Complementary medicines in psychiatry: review of effectiveness and safety.

BACKGROUND: The use of complementary medicines in those with mental health problems is well documented. However, their effectiveness is often not established and they may be less harmless than commonly assumed. AIMS: To review the complementary medicines routinely encountered in psychiatric practice, their effectiveness, potential adverse effects and interactions. METHOD: Electronic and manual literature search on the effectiveness and safety of psychotropic complementary medicines. RESULTS: Potentially useful substances include ginkgo and hydergine as cognitive enhancers, passion flower and valerian as sedatives, St John's wort and s-adenosylmethionine as antidepressants, and selenium and folate to complement antidepressants. The evidence is less conclusive for the use of omega-3 fatty acids as augmentation treatment in schizophrenia, melatonin for tardive dyskinesia and 18-methoxycoronaridine, an ibogaine derivative, for the treatment of cocaine and heroin addiction. CONCLUSIONS: Systematic clinical trials are needed to test promising substances. Meanwhile, those wishing to take psychotropic complementary medicines require appropriate advice.

Pharmacological treatments of cerebellar ataxia.

The confirmed pharmacological treatment of cerebellar ataxia is still lacking. In a recent preliminary trial, we showed that D-cycloserine, a partial NMDA allosteric agonist, may relieve the symptoms. In this paper, major clinical trials to relieve ataxic symptoms are reviewed. Previous studies showed some efficacy of physostigmine in ataxic patients. However, physostigmine did not improve the ataxia in a recent double-blind crossover study. The replacement therapy of the deficient cholinergic system with choline or choline derivatives was tried in patients with Friedreich's ataxia and other ataxic patients, but the result was not definitive. A levorotatory form of hydroxytryptophan (a serotonin precursor), a serotoninergic 5-HT1A agonist, a serotoninergic 5-HT3 antagonist, and a serotonin reuptake inhibitor were also used for the therapy for ataxia. In a double-blind randomized study, buspirone, a 5-HT1A agonist was active in cerebellar ataxia, but the effect is partial and not major. The effects of the studies with the other serotoninergic drugs were not consistent. The effect of sulfamethoxazole-trimethoprim therapy in spinocerebellar ataxia type3/Machado-Joseph disease (MJD) was reported, although the therapy improved spasticity or rigidity, rather than ataxia. In contrast to previous studies, sulfamethoxazole-trimethoprim therapy in MJD had no effect in a 2001 double-blind crossover study. The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy. However, a well-designed double-blind crossover trial is needed to confirm the effect.

Use of cognitive enhancement medication in persons with Alzheimer disease who have a family caregiver: results from the Resources for Enhancing Alzheimer's Caregiver Health (REACH) project.

OBJECTIVE: Aging populations show increased prevalence of cognitive impairment and dementia. Recent efficacy studies report on prescription medications and herbal preparations that affect cognitive functioning, but the prevalence and correlates of cognitive-enhancement (CE) medication use among community-dwelling older persons is not well studied. The authors examined the frequency and appropriateness of use, the importance of a family caregiver in medication decisions for dementia patients, and differences in access to medical care. METHODS: REACH is a multisite feasibility study of several approaches to reducing the negative impacts of caregiving on those living with a family member with dementia. Data on medication use by care-recipients were collected at baseline and 1 year later. RESULTS: At baseline, 31% of 1,222 care-recipients were using a CE medication. Factors independently related to CE use were age, education, functional status, and caregiver vigilance. Within 1 year, 14% started and 30% quit taking CE. Care-recipients more likely to be Starters had spouse-caregivers, more education, and fewer baseline ADL impairments. Quitters had more ADL deficits at baseline and became less able to perform ADL at follow-up than those who continued on CE. CONCLUSIONS: CE medication use among dementia patients with a family caregiver is relatively common, though there is substantial geographic variability. Our findings are mixed with respect to appropriate use of CE medications, suggesting areas for physician education. Our data indicate the importance of the caregiver in CE medication use and suggest that there may be disparities in access to healthcare among people with cognitive impairment.

[Clinical study on effect of yuantong capsule in treating vascular dementia].

OBJECTIVE: To observe the clinical effect of Yuantong Capsule (YTC) in treating vascular dementia (VD). METHODS: Eighty-three patients of VD were randomized on ratio of 2:1 into two groups, the 54 patients in the treated group were treated with YTC orally administered, 3 times a day, 1 capsule in each time. The remaining 29 patients in the control group were treated with Hydergine orally, 3 times a day, 2 mg in each time. The therapeutic course for both groups was 2 months. RESULTS: The therapeutic effect in the treated group was significantly better than that in the control group, significant difference (P < 0.05 or P < 0.01) was shown in comparison of the two groups in terms of the mini-mental state examination (MMSE) and activity of daily living (ADL) test, symptoms scoring, total effective rate, and laboratory indexes findings. CONCLUSION: The therapeutic effect of YTC in treating VD was obvious.

[Pathogenetic basis for using prodectin and teonicol, redergin and aescuzan in complex treatment of chronic gastritis]. / Patogeneticheskie osnovy primeneniia prodektina i teonikola, redergina i éskuzana pri kompleksnom lechenii khronicheskogo gastrita.

The study of the microvessels in bioptates of gastric mucosa and micro haemocirculation in the conjunctiva of 254 patients with chronic gastritis revealed that exacerbation of the gastric process is going on the background of hard terminal bloodstream disorders. They have the generalized character and picture of the typical chronic relapsing trombohaemorrhagic syndrome. The use of Prodectin (250 mg), Teonicolum (150 mg), Redergin (1 tab.) and Aescuzan (25 dr.) 4 times per day during 3 weeks helps to eliminate the microcirculatory disorders and exacerbation of the chronic gastritis.

The effect of topically applied vasoactive agents and testosterone versus testosterone in the treatment of erectile dysfunction in aged men with low sexual interest.

The objective was to evaluate the efficacy and safety of topically applied cream containing testosterone, isosorbide dinitrate and co-dergocrine mesylate compared to testosterone cream in the treatment of erectile dysfunction in aged men with low sexual interest. A randomised double-blind crossover trial was performed over two months. The subjects were 42 men with erectile dysfunction and low normal or slightly depressed testosterone level randomly allocated to two equal groups. Polypharmacy cream containing testosterone 0.8%, isosorbide dinitrate 0.5% and co-dergocrine mesylate 0.06% was applied for one month, and testosterone 0.8% cream for another month. The serum level of total testosterone was measured before and after each phase of treatment. Response to each therapy was assessed by a sexual questionnaire, measurement of tumescence and repeat penile duplex ultrasonography. Twenty-eight patients reported full erection and satisfactory intercourse with the polypharmacy cream. Thirteen men reported full erection and satisfactory intercourse with either cream. Polypharmacy cream increased penile arterial flow (P<0.001) and induced tumescence in 34 patients in lab. No patient in either phase of the study has tumescence or a significant increase in cavernous arterial peak systolic velocities after the application of testosterone cream. Serum level of total testosterone increased in all patients (P<0.05). Sexual desire was improved in 85% and 62% of patients during the treatment with polypharmacy cream and testosterone cream, respectively. No marked side effects were reported after either of them. Topical treatment with cream containing testosterone and vasoactive agents may represent a new effective treatment for erectile dysfunction associating with aging.

Hydergine for dementia.

BACKGROUND: Currently hydergine is used almost exclusively for treating patients with either dementia, or 'age-related' cognitive symptoms. Since the early eighties there have been over a dozen more clinical trials, yet hydergine's efficacy remains uncertain. Although previous reviews offer generally favorable support for hydergine's efficacy, they were, however, limited by a bias with respect to the particular clinical studies chosen (eg, the inclusion of case reports, and uncontrolled trials), and by authors' impressionistic assessments of results. Not surprisingly, there has been a lack of consensus among reviewers with regard to the efficacy of hydergine. In 1994, a meta-analysis was published by the present reviewers who reported that overall, hydergine was more effective than placebo. However they also observed that the statistical evidence for efficacy in 'possible or probable Alzheimer's disease' patients was so modest that one additional statistically non-significant trial would have reduced the results to non significance. OBJECTIVES: Because of uncertainty surrounding the efficacy of hydergine, the goals of this overview were to assess its overall effect in patients with possible dementia, and to investigate potential moderators of an effect. SEARCH STRATEGY: The trials were identified from a search of the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group on 15 November 2000 using the terms hydergin*, ergoloid* and dihydroergo*. Two proprietary databases were searched also. Published reviews were inspected for further sources. SELECTION CRITERIA: Trials to be included must be randomized, double-blind, parallel-group, and unconfounded comparisons of hydergine with placebo for a treatment duration of greater than 1 week in subjects with dementia or symptoms consistent with dementia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers, pooled where appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. Outcomes of interest included clinical global impressions of change and comprehensive rating scales. Potential moderating variables of a treatment effect included: inpatient/outpatient status, trial duration, age, sex, medication dose, publication year, and diagnostic grouping. MAIN RESULTS: There were a total of nineteen trials that met inclusion criteria and that had data sufficient for analysis. Thirteen trials reported sufficient information to use a global rating of improvement and nine trials provided information on a comprehensive rating scale. Three trials provided both outcome measures. It was not possible to use many of the published results in a combined analysis owing to the lack of sufficient data to perform statistical analyses. For the twelve trials that used global ratings, there was a significant effect favoring hydergine (OR 3.78, 95%CI, 2.72-5.27). For the nine trials that used comprehensive ratings, there was a significant mean difference favoring hydergine (WMD 0.96, 95%CI, 0.54-1.37). Hydergine was well tolerated in these trials, with 78% of randomized subjects available for data analyses. Greater effect sizes on global ratings were associated with younger age, and possibly higher dose, although most of the subgroup analyses were statistically insignificant. REVIEWER'S CONCLUSIONS: As in an earlier systematic review, we found hydergine to show significant treatment effects when assessed by either global ratings or comprehensive rating scales (based here on a smaller set of trials than in the earlier published systematic review because trials were required to have data that could conform with MetaView, the Cochrane Collaboration statistics software). The small number of trials available for analysis, however, limited the ability of subgroup analyses to identify statistically significant moderating effects. Unfortunately, most of the randomized, double-blind, and placebo-controlled trials of hydergine were conducted and published before the advent of consensus-based diagnostic standards of dementia in 1984; therefore diagnostic criteria were less specific. As a result, uncertainty remains regarding hydergine's efficacy in dementia.

Alpha-dihydroergocryptine and predictive factors in migraine prophylaxis.

OBJECTIVE: A double-blind, crossover study was carried out to compare the efficacy of alpha-dihydroergocryptine mesylate (10 mg twice daily) vs propranolol (40 mg twice daily) in the prophylaxis of migraine without aura, and to identify possible predictors of therapeutic response by evaluating the symptomatological profile of individual migraine attacks and the autonomic cardiovascular response to noradrenergic and dopaminergic (cold pressor, bromocriptine) tests. PATIENTS AND METHODS: Forty migraineurs (10 males, 30 females) were randomized according to a two-period (3-month), two-treatment, crossover design. Efficacy was assessed using quantitative data recorded in the patient's headache diary. Data were evaluated using the Wallenstein's method. RESULTS: Both drugs showed a significant reduction in all the efficacy variables (headache attacks, days with headache, analgesic consumption) with no difference between treatments. Neither a bromocriptine test, nor a cold pressor test nor the symptomatological profile of individual migraine attacks differed between the two groups of migraine patients. Ten patients experienced at least one adverse drug reaction during the first period of the crossover design, 5 being treated with alpha-dihydroergocryptine and 5 with propranolol. CONCLUSIONS: It is concluded that alpha-dihydroergocryptine is an effective medication for migraine prophylaxis. The biochemical tests and the type of psychological profile cannot be used to predict drug response.

Hydergine for dementia.

BACKGROUND: Currently hydergine is used almost exclusively for treating patients with either dementia, or 'age-related' cognitive symptoms. Since the early eighties there have been over a dozen more clinical trials, yet hydergine's efficacy remains uncertain. Although previous reviews offer generally favorable support for hydergine's efficacy, they were, however, limited by a bias with respect to the particular clinical studies chosen (eg, the inclusion of case reports, and uncontrolled trials), and by authors' impressionistic assessments of results. Not surprisingly, there has been a lack of consensus among reviewers with regard to the efficacy of hydergine. In 1994, a meta-analysis was published by the present reviewers who reported that overall, hydergine was more effective than placebo. However they also observed that the statistical evidence for efficacy in 'possible or probable Alzheimer's disease' patients was so modest that one additional statistically non-significant trial would have reduced the results to non significance. OBJECTIVES: Because of uncertainty surrounding the efficacy of hydergine, the goals of this overview were to assess its overall effect in patients with possible dementia, and to investigate potential moderators of an effect. SEARCH STRATEGY: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'hydergine', 'ergoloids,' 'ergoloid mesylates,' 'dihydroergocristine,' 'dihydroergocryptine,' 'dihydroergotoxine,' and 'dihydroergocornine. MEDLINE, EMBASE, and two proprietary databases were searched also. Published reviews were inspected for further sources. SELECTION CRITERIA: Trials to be included must be randomized, double-blind, parallel-group, and unconfounded comparisons of hydergine with placebo for a treatment duration of greater than 1 week in subjects with dementia or symptoms consistent with dementia. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers, pooled where appropriate and possible, and the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated. Where possible, intention-to-treat data were used. Outcomes of interest included clinical global impressions of change and comprehensive rating scales. Potential moderating variables of a treatment effect included: inpatient/outpatient status, trial duration, age, sex, medication dose, publication year, and diagnostic grouping. MAIN RESULTS: There were a total of nineteen trials that met inclusion criteria and that had data sufficient for analysis. Thirteen trials reported sufficient information to use a global rating of improvement and nine trials provided information on a comprehensive rating scale. Three trials provided both outcome measures. It was not possible to use many of the published results in a combined analysis owing to the lack of sufficient data to perform statistical analyses. For the twelve trials that used global ratings, there was a significant effect favoring hydergine (OR 3.78, 95%CI, 2.72-5.27). For the nine trials that used comprehensive ratings, there was a significant mean difference favoring hydergine (WMD 0.96, 95%CI, 0. 54-1.37). Hydergine was well tolerated in these trials, with 78% of randomized subjects available for data analyses. Greater effect sizes on global ratings were associated with younger age, and possibly higher dose, although most of the subgroup analyses were statistically insignificant. REVIEWER'S CONCLUSIONS: As in an earlier systematic review, we found hydergine to show significant treatment effects when assessed by either global ratings or comprehensive rating scales (based here on a smaller set of trials than in the earlier published systematic review because trials were required to have data that could conform with MetaView, the Cochrane Collaboration statistics software). The small number of trials available for analysis, however, limited the ability of subgroup analyses to identify statistically significant modera

Hipoacusia súbita idiopática / Idiopathic sudden hearing loss

Los autores presentan su experiencia clínica en el manejo de la hipoacusia súbita idiopática (HS) en un trabajo prospectivo realizado entre los años 1980 y 1998. En 53 pacientes con enfermedad, estudiaron sus características clínicas más relevantes y los exámenes de laboratorio más útiles. En este análisis, se concluye que en la gran mayoría de las HSI, no se puede establecer una etiología, y que la tardanza en el tratamiento, la aparición de vértigo en forma concomitante y la hipoacusia severa son síntomas ominosos. En su estudio, los autores establecen distintos grupos según el tipo de curva audiométrica (ascendente, plana y descendente), buscando diferencias de comportamiento. En relación al tratamiento, los autores establecieron tres grupos aleatorios que fueron tratados con vasodilatadores, corticoides o vitaminas. En el trabajo, se puedo establecer que los mejores resultados se obtuvieron con la corticoterapia en todos los tipos de curva audiométrica

[Redergin treatment of hypertensive menopausal women]. / Opyt primeneniia redergina u bol'nykh arterial'noi gipertoniei klimaktericheskogo perioda.

AIM: To assess a hypotensive effect of redergin (dihydroergotoxin)--agonist of dopaminergic receptors--in monotherapy (4.5-6 mg/day) and in combination with enalapril and amlodipin (10 mg/day). MATERIAL AND METHODS: Redergin in monotherapy or combined therapy was given to 106 hypertensive women in pre- or postmenopause and 24 hypertensive women of reproductive age. Antihypertensive effect was assessed by changes in arterial pressure, frequency and severity of hypertensive crises, diuresis, clinical symptoms of menopausal syndrome. RESULTS: A significant fall in arterial pressure, intensive diuresis, less frequent or absent hypertensive crises, relief of menopausal symptoms were observed on day 10-14 of redergin monotherapy of menopausal patients with mild hypertension and in combined treatment of menopausal women with moderate and severe hypertension. CONCLUSION: Antihypertensive and diuretic effect of redergin confirm a pathogenetic role of deficient dopaminergic activity in development of menopausal hypertension.

Inappropriate medication prescribing in homebound older adults.

OBJECTIVES: Little is known about the prescribing of medications in the growing population of homebound older adults. We report on the prevalence and pattern of inappropriate medications in a nursing home-eligible, homebound population. DESIGN: A cross-sectional design. SETTING: A managed care plan for individuals meeting nursing home eligibility. PARTICIPANTS: 2193 homebound people older than age 60. MEASUREMENTS: We reviewed the pharmacy profiles of all older homebound enrollees. We identified the average number of medications per patient and the most commonly prescribed classes of drugs. The medication profiles were also analyzed in the context of the 26 drugs/groups listed as inappropriate by the explicit criteria of Beers [Arch Intern Med 1997; 157:1531-1536]. RESULTS: A total of 2193 people aged 60 to 106 (mean 82.8 +/- 8.8) were taking an average of 5.3 +/- 2.9 drugs (range 0-22). Cardiac drugs and benzodiazepines were the medications most commonly prescribed. We found 1152 of the total 11,689 prescriptions (9.9%) to be inappropriate. Eight hundred seventy-one (39.7%) of these 2193 residents had at least one inappropriate prescription, and 230 (10.4%) had two or more. Of particular concern were 285 people prescribed excessive doses of temazepam and zoldipem, 211 people taking first-generation antihistamines, 115 taking doxepin or amitriptyline, 106 taking an ergoloid, 98 taking dipyridamole, and 85 prescribed a long-acting benzodiazepine. CONCLUSIONS: Our study revealed a high prevalence of psychotropic medications and inappropriate drug use among older homebound residents, a group that is at the highest risk for adverse drug reactions. Because this group is not subject to oversight by regulatory agencies, further interventional studies and provider education will be important.

Pharmacologic management of Alzheimer disease, Part II: Antioxidants, antihypertensives, and ergoloid derivatives.

OBJECTIVE: To provide information about research evaluating antioxidants in Alzheimer disease (AD) and to discuss the potential role of beta-blockers, angiotensin-converting enzyme inhibitors, clonidine, guanfacine, nimodipine, and ergoloid derivatives in AD therapy. DATA SOURCES: Studies, review articles, and editorials identified from MEDLINE searches (from 1989 to 1997) and bibliographies of identified articles. STUDY SELECTION: Studies and review articles addressing antioxidant, antihypertensive, and ergoloid derivative pharmacotherapy research. DATA EXTRACTION: Pertinent information was selected and the data synthesized into a review format. DATA SYNTHESIS: AD is a progressive neuropsychiatric disorder of unknown etiology. Studies evaluating the possible association between a free radical mechanism in AD and the potential role of antioxidants are reviewed. Additionally, the role of beta-blockers, angiotensin-converting enzyme inhibitors, clonidine, guanfacine, nimodipine, and ergoloid derivatives in AD management are discussed. CONCLUSIONS: Preliminary evidence suggests that antioxidants may have a protective effect against the development of AD. Additional prospective, double-blind, placebo-controlled studies are needed to determine the role of antioxidants in the prevention and management of AD. Understanding the role of antioxidants in AD may suggest alternative agents that have similar pharmacologic activity. Beta-blockers may be an option to control agitation in AD patients for whom anxiolytics or antipsychotics are ineffective or are contraindicated because of their adverse effect profiles. Other agents that may have a role in AD therapy include angiotensin-converting enzyme inhibitors, nimodipine, and ergoloid derivatives. Clonidine and guanfacine have thus far shown little promise in improving cognitive function in AD. Further prospective, double-blind, placebo-controlled trials will be necessary to elucidate the role of these agents in AD management.

New drugs for Alzheimer's disease.

Alzheimer's disease is characterized by degeneration of various structures in the brain, with development of amyloid plaques and neurofibrillary tangles. Deficiencies of acetylcholine and other neurotransmitters also occur. Pharmacologic treatment of the disease generally seeks to correct the histopathology, the biochemical derangements or their effects. The only drugs labeled to date for the treatment of cognitive symptoms in patients with Alzheimer's disease are two cholinesterase inhibitors that prevent the breakdown of acetylcholine in the synapse. Both medications are associated with modest improvements in cognitive function. However, all benefit is lost when these drugs are discontinued; the disease then progresses to the level seen in placebo-treated patients. Tacrine, the first cholinesterase inhibitor to be so labeled, must be taken four times daily and is associated with hepatic toxicity. Donepezil is taken once daily. Side effects of the cholinesterase inhibitors include nausea, vomiting and diarrhea, which tend to subside after the titration period. Other drugs that have shown some promise in the treatment of Alzheimer's disease are vitamin E, estrogen, selegiline and a mixture of ergoloid mesylates. Anti-inflammatory drugs and nicotine are also being studied for their effects as neuroprotectors or neurotransmitter enhancers. The caregivers of patients with Alzheimer's disease may see little effect from these or other investigational agents, but nursing home placement may be delayed.

Drug treatment of Alzheimer's disease. Effects on caregiver burden and patient quality of life.

Alzheimer's disease is a devastating illness that will become more common as the population ages. Although clinical diagnosis of the illness is not certain without histological examination of the brain, and misdiagnosis may occur, broad working criteria to help diagnose the likely presence of Alzheimer's disease are available. Thoughtful clinical evaluation improves diagnostic accuracy, and appropriately diagnosed patients are critical for involvement in research into new antidementia agents. Essential to the discovery of new drugs is careful measurement of illness response. A variety of scales--some aimed at patients, others at their caregivers, and yet others for clinicians--assess Alzheimer's disease severity, progression, symptom response, and quality of life. Of note, patient response is not the only measurement of treatment benefit today. Growing interest is also being placed on tracking the possible amelioration of caregiver 'burden'. This burden refers to the psychological, physical, and material costs of providing care for an Alzheimer's patient over long periods of time. A number of scales and questionnaires have been developed and are occasionally used. Many drugs have been tried in Alzheimer's disease, but very few have produced any benefit, and this is often modest. Ergoloid mesylates, initially thought to be effective, are now considered of little value. The cholinomimetic drugs, especially the acetylcholinesterase inhibitor tacrine, have provided a very modest benefit, slowing the progression of the illness for a number of months. No cognitive improvement has been noted with the various nootropic agents such as piracetam. Early studies with levacecarnine (acetyl-L-carnitine), a substance that facilitates the use of fatty acids, memantidine, the dimethyl derivative of amantidine, and the calcium channel blocker nimodipine, have shown some promise, but require larger, more rigorous studies. As mentioned above, documenting effects in individual patients is crucial; examining for potential benefit to caregivers is a growing part of research design. Current treatment efforts will become more sophisticated as a deeper understanding of the neurobiology of Alzheimer's disease develops. For the immediate future, the goal is not cure but slowing of the disease process. Achieving this limited goal would have a substantial impact on the financial and human costs of the illness.