Psychopharmacology
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Randomized Controlled Trial Multicenter Study
Multi-center, randomized, double-blind, placebo-controlled study of quetiapine extended-release formulation in Japanese patients with bipolar depression.
Quetiapine fumarate is an atypical antipsychotic indicated for various mental disorders, but it has not been studied in Japanese patients with bipolar depression. ⋯ Once-daily monotherapy with quetiapine XR is an effective and well-tolerated treatment for bipolar depression in Japanese patients.
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Randomized Controlled Trial
Assessment of pioglitazone and proinflammatory cytokines during buprenorphine taper in patients with opioid use disorder.
Preliminary evidence suggested that the PPARγ agonist pioglitazone reduces opioid-withdrawal symptoms, possibly by inhibiting increases in proinflammatory cytokines. ⋯ Results from this study provide no evidence that pioglitazone reduces opioid withdrawal symptoms during buprenorphine taper. High correlations between MCP-1 and opioid withdrawal symptoms support a role of proinflammatory processes in opioid withdrawal.
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Randomized Controlled Trial
The effect of dopamine on conditioned placebo analgesia in healthy individuals: a double-blind randomized trial.
Better means to control placebo effects are key to optimizing treatment outcomes. Dopamine-based reward and learning mechanisms have been hypothesized to drive placebo effects. Here, we tested whether dopamine augmentation can modulate learned placebo effects. ⋯ In summary, the present study could not provide evidence for a placebo augmenting effect of levodopa-enhanced dopamine levels in healthy subjects. Further studies are needed to elucidate whether placebo enhancement can be achieved through dopamine augmentation.
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Two mechanisms underlie smoking cessation efficacies of α4β2* nicotinic acetylcholine receptor (nAChR) agonists: a "nicotine-like" agonist activity reduces craving by substituting for nicotine during a quit attempt, and a "nicotine-blocking" antagonist activity attenuates reinforcement by competing with inhaled nicotine during a relapse. To evaluate the contribution of each mechanism to clinical efficacy, we estimated the degree of agonist and antagonist activities of nicotine replacement therapy (NRT), varenicline, cytisine, and the discontinued nAChR agonists dianicline, ABT-418, ABT-089, CP-601927, and CP-601932, relative to the functional effects of nicotine from smoking. ⋯ Three pharmacological effects appear to be key factors underlying smoking cessation efficacy: the degree of activation of α6β2* nAChRs, desensitization of α4β2 and α6β2* nAChRs (agonist activity), and the reduction of nicotine occupancy at α4β2 and α6β2* nAChRs (antagonist activity). No single activity is dominant, and the level of smoking cessation efficacy depends on the profile of these activities achieved at clinical doses. While adequate agonist activity alone seems sufficient for a clinical effect (e.g., NRT, cytisine), clinical efficacy is improved with substantial competitive antagonism of α4β2 nAChRs, i.e., if the drug has a dual agonist-antagonist mechanism of action (e.g., varenicline).
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Valproate (VPA) is a choice for the treatment of primary generalized epilepsies and partial epilepsies. Unfortunately, weight gain or obesity is one of the most frequent adverse effects of VPA treatment. Genetic factors were shown to be involved in the effect. ⋯ Our data first indicated that CD36 and PPARγ polymorphisms may be associated with VPA-induced obesity and weight gain, suggesting that CD36 and PPARγ may have potential value in predicting VPA-induced obesity in Chinese Han epileptic patients.