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The CRH2-receptor density is high relative to control samples (241 generic geriforte syrup 100 caps visa herbals benefits,242) purchase geriforte syrup 100 caps mastercard rumi herbals chennai. Although these obser- in the cingulate cortex buy generic geriforte syrup 100 caps line shivalik herbals, the mPFC generic geriforte syrup 100caps with amex juvena herbals, the CE, the CA-1 region vations would appear most consistent with findings that of the hippocampus, and the PVN and supraoptic nucleus basal cortisol secretion and excretion are abnormally in- of the hypothalamus. An important avenue of future re- creased in PTSD (190,192,232,233), they do not clearly search will involve assessments of the homeostatic balance contradict the findings of normal or reduced peripheral cor- between CRH1- and CRH2-receptor systems in anxiety dis- orders. Disorders Nevertheless, the studies that either identified reductions or were unable to identify elevations in peripheral cortisol The anxiety disorder for which abnormalities of CRH or concentrations in PTSD present a challenge to the hypothe- HPA-axis function has been most commonly reported is sis that the reduced hippocampal volume found in MRI PTSD. Nevertheless, the nature of such abnormalities has studies of PTSD (reviewed earlier) are accounted for by been inconsistent across studies, because basal plasma or cortisol hypersecretion (150). This hypothesis may still be 24-hour urine cortisol concentrations have been reported reconciled with the peripheral cortisol measures associated to be abnormally decreased (227–229), not different (230, with chronic PTSD if the cortisol secretion was elevated 231), or abnormally increased (190,192,232,233) in PTSD near the time of the stressor (191,243). Longitudinal studies samples relative to healthy or trauma-matched control sam- in male patients who developed PTSD after motor vehicle ples. Differences across these studies may reflect effects of accidents suggest that cortisol secretion is elevated 1 month gender, age of illness onset (i. During provoca- Hippocampal damage may thus conceivably occur in PTSD tion of PTSD symptoms by exposure to combat sounds, during a period of excessive cortisol secretion that follows the changes in plasma cortisol and ACTH concentrations the traumatic event and is prolonged enough so that hippo- did not differ between patients with combat-related PTSD campal neuronal atrophy becomes irreversible. An alterna- and either healthy or combat-matched, non-PTSD control tive hypothesis for the reduction of hippocampal volume subjects (232). In response to dexamethasone administra- in PTSD, however, is that this abnormality antedates the Chapter 63: Neurobiological Basis of Anxiety Disorders 915 TABLE 63. EVIDENCE OF ALTERATIONS IN Functional Interactions among CRF-HPA AXIS FUNCTION IN ANXIETY DISORDERSa Noradrenergic, HPA, and CRH Systems PTSD Panic Disorder Coordinated functional interactions between the HPA axis Alteration in urinary cortisol +/–a +/– and the noradrenergic systems play major roles in producing Altered plasma cortisol with + (dec. The secretion 24-hour sampling of CRH increases LC neuronal firing activity and results in Supersuppression with DST ++b – enhanced NE release in a variety of cortical and subcortical Blunted ACTH response to ++ +/– regions (252,253). Conversely, NE release stimulates CRH CRF Elevated CRF in CSF ++ – secretion in the PVN (the nucleus containing most of the Increased lymphocyte ++ NS CRH-synthesizing neurons in the hypothalamus). During glucocorticoid receptors chronic stress in particular, the LC is the brainstem nora- a drenergic nucleus that appears preferentially to mediate NE Findings of decreased urinary cortisol in older male combat veterans and holocaust survivors and increased cortisol in younger release in the PVN (254). Conversely, as CRH release in female abuse survivors may be explainable by differences in gender, the PVN stimulates ACTH secretion from the pituitary and age, trauma type, developmental epoch at the time of the trauma, thereby increases cortisol secretion from the adrenal glands, or timing within illness course. Glucocorticoid-mediated +/–, an equal number of studies support this finding and do not inhibition of NE-induced CRH stimulation may be evident support this finding; +, atleast one study supports this finding and primarily during stress, rather than under resting condi- no studies do not, or the majority of studies support the finding; ++, two or more studies support this finding, and no studies do not tions, as an adaptive response that restrains stress-induced support the finding; +++, three or more studies support this finding, neuroendocrine and cardiovascular effects mediated by the and no studies do not; ACTH, adrenocorticotropic hormone; CRF, corticotropin-releasing factor; CSF, cerebrospinal fluid; dec. NE, cortisol, and CRH thus appear tightly decrease; DST, dihydrostreptomycin; HPA, hypothalamic pituitary linked as a functional system that offers a homeostatic mech- adrenal axis; inc. A clinical phenomenon of anxiety disorders that may be specifically regulated by interactions between NE and glucocorticoid secretion involves the acquisition and consol- idation of traumatic memories. A characteristic feature of PTSD and PD is that memories of the traumatic experience development of PTSD and may comprise a risk factor for or the original panic attack, respectively, persist for decades developing PTSD in response to traumatic stress. In PD, the results of studies examining CRH-receptor In experimental animals, alterations of both brain catechol- and HPA-axis function have been less consistent (Table amine and glucocorticoid levels affect the consolidation and 63. Elevated plasma cortisol levels were reported in one retrieval of emotional memories (50,51). Glucocorticoids study (244), but not in another (245), and the results of influence memory storage by activation of glucocorticoid studies assessing urinary free cortisol have been similarly receptors in the hippocampus, whereas NE effects are me- inconsistent (177,246). In a study of 24-hour secretion of diated in part through -adrenoreceptor stimulation in the ACTH and cortisol, PD subjects had subtle elevations of amygdala (255). In humans, adrenocortical suppression nocturnal cortisol secretion and greater amplitude of ul- blocks the memory-enhancing effects of amphetamine and traradian secretory episodes relative to control subjects epinephrine (256), and propranolol impairs memory for an (247), but these findings await replication. Both normal emotionally provocative story, but not for an emotionally and elevated rates of cortisol nonsuppression after dexa- 'neutral' story (257). These data suggest that the acute methasone administration have been reported in PD (248). It is axis response was higher in PD subjects than in healthy conceivable that long-term alterations in these systems may controls, but the magnitude of this abnormality was less account for memory distortions seen in PTSD, such as the than that seen in depressed samples (249,250). The ACTH memory fragmentation, hypermnesia, and deficits in declar- ative memory. The extent to which pathophysi- ologic heterogeneity within PD samples may account for Several lines of preclinical and clinical evidence have estab- the inconsistency of these findings remains unclear. Central BZD receptors are ex- mediated through a GABAergic mechanism. These agents pressed are present throughout the brain, but they are most are effective for the treatment of a spectrum of anxiety disor- densely concentrated in the cortical gray matter. The BZD ders including social anxiety disorder, generalized anxiety and GABAA receptors form parts of the same macromolecu- disorder, PD, and PTSD. One of the multiple secondary lar complex, and although they constitute distinct binding effects of these agents involves potentiation of GABAergic sites, they are functionally coupled and regulate each other function. For example, in rats, the effective dose of phenel- in an allosteric manner (258). Central BZD-receptor ago- zine (15mg/kg) on the elevated plus maze administered nists potentiate and prolong the synaptic actions of the in- produces a more than twofold increase in whole-brain level hibitory neurotransmitter, GABA, by increasing the fre- GABA concentrations, whereas an ineffective dose of phe- quency of GABA-mediated chloride channel openings (258, nelzine (5. Microinjection of BZD-receptor agonists in limbic (267). Moreover, the N-acetylated metabolite of phenelzine, and brainstem regions such as the amygdala and the PAG N-2-acetylphenelzine, which potently inhibits monoamine exert antianxiety effects in animal models of anxiety and fear oxidase but does not change whole-brain GABA concentra- (260). Conversely, administration of BZD-receptor inverse tions, does not produce anxiolytic effects in the elevated agonists, such as -carboline-3-carboxylic acid ethylester, plus-maze test (267). Transgenic mouse studies have identified behavioral roles for specific GABAA-receptor subunits. The anxiolytic action of diazepam appears absent in mice with 2 subunit point Effects of Stress on Benzodiazepine-GABAA mutations, but it is present in mice with 1 or 3 subunit Receptors point mutations (264,265). These data suggest that the an- xiolytic effect of BZD agonists is at least partly mediated BZD- and GABA-receptor function can be altered by expo- by the GABA -receptor subunit, which is largely ex- sure to stress in some brain regions. In experimental animals A 2 pressed in the limbic system, but not by the subunit, exposed to inescapable stress in the form of cold swim or 3 which is predominately expressed in the reticular activating foot shock, the BZD-receptor binding decreases in the fron- system, or the subunit, which is implicated in mediating tal cortex, with less consistent reductions occurring in the 1 the sedative, amnestic, and anticonvulsive effects of BZDs hippocampus and hypothalamus, but no changes in the oc- (265,266). These findings hold clear implications for inves- cipital cortex, striatum, midbrain, thalamus, cerebellum, or tigations of the pathophysiology of anxiety disorders and for pons (268). Chronic stress in the form of repeated foot the development of anxioselective BZD-receptor agonists. The neurosteroid, allopregnenolone, ex- in BZD-receptor binding were associated with deficits in erts antianxiety effects in conflict paradigms that serve as maze escape behaviors that may have reflected alterations putative animal models of anxiety. The anticonflict effects in mnemonic processing (269,270). Some of these stress of allopregnenolone are reversed by either isopropylbicyclo- effects may be mediated by glucocorticoids, because chronic phosphate, which binds at the picrotoxinin site on the exposure to stress levels of CORT alters mRNA levels of GABAA receptors, or RO15-4513 (ethyl-8-azido-5,6-dihy- multiple GABAA-receptor subunits (271). Consistent with dro-5-methyl-6-oxo-4H-imidazo[1,5- ]-[1,4]benzodiaze- the effects of chronic stress on BZD-receptor expression, pine-3-carboxylate), a BZD-receptor inverse agonist that the Maudsley 'genetically fearful' rat strain shows decreased inhibits GABAA-activated chloride flux in neuronal mem- BZD-receptor density relative to other rats in several brain branes. In contrast, administration of the BZD-receptor an- structures including the hippocampus (272). Allopregnenolone may thus exert reduced BZD-receptor sites in the LC, the NTS, the frontal anxiolytic-like effects by stimulating the chloride channel cortex, and the CE and the LA of the amygdala, and reduced in GABAA receptors by binding at the picrotoxinin site or mRNA levels for the 2 subunit of the GABAA-receptor at a site specific for RO15-4513.
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You have registered your website with Google, FreeBooks4Doctors, etc. Grant yourself the luxury of offering your students the book for half-price at a class or lecture. But whatever you do: your best advertising medium is your website. You should also start a new folder with the heading “2nd Edition”, where you can collect the ideas and thoughts which your readers will enjoy next year. Marketing There are three distribution channels for medical textbooks: bookstores, direct shipping to the reader and the sale of part editions to foundations or pharmaceutical companies. This would be a tragedy if we wanted to market poems or fiction, but fortunately we are producing medical textbooks, 90% of which are sold in specialist bookstores. This means that to cover the market as broadly as possible, it is sufficient to place your books in the 20 to 50 most important medical bookstores in your country. Call them and take 30 seconds to explain what you have to offer. 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Less harmful, but a lot more embarrassing, are attitudes such as “well, you know I can just as well use the products of your competitors” in order to get rid of your own books. The number of books which a pharmaceutical company can buy up ranges from a few hundred to a few thousand – depending on the subject and the involvement of the company in the field about which you are writing. If a company asks you if they can have the part edition exclusively (i. Ora et labora The time has come: you are holding the first copy of the book in your hands. It is one of the moments in life which cannot be repeated endlessly. As soon as a book is out in the world, it develops a life of its own. Books are like children: they only belong to you up to a certain point. Putting a book out into the word is like starting a consensus. On the ballot paper is the question “Is book X good? It is best to carry on tinkering: pocket version, upgrading the website, removal of the copyright and – why not? 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Similarly to the goals of nurse use of the PCAM Organisational processes and arrangements Empowered cheap geriforte syrup 100 caps herbs de provence recipes, Multidisciplinary activated and health and social engaged Person-centred care care team individuals and planning carers Additional non-medical support (formal and informal) FIGURE 10 A composite version of the HoC model purchase generic geriforte syrup online herbs uses. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed 100caps geriforte syrup with amex xena herbals, the full report) may be included in professional journals 73 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising generic geriforte syrup 100 caps mastercard herbs provence. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. DISCUSSION with patients, the rationale for links workers is that, if individuals feel supported in their lives, then they are more likely to respond to information on ways to improve their health and to live well. If these people were to be successfully supported sooner rather than later, then there is a potential that their risk of developing LTCs would be reduced, or further complications delayed or prevented if they have already contracted long-term illness(es). The PCAM is probably most similar to the Links Worker model in its aims. The Links Worker Programme commenced during the PCAM study and its evaluation is still under way. Therefore, the evidence base for the Links Worker Programme is still unclear. However, there is still a need in primary care for nurses (and GPs) who see the majority of patients with LTCs to be able to feel confident in determining whether or not patients have any problems that could be dealt with by the links worker. The completion of the PCAM tool in annual reviews could act as a facilitator for referral to those in links worker-type roles, who could then facilitate access to community-based resources. The two initiatives are more compatible than incompatible, and could strengthen the identification of needs and communication between the primary care team and the links worker. It is also unclear who will fund, and whether or not they will fund, the continuation of the links worker roles in Scotland, and these are not available across the UK. Therefore, the PCAM may still be the best method available for the promotion of biopsychosocial assessment in primary care and, with the development of a locally derived resource pack, could also be the best-available method for facilitating access to a broader range of psychosocial supports. In conclusion, we believe that the PCAM is uniquely developed for primary care and we are not aware of directly comparable assessment tools that have been prepared for and tested in primary care. The PCAM provides a comprehensive and practical approach via the three components of training, the PCAM tool and the resource toolkit. Other initiatives like HoC lack an easily understood and easy-to-use practical tool. The use of the PCAM by primary care nurses as a decision aid for referral to links-type roles in primary care would work really well. Links-type roles could also make use of the PCAM itself. The PCAM could serve as a systematic way of recording needs and actions to be shared across the primary care team (GPs, nurses, links or other social care roles). Patient and public involvement One of the key benefits of including PPI in clinical trials and on trial design is that they are likely to make studies more feasible, at least in terms of patient recruitment. Research has shown that trials with higher levels of PPI are four times more likely to recruit to target. These can help to identify necessary adjustments to improve recruitment and retention. The PPI partners in this study did indeed help to shape the recruitment strategy for patients, which was to opt in to either a focus group study or involved opting in to completing questionnaires and a possible interview. The outcomes needed to include measures of physical health, mental health and social needs. We also required information on actions undertaken by nurses (advice, referrals, signposting) and on whether or not patients had taken up this advice, referral or signposting to services. The complexity of the study design, and its attempt to gather multiple outcomes at both the nurse level and the patient level, was not lost on our PPI members, as we worked together to gather the required knowledge in the most efficient manner. This was probably helped by the degree of knowledge of research that our PPI members had and their enthusiasm for the study. They contributed to the many discussions throughout the study on how to address this and were reassured that the team had tried all possible avenues within the time scale available to achieve practice recruitment and retention. In reflecting on our PPI as a team, we thought it best to allow our PPI members to write their own contributions to this. We asked them to reflect on their experience of working with us and whether or not we could have done anything differently to enable their participation in the study. Their responses are included in the following two subsections. My experience and comments on the Patient Centred Assessment Method process; by patient representative 1 As a patient representative I appreciate the requirement and desirability for academia to be sometimes balanced by a lay point of view and if not present the journey from concept to publication may not be as comprehensive as it could be. I sit as a patient representative (I prefer the term representative patient) on several committees and research groups so feel qualified to state that my experience with this feasibility study was one of the best in terms of support, inclusiveness, consideration and birthday cakes. The panel made an effort to explain any terms or acronyms I or my fellow PR [patient representative] were unfamiliar with and always listened to our viewpoints and took the time to solicit our thoughts. As to the actual content of the study I share the disappointment on the paucity of the total numbers of patients and practices involved but strongly believe that this holistic approach will show many benefits. My particular thanks must go to Professor Maxwell, Dr Carina Hibberd and Ms Nadine Dougall. My experience and comments on the Patient Centred Assessment Method process; by patient representative 2 As a sufferer from a sluggish (not to say absent) NHS protocol in dealing with anxiety issues caused by the diagnosis of a cardiac problem, I joined the Living Better Project Steering Committee which was an RCGP-led study aiming to improve the care of people with LTCs in primary care, hoping for procedural improvement. Unfortunately the results of the research resulting from the Living Better project did not translate into the hoped for improved protocol to establish a route to identify co-lateral problems which frequently resulted alongside a chronic disease diagnosis. But, in PCAM, I saw an opportunity to introduce a method to improve this situation within the existing structure. Encouraged to be involved from the start in discussing the initial documentation and to join the Steering Committee by the key researchers it has been a pleasure to be involved with and to follow the development of this ambitious project. Always encouraged to participate fully in committee discussions and to contribute ideas throughout, and to feel free to criticise, my lay colleague and I were kept involved in all of the developing problems by the project leaders as well as in the successes. Our involvement in the discussion of the final report has also been thorough. The infectious enthusiasm of the researchers and their stoicism when things were difficult have been singular. There is no doubt in my mind that, in PCAM, there is the germ of an idea which will become part of NHS protocol in the years to come. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 75 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. DISCUSSION Strengths and limitations The strength of this study is that it was designed as a feasibility study that has fully tested practice, nurse and patient recruitment and retention. The combination of the five studies, which all contribute to the overall aims of the study, means that, often, multiple sources of information could be used to contribute to overall study findings. For example, studies A, C and D contributed to the acceptability and feasibility of using the PCAM in primary care nurse-led annual reviews, as well as the overall process evaluation (study E). Practices were recruited from very different areas of Scotland, for example from NHS GGC, which has the highest proportion of deprived practices in Scotland, and from NHS Grampian, which has small urban towns and rural areas.
More recently order cheap geriforte syrup on line kan herbals, 4% to 9% of both HIV-1-infected and uninfected homosex- the availability of HAART has led to a still greater sense of ual men reported a major depression in the month before hope order geriforte syrup 100caps line herbals for arthritis. Therefore order geriforte syrup online now 840 herbals, coping strategies in HIV-infected persons study evaluation cheap geriforte syrup 100caps with mastercard himalaya herbals 52, and in the study of Perkins and colleagues may influence the development of depression or anxiety. Evidence also indicates that similar proportions HIV epidemic change. Early studies are difficult to interpret (from zero to 5%) of HIV-1-infected and uninfected per- because study methodology and populations differed con- sons meet DSM-III-R criteria for current anxiety disorders siderably (74). Thus, after more than 15 years of research, the avail- in women using intravenous drugs, but this rate did not able data suggest that the prevalence of major depression is differ from that of men using intravenous drugs (139,140); high in asymptomatic HIV-1-infected gay men in compari- high rates of major depression were found in both seroposi- son with the prevalence in men of similar age in the popula- tive and seronegative men and women using intravenous tion at large, but no higher than that in seronegative gay drugs. However, a gender difference was found; the preva- men of similar age and somewhat lower than that in patients lence of depressive and anxiety symptoms, but not syn- with serious medical illnesses, such as cancer and heart dis- dromes, was higher in women than in men. These findings underscore the issue that held for both seropositive and seronegative subjects. In a mood disorders should not be considered a 'normal' phe- related study of Boland et al. Rather, they should related to depressive symptoms at baseline in a large, multi- be assessed carefully and treated appropriately. Both seronega- Diagnosing major depression in HIV-1-infected patients tive and seropositive women had a high prevalence of de- can be complicated because several symptoms of major pressive symptoms on the Center for Epidemiological depression (i. However, although complaints of fatigue and rison et al. Although psychiatric quently found in patients with significant AIDS-related symptoms in HIV-1-infected persons in the later stages of neurocognitive impairment than in patients in earlier stages illness may represent new-onset psychiatric disorders, it is of the disease. In one retrospective chart review of 46 pa- more likely that these symptoms reflect the direct CNS ef- tients identified with HIV-1-associated dementia, Navia fects of HIV-1, HIV-1-related CNS disturbances, and CNS and Price (148) found that psychotic symptoms had devel- effects of medications used in the treatment of AIDS. Relatedly, data from the San Diego HIV although Leserman and colleagues (138) found an increase Neurobehavioral Research Center (149) suggest that HIV- in depressive symptoms approximately 1. Thus, new-onset psychosis may be worsening HIV infection during a 4-year period. Accordingly, a Evidence from earlier stages of the epidemic suggests that complete organic workup should be considered for HIV- HIV-1 may cause organic mood disturbance. In a 17-month 1-infected patients with significant disturbance of mood or retrospective chart review of patients with AIDS, Lyketsos psychosis. They used a family history of mood disor- HIV-1 Infection der as a 'marker' for functional mood disorders. They fur- ther assumed that coexisting dementia and a low CD4 Available evidence suggests that mood symptoms and syn- count are 'markers' of HIV-1-related mood disorders. In addition, among the holds true in the symptomatic stages of the disease. Although these findings suggest that mania may be a consequence of the direct or indirect Only a small proportion of the published studies of the effects of HIV-1 on the brain, controlled studies have yet treatment of mood disorders in patients with HIV-1 infec- to find this relationship (74). Vitamin B12 deficiency may tion have been double-blinded, randomized, placebo-con- also place HIV-1-infected patients at risk for organic mood trolled studies. Between 20% and 30% of patients with AIDS mine was effective in 97 HIV-infected patients. At 6 weeks, and 7% of asymptomatic HIV-1-infected patients have they found a response rate of 74% in the imipramine group been reported to have a vitamin B deficiency. No changes in CD4 12 more, vitamin B12 deficiency has previously been shown to helper/inducer cell counts were found in the imipramine- be associated with depression and can occur in the absence treated subjects. However, adverse anticholinergic side ef- of hematologic or neurologic signs (146). Although the rela- fects led to discontinuation of imipramine within 6 months tionship between vitamin B12 level and depressive symp- in more than one-third of the responders. Elliott and co- tomatology in HIV-1-infected patients is not clear (147), workers (151) blindly and randomly assigned 75 HIV-sero- it is prudent that the medical evaluation of depressive symp- positive patients to treatment with imipramine, paroxetine, toms in HIV-1-infected patients include an assessment of or placebo. Of the 75 enrolled subjects, 75% completed 6 serum B12 levels. The two antidepressants were found to be equally effi- from HIV-1 involvement of the CNS. Earlier case studies cacious at 6, 8, and 12 weeks, and both were significantly of symptomatic HIV-1-infected persons have reported psy- more efficacious than placebo. Side effects of the tricyclic chotic symptoms, including delusions, bizarre behavior, and antidepressants markedly influenced attrition. Mood disturbances, including euphoria, ir- rate in the imipramine group was 48%, 20% in the paroxe- ritability, and labile or flat affect, have often accompanied tine group, and 24% in the placebo group. Similarly, anxiety and colleagues (152) reported that fluoxetine was more effective agitation were reported in almost half of the reported cases. Rabkin and colleagues (153) recently described had a progressively worsening course, with de- completed a double-blinded, placebo-controlled, 8-week mentia or death occurring within a few months after the trial with fluoxetine in 120 HIV-seropositive subjects. Psychosis may be more fre- Among the subjects who completed the 8-week trial, 74% of Chapter 90: Neuropsychiatric Manifestations of HIV-1 Infection and AIDS 1291 the fluoxetine group responded to treatment, in comparison of the potential for drug interactions between antidepres- with 47% of the placebo group. When intention-to-treat sants that potentially inhibit the CPY450 3A4 isoenzyme analysis was used, the differences between the treatment system and protease inhibitors and for adverse effects of groups were less remarkable (57% of the fluoxetine-treated herbal therapy. Although the outcomes of the open-label subjects responded compared with 41% of the placebo studies have generally been consistent with those of the group). Drug treatment did not alter levels of CD4 cell available double-blinded, randomized, placebo-controlled counts. Thus, the available data suggest that the selective trials, these findings must nonetheless be interpreted cau- serotonin re-uptake inhibitors (SSRIs) are effective and well tiously. Effects of Psychostimulants and Novel Agents Fernandez et al. With either In a study related to the one described above, Rabkin and agent, subjects showed a response rate of approximately colleagues (154) enrolled HIV-infected subjects with 50%; however, subjects treated with desipramine experi- depression who had failed imipramine treatment (i. Although depression at baseline as measured on the and a DSM-III-R diagnosis of depressive disorder, the re- Hamilton Depression Scale (HAM-D) was more severe in sponse rate to dextroamphetamine treatment was 75%. Although systematic follow- tions in their HAM-Dscores. Fluoxetine treatment did not up evaluations were not conducted, anecdotal evidence sug- alter CD4 counts. Fluoxetine was tolerated better than gested that the treatment effect (improved mood and en- imipramine. In an open-label trial of 28 depressed HIV- ergy) was maintained for up to 2 years in some subjects. Side effects resulted in a loss of 18% of the total troamphetamine (5 to 25 mg/d) responded during the 12- sample. Sertraline did not alter the counts of either CD4 week course of treatment, another preliminary observation cells or natural killer cells.