Ginkgo Biloba: No-Go for Alzheimer's PreventionAnother large trial shows no benefit from ginkgo biloba extract in preventing Alzheimer disease, researchers report in the Lancet Neurology.Nearly 2900 older adults without dementia who spontaneously reported memory complaints to their physicians were randomized to consume standardized ginkgo biloba extract or placebo for 5 years. Overall, the rate of diagnosis with probable Alzheimer's did not differ significantly between the ginkgo and placebo groups (1.2 and 1.4 cases per 100 person-years).The authors note that a lower-than-expected Alzheimer's rate in both groups reduced the study's power, while a Lancet Neurology editorialist concludes: "For adults aged 70 years or older with a memory complaint who might be mildly cognitively impaired, use of [ginkgo biloba extract] does not decrease the risk of Alzheimer's disease over 5 years.
Показаны сообщения с ярлыком Гинго Билоба. Показать все сообщения
Показаны сообщения с ярлыком Гинго Билоба. Показать все сообщения
вторник, 25 сентября 2012 г.
Гинго билоба не эффективен в профилактике болезни Альгеймера
пятница, 29 октября 2010 г.
Альтернативные методы лечения шизофрении
Outside of India, however, Sen and Bose's observations on the use of rauwolfia for psychotic disorders were generally ignored. It was not until 1954, when Nathan Kline2 reported that both whole root rauwolfia extract and reserpine—a purer preparation—seemed to be somewhat more effective than placebo in more than 400 inpatients with neuropsychiatric conditions, that clinicians in the West took notice. Although it soon became apparent that phenothiazines were generally more tolerable than reserpine, and even after our enthusiastic embrace of clozapine, a respected 1991 review3 still listed reserpine as 1 of 8 reasonable, evidence-based treatment options for persons affected with the refractory symptoms of schizophrenia.
Two essential omega-3 fatty acids were compared in a 3-month, double-blind pilot study that found that augmentation with eicosapentaenoic acid (EPA) was superior to docosahexaenoic acid (DHA) or placebo in significantly reducing Positive and Negative Syndrome Scale (PANSS) scores; a second study using EPA suggested that supplementation with omega-3 for extended periods can benefit some patients even without antipsychotics.
On the other hand, a 16-week trial in 87 patients that compared 3 g/d of e-EPA with placebo found no difference in positive, negative, mood, or cognitive symptoms of schizophrenia.26 Noting that both the active and placebo groups had improvements in their PANSS ratings, these investigators evaluated the placebo response in 37 study participants and found that the 9.5% improvement in the PANSS total score usually occurred by the end of the first 2 weeks of participation, which argues for the value of a placebo run-in phase for future studies.27
Revisiting the initial findings of plasma membrane abnormalities, a 24-hour dietary recall in 146 community-dwelling patients with schizophrenia found little difference in dietary fatty acid and antioxidant intake from controls.28 However, a more elaborate evaluation of 72 subjects with schizophrenia found that the previously reported membrane lipid abnormalities could be explained by the fact that many of the subjects were smokers and had a significantly different omega-3 dietary intake from that of the controls.
Sitting between mainstream and alternative therapies are amino acid treatments, derived from the recognition that phencyclidine (PCP) psychosis was a better model for schizophrenia than the previous model of amphetamine psychosis. Among other observations, those with PCP intoxication presented with negative as well as positive symptoms. The mechanism of PCP's action was eventually elucidated; it specifically blocked the ion channel in NMDA (N-methyl-d-aspartate) glutamate receptors in the brain. An allosteric modulatory site on this complex receptor has been referred to as the "glycine" site, and its endogenous ligands plausibly may be the amino acids glycine, d-serine, and d-alanine (the latter 2 unusual d-forms present in the brain because of a racemizing enzyme).
A meta-analysis of short-term clinical trials found that treatment augmented with the agonists glycine and d-serine moderately reduced negative symptoms, while partial agonist d-cycloserine was less efficacious.35 These agents do not appear helpful for patients treated with clozapine, although glycine and d-serine may be effective for those being treated with olanzapine or risperidone.
High homocysteine levels have been found to interfere with NMDA receptors in animal studies. Neeman and coauthors46 reported finding lower plasma glycine levels and higher homocysteine levels in patients with schizophrenia compared with controls, and glycine levels correlated with increased negative symptoms. Findings of higher homocysteine levels in patients with schizophrenia may often involve folate-deficient dietary choices, obesity, or cigarette smoking, but one study found that these variables explained relatively little of the high homocysteine levels
Oxidative stress/free radical damage has been proposed as mediating pathology in various neuropsychiatric disorders, including schizophrenia. Small initial trials failed to shed adequate light on the value of ascorbic acid (vitamin C) in the treatment of schizophrenia,49,50 although a recent 8-week study reported significant improvement in Brief Psychiatric Rating Scale scores for those receiving an adjunctive 500 mg/d dosage of vitamin C.51 In addition, one study25 with positive findings used adjunctive omega-3 with vitamins C and E. Additional studies are needed to evaluate this approach.
Another putative adjunctive antioxidant strategy in schizophrenia involves the addition of EGb, a standardized Ginkgo biloba extract. Although several studies have shown fairly consistent preliminary results,52-54 larger and more definitive studies are still needed.
The higher rates of schizophrenia in those born in winter or spring, and the reported association between prenatal exposure to the 1945 famine of the "Dutch Hunger Winter" and later development of schizophrenia in offspring may be rationalized by the hypothesis that schizophrenia is more prevalent in those who have had vitamin D deficiency during the first year of life. The results of a 1966 study of a Finnish-birth cohort lend support to this theory.63 However, as there were very few children not given the then-recommended vitamin D supplement, and since not receiving the supplement may have been associated with other plausible risk factors, this single study provides only weak support for this interesting idea.
Treatment Resistance in Schizophrenia: The Role of Alternative Therapies
четверг, 9 июля 2009 г.
Treatment of Sexual Side Effects: Antidotes
Treatment of Sexual Side Effects: Antidotes
A variety of antidotes have been reported to treat SSRI-induced sexual dysfunction effectively; however, virtually all the data on these agents are derived from open case reports and case series. Insofar as sexual function improvement may be responsive to placebo effects, it is impossible to estimate the true efficacy of these antidotes.[27]
Most of these antidotes either have serotonin-blocking properties (especially 5HT-2 antagonistic effects) or augment catecholamine activity, especially that of dopamine. The antiserotonergic antidotes are cyproheptadine, buspirone, nefazodone, and mianserin. Medications enhancing dopaminergic tone include amantadine, bupropion, and stimulants, with yohimbine showing noradrenergic effects. Among the reported antidotes, the only 2 without antiserotonergic effects or catecholaminergic activity are gingko biloba and urecholine.
Cyproheptadine is an antihistamine with antiserotonergic properties that has been reported for over a decade to reverse antidepressant-induced sexual dysfunction. Only case reports and case series attest to its efficacy.[13,42-44] Effective doses range from 2mg to 16mg. In the most recent and largest case series, 12 of 25 patients described improvement in sexual function when treated with cyproheptadine (mean dose, 8.6mg).[13] Anorgasmia is the sexual side effect most often reported to be alleviated by cyproheptadine. Cyproheptadine is effective when taken either on an as-needed basis (typically, 1 to 2 hours before intercourse) or on a regular basis.
However, cyproheptadine's utility is often limited by its potential side effects. Excessive sedation and the reversal of the therapeutic effect of the antidepressant are major problems that limit its usefulness. Effectively treated depression and bulimic symptoms have been reported to reemerge soon after cyproheptadine was started.[42,45-48] This reversal of therapeutic effects is itself reversible upon discontinuation.
Buspirone is a serotonin-IA partial agonist typically prescribed to treat persistent anxiety. One case series reported that buspirone reversed both decreased sexual interest and orgasmic dysfunction caused by SSRIs.[49] Most patients using buspirone to treat sexual dysfunction take it daily. The dosage is the same as that used for anxiety (15mg to 60mg daily). The mechanism of action of buspirone in treating sexual dysfunction may be reduction of serotonergic tone via stimulation of presynaptic autoreceptors or the alpha-2 antagonist effects of one of buspirone's major metabolites, 1-pyrimidinylpiperazine.
Nefazodone and mianserin are antidepressants with strong postsynaptic blocking properties. In one case report, nefazodone 150mg taken 1 hour prior to sexual activity completely reversed sertraline-induced anorgasmia.[50] Mianserin, an antidepressant with 5HT-2 and alpha-2 adrenergic antagonist properties, is available in many countries but not in the US. It has been reported to reverse serotonin reuptake inhibitor-induced sexual dysfunction in 9 of 15 patients.[51] Mirtazapine is similar in its biological activity to mianserin and might also be effective in reversing sexual side effects. No case reports or case series have yet been published attesting to this, although clinicians have described such an effect. The putative capacity of mianserin and mirtazapine to reverse sexual side effects can be attributed either to their serotonergic activity or presynaptic alpha-2 activity.
Amantadine, a dopamine agonist, is used both as an antiviral agent and as a treatment for Parkinson's disease. It has been shown in a number of small case series to reverse anorgasmia.[13,52-54] Reported effective doses have ranged between 100mg to 400mg taken either on a daily or as-needed basis. In the most recent case series, 8 (42%) out of 19 patients with SSRI-induced sexual dysfunction improved with amantadine 200mg daily.[13] Given dopamine's consistent effect as a neurotransmitter involved in sexual arousal, a number of other dopamine agonists have been explored as treatments for sexual side effects.[2,55,56]
Bupropion is another commonly touted antidote for SSRI-induced sexual dysfunction.[57,58] It is assumed that the mechanism of action by which bupropion reverses sexual side effects is its weak dopamine agonism. The evidence for bupropion's efficacy is scant, except for unpublished, anecdotal reports, one case report,[57] and a case series[58] in which 31 (66%) of 47 patients showed improvement when bupropion was added to the regimen along with the serotonergic antidepressant. Most patients (18/31) with a successful outcome responded to as-needed use of bupropion 75mg to 150mg. Libido, arousal, and orgasmic difficulties were all effectively reversed. Fifteen percent of treated patients stopped taking bupropion because of its stimulation side effects. It is unclear whether bupropion doses need to be somewhat lower than usual when added to fluoxetine or paroxetine, to compensate for pharmacokinetic interactions resulting in increased bupropion levels.[59]
Stimulants, such as methylphenidate, D-amphetamine, and pemoline, are reported to reverse a variety of sexual side effects caused by SSRIs or MAOIs.[60-62] Low doses of 10mg-25mg of methylphenidate or D-amphetamine have been effective. One should add stimulants to an MAOI with extreme caution because of the risk of a hypertensive episode. However, use of an MAOI/stimulant combination has been shown to be safe in a case series.[63] SSRI/stimulant combinations show no similar risks.
Yohimbine is available with or without a prescription (and with unclear purity) in health food stores. It is an alkaloid from the bark of Corynanthe yohimbi (family, Rubiaceae) and has been used for decades to reverse erectile dysfunction.[64-66] Its efficacy in treating sexual dysfunction may be associated with its ability to block presynaptic alpha-2 adrenergic sites, leading to enhanced adrenergic tone.[65] A variety of sexual side effects have been reported to be alleviated by yohimbine in doses ranging from 2.7mg to 16.2mg daily, prescribed either on a regular 5.4mg 3 times daily basis or on an as-needed basis with single doses up to 16.2mg.[13,67-69] In the largest case series, 17 (81%) of 21 patients showed improvement of sexual side effects when treated with yohimbine (mean dose, 16.2mg).[12]
Typical side effects associated with yohimbine include anxiety, nausea, flushing, urinary urgency, and sweating. Yohimbine has been the subject of the only double-blind, placebo-controlled study to evaluate treatment of sexual dysfunction occurring as a drug side effect.[27] Unfortunately, the placebo effect was marked, showing a minimal drug-placebo difference with yohimbine given at a dose of 5.4mg 3 times daily. Yohimbine is also available in lower potency without a prescription. The purity, potency, and safety of these preparations, however, are unknown.
Bethanechol is a cholinergic agonist that has occasionally been useful in reversing sexual dysfunction associated with TCAs and MAOIs.[70-73] Typical doses are 10mg to 20mg as needed or 30mg to 100mg daily in a divided dose. Potential side effects with bethanechol include diarrhea, cramps, and diaphoresis. No reports have evaluated or suggested the efficacy of bethanechol for treating SSRI-induced sexual side effects.
Gingko biloba is an herbal extract reported to reverse a variety of sexual dysfunctions associated with antidepressants. Information about gingko's ability in this regard is derived from the experience of 1 clinician presenting a large case series.[74] The response rate was greater than 80%, with doses ranging from 60mg twice daily to 120mg twice daily (mean daily dose, 207mg). Reported side effects include gastrointestinal upset, lightheadedness, and stimulation effects. Because gingko may inhibit platelet-activating factor, caution should be used in considering its use by any patient with a bleeding diathesis. The mechanism by which gingko might alleviate sexual dysfunction is unknown.
http://www.medscape.com/viewarticle/430614_5
A variety of antidotes have been reported to treat SSRI-induced sexual dysfunction effectively; however, virtually all the data on these agents are derived from open case reports and case series. Insofar as sexual function improvement may be responsive to placebo effects, it is impossible to estimate the true efficacy of these antidotes.[27]
Most of these antidotes either have serotonin-blocking properties (especially 5HT-2 antagonistic effects) or augment catecholamine activity, especially that of dopamine. The antiserotonergic antidotes are cyproheptadine, buspirone, nefazodone, and mianserin. Medications enhancing dopaminergic tone include amantadine, bupropion, and stimulants, with yohimbine showing noradrenergic effects. Among the reported antidotes, the only 2 without antiserotonergic effects or catecholaminergic activity are gingko biloba and urecholine.
Cyproheptadine is an antihistamine with antiserotonergic properties that has been reported for over a decade to reverse antidepressant-induced sexual dysfunction. Only case reports and case series attest to its efficacy.[13,42-44] Effective doses range from 2mg to 16mg. In the most recent and largest case series, 12 of 25 patients described improvement in sexual function when treated with cyproheptadine (mean dose, 8.6mg).[13] Anorgasmia is the sexual side effect most often reported to be alleviated by cyproheptadine. Cyproheptadine is effective when taken either on an as-needed basis (typically, 1 to 2 hours before intercourse) or on a regular basis.
However, cyproheptadine's utility is often limited by its potential side effects. Excessive sedation and the reversal of the therapeutic effect of the antidepressant are major problems that limit its usefulness. Effectively treated depression and bulimic symptoms have been reported to reemerge soon after cyproheptadine was started.[42,45-48] This reversal of therapeutic effects is itself reversible upon discontinuation.
Buspirone is a serotonin-IA partial agonist typically prescribed to treat persistent anxiety. One case series reported that buspirone reversed both decreased sexual interest and orgasmic dysfunction caused by SSRIs.[49] Most patients using buspirone to treat sexual dysfunction take it daily. The dosage is the same as that used for anxiety (15mg to 60mg daily). The mechanism of action of buspirone in treating sexual dysfunction may be reduction of serotonergic tone via stimulation of presynaptic autoreceptors or the alpha-2 antagonist effects of one of buspirone's major metabolites, 1-pyrimidinylpiperazine.
Nefazodone and mianserin are antidepressants with strong postsynaptic blocking properties. In one case report, nefazodone 150mg taken 1 hour prior to sexual activity completely reversed sertraline-induced anorgasmia.[50] Mianserin, an antidepressant with 5HT-2 and alpha-2 adrenergic antagonist properties, is available in many countries but not in the US. It has been reported to reverse serotonin reuptake inhibitor-induced sexual dysfunction in 9 of 15 patients.[51] Mirtazapine is similar in its biological activity to mianserin and might also be effective in reversing sexual side effects. No case reports or case series have yet been published attesting to this, although clinicians have described such an effect. The putative capacity of mianserin and mirtazapine to reverse sexual side effects can be attributed either to their serotonergic activity or presynaptic alpha-2 activity.
Amantadine, a dopamine agonist, is used both as an antiviral agent and as a treatment for Parkinson's disease. It has been shown in a number of small case series to reverse anorgasmia.[13,52-54] Reported effective doses have ranged between 100mg to 400mg taken either on a daily or as-needed basis. In the most recent case series, 8 (42%) out of 19 patients with SSRI-induced sexual dysfunction improved with amantadine 200mg daily.[13] Given dopamine's consistent effect as a neurotransmitter involved in sexual arousal, a number of other dopamine agonists have been explored as treatments for sexual side effects.[2,55,56]
Bupropion is another commonly touted antidote for SSRI-induced sexual dysfunction.[57,58] It is assumed that the mechanism of action by which bupropion reverses sexual side effects is its weak dopamine agonism. The evidence for bupropion's efficacy is scant, except for unpublished, anecdotal reports, one case report,[57] and a case series[58] in which 31 (66%) of 47 patients showed improvement when bupropion was added to the regimen along with the serotonergic antidepressant. Most patients (18/31) with a successful outcome responded to as-needed use of bupropion 75mg to 150mg. Libido, arousal, and orgasmic difficulties were all effectively reversed. Fifteen percent of treated patients stopped taking bupropion because of its stimulation side effects. It is unclear whether bupropion doses need to be somewhat lower than usual when added to fluoxetine or paroxetine, to compensate for pharmacokinetic interactions resulting in increased bupropion levels.[59]
Stimulants, such as methylphenidate, D-amphetamine, and pemoline, are reported to reverse a variety of sexual side effects caused by SSRIs or MAOIs.[60-62] Low doses of 10mg-25mg of methylphenidate or D-amphetamine have been effective. One should add stimulants to an MAOI with extreme caution because of the risk of a hypertensive episode. However, use of an MAOI/stimulant combination has been shown to be safe in a case series.[63] SSRI/stimulant combinations show no similar risks.
Yohimbine is available with or without a prescription (and with unclear purity) in health food stores. It is an alkaloid from the bark of Corynanthe yohimbi (family, Rubiaceae) and has been used for decades to reverse erectile dysfunction.[64-66] Its efficacy in treating sexual dysfunction may be associated with its ability to block presynaptic alpha-2 adrenergic sites, leading to enhanced adrenergic tone.[65] A variety of sexual side effects have been reported to be alleviated by yohimbine in doses ranging from 2.7mg to 16.2mg daily, prescribed either on a regular 5.4mg 3 times daily basis or on an as-needed basis with single doses up to 16.2mg.[13,67-69] In the largest case series, 17 (81%) of 21 patients showed improvement of sexual side effects when treated with yohimbine (mean dose, 16.2mg).[12]
Typical side effects associated with yohimbine include anxiety, nausea, flushing, urinary urgency, and sweating. Yohimbine has been the subject of the only double-blind, placebo-controlled study to evaluate treatment of sexual dysfunction occurring as a drug side effect.[27] Unfortunately, the placebo effect was marked, showing a minimal drug-placebo difference with yohimbine given at a dose of 5.4mg 3 times daily. Yohimbine is also available in lower potency without a prescription. The purity, potency, and safety of these preparations, however, are unknown.
Bethanechol is a cholinergic agonist that has occasionally been useful in reversing sexual dysfunction associated with TCAs and MAOIs.[70-73] Typical doses are 10mg to 20mg as needed or 30mg to 100mg daily in a divided dose. Potential side effects with bethanechol include diarrhea, cramps, and diaphoresis. No reports have evaluated or suggested the efficacy of bethanechol for treating SSRI-induced sexual side effects.
Gingko biloba is an herbal extract reported to reverse a variety of sexual dysfunctions associated with antidepressants. Information about gingko's ability in this regard is derived from the experience of 1 clinician presenting a large case series.[74] The response rate was greater than 80%, with doses ranging from 60mg twice daily to 120mg twice daily (mean daily dose, 207mg). Reported side effects include gastrointestinal upset, lightheadedness, and stimulation effects. Because gingko may inhibit platelet-activating factor, caution should be used in considering its use by any patient with a bleeding diathesis. The mechanism by which gingko might alleviate sexual dysfunction is unknown.
http://www.medscape.com/viewarticle/430614_5
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