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    The use of decision analysis in the phar- coeconomics 1997;11:464–472 proven 260mg extra super avana. Psychopharmacol Bull 1995;31: a medical-offset effect among patients receiving antidepressant 249–258 purchase extra super avana 260mg visa. Tricyclic antidepres- effectiveness of antidepressant treatment in primary care buy extra super avana 260mg amex. Phar- sant and selective serotonin reuptake inhibitors antidepressant macoeconomics 1995;8:524–540. Antidepressant selection citalopramversus standard therapy in major depression. Pharma- and use and healthcare expenditures—an empirical approach. A pharmacoeconomic study of the manage- the cost-effectiveness of oral therapies in the management of pa- ment of major depression: patients in a TennCare HMO. Cost-effectiveness of antidepressant treat- second-line therapies for depression. J Clin Psychiatry 2000;61: ment reassessed [see Comments]. Pharmacoeconomic analysis use and cost of venlafaxine or tricyclic antidepressant therapy of venlafaxine in the treatment of major depressive disorder. Phar- following selective serotonin reuptake inhibitor therapy for macoeconomics 1997;12:286–296. Canadian Coordinating Office for Health Technology Assess- 97. Selective serotonin uptake inhibitors (SSRIs) for major therapy: economic evaluation of fluoxetine, paroxetine, and ser- depression. Part II: The cost effectiveness of SSRIs in treatment traline in a health maintenance organization. Cost-effectiveness of ment for depression with fluoxetine, paroxetine, and sertraline. LENOX ALAN FRAZER Bipolar disorder (BPD), the province of mood stabilizers, the more recent understanding that antidepressants share has long been considered a recurrent disorder. For more this property in UPD have focused research on long-term than 50 years, lithium, the prototypal mood stabilizer, has events, such as alterations in gene expression and neuroplas- been known to be effective not only in acute mania but ticity, that may play a significant role in stabilizing the clini- also in the prophylaxis of recurrent episodes of mania and cal course of an illness. By contrast, the preponderance of past research and stabilization stem from the acute pharmacologic effects in depression has focused on the major depressive episode of antidepressants and mood stabilizers; thus, both the acute and its acute treatment. It is only relatively recently that and longer-term pharmacologic effects of both classes of investigators have begun to address the recurrent nature of drugs are emphasized in this chapter. Thus, it is timely that we address in a single chapter the most promising research rele- vant to the pharmacodynamics of both mood stabilizers and MOOD STABILIZERS antidepressants. Effective treatments exist for However, for the purpose of our discussion, it is important the acute phases of both disorders; maintaining both types to differentiate the three clinical phases of BPD—acute of patients on such drugs on a long-term basis decreases the mania, acute depression, and long-term prophylactic treat- likelihood and intensity of recurrences. Further, because the ment for recurrent affective episodes. Although a variety of drugs are given long-term, they produce a cascade of phar- drugs are used to treat BPD (i. Both classes of psychotropic drugs incur a lag that only a drug with properties of prophylaxis should be period for therapeutic onset of action, even in the acute referred to as a mood stabilizer and included in this chapter. Consequently, it is widely subset of patients with BPD 1. However, the data for long- thought that the delayed pharmacologic effects of these term prophylaxis with anticonvulsants (i. The early realiza- In the absence of a suitable animal model, an experimental tion that lithium is effective prophylactically in BPD and approach, used to ascribe therapeutic relevance to any ob- served biochemical finding, is the identification of shared biochemical targets that are modified by drugs belonging to the same therapeutic class (e.

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    Other work shows that ADHD in children predicts depression in mothers generic 260 mg extra super avana mastercard, but maternal depression provides no Brain Systems additional information for predicting ADHD in siblings of ADHD probands order 260 mg extra super avana fast delivery. This finding suggests that maternal Several types of study provide information about the locus depression is a heterogeneous disorder buy extra super avana 260 mg otc. This idea fits more, it is possible that maternal depression exacerbates with the pharmacotherapy of ADHD because a plausible family conflict and poor parenting, both of which could model for the effects of stimulants is that, through dopami- exacerbate ADHD symptoms. Thus, they can be con- ies implicate orbitofrontal and dorsolateral prefrontal cortex ceptualized as nonspecific triggers of an underlying or regions projecting to these regions; (b) the monkey model predisposition or as modifiers of the course of illness. Nevertheless, converging evi- callosum; (e) the I/LnJ mouse strain shows total callosal dence from the studies reviewed in this chapter supports agenesis along with behavioral features that resemble several empiric generalizations, which should be useful in ADHD; (f) functional neuroimaging finds hypoactivity of guiding future research and theory. The key data supporting this idea are as follows: (a) striatal DAT functioning, abnormal synaptic plasticity at anti-ADHD medications have noradrenergic and dopami- corticostriatal synapses, and long-term changes in synaptic nergic effects; (b) lesion studies in mouse and monkey efficacy in the striatum; and (j) the coloboma mouse shows models implicate dopaminergic pathways; (c) the SHR rat deficient dopamine release in dorsal striatum. Although rare Although the role of catecholamine systems cannot be cases may have a single cause such as lead exposure, general- disputed, future work must also consider other neurotrans- ized resistance to thyroid hormone, head injury, and frontal mitter systems that exert upstream effects on catechola- lobe epilepsy, most cases of ADHD are probably caused by mines. Two prime candidates are nicotinic and serotonergic a complex combination of risk factors. Nicotinic agonists help to control the symptoms From the many twin studies of ADHD, we know for of ADHD, and nicotinic activation enhances dopaminergic certain that genes mediate susceptibility to ADHD. Serotonergic drugs have not been shown ular genetic studies suggest that two of these genes may be to be effective anti-ADHD agents, but knockout mice stud- the DRD4 gene and the DAT gene. To confirm these find- ies suggest that the paradoxical effects of stimulants on hy- ings, we need much more work because, even if the positive 590 Neuropsychopharmacology: The Fifth Generation of Progress studies are correct, they may implicate neighboring genes us with more accurate assessments of the brain along with instead of those targeted by the studies. It seems unlikely a complete sequence of the human genome. These advances that a single 'ADHD gene' causes ADHD with certainty. When the ADHD-related variants of these genes are dis- covered, they will probably be 'normal' variants and will DISCLAIMERS most certainly not have the devastating effects seen in knockout mouse models. Biederman receives research support from Shire Labora- confirms that the 7-repeat allele is a risk factor for ADHD. In addition, he serves on speaking bu- 20% of people who do not have ADHD carry this version reaus for SmithKline Beecham, Eli Lilly & Company, and of the DRD4 gene. Most of these people do not develop Pfizer Pharmaceuticals. ADHD despite the blunted dopaminergic transmission as- sociated with that allele, and many patients with ADHD do not carry the allele. Thus, the 7-repeat allele cannot be REFERENCES a necessary or sufficient cause of the disorder. Attention deficit hyperactivity disorder: a handbook acts in concert with other genes and environmental risk for diagnosis and treatment. Is attention deficit Like genetic studies, studies of environmental risk factors hyperactivity disorder in adults a valid disorder? Harvard Rev suggest that most of these risks exert small but significant Psychiatry 1994;1:326–335. Age-dependent decline of attention deficit hyperactivity disorder. Comorbidity of attention most children with ADHD do not have a history of ADHD. Comorbidity in child psychopathology: concepts, issues and research strategies. J Child Psychol Psychiatry These considerations lead us to conclude that the origin 1991;32:1063–1080. Estimates of the posits ADHD to arise a pool of genetic and environmental prevalence of childhood maladjustment in a community survey variables—each of small effect—that act in concert to pro- in Puerto Rico: the use of combined measures. DSM-III disorders nerability exceeds a certain threshold, he or she will manifest in preadolescent children: prevalence in a large sample from the the signs and symptoms of ADHD.

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    Following good reviews from the first PN about using the PCAM approach discount extra super avana 260 mg mastercard, one practice began to discuss whether or not it could also be used generic extra super avana 260mg amex, to some extent extra super avana 260mg overnight delivery, by GPs. Issues that arose from the PCAM were discussed at MDT case meetings in one practice. This potentially acted to reinforce the embedding of the PCAM. In terms of thinking about using the PCAM in consultations, nurses were often considering its application to the most complex cases in primary care and how they would cope with addressing these complex issues all at once. When asked for examples of patients for role playing, PNs tended to come up with highly complex scenarios, with issues beyond the scope of the PCAM. There was less reflection of its use for less highly complex cases in which less urgent/severe problems could still be addressed to the benefit of patients. However, one practice had also begun to use a HoC approach by the second phase of the study, prompting reflections on the two different approaches. In that practice, it was felt that the PCAM offered a tangible way of supporting patients, which complemented other approaches, and was revealing relevant and important patient issues. During an initial presentation of the PCAM study, one PN recounted that, as a Keep Well practice, PNs were already inviting patients to talk about well-being issues and that it was difficult to contain and manage these types of discussions within an appointment time limit. Concerns about issues being raised that could not be addressed through known resources contributed to this, and the resource pack element of the PCAM was welcomed, as it increased confidence in being able to offer some potential solutions. In training, several reminders to use the resource packs were needed during role plays. However, once PNs began to use the resource packs they praised the relevance of its contents and ease of use. There were many local suggestions for how to improve the resource packs and how they could or would take these forward once the PCAM study had ended. Most wanted a version they could control so that a practice could adapt it in the future. One practice reported that they were copying the resource packs for GPs to also use in consultations. The completion of the PCAM on paper was sometimes seen as an added burden, as it did not fit with the on-screen completion of other data collected during an annual review. This could feel like having multiple tasks to achieve in a consultation and the storage of additional paperwork then has to be considered. Practice interest and attention to psychosocial needs was very common in practices in the most deprived areas. However, even in less deprived practices, having one enthusiast for supporting psychosocial needs in the practice could help push others into trying the PCAM. The consideration of evidence within the process evaluation suggests that the PCAM is more likely to be feasible under the following conditions: l when nurses consider the asking of these questions to be part of the role of nursing l when nurses view their role as facilitating links to information or resources that can address concerns (rather than feeling that they have to address the concerns themselves) l when nurses have the information about resources available to them l when there is a whole-practice commitment to the approach, although in some large nurse-led units, this may be less important. Being aware of this was often helpful in opening discussion with nurses about potential benefits to their practice. A full explanation of each of the domains allowed nurses to consider cases in which touching on an issue might be of value, and increased interest in using the PCAM. The MDT meetings provided an opportunity for the PCAM to be used and discussed, and this helped practices to see the overall value to patients and PNs in using the PCAM. When this happened, nurses commented that it might then encourage the practice to continue to use the PCAM. The resource pack for facilitating signposting and referral was influential in securing practice participation, as it acted as an incentive; it provided nurses with a resource that they already recognised they needed, but did not have available in an easily accessible and LTC-focused format. The low-technology aspect of the paper-based version did appeal to users. Maintaining this resource would be integral to maintaining use of the PCAM. Some PNs reported that patient reluctance to take up referrals may limit the potential impact of the PCAM, reflecting that, in their view, patients were resistant to referrals because of real/perceived barriers, such as the cost and time of travel, shift patterns at work or childcare issues. However, it was recognised that such issues are not limited to the PCAM.

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