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The roles of either the continuous outcome measures cyklokapron 500mg with amex, including the HAM-D 500 mg cyklokapron fast delivery, SAMe or St purchase cyklokapron 500 mg without a prescription. The very low rate of response both to active may be a useful focus of study. Acupuncture Thus, although the randomized clinical studies using pla- cebo suggest that hypericum has some antidepressant effect As reviewed in Ernst and colleagues (171), several case series in humans (and has effects in animal models for depression), and open clinical trials suggest possible efficacy of acupunc- the data are simply inadequate to say how well St. The NIMH and National Institutes of Health Office ture to amitriptyline. One study (172) compared 5 weeks on Alternative Medicine is currently funding a study of of amitriptyline (average daily dose 142 mg) to electro-acu- hypericum perforatum versus SSRI or placebo, which may puncture in a total of 47 subjects and found no significant further elucidate the efficacy of this compound. A larger replication found no significant difference in outcome between amitriptyline and electro-acupuncture in a 6-week RCT in a total of 241 S-adenosyl-L-methionine depressed inpatient subjects (173). As is well understood, lack of statistically significant difference of a putative treat- S-adenosyl-L-methionine (SAMe) has been tested as a po- ment from a 'known effective' treatment is not strong evi- tential antidepressant over the past 25 years. It is the primary dence for the efficacy of a treatment. In addition, the dura- methyl donor in the CNS for methyl acceptor molecules tion of treatment was relatively short, which would including catecholamines and phospholipids. A 1994 underestimate the maximal amitriptyline effect in these metaanalysis (167) examined the literature through 1992, studies. Although those authors be specific to the treatment of depression), placebo acu- found the aggregate data to show statistically significant puncture (acupuncture at nonspecific locations) or no acu- superiority of SAMe to placebo and equivalence of SAMe puncture. Both the specific and control acupuncture treat- to TCAs, all but two of the comparisons with placebo and ments showed statistical superiority to the no acupuncture two of the comparisons with TCAs were 21 days or less in group on several of the measures, although the differences duration. Equivalence to TCA for such a short interval (be- were not large. There was no difference on any measure fore most of the TCAs effects have been realized) is uncon- between the specific and control acupuncture treatments in vincing. Of the two placebo comparisons of longer duration, this study. Thus, the results of this study are compatible one trial of 30 days was positive and one of 42 days was with a nonspecific effect of the additional attention and negative. A large open investigation (169) efficacy in the treatment of major depression. However, suggested, as did earlier studies, efficacy and very rapid onset results of a recently published small, but randomized, con- of antidepressant effect of parenteral SAMe in humans. One trolled, and double-masked study of women with major study found imipramine-like 'antidepressant' effects of depression (n 38) suggest that acupuncture can provide 1090 Neuropsychopharmacology: The Fifth Generation of Progress significant symptom relief from depression, at rates compa- or managing the illness. Research to find clinically obtain- rable to those of psychotherapy and pharmacotherapy able measures of the disease process would remarkably im- (175). FUTURE RESEARCH ACKNOWLEDGMENTS The aim of treatment is remission, not simply response, Supported in part by the Betty Jo Hay Distinguished Chair given the better prognosis and better function associated in Mental Health, the Rosewood Corporation Chair in with remission. Clinical issues raised by this recognition Biomedical Science, and the Sara M. Seay include: (a) Do medications truly differ in their ability to Center for Basic and Applied Research in Psychiatry. Altshuler, Stanton Sharp combinations of more selective monotherapies) are used Distinguished Chair and Professor, Department of Psychia- compared to more neurotransmitter-selective agents? How much time and effort should be expended to attain Dr. Rush has received research support from: Abbott remission? Wood Johnson Foundation, Meadows Foundation, Na- The importance of functional recovery, in addition to tional Institute of Mental Health, Novartis, Organon, Inc. Some prelimi- Stanley Foundation, Wyeth-Ayerst, and Zeneca. This contention deserves more thorough and Cyberonics, Inc. More research to develop evidence to establish valid pathways and to test their impact compared A. John Rush has received $5,000 per year or more in the to treatment as usual is needed. Mental Health, Stanley Foundation, Robert Wood Johnson Does a particular treatment history (or family history of Foundation, Cyberonics, Inc. Additionally, earlier intervention with less complex treat- Neal Ryan has received $5,000 per year or more in the ments, perhaps in the prodromal stages of the disorder, de- form of honoraria and/or research grant support for the last serves further evaluation—especially with the potential 3 years from the following entities: National Institute of availability of CRF antagonists. If these agents modify the Mental Health, National Library of Medicine, Forest Labo- stress response, could they be given quickly, close in time ratories, Pfizer, Pharmacia & Upjohn, Solvay, SmithKline to the stress, before a full depressive episode appears in those Beecham, and Wyeth-Ayerst. Finally, we still are hampered by having to rely on symp- REFERENCES toms and signs to gauge the adequacy of our treatments. American Psychiatric Press Most of medicine can rely in part on laboratory measures textbook of psychopharmacology, second ed. Washington, DC: to also inform clinicians about modifying the treatment plan American Psychiatric Press, 1998. Chapter 75: Current and Emerging Therapeutics for Depression 1091 2. WPA series in evidence and residual depression by cognitive therapy. Affective disorders: course over the life- depression with cognitive therapy: preliminary findings. Six-year outcome for cott Williams & Wilkins, this volume. 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