Introduction: Restless legs syndrome (RLS) is a common neurological disorder affecting 10% of the population. Most antidepressants exacerbate symptoms; however, correlational studies have noted symptom improvement with bupropion. The purpose of the current study was to examine whether, in a controlled study, bupropion would improve the symptoms of RLS, or at least not exacerbate them. Methods: This was a double-blinded, randomized controlled trial. Twenty-nine participants with moderate to severe RLS received 150 mg sustained-release bupropion once daily, and 31 control participants received a placebo. Participants were followed for 6 weeks and completed standardized tools, including the International Restless Legs Syndrome Study Group (IRLSSG) severity scale. Results: The primary outcome was change from baseline in IRLSSG severity score; lower scores were associated with improved symptoms. At 3 weeks, IRLSSG scores were 10.8 points lower in the bupropion group and 6.0 points lower in the placebo group (P = .016). At 6 weeks, IRLSSG scores were 10.4 points lower in the bupropion group and 7.6 points lower in the placebo group (P = .108). Bupropion was more effective than placebo in the treatment of RLS at 3 weeks; however, this difference was not statistically significant at 6 weeks. Conclusions: The data from our study suggest that bupropion does not exacerbate the symptoms of RLS and may be a reasonable choice if an antidepressant is needed in individuals with RLS. Larger studies that include titration of bupropion should be considered to determine if bupropion is appropriate for primary treatment of RLS, particularly considering the lower cost and favorable side effect profile compared with currently recommended first-line dopamine agonists.

One of the main reasons smokers struggle to quit is the cognitive deficits caused by abstinence. Bupropion (BUP) and nicotine replacement therapy (NRT) are two of the three FDA-approved efficacious pharmacotherapies to assist in nicotine abstinence. Very little is known about the differences between the neurocognitive effects of NRT and BUP. This dissertation analyzed a dataset of electroencephalogram (EEG) collected while participants performed a visuospatial dot-localization task (DOTLOC). In the study, 119 smokers were randomly divided into 4 groups (BUP, NRT, placebo, and delayed-quit controls) for 6 sessions – one baseline experimental session, four treatment sessions and one post-treatment session after 67 days of abstinence. During the task, source-localized theta, alpha, and beta activity were obtained for the four groups (NRT and BUP, placebo, and delay-quit smokers) at three network-related regions of interest (ROIs). After 3 and 24 days of abstinence, NRT contrasted with placebo showed increases in high frequency current source density (CSD) and decrease in low-frequency CSD. After 3 days of abstinence, BUP contrasted with placebo showed increase in theta and beta CSD at parietal sites and decrease in spectral CSD at frontal and temporal sites. When contrasted with NRT, BUP showed an increase in low-frequency CSD at parietal regions, and decrease in low and high-frequency at temporal and frontal regions. A significant difference was also found in abstinent smokers at 66 days compared to pre-quit session and smoking controls, with a significant increase in parietal alpha activity and a significant decrease in beta CSD. This was the first research to look at the neurocognitive effects of bupropion compared to NRT, as well as the first to identify the long-term changes caused by tobacco abstinence on task-related cortical activity.

While selective serotonin (5-HT) reuptake inhibitors (SSRIs) are utilized as the first-line strategy in treating depression, new approaches are still desired. Using in vivo electrophysiological techniques, the effects of co-administration of bupropion with the SSRI escitalopram on the firing rate of dorsal raphe 5-HT and locus coeruleus norepinephrine (NE) neurons were investigated. Escitalopram significantly decreased the firing of 5-HT and NE neurons at day 2. The 5-HT firing rate, unlike that of NE, recovered after the 14-day escitalopram regimen. Bupropion did not increase 5-HT firing but decreased that of NE after 2 days. Following 14-day bupropion, 5-HT firing was markedly enhanced, and NE firing was back to baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing after 2 and 14 days, whereas NE neurons were inhibited after 2, but partially recovered after 14 days. Although sustained bupropion administration did not alter the sensitivity of 5-HT1A receptors in hippocampus, the tonic activation of postsynaptic 5-HT1A receptors was enhanced in 14-day bupropion-treated rats to a greater extent than in the 2-day and control rats. The function of terminal 5-HT1B autoreceptors was not changed. The inhibitory action of α2-adrenergic receptors on 5-HT terminals was, however, diminished. The function of terminal α2-adrenergic autoreceptors was also attenuated in rats given bupropion for 14 days. Administration of the antidepressant trazodone suppressed the 5-HT firing at day 2, which recovered to baseline following 14 days. Prolonged trazodone-administration enhanced the tonic activation of postsynaptic 5-HT1A receptors in hippocampus, and decreased the function of terminal 5-HT1B autoreceptors. Finally, a novel psychotropic agent asenapine showed potent antagonistic activity at 5-HT2A, D2, and α2-adrenoceptors. Asenapine, however, acted as a partial agonist at 5-HT1A receptors in dorsal raphe and hippocampus. Overall, the therapeutic effects of various antidepressants may be, at least in part, due to the enhancement of 5-HT and/or NE neurotransmission.

While selective serotonin (5-HT) reuptake inhibitors (SSRIs) are utilized as the first-line strategy in treating depression, new approaches are still desired. Using in vivo electrophysiological techniques, the effects of co-administration of bupropion with the SSRI escitalopram on the firing rate of dorsal raphe 5-HT and locus coeruleus norepinephrine (NE) neurons were investigated. Escitalopram significantly decreased the firing of 5-HT and NE neurons at day 2. The 5-HT firing rate, unlike that of NE, recovered after the 14-day escitalopram regimen. Bupropion did not increase 5-HT firing but decreased that of NE after 2 days. Following 14-day bupropion, 5-HT firing was markedly enhanced, and NE firing was back to baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing after 2 and 14 days, whereas NE neurons were inhibited after 2, but partially recovered after 14 days. Although sustained bupropion administration did not alter the sensitivity of 5-HT1A receptors in hippocampus, the tonic activation of postsynaptic 5-HT1A receptors was enhanced in 14-day bupropion-treated rats to a greater extent than in the 2-day and control rats. The function of terminal 5-HT1B autoreceptors was not changed. The inhibitory action of α2-adrenergic receptors on 5-HT terminals was, however, diminished. The function of terminal α2-adrenergic autoreceptors was also attenuated in rats given bupropion for 14 days. Administration of the antidepressant trazodone suppressed the 5-HT firing at day 2, which recovered to baseline following 14 days. Prolonged trazodone-administration enhanced the tonic activation of postsynaptic 5-HT1A receptors in hippocampus, and decreased the function of terminal 5-HT1B autoreceptors. Finally, a novel psychotropic agent asenapine showed potent antagonistic activity at 5-HT2A, D2, and α2-adrenoceptors. Asenapine, however, acted as a partial agonist at 5-HT1A receptors in dorsal raphe and hippocampus. Overall, the therapeutic effects of various antidepressants may be, at least in part, due to the enhancement of 5-HT and/or NE neurotransmission.

El Bupropion es el primer fármaco no nicotínico con eficacia demostrada en la deshabituación tabáquica, sin embargo no todos los pacientes que se someten a este tratamiento consiguen dejar de fumar. El objetivo de la presente tesis ha sido el de identificar aquellas variable que son por sí mismas predictivas del éxito del tratamiento y desarrollar una ecuación matemática capaz de cuantificar la probabilidad de dejar de fumar . Para ello han sido estudiados 150 pacientes, seguidos durante un año. Eran todos fumadores de más de 15/cigarrillos día y en fase de preparación. Fueron tratados con 300 mg de Bupropión al día y durante 8 semanas. Se tomaran en cuenta una serie de variables divididas por categorías: a) Variables Clínicas: edad del paciente, número de paquetes/año fumados, número de intentos previos para dejar de fumar, si no habían fumado nada durante la primera semana de tratamiento y si habían sido diagnosticados de EPOC. b) Variables Funcionales: FVC, FEV1, FEV1/FVC, FEF 25-75%. C) Variables Psicométricos: ansiedad y depresión. d) Variables de Tabaquismo: Fagëstrom, CO espirado. Después de un año de seguimiento un 50,7% de nuestros pacientes habían conseguido dejar de fumar. Posteriormente se realizó un análisis univariante para conocer si alguna variable presentaba diferencias significativas entre los pacientes que habían conseguido dejar de fumar y los que no. Encontramos tres variables con significación estadística: la ansiedad, el no haber fumado nada durante la primera semana de tratamiento y el FEF25-75%. Posteriormente, mediante la regresión logística, según técnica descrita por Domenech, construimos un modelo más parsimonioso donde fueron incluidas dos variables más: la depresión y el ser o no EPOC. Un dato importante es el signo de las variables: el signo positivo indica que la presencia de ésta será un factor positivo, es decir que si el paciente es ansioso, depresivo y no fuma durante la primera semana, sus probabilidades de dejar de fumar aumentarán. Por el contrario si el paciente es EPOC sus probabilidades disminuirán. El FEF 25-75 es una variable continua, siendo su interpretación más difícil: nuestros resultados demostraban que aquellos pacientes con FEF 25-75 bajos tenían más posibilidades en dejar de fumar, posiblemente este hecho fuese debido a que nosotros siempre enseñamos a los pacientes los resultados espirométricos, la mejoría del FEF25-75 podría estar funcionando como un reforzador positivo, al igual que pequeñas pérdidas de peso ayudan a determinados a pacientes a seguir dietas hipocalóricas. Por último trasladamos nuestras cinco variables a la ecuación de la regresión logística, construyendo así un modelo matemático que permite predecir cual es la probabilidad de cada paciente de poder abandonar su hábito tabáquico. Al testar el valor predictivo de la ecuación esta tenía un área bajo la curva ROC del 88%. / The Bupropion is the first medication without nicotine and effectiveness demonstrated in the smoking cessation. However not all the patients that undergo this treatment are able to stop to smoke. The objective of the present thesis has been the one of to identify those variables that they are for themselves predictive of the success of the treatment and to develop a mathematical equation able to quantify the probability of stopping to smoke. For 150 patients they have been studied, followed during one year. They were all smokers of more than 15cigarettes/day and in preparation phase. They were been with 300 mg from Bupropion to day and during 8 weeks. They took into account a series of variables divided by categories: to) Clinical Variables: the patient's age, number of smoked package/year, number of previous intents to stop to smoke, if they had not smoked anything during the first week of treatment and if they had been diagnosed of COPD. b) Functional Variables: FVC, FEV1, FEV1/FVC, FEF 25-75%. C) Psychological Variables: anxiety and depression. d) Tobacco Variables: Fagëstrom test and CO exhaled. After a year of follow-up 50,7% of our patients had been able to stop to smoke. Later on we was carried out an univariant analysis to know if some variable presented significant differences among the patients that had been able to stop to smoke and those that not. We find three variables with statistical significance: the anxiety, not having smoked anything during the first week of treatment and FEF25-75%. Later on, by means of the logistical regression, according to technique described by Domenech, we build a more parsimonious model where two variables were included more: the depression and the being or non COPD. An important fact is the sign of the variables: the positive sign indicates that the presence of this will be a positive factor, that is to say that if the patient is anxious, depressive and doesn't smoke during the first week, their probabilities of stopping to smoke will increase. On the contrary if the patient is COPD her probabilities they will diminish. The FEF 25-75 is a continuous variable, being its more difficult interpretation: our results demonstrated that those patients with FEF 25-75 diminished values initials, had more possibilities in stopping to smoke. This fact was possibly because we always showed the spirometric results to the patients, the improvement of the FEF25-75 could be working as a positive reinforce, the same as small losses of weight they help to certain to patient to follow diets with few calories. Lastly we transfer our five variables to the equation of the logistical regression, building this way a mathematical model that allows predicting which is each patient's probability of being able to abandon their smoke dependence. When making a will the predictive value of the equation this had an area under the curve ROC to 88%.

While selective serotonin (5-HT) reuptake inhibitors (SSRIs) are utilized as the first-line strategy in treating depression, new approaches are still desired. Using in vivo electrophysiological techniques, the effects of co-administration of bupropion with the SSRI escitalopram on the firing rate of dorsal raphe 5-HT and locus coeruleus norepinephrine (NE) neurons were investigated. Escitalopram significantly decreased the firing of 5-HT and NE neurons at day 2. The 5-HT firing rate, unlike that of NE, recovered after the 14-day escitalopram regimen. Bupropion did not increase 5-HT firing but decreased that of NE after 2 days. Following 14-day bupropion, 5-HT firing was markedly enhanced, and NE firing was back to baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing after 2 and 14 days, whereas NE neurons were inhibited after 2, but partially recovered after 14 days. Although sustained bupropion administration did not alter the sensitivity of 5-HT1A receptors in hippocampus, the tonic activation of postsynaptic 5-HT1A receptors was enhanced in 14-day bupropion-treated rats to a greater extent than in the 2-day and control rats. The function of terminal 5-HT1B autoreceptors was not changed. The inhibitory action of α2-adrenergic receptors on 5-HT terminals was, however, diminished. The function of terminal α2-adrenergic autoreceptors was also attenuated in rats given bupropion for 14 days. Administration of the antidepressant trazodone suppressed the 5-HT firing at day 2, which recovered to baseline following 14 days. Prolonged trazodone-administration enhanced the tonic activation of postsynaptic 5-HT1A receptors in hippocampus, and decreased the function of terminal 5-HT1B autoreceptors. Finally, a novel psychotropic agent asenapine showed potent antagonistic activity at 5-HT2A, D2, and α2-adrenoceptors. Asenapine, however, acted as a partial agonist at 5-HT1A receptors in dorsal raphe and hippocampus. Overall, the therapeutic effects of various antidepressants may be, at least in part, due to the enhancement of 5-HT and/or NE neurotransmission.

While selective serotonin (5-HT) reuptake inhibitors (SSRIs) are utilized as the first-line strategy in treating depression, new approaches are still desired. Using in vivo electrophysiological techniques, the effects of co-administration of bupropion with the SSRI escitalopram on the firing rate of dorsal raphe 5-HT and locus coeruleus norepinephrine (NE) neurons were investigated. Escitalopram significantly decreased the firing of 5-HT and NE neurons at day 2. The 5-HT firing rate, unlike that of NE, recovered after the 14-day escitalopram regimen. Bupropion did not increase 5-HT firing but decreased that of NE after 2 days. Following 14-day bupropion, 5-HT firing was markedly enhanced, and NE firing was back to baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing after 2 and 14 days, whereas NE neurons were inhibited after 2, but partially recovered after 14 days. Although sustained bupropion administration did not alter the sensitivity of 5-HT1A receptors in hippocampus, the tonic activation of postsynaptic 5-HT1A receptors was enhanced in 14-day bupropion-treated rats to a greater extent than in the 2-day and control rats. The function of terminal 5-HT1B autoreceptors was not changed. The inhibitory action of α2-adrenergic receptors on 5-HT terminals was, however, diminished. The function of terminal α2-adrenergic autoreceptors was also attenuated in rats given bupropion for 14 days. Administration of the antidepressant trazodone suppressed the 5-HT firing at day 2, which recovered to baseline following 14 days. Prolonged trazodone-administration enhanced the tonic activation of postsynaptic 5-HT1A receptors in hippocampus, and decreased the function of terminal 5-HT1B autoreceptors. Finally, a novel psychotropic agent asenapine showed potent antagonistic activity at 5-HT2A, D2, and α2-adrenoceptors. Asenapine, however, acted as a partial agonist at 5-HT1A receptors in dorsal raphe and hippocampus. Overall, the therapeutic effects of various antidepressants may be, at least in part, due to the enhancement of 5-HT and/or NE neurotransmission.

A defined group of medical records was surveyed for patients who showed onset of major depression with melancholic features while taking an antidepressant medication. Nine cases resulted. In all the antidepressants being taken while melancholia began were SSRIs and the melancholic depression remitted rapidly with the first treatment given, bupropion in five males, nortriptyline with triiodothyronine in two females, and ECT in one male and one female. This suggests that patients who take SSRIs and are melancholic respond well to bupropion, nortriptyline, or ECT. These observations complement reports of low responsivity of melancholic depression to SSRIs and distinctions between melancholic and nonmelancholic depressions.

Neuropathic pain is a common problem in clinical practice, affecting patients physically, emotionally, financially, and socially. Current treatment includes antidepressants, antiepileptics, and opioid analgesics. Bupropion is a specific inhibitor of neuronal noradrenaline reuptake and a weak inhibitor of dopamine reuptake, which shows some promise in the treatment of neuropathic pain.

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Vita. Bibliography: pp. 246-266.