivision maps, comprised of limbic, associative and sensorimotor regions, were used to sample individual dynamic [18F]-DOPA PET images. Ki values for each region were estimated by a Patlak analysis using the cerebellum as a reference region. Impulsivity was assessed for each volunteer using the Barratt Impulsiveness Scale (BIS-11) and the Eysenck Impulsivity, Venturesomeness and Empathy questionnaire (EPQ-IVE). [18F]-DOPA Ki values and personality scores were assessed for normality of distribution. Relationships between personality scores and [18F]-DOPA Ki values were examined using Pearson’s correlation for normally distributed variables and Spearman’s correlation for nonnormally distributed variables. All statistical analyses were performed using SPSS 19. Results: There were no significant correlations between overall striatal dopamine synthesis capacity and EPQIVE impulsivity scores (rho = 0.08, p = 0.7), first order self control BIS scores (rho = −0.17, p = 0.5), second order non-planning impulsivity BIS scores (rho = −0.08, p = 0.7) or total BIS scores (rho = −0.03, p = 0.9). Scores for these impulsivity scales also did not correlate to presynaptic dopamine synthesis capacity in any functional striatal subdivision (p values for all correlations >0.05). Conclusions: We found that human impulsivity is not associated with variation in striatal presynaptic dopamine synthesis capacity in healthy volunteers. This result indicates that although impulsivity may be related to markers of postsynaptic dopaminergic function such as
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P.3.016 Oxcarbazepine, topiramate and lamotrigine in the treatment of alcohol craving B. Bajovic1 ° , N. Zivkovic2 , G. Djokic3 , D. Pavicevic4 . Neuropsychiatry Hospital “Dr Laza Lazarevic”, K department, Belgrade, Serbia; 2 Neuropsychiatry Hospital “Dr Laza Lazarevic”, M department, Belgrade, Serbia; 3 Neuropsychiatry Hospital “Dr Laza Lazarevic”, Scientific Research Centre, Belgrade, Serbia; 4 Neuropsychiatry Hospital “Dr Laza Lazarevic”, Intensive Care Unit, Belgrade, Serbia 1
Substance use disorders (SUD) are both very common and very severe psychiatric disorders, with a high prevalence in the general population. It is supposed that the midbrain dopaminergic system and neuroadaptive changes in almost all neurotransmitter systems have significant roles in the neurobiochemical basis of SUD. Oxcarbazepine (OXC) blocks voltage-sensitive sodium channels and reduces high-voltage activated calcium currents in striatal and cortical neurons. Topiramate (TPA) is a modulator of voltage-sensitive sodium channels; its mechanism of action is uncertain, altough it does potentiate GABA activity in the brain. Lamotrigine (LTG) blocks voltagedependent sodium channels and reduces the release of excitatory neurotransmitters, in particular that of glutamate. Aim of this study was to investigate the efficacy of the antiepileptics/mood stabilisers OXC, TPA and LTG in the treatment of alcohol-induced craving. Methods: This prospective clinical study included 182 patients with ICD-10 criteria for alcohol dependence, who were randomly divided into four groups − a control group (C), N = 40, and three experimental groups: Oxcarbazepine (O), N = 51; Topiramate (T), N = 42 and Lamotrigine (L), N = 49. Patients were observed for 6 months in hospital and outpatient conditions, according to a specially designed protocol, which included the clinical score on the alcohol craving scale (ACS). The control group was treated with symptomatic therapy, and the experimental groups were treated with symptomatic therapy and OXC (600–1200 mg/24 h), TPA (100– 200 mg/24 h), and LTG (75–200 mg/24 h), respectively. Results: There was no statistical significance in pretrial scores between the groups, p = 0.847 for ACS. In all experimental groups there was a statistically significant reduction in ACS score versus baseline both after 30 days (p = 0.001) and after 180 days (p = 0.001). There was no statistically significant reduction in ACS score between 30 and 180 days (p = 0.724). Results of ACS reduction between all experimental groups are as follows: O vs. C,
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p = 0.001 after 30 and 180 days (highly statistically significant); O vs. T, p = 0.011 after 30 and p = 0.009 after 180 days (highly statistically significant); O vs. L, p = 0.856 after 30 and p = 0.232 after 180 days (not statistically significant); L vs. C, p = 0.001 after 30 and 180 days (highly statistically significant); L vs. T, p = 0.021 after 30 and p = 0.039 after 180 days (highly statistically significant); T vs. C, p = 0.001 after 30 and 180 days (highly statistically significant). After 180 days ACS reduction was significant in all four groups: 78.41% in O; 71.82% in L; 69.52% in T and 57.11% in C. The relapse rate was significantly lower in all three experimental groups than in the control group. No severe side effects were observed during this study. Conclusion: OXC, TPA and LTG have potent anticraving effect in alcohol dependents. OXC, TPA and LTG are efficacious in reducing ACS score. At the end of the study OXC showed the best efficacy. OXC, TPA and LTG all three significantly lowered the risk of relapse in comparison with the control group. Reference(s) [1] Johnson BA, Swift RM, Ait-Daoud N, DiClemente CC, Javors MA, Malcolm RJ Jr. Development of novel pharmacotherapies for the treatment of alcohol dependence: focus on antiepileptics. Alcohol Clin Exp Res 2004. 28 (2): 295–301. [2] Mason BJ, Shaham Y, Weiss F, Le AD. Stress, alcohol craving, and relapse risk: mechanisms and viable treatment targets. Alcohol 2009. 43 (7): 541–543. [3] Boykoff N., Schneekloth TD, Hall-Flavin D, Loukianova L, Karpyak VM, Stevens SR, Biernacka JM, Mrazek DA, Frye MA. Gender differences in the relationship between depressive symptoms and craving in alcoholism. Am J Addict. 2010. 19 (4): 352–356. P.3.017 Human impulsivity is not associated with variation in presynaptic striatal dopamine synthesis capacity P.R.A. Stokes1 ° , A. Benecke1 , J.P. Shotbolt2 , D.J. Nutt1 , O.D. Howes2 , A.R. Lingford-Hughes1 . 1 Imperial College London, Neuropsychopharmacology Unit 5th Floor Burlington Danes Building, London, United Kingdom; 2 Imperial College London, Psychiatric Imaging Group MRC Clinical Sciences Centre, London, United Kingdom Introduction: Impulsivity is a personality trait which encompasses the tendency to initiate actions without forethought and the inability to inhibit inappropriate behaviour. Impulsivity plays an important role in a number
of psychiatric disorders including substance misuse and addiction, ADHD and impulse control disorders. Increased levels of trait impulsivity in healthy human volunteers are associated with decreased midbrain dopamine D2 /D3 receptor availability and greater amphetamine induced striatal dopamine release [1]. Moreover, healthy human TT homozygotes of the dopamine D2 receptor polymorphism C957T, which affects postsynaptic striatal receptor density, show higher levels of dysfunctional impulsivity [2]. Although there is increasing evidence that variation in postsynaptic striatal dopamine function influences human impulsivity, no studies have so far examined whether this is the case for presynaptic striatal dopamine function. Aims: To determine whether human impulsivity is associated with variation in presynaptic striatal dopamine synthesis capacity using [18F]-DOPA positron emission tomography (PET). Methods: 20 healthy volunteers (11 males, mean age 37 years (SD: 14)) were recruited to the study. Each volunteer underwent one [18F]-DOPA PET scan to determine presynaptic dopamine synthesis capacity. Volunteers were scanned using a high resolution ECAT EXACT3D PET scanner. All scans were corrected for head movement using frame by frame realignment. Normalised striatal functional subdivision maps, comprised of limbic, associative and sensorimotor regions, were used to sample individual dynamic [18F]-DOPA PET images. Ki values for each region were estimated by a Patlak analysis using the cerebellum as a reference region. Impulsivity was assessed for each volunteer using the Barratt Impulsiveness Scale (BIS-11) and the Eysenck Impulsivity, Venturesomeness and Empathy questionnaire (EPQ-IVE). [18F]-DOPA Ki values and personality scores were assessed for normality of distribution. Relationships between personality scores and [18F]-DOPA Ki values were examined using Pearson’s correlation for normally distributed variables and Spearman’s correlation for nonnormally distributed variables. All statistical analyses were performed using SPSS 19. Results: There were no significant correlations between overall striatal dopamine synthesis capacity and EPQIVE impulsivity scores (rho = 0.08, p = 0.7), first order self control BIS scores (rho = −0.17, p = 0.5), second order non-planning impulsivity BIS scores (rho = −0.08, p = 0.7) or total BIS scores (rho = −0.03, p = 0.9). Scores for these impulsivity scales also did not correlate to presynaptic dopamine synthesis capacity in any functional striatal subdivision (p values for all correlations >0.05). Conclusions: We found that human impulsivity is not associated with variation in striatal presynaptic dopamine synthesis capacity in healthy volunteers. This result indicates that although impulsivity may be related to markers of postsynaptic dopaminergic function such as