[PMC free content] [PubMed] [Google Scholar]Johnson BA
[PMC free content] [PubMed] [Google Scholar]Johnson BA. B topics acquired early-onset alcoholism; 67% of Type A topics acquired late-onset alcoholism. The A/B typology better discriminated two clusters based on baseline intensity of alcoholism. There is a significant impact ( 0.05) for Type B alcoholics to react to ondansetron (4 g/kg); nevertheless, Type A alcoholics getting ondansetron demonstrated no beneficial impact. Early-vs. late-onset classification forecasted ondansetron response much better than Type A/B classification significantly, which didn’t enhance the prediction of treatment final result. Further analyses demonstrated that ondansetron was effective in the 33% of Type A alcoholics with early-onset alcoholism but inadequate in the 28% of Type B alcoholics with late-onset alcoholism. Conclusions Type A/B classification greatest discriminates alcoholic subtypes based on baseline intensity. Early- vs. late-onset classification is certainly, nevertheless, an improved predictor of response to ondansetron treatment since it might be even more closely linked to fundamental neurobiological procedures from the root pathophysiology of alcoholism. sorting of issue drinkers into dichotomous types has reproducibly confirmed a schema to recognize a sort B cluster known by a youthful onset of disease, more serious dependence symptoms, and, general, a worse prognosis. Many research show that subgroups of alcoholics may react to treatment with serotonergic medication differently. Our group reported that age group of starting point of alcohol-related complications is an efficient predictor of response to treatment using the 5-HT3 antagonist ondansetron (Johnson et al., 2000c). In that scholarly study, age of starting point (25 years vs. 26 years) was utilized as a way of classification of two alcoholism subtypes referred to as early-onset alcoholism (EOA) vs. late-onset alcoholism (LOA), respectively, ahead of randomized treatment with placebo or among three dosages (1, 4, or 16 g/kg double daily) of ondansetron. Ondansetron was more advanced than placebo among EOA however, not LOA topics. The optimal dosage in that research was determined to become 4 g/kg of ondansetron even though some excellent results also had been attained with lower (1 g/kg) and higher (16 g/kg) dosages. This acquiring was extended showing that the mix of ondansetron (4 g/kg) and naltrexone (25 mg) was effective in the treating EOA topics (Johnson et al., 2000a). Within a following open-label trial with ondansetron (4 g/kg), Kranzler et al. (2003) replicated our discovering that EOA topics responded much better than LOA topics to treatment. These research clearly create that alcoholics with an early on age of starting point could be treated successfully using the 5-HT3 antagonist, ondansetron, and additional indicate that age group of onset is certainly a solid predictor of response to treatment with ondansetron. Significantly, response to treatment with selective serotonin reuptake inhibitors (SSRIs) also is apparently forecasted by alcoholism subtype. Whereas experimental research among issue drinkers possess reported that SSRIs including zimelidine, citalopram, viqualine, and fluoxetine each decreased alcoholic beverages intake in comparison to placebo (Naranjo et al., 1984, 1987, 1989, 1990), SSRIs including fluvoxamine and fluoxetine weren’t found to become efficacious for the treating a heterogeneous band of alcohol-dependent outpatients (Kranzler et al., 1993, 1995). In the last mentioned of these research (Kranzler et al., 1995), fluoxetine was more advanced than placebo at enhancing depressive symptoms within a subgroup of sufferers with comorbid despair even though this is not connected with a decrease in alcoholic beverages intake. Subsequently, these researchers reanalyzed their data (Kranzler et al., 1996) utilizing a cluster evaluation to divide topics into Babors Type A/B groupings. They discovered that fluoxetine had not been much better than placebo at enhancing taking in final results among Type A alcoholics (n = 60); on the other hand, fluoxetine treatment, weighed against placebo, was connected with considerably worse taking in final results among Type B alcoholics Calcineurin Autoinhibitory Peptide (n = 35). Subsequently, Pettinati et al. (2001) likened the consequences of sertraline (200 mg/time) vs. placebo in 53 alcohol-dependent sufferers with life time histories of despair and 47 sufferers without histories of despair. They didn’t identify an antidepressant aftereffect of sertraline; nevertheless, they do discover that sertraline decreased the consuming of topics who acquired no life time background of despair. To understand this paradoxical obtaining, their data were reanalyzed by cluster analyses (Pettinati et al., 2000), after which sertraline treatment was shown to be substantially superior to placebo at reducing drinking in Type A alcoholics (n = 55) but not in Type B alcoholics (n = 45). At 6-month longitudinal follow-up (Dundon et al., 2004), the Type A alcoholics previously treated with sertraline continued to do better than those treated with placebo. Calcineurin Autoinhibitory Peptide In contrast, among the Type B.Chichester, United Kingdom: John Wiley & Sons; 1990. early- and late-onset alcoholics. Results Seventy-two percent of Type B subjects had early-onset alcoholism; 67% of Type A subjects had late-onset alcoholism. The A/B typology better discriminated two clusters based upon baseline severity of alcoholism. There was a significant effect ( 0.05) for Type B alcoholics to respond to ondansetron (4 g/kg); however, Type A alcoholics receiving ondansetron showed no beneficial effect. Early-vs. late-onset classification predicted ondansetron response substantially better than Type A/B classification, which did not add to the prediction of treatment outcome. Further analyses showed that ondansetron was effective in the 33% of Type A alcoholics with early-onset alcoholism but ineffective in the 28% of Type B alcoholics with late-onset alcoholism. Conclusions Type A/B classification best discriminates alcoholic subtypes based upon baseline severity. Early- vs. late-onset classification is usually, however, a better predictor of response to ondansetron treatment because it might be more closely related to fundamental neurobiological processes associated with the underlying pathophysiology of alcoholism. sorting of problem drinkers into dichotomous categories has reproducibly verified a schema to identify a Type B cluster known by an earlier onset of illness, more severe dependence symptoms, and, overall, a worse prognosis. Several studies have shown that subgroups of alcoholics may respond differently to treatment with serotonergic medication. Our group reported that age of onset of alcohol-related problems is an effective predictor of response to treatment with the 5-HT3 antagonist ondansetron (Johnson et al., 2000c). In that study, age of onset (25 years vs. 26 years) was used as a means of classification Plxnc1 of two alcoholism subtypes known as early-onset alcoholism (EOA) vs. late-onset alcoholism (LOA), respectively, prior to randomized treatment with placebo or one of three doses (1, 4, or 16 g/kg twice daily) of ondansetron. Ondansetron was superior to placebo among EOA but not LOA subjects. The optimal dose in that study was determined to be 4 g/kg of ondansetron although some positive results also were obtained with lower (1 g/kg) and higher (16 g/kg) doses. This obtaining was extended to show that the combination of ondansetron (4 g/kg) and naltrexone (25 mg) was effective in the treatment of EOA subjects (Johnson et al., 2000a). In a subsequent open-label trial with ondansetron (4 g/kg), Kranzler et al. (2003) replicated our finding that EOA subjects responded better than LOA subjects to treatment. These studies clearly establish that alcoholics with an early age of onset can be treated effectively with the 5-HT3 antagonist, ondansetron, and further indicate that age of onset is usually a strong predictor of response to treatment with ondansetron. Importantly, response to treatment with selective serotonin reuptake inhibitors (SSRIs) also appears to be predicted by alcoholism subtype. Whereas experimental studies among problem drinkers have reported that SSRIs including zimelidine, citalopram, viqualine, and fluoxetine each reduced alcohol intake in comparison with placebo (Naranjo et al., 1984, 1987, 1989, 1990), SSRIs including fluvoxamine and fluoxetine were not found to be efficacious for the treatment of a heterogeneous group of alcohol-dependent outpatients (Kranzler et al., 1993, 1995). In the latter of these studies (Kranzler et al., 1995), fluoxetine was superior to placebo at improving depressive symptoms in a subgroup of patients with comorbid depressive disorder even though this was not associated with a reduction in alcohol consumption. Subsequently, these investigators reanalyzed their data (Kranzler et al., 1996) using a cluster analysis to divide subjects into Babors Type A/B groupings. They found that fluoxetine was not better than placebo at improving drinking outcomes among Type A alcoholics (n = 60); in contrast, fluoxetine treatment, compared with placebo, was associated with significantly worse drinking outcomes among Type B alcoholics (n = 35). Subsequently, Pettinati et al. (2001) compared the effects of sertraline (200 mg/day) vs. placebo in 53 alcohol-dependent patients with lifetime histories of depressive disorder and 47 patients without histories of depressive disorder. They failed to detect an antidepressant effect of sertraline; however, they did observe that sertraline reduced the drinking of subjects who had no lifetime history of depression. To understand this paradoxical obtaining, their data were reanalyzed by cluster analyses (Pettinati et al., 2000), after which sertraline treatment was shown to be substantially superior to placebo at reducing drinking in Type A alcoholics (n = 55) but not in Type B alcoholics (n = 45). At 6-month longitudinal follow-up (Dundon et al., 2004), the Type A alcoholics previously treated with sertraline continued to do better than those treated with placebo. In contrast, among the Type B alcoholics,.pp. discriminated two clusters based upon baseline severity of alcoholism. There is a significant impact ( 0.05) for Type B alcoholics to react to ondansetron (4 g/kg); nevertheless, Type A alcoholics getting ondansetron demonstrated no beneficial impact. Early-vs. late-onset classification expected ondansetron response considerably much better than Type A/B classification, which didn’t enhance the prediction of treatment result. Further analyses demonstrated that ondansetron was effective in the 33% of Type A alcoholics with early-onset alcoholism but inadequate in the 28% of Type B alcoholics with late-onset alcoholism. Conclusions Type A/B classification greatest discriminates alcoholic subtypes based on baseline intensity. Early- vs. late-onset classification can be, nevertheless, an improved predictor of response to ondansetron treatment since it might be even more closely linked to fundamental neurobiological procedures from the root pathophysiology of alcoholism. sorting of issue drinkers into dichotomous classes has reproducibly confirmed a schema to recognize a sort B cluster known by a youthful onset of disease, more serious dependence symptoms, and, general, a worse prognosis. Many studies show that subgroups of alcoholics may react in a different way to treatment with serotonergic medicine. Our group reported that age group of starting point of alcohol-related complications is an efficient predictor of response to treatment using the 5-HT3 antagonist ondansetron (Johnson et al., 2000c). For the reason that research, age of starting point (25 years vs. 26 years) was utilized as a way of classification of two alcoholism subtypes referred to as early-onset alcoholism (EOA) vs. late-onset alcoholism (LOA), respectively, ahead of randomized treatment with placebo or among three dosages (1, 4, or 16 g/kg double daily) of ondansetron. Ondansetron was more advanced than placebo among EOA however, not LOA topics. The optimal dosage in that research was determined to become 4 g/kg of ondansetron even though some excellent results also had been acquired with lower (1 g/kg) and higher (16 g/kg) dosages. This locating was extended showing that the mix of ondansetron (4 g/kg) and naltrexone (25 mg) was effective in the treating EOA topics (Johnson et al., 2000a). Inside a following open-label trial with ondansetron (4 g/kg), Kranzler et al. (2003) replicated our discovering that EOA topics responded much better than LOA topics to treatment. These research clearly set up that alcoholics with an early on age of starting point could be treated efficiently using the 5-HT3 antagonist, ondansetron, and additional indicate that age group of onset can be a solid predictor of response to treatment with ondansetron. Significantly, response to treatment with selective serotonin reuptake inhibitors (SSRIs) also is apparently expected by alcoholism subtype. Whereas experimental research among issue drinkers possess reported that SSRIs including zimelidine, citalopram, viqualine, and fluoxetine each decreased alcoholic beverages intake in comparison to placebo (Naranjo et al., 1984, 1987, 1989, 1990), SSRIs including fluvoxamine and fluoxetine weren’t found to become efficacious for the treating a heterogeneous band of alcohol-dependent outpatients (Kranzler et al., 1993, 1995). In the second option of these research (Kranzler et al., 1995), fluoxetine was more advanced than placebo at enhancing depressive symptoms inside a subgroup of individuals with comorbid melancholy even though this is not connected with a decrease in alcoholic beverages usage. Subsequently, these researchers reanalyzed their data (Kranzler et al., 1996) utilizing a cluster evaluation to divide topics into Babors Type A/B groupings. They discovered that fluoxetine had not been much better than placebo at enhancing taking in results among Type A alcoholics (n = 60); on the other hand, fluoxetine treatment, weighed against placebo, was connected with considerably worse taking in results among Type B alcoholics (n = 35). Subsequently, Pettinati et al. (2001) likened the consequences of sertraline (200 mg/day time) vs. placebo in 53 alcohol-dependent individuals with life time histories of melancholy and 47 individuals without histories of melancholy. They didn’t identify an antidepressant aftereffect of sertraline; nevertheless, they did discover that sertraline decreased the consuming of topics who got no lifetime background of depression. To comprehend this paradoxical locating, their data had been reanalyzed by cluster analyses (Pettinati et al., 2000), and sertraline treatment was been shown to be considerably more advanced than placebo at reducing taking in in Type A alcoholics (n = 55) however, not in Type B alcoholics (n = 45). At 6-month longitudinal follow-up (Dundon.While described previously (Johnson et al., 2000c), age onset for every Calcineurin Autoinhibitory Peptide subject was established during a medical interview using the In depth Drinker Profile (Miller and Marlatt, 1984), which evaluated drinking-related complications in multiple domains of psychosocial dysfunction (we.e., employment complications, legal complications, marital complications, etc.) and asked the query (item #28), at what age did taking in turn into a nagging problem for you personally? For alcohol-dependent individuals, this age group of the 1st symptoms of issue taking in constitutes the original onset from the symptoms of dependence. with Type A/B classification. Subjects were subdivided into early- and late-onset alcoholics. Results Seventy-two percent of Type B subjects experienced early-onset alcoholism; 67% of Type A subjects experienced late-onset alcoholism. The A/B typology better discriminated two clusters based upon baseline severity of alcoholism. There was a significant effect ( 0.05) for Type B alcoholics to respond to ondansetron (4 g/kg); however, Type A alcoholics receiving ondansetron showed no beneficial effect. Early-vs. late-onset classification expected ondansetron response considerably better than Type A/B classification, which did not add to the prediction of treatment end result. Further analyses showed that ondansetron was effective in the 33% of Type A alcoholics with early-onset alcoholism but ineffective in the 28% of Type B alcoholics with late-onset alcoholism. Conclusions Type A/B classification best discriminates alcoholic subtypes based upon baseline severity. Early- vs. late-onset classification is definitely, however, a better predictor of response to ondansetron treatment because it might be more closely related to fundamental neurobiological processes associated with the underlying pathophysiology of alcoholism. sorting of problem drinkers into dichotomous groups has reproducibly verified a schema to identify a Type B cluster known by an earlier onset of illness, more severe dependence symptoms, and, overall, a worse prognosis. Several studies have shown that subgroups of alcoholics may respond in a different way to treatment with serotonergic medication. Our group reported that age of onset of alcohol-related problems is an effective predictor of response to treatment with the 5-HT3 antagonist ondansetron (Johnson et al., 2000c). In that study, age of onset (25 years vs. 26 years) was used as a means of classification of two alcoholism subtypes known as early-onset alcoholism (EOA) vs. late-onset alcoholism (LOA), respectively, prior to randomized treatment with placebo or one of three doses (1, 4, or 16 g/kg twice daily) of ondansetron. Ondansetron was superior to placebo among EOA but not LOA subjects. The optimal dose in that study was determined to be 4 Calcineurin Autoinhibitory Peptide g/kg of ondansetron although some positive results also were acquired with lower (1 g/kg) and higher (16 g/kg) doses. This getting was extended to show that the combination of ondansetron (4 g/kg) and naltrexone (25 mg) was effective in the treatment of EOA subjects (Johnson et al., 2000a). Inside a subsequent open-label trial with ondansetron (4 g/kg), Kranzler et al. (2003) replicated our finding that EOA subjects responded better than LOA subjects to treatment. These studies clearly set up that alcoholics with an early age of onset can be treated efficiently with the 5-HT3 antagonist, ondansetron, and further indicate that age of onset is definitely a strong predictor of response to treatment with ondansetron. Importantly, response to treatment with selective serotonin reuptake inhibitors (SSRIs) also appears to be expected by alcoholism subtype. Whereas experimental studies among problem drinkers have reported that SSRIs including zimelidine, citalopram, viqualine, and fluoxetine each reduced alcohol intake in comparison with placebo (Naranjo et al., 1984, 1987, 1989, 1990), SSRIs including fluvoxamine and fluoxetine were not found to be efficacious for the treatment of a heterogeneous group of alcohol-dependent outpatients (Kranzler et al., 1993, 1995). In the second option of these studies (Kranzler et al., 1995), fluoxetine was superior to placebo at improving depressive symptoms inside a subgroup of individuals with comorbid major depression even though this was not associated with a reduction in alcohol usage. Subsequently, these investigators reanalyzed their data (Kranzler et al., 1996) using a cluster analysis to divide subjects into Babors Type A/B groupings. They found that fluoxetine was not better than placebo at improving drinking results among Type A alcoholics (n = 60); in contrast, fluoxetine treatment, compared with placebo, was associated with significantly worse drinking results among Type B alcoholics (n = 35). Subsequently, Pettinati et al. (2001).