S M Stahl

..Thus, blocking norepinephrine transporters leads to an increase in both dopamine and norepinephrine levels in prefrontal cortex as well as improvement in cognition in attention-deficit/hyperactivity disorder...

..The leading notion of how therapeutic effects occur in psychiatric disorders is that they happen when symptoms are reduced by improving the efficiency of information processing in hypothetically malfunctioning brain circuits...

..In many cases, the new indications are the more important therapeutic contributions and the most successful commercial application of a drug. Here we describe this strategy of psychiatric drug development and provide numerous examples...

..This study assessed patterns of antipsychotic use to identify uses that are associated with high economic cost but for which there is no documented efficacy...

..The introduction of antidepressants with novel mechanisms of action could potentially revolutionize the treatment of depression...

..Although efforts thus far to elucidate a distinct schizophrenia subtype based upon negative symptoms have yielded mixed results, there are nevertheless neurobiological correlates of the negative symptom typology...

..This study examined whether galantamine, an AChEI with nicotinic modulation, is associated with nighttime sleeprelated problems...

..Generalized anxiety disorder (GAD) is a chronic illness with psychic and somatic symptoms that do not respond uniformly in the first weeks of treatment...

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..This study evaluated the safety and efficacy of escitalopram in outpatients diagnosed with panic disorder...

..Efficacy and tolerability data from trials to date indicate that ziprasidone's clinical activity is consistent with its receptor profile...

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..A dysfunction at the level of the serotonergic and noradrenergic neurons can thus affect both the ascending and descending pathways resulting in the psychological and somatic symptoms of depression but also in physical painful symptoms...

..To evaluate the efficacy, safety, and tolerability of fixed-dose agomelatine 25 and 50 mg/d in the treatment of outpatients with moderate-to-severe major depressive disorder (MDD) compared to placebo...

..Dysphoric mania is a common and often difficult to treat subset of bipolar mania that is associated with significant depressive symptoms...

..Existing evidence suggests that the best treatments for schizophrenia and psychosis may be long-term trials of a sequence of atypical antipsychotic monotherapies at therapeutic doses...

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..ISSUE: Selective norepinephrine reuptake inhibitors such as atomoxetine increase both dopamine and norepinephrine in frontal cortex and may thereby enhance cognitive functioning in attention-deficit/hyperactivity disorder...

..CONCLUSIONS: Venlafaxine was significantly more effective than SSRIs in improving depression, perhaps due to enhancing both serotonin and norepinephrine...

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..The spectral non-REM sleep EEG profile might be used to investigate central 5-HT function in humans...

..The current study was intended to evaluate the effects of the novel antipsychotic risperidone, the selective serotonin reup-take inhibitor (SSRI) paroxetine, and the combination in patients with bipolar disorder...

..Despite these results, the best treatment of depression currently recognizes the 3 types of symptoms and targets them all for complete remission no matter which drug is used...

..In this article we present a discussion of some of the receptor targets that are currently thought to mediate symptoms of schizophrenia, as well as their possible implications for the design of future multifunctional antipsychotics...

..Synthesis of the monoamine neurotransmitters serotonin, dopamine, and norepinephrine is regulated by L-methylfolate, a derivate of the vitamin folate...

..Actions of certain anticonvulsants upon voltage-gated sodium channels may not only explain why they are effective mood stabilizers but may also explain why they could be useful adjuncts to antipsychotics for resistant psychosis...

..Here, we review deficits in the processing of emotion in schizophrenia, the role of the amygdala in the context of these deficits, and the functional implications of this relationship upon patient outcome...

..Duloxetine and milnacipran appear better tolerated and essentially devoid of cardiovascular toxicity...

..However, no two atypical antipsychotics possess the same portfolio of actions upon all of these additional neurotransmitter systems...

..Schizophrenia is composed of not only positive symptoms, but also cognitive and affective symptoms that contribute significantly to morbidity. Each of these symptoms may be mediated by a separate and distinct neuronal circuit...

..The incidence of treatment-emergent agitation or anxiety was comparable between treatment groups...

..Selectively inducing normal wakefulness without stimulating external vigilance may lead to therapeutic benefits not only in sleep disorders but also in cognitive disorders and conditions associated with fatigue...

..With this approach, the frequently residual symptoms of sleepiness, fatigue, and executive dysfunction can be targeted with bupropion, atomoxetine, modafinil, atypical antipsychotics, and stimulants...

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..Initial enthusiasm that second-generation antipsychotics would prove to be powerful agents to improve negative symptoms has given way to relative pessimism that the effects of current pharmacological treatments are at best modest...

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..Because sleep quality may be a critical issue for persons with AD and their caregivers, more rigorous evaluation of sleep problems linked to AChE-inhibitor treatment is indicated...

..To attain optimal outcomes, modern psychopharmacologists must tailor treatment of depression to a woman's reproductive stage of life...

..Extracts of St John's wort are widely used to treat depression. Although more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful interpretation...

..ISSUE: Since the frontal cortex has a low density of dopamine transporters, dopamine has to be inactivated there by hitching a ride on the norepinephrine transporter of neighboring norepinephrine neurons...

..Issue: Both serotonin and GABA powerfully regulate the neuroanatomical circuit that mediates fear in anxiety disorders. This suggests that use of pharmacotherapies acting on both systems may provide synergistic therapeutic actions...

..quot; The concept is presented in overview here. Future installments will cover specific drugs in greater depth. Multifunctional drugs include those agents with more than one putative therapeutic mechanism of action...

..Those with no previous interest in MAOIs may discover in this article a new "secret weapon" to add to their therapeutic armamentarium for patients who fail to respond to the better-known agents...

..ISSUE: Major depressive disorder comprises multiple symptoms. Each symptom may be mediated by separate and distinct neuronal circuits...

..Adequately managing residual symptoms will hopefully lead to increased remission in these patients. This supplement focuses on the different types of residual symptoms that patients experience and suggests various treatment options...

..ISSUE: Norepinephrine and dopamine work in a cooperative yet reciprocal manner to regulate information processing at pyramidal neurons in the prefrontal cortex...

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..It is possible that blocking NK(1) receptors elsewhere in the CNS will lead to therapeutic actions in depression and other stress-related disorders...

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..ISSUE: Anticonvulsants are not a single therapeutic class, but are composed of multiple distinct subclasses with different mechanisms of action, efficacies, and side effects...

..Levetiracetam binds selectively and with high affinity to a synaptic vesicle protein known as SV2A, thought to be involved with synaptic vesicle exocytosis and presynaptic neurotransmitter release...

..ISSUE: Early treatment of pain could thwart the development of chronic persistent painful conditions...

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..Selective H1 antagonism is emerging as a novel approach to the treatment of insomnia, without tolerance, weight gain, or the need for the restrictive prescription scheduling required of other hypnotics...

..Numerous psychotropic drugs exist as a mixture of 2 mirror-image stereoisomers of each other, each called an enantiomer and the mixture called a racemate. Often the drug can be improved when only 1 of the enantiomers is administered...

..Modulation of VSCCs by certain drugs such as pregabalin and gabapentin via binding to the alpha2delta subunits of VSCCs can lead to anticonvulsant, anxiolytic, and chronic pain-relieving actions...

..ISSUE: Anticonvulsants that act as ligands at alpha(2)delta subunits of voltage-gated calcium channels are proving to be novel treatments for chronic pain...

..Recent understanding of interactions between monoaminergic neurons may help explain why some antidepressants may be more rapidly energy restoring than others...

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..Taken as a whole, these findings indicate that the pharmacological stimulation of beta3 adrenoceptors may represent an innovative approach for the treatment of anxiety and depressive disorders...

..The use of adjunctive psychotropics and the costs of polypharmacy in patients randomized to receive risperidone or quetiapine were compared in a placebo-controlled double-blind study conducted in India, Romania, and the United States...

..A continuation study of an extract of St. John's wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John's wort extract and placebo...

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..ISSUE: Numerous anxiety disorders may have malfunctioning neuronal circuits in common, which may account for the overlapping symptoms and frequent comorbidity of many anxiety disorders with one another...

..Its effectiveness in specific subgroups of OCD patients with co-morbid anxiety disorders or as an augmentation strategy added to SSRIs remains to be determined...